Signs and symptoms.

The epileptic seizures which can be observed in infants with West syndrome fall into three categories, collectively known as infantile spasms. Typically, the following triad of attack types appears; while the three types usually appear simultaneously, they also can occur independently of each other:

Cause.

It is still unknown which bio-chemical mechanisms lead to the occurrence of West syndrome. It is conjectured that it is a malfunction of neurotransmitter function, or more precisely, a malfunction in the regulation of the GABA transmission process. Another possibility being researched is a hyper-production of the Corticotropin-releasing hormone (CRH). It is possible that more than one factor is involved. Both hypotheses are supported by the effect of certain medications used to treat West syndrome.  Cases of epilepsy have been historically divided into three different groups: symptomatic, cryptogenic, and unknown. The International League Against Epilepsy (ILAE) recommended in 2011 to abandon these terms for reasons of clarity and instead try to place individual cases into one of the following 3 groups: genetic, structural/metabolic, and unknown. The new terms are more immediately clear in their meaning, except that the structural and metabolic group includes cases that have a genetic component that does not always directly lead to the condition. Only the genetic grouping has a known direct genetic cause. "Unknown" cases may be of "unknown" genetic, structural, metabolic, or other unknown cause.  The old terminology was defined by the ILAE as follows:  The remainder of this section will refer to the older terminology.

Symptomatic.

If a cause presents itself, the syndrome is referred to as "symptomatic" West syndrome, as the attacks manifest as a symptom of another problem. Almost any cause of brain damage could be associated, and these are divided into prenatal, perinatal, and post-natal. The following is a partial list:

Down syndrome.

West syndrome appears in 1% to 5% of infants with Down syndrome. This form of epilepsy is relatively difficult to treat in children who do not have the chromosomal abnormalities involved in Down syndrome. However, in children with Down syndrome, the syndrome is often far more mild, and the children often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one.  EEG records for children with Down syndrome are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down syndrome is not known.  If, however, a child with Down syndrome has seizures that are difficult to control, the child should be assessed for autistic spectrum disorder.

Cryptogenic.

When a direct cause cannot be determined but the child has other neurological disorder, the case is referred to as "cryptogenic" West syndrome. The cryptogenic group is often considered idiopathic while referred to as "cryptogenic".  Sometimes multiple children within the same family develop West syndrome. In this case it is also referred to as "cryptogenic", in which genetic and sometimes hereditary influences play a role. There are known cases in which West syndrome appears in successive generations in boys; this has to do with X-chromosomal heredity.

Genetic.

Mutations in several genes have been associated with West syndrome. These include the Aristaless related homeobox (ARX) and cyclin dependent kinase like 5 (CDKL5) genes. The ARX gene in particular seems to be responsible for at least some of the X linked cases.

Idiopathic.

Occasionally the syndrome is referred to as "idiopathic" West syndrome, when a cause cannot be determined. Important diagnostic criteria are:  Those are becoming rare due to modern medicine.

Diagnosis.

Diagnosis can be made by EEG. In case of epileptic spasms, EEG shows typical hypsarrhythmia patterns.

Treatment.

As of 2017, data on optimal treatment was limited. Therapies with hormones is the standard of care, namely adrenocorticotrophic hormone (ACTH), or oral corticosteroids such as prednisone. Vigabatrin is also a common consideration, though there is a risk of visual field loss with long term use. The high cost of ACTH leads doctors to avoid it in the US; higher dose prednisone appears to generate equivalent outcomes.  As of 2017 data from clinical trials of the ketogenic diet for treating infantile spams was inconsistent; most trials were as a second-line therapy after failure of drug treatment, and as of 2017 it had not been explored as a first line treatment in an adequately designed clinical trial. Epilepsy surgery is recommended in patients with seizures arising from a restricted region.

Prognosis.

It is not possible to make a generalised prognosis for development due to the variability of causes, as mentioned above, the differing types of symptoms and cause. Each case must be considered individually.  The prognosis for children with idiopathic West syndrome are mostly more positive than for those with the cryptogenic or symptomatic forms. Idiopathic cases are less likely to show signs of developmental problems before the attacks begin, the attacks can often be treated more easily and effectively and there is a lower relapse rate. Children with this form of the syndrome are less likely to go on to develop other forms of epilepsy; around two in every five children develop at the same rate as healthy children.  In other cases, however, treatment of West syndrome is relatively difficult and the results of therapy often dissatisfying; for children with symptomatic and cryptogenic West syndrome, the prognosis is generally not positive, especially when they prove resistant to therapy.  Statistically, 5 out of every 100 children with West syndrome do not survive beyond five years of age, in some cases due to the cause of the syndrome, in others for reasons related to their medication. Only less than half of all children can become entirely free from attacks with the help of medication. Statistics show that treatment produces a satisfactory result in around three out of ten cases, with only one in every 25 children's cognitive and motoric development developing more or less normally.  A large proportion (up to 90%) of children suffer severe physical and cognitive impairments, even when treatment for the attacks is successful. This is not usually because of the epileptic fits, but rather because of the causes behind them (cerebral anomalies or their location or degree of severity). Severe, frequent attacks can (further) damage the brain.  Permanent damage often associated with West syndrome in the literature include cognitive disabilities, learning difficulties and behavioural problems, cerebral palsy (up to 5 out of 10 children), psychological disorders and often autism (in around 3 out of 10 children). Once more, the cause of each individual case of West syndrome must be considered when debating cause and effect.  As many as 6 out of 10 children with West syndrome suffer from epilepsy later in life. Sometimes West syndrome turns into a focal or other generalised epilepsy. Around half of all children develop Lennox-Gastaut syndrome.

Epidemiology.

Incidence is around 1:3200 to 1:3500 of live births. Statistically, boys are more likely to be affected than girls at a ratio of around 3:2. In 9 out of every 10 children affected, the spasms appear for the first time between the third and the twelfth month of age. In rarer cases, spasms may occur in the first two months or during the second to fourth year of age.

History.

West syndrome was named after the English doctor and surgeon William James West (1793–1848), who lived in Tonbridge. In 1841 he observed this type of epilepsy in his own son, James E West, who was approximately four months old at the time. He published his observations from a scientific perspective in an article in The Lancet. He named the seizures "Salaam Tics" at the time.

Epileptic spasms, is an uncommon-to-rare epileptic disorder in infants, children and adults. It is named after the English physician, William James West (1793–1848), who first described it in an article published in "The Lancet" in 1841. The original case actually described his own son, James Edwin West (1840–1860). Other names for it are "generalized flexion epilepsy", "infantile epileptic encephalopathy", "infantile myoclonic encephalopathy", "jackknife convulsions", "massive myoclonia" and "Salaam spasms". The term "infantile spasms" can be used to describe the specific seizure manifestation in the syndrome, but is also used as a synonym for the syndrome itself. West syndrome in modern usage is the triad of infantile spasms, a pathognomonic EEG pattern (called hypsarrhythmia), and developmental regression – although the international definition requires only two out of these three elements.

Le syndrome de West, aussi connu sous le nom de spasmes infantiles, est une forme rare d'épilepsie du nourrisson. Nommé d'après le médecin anglais (1793-1848), qui le premier en a fait la description dans un article publié dans la revue "The Lancet" en 1841. D'autres termes sont utilisés pour le décrire : « épilepsie en flexion généralisée », « encéphalite myclonique infantile avec hypsarythmie », « tic de salaam » ("paix" en arabe, utilisé pour dire "bonjour") ou « spasme infantile ».


History.

Thusis is first mentioned in 1156 as "Tosana".

Geography.

Thusis has an area,, of. Of this area, 18% is used for agricultural purposes, while 58.2% is forested. Of the rest of the land, 15.2% is settled (buildings or roads) and the remainder (8.6%) is non-productive (rivers, glaciers or mountains). The municipality is the capital of the Thusis sub-district, of the Hinterrhein district, after 2017 it was part of the Viamala Region. It is the center of the Hinterrhein valley and is located at the confluence of the Hinterrhein and Nolla rivers. Thusis is also at the end of the Viamala canyon. It consists of the village of Thusis and, since 1875, includes Übernolla.

Demographics.

Thusis has a population (as of ) of., 23.6% of the population was made up of foreign nationals. Over the last 10 years the population has grown at a rate of 0.7%. , the gender distribution of the population was 50.4% male and 49.6% female. The age distribution,, in Thusis is; 304 people or 11.2% of the population are between 0 and 9 years old. 142 people or 5.2% are 10 to 14, and 141 people or 5.2% are 15 to 19. Of the adult population, 354 people or 13.0% of the population are between 20 and 29 years old. 460 people or 16.9% are 30 to 39, 402 people or 14.8% are 40 to 49, and 333 people or 12.3% are 50 to 59. The senior population distribution is 255 people or 9.4% of the population are between 60 and 69 years old, 195 people or 7.2% are 70 to 79, there are 104 people or 3.8% who are 80 to 89, and there are 27 people or 1.0% who are 90 to 99.  In the 2007 federal election the most popular party was the SVP which received 31.4% of the vote. The next three most popular parties were the SPS (27.2%), the FDP (24.8%) and the CVP (15.1%).  In Thusis about 63.5% of the population (between age 25-64) have completed either non-mandatory upper secondary education or additional higher education (either university or a "Fachhochschule").  Thusis has an unemployment rate of 1.65%., there were 15 people employed in the primary economic sector and about 5 businesses involved in this sector. 525 people are employed in the secondary sector and there are 36 businesses in this sector. 1,325 people are employed in the tertiary sector, with 190 businesses in this sector.  From the, 1,085 or 39.9% are Roman Catholic, while 1,096 or 40.3% belonged to the Swiss Reformed Church. Of the rest of the population, there are 134 individuals (or about 4.93% of the population) who belong to the Orthodox Church, and there are 46 individuals (or about 1.69% of the population) who belong to another Christian church. There are less than 5 individuals who are Jewish, and 96 (or about 3.53% of the population) who are Islamic. There are 64 individuals (or about 2.36% of the population) who belong to another church (not listed on the census), 101 (or about 3.72% of the population) belong to no church, are agnostic or atheist, and 95 individuals (or about 3.50% of the population) did not answer the question.  The historical population is given in the following table:

Languages.

Most of the population () speaks German (the local Swiss German dialect is known as "Thusnerdeutsch") (77.7%), with Serbo-Croatian being second most common ( 5.2%) and Italian being third ( 4.7%).

Weather.

Thusis has an average of 101.6 days of rain per year and on average receives of precipitation. The wettest month is August during which time Thusis receives an average of of precipitation. During this month there is precipitation for an average of 10.7 days. The month with the most days of precipitation is June, with an average of 10.7, but with only of precipitation. The driest month of the year is February with an average of of precipitation over 10.7 days.

Transport Connections.

Located a short distance to the southwest of Chur, Thusis is accessible using the A13 Autobahn (Junctions 20 and 21). Rhätische Bahn operates services to Thusis (Rhaetian Railway station).

Thusis (, "Romansh: Tusàn") is a municipality in the Viamala Region in the Swiss canton of Graubünden. On 1 January 2018 the former municipality of Mutten merged into the municipality of Thusis.

Thusis est une commune suisse du canton des Grisons, située dans la région de Viamala. Le, Thusis absorbe la commune voisine de Mutten.


History.

Degen is first mentioned about 840 as "Higenae/Egenae". Rumein was mentioned at about the same time as "villa Ramnensis", and in 1325 Vattiz was mentioned as "Vatigis".

Geography.

Degen had an area,, of. Of this area, 78.1% is used for agricultural purposes, while 10.9% is forested. Of the rest of the land, 4% is settled (buildings or roads) and the remainder (7%) is non-productive (rivers, glaciers or mountains).  The former municipality is located in the Lugnez sub-district of the Surselva district. It is on a terrace about above the Glenner valley floor. It consists of the village of Degen and the hamlets of Rumein und Vattiz. Until 1983 Degen was known as Igels.

Coat of arms.

The municipal coat of arms is "Per bend Sable a Mullet Or and of the last a Bend embattled bretessé Sable in bend couped of the first."

Demographics.

Degen had a population (as of 2011) of 235., 5.3% of the population was made up of foreign nationals. Over the last 10 years the population has decreased at a rate of -14.6%. Most of the population () speaks Romansh(73.7%), with German being second most common (20.6%) and Albanian being third ( 3.6%). , the gender distribution of the population was 53.8% male and 46.2% female. The age distribution,, in Degen is; 30 children or 12.1% of the population are between 0 and 9 years old and 34 teenagers or 13.8% are between 10 and 19. Of the adult population, 15 people or 6.1% of the population are between 20 and 29 years old. 34 people or 13.8% are between 30 and 39, 36 people or 14.6% are between 40 and 49, and 40 people or 16.2% are between 50 and 59. The senior population distribution is 28 people or 11.3% of the population are between 60 and 69 years old, 16 people or 6.5% are between 70 and 79, there are 12 people or 4.9% who are between 80 and 89 there are 2 people or 0.8% who are between 90 and 99.  In the 2007 federal election the most popular party was the CVP which received 60.8% of the vote. The next three most popular parties were the SVP (16.2%), the FDP (14.9%) and the SP (8.1%).  The entire Swiss population is generally well educated. In Degen about 59.7% of the population (between age 25-64) have completed either non-mandatory upper secondary education or additional higher education (either University or a "Fachhochschule").  Degen has an unemployment rate of 0.4%., there were 42 people employed in the primary economic sector and about 23 businesses involved in this sector. 17 people are employed in the secondary sector and there are 3 businesses in this sector. 18 people are employed in the tertiary sector, with 10 businesses in this sector.

Heritage sites of national significance.

The Chapel of St. Sebastian is listed as a Swiss heritage site of national significance.

Degen (, ) is a former municipality in the district of Surselva in the Swiss canton of Graubünden. Until 1983, it was officially known as Igels. The municipalities of Cumbel, Degen, Lumbrein, Morissen, Suraua, Vignogn, Vella, and Vrin merged on 1 January 2013 into the new municipality of Lumnezia.

Degen (, ) est une localité et une ancienne commune suisse du canton des Grisons, située dans la région de Surselva.


Precedence Relations.

Operator precedence grammars rely on the following three precedence relations between the terminals:  These operator precedence relations allow to delimit the handles in the right sentential forms: formula_1 marks the left end, formula_2 appears in the interior of the handle, and formula_3 marks the right end. Contrary to other shift-reduce parsers, all nonterminals are considered equal for the purpose of identifying handles. The relations do not have the same properties as their un-dotted counterparts; e. g. formula_4 does not generally imply formula_5, and formula_6 does not follow from formula_7. Furthermore, formula_8 does not generally hold, and formula_9 is possible.  Let us assume that between the terminals and there is always exactly one precedence relation. Suppose that $ is the end of the string. Then for all terminals we define: formula_10 and formula_11. If we remove all nonterminals and place the correct precedence relation: formula_1, formula_2, formula_3 between the remaining terminals, there remain strings that can be analyzed by an easily developed bottom-up parser.

Example.

For example, the following operator precedence relations can be introduced for simple expressions:  They follow from the following facts:  The input string after adding end markers and inserting precedence relations becomes

Operator Precedence Parsing.

Having precedence relations allows to identify handles as follows:  It is generally not necessary to scan the entire sentential form to find the handle.

Operator Precedence Parsing Algorithm.

Initialize: Set ip to point to the first symbol of w$

Precedence Functions.

An operator precedence parser usually does not store the precedence table with the relations, which can get rather large. Instead, precedence functions "f" and "g" are defined. They map terminal symbols to integers, and so the precedence relations between the symbols are implemented by numerical comparison:  Not every table of precedence relations has precedence functions, but in practice for most grammars such functions can be designed.

Example.

Consider the following table (repeated from above):  Using the algorithm leads to the following graph:  from which we extract the following precedence functions from the maximum heights in the directed acyclic graph:

Operator-precedence languages.

The class of languages described by operator-precedence grammars, i.e., operator-precedence languages, is strictly contained in the class of deterministic context-free languages, and strictly contains visibly pushdown languages.  Operator-precedence languages enjoy many closure properties: union, intersection, complementation, concatenation, and they are the largest known class closed under all these operations and for which the emptiness problem is decidable. Another peculiar feature of operator-precedence languages is their local parsability, that enables efficient parallel parsing.  There are also characterizations based on an equivalent form of automata and monadic second-order logic.

An operator precedence grammar is a kind of grammar for formal languages. Technically, an operator precedence grammar is a context-free grammar that has the property (among others) that no production has either an empty right-hand side or two adjacent nonterminals in its right-hand side. These properties allow precedence relations to be defined between the terminals of the grammar. A parser that exploits these relations is considerably simpler than more general-purpose parsers such as LALR parsers. Operator-precedence parsers can be constructed for a large class of context-free grammars.

Les grammaires d'opérateurs permettent d'analyser un sous-ensemble des langages de type 2 (voir Langage formel). Elles permettent en particulier de décrire des expressions mathématiques. Par exemple, il est possible de décrire des expressions mathématiques simples à l'aide de la syntaxe suivante :


Signs and symptoms.

Adult worms remain in subcutaneous nodules, limiting access to the host's immune system. Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. "Wolbachia" species have been found to be endosymbionts of "O. volvulus" adults and microfilariae, and are thought to be the driving force behind most of "O. volvulus" morbidity. Dying microfilariae have been recently discovered to release "Wolbachia" surface protein that activates TLR2 and TLR4, triggering innate immune responses and producing the inflammation and its associated morbidity. The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response.  Skin involvement typically consists of intense itching, swelling, and inflammation. A grading system has been developed to categorize the degree of skin involvement:  Ocular involvement provides the common name associated with onchocerciasis, river blindness, and may involve any part of the eye from conjunctiva and cornea to uvea and posterior segment, including the retina and optic nerve. The microfilariae migrate to the surface of the cornea. Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. Over time, the entire cornea may become opaque, thus leading to blindness. Some evidence suggests the effect on the cornea is caused by an immune response to bacteria present in the worms.  The infected person's skin is itchy, with severe rashes permanently damaging patches of skin.

Mazzotti reaction.

The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine (DEC). Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis. The phenomenon is so common when DEC is used that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with "O. volvulus" microfilaria, localized pruritus and urticaria are seen at the application site.

Nodding disease.

This is an unusual form of epidemic epilepsy associated with onchocerciasis although definitive link has not been established. This syndrome was first described in Tanzania by Louise Jilek-Aall, a Norwegian psychiatric doctor in Tanzanian practice, during the 1960s. It occurs most commonly in Uganda and South Sudan. It manifests itself in previously healthy 5–15-year-old children, is often triggered by eating or low temperatures and is accompanied by cognitive impairment. Seizures occur frequently and may be difficult to control. The electroencephalogram is abnormal but cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) are normal or show non-specific changes. If there are abnormalities on the MRI they are usually present in the hippocampus. Polymerase chain reaction testing of the CSF does not show the presence of the parasite.

Cause.

The cause is "Onchocerca volvulus".

Life cycle.

The life of the parasite can be traced through the black fly and the human hosts in the following steps:

Diagnosis.

Classification.

Onchocerciasis causes different kinds of skin changes, which vary in different geographic regions; it may be divided into the following phases or types:  Additionally, the various skin changes associated with onchocerciasis may be described as follows:

Prevention.

Various control programs aim to stop onchocerciasis from being a public health problem. The first was the Onchocerciasis Control Programme (OCP), which was launched in 1974, and at its peak, covered 30 million people in 11 countries. Through the use of larvicide spraying of fast-flowing rivers to control black fly populations, and from 1988 onwards, the use of ivermectin to treat infected people, the OCP eliminated onchocerciasis as a public health problem. The OCP, a joint effort of the World Health Organization, the World Bank, the United Nations Development Programme, and the UN Food and Agriculture Organization, was considered to be a success, and came to an end in 2002. Continued monitoring ensures onchocerciasis cannot reinvade the area of the OCP.  In 1995, the African Programme for Onchocerciasis Control (APOC) began covering another 19 countries, mainly relying upon the use of the drug ivermectin. Its goal was to set up community-directed treatment with ivermectin for those at risk of infection. In these ways, transmission has declined. APOC closed in 2015 and aspects of its work taken over by the WHO Expanded Special Programme for the Elimination of Neglected Tropical Diseases (ESPEN). As in the Americas, the objective of ESPEN working with Government Health Ministries and partner NGDOs, is the elimination of transmission of onchocerciasis. This requires consistent annual treatment of 80% of the population in endemic areas for at least 10-12 years - the life span of the adult worm. No African country has so far verified elimination of onchocerciasis, but treatment has stopped in some areas (e.g. Nigeria), following epidemiological and entomological assessments that indicated that no ongoing transmission could be detected. In 2015, WHO facilitated the launch of an elimination program in Yemen which was subsequently put on hold due to conflict.  In 1992, the Onchocerciasis Elimination Programme for the Americas, which also relies on ivermectin, was launched. On July 29, 2013, the Pan American Health Organization (PAHO) announced that after 16 years of efforts, Colombia had become the first country in the world to eliminate onchocerciasis. In September 2015, the Onchocerciasis Elimination Program for the Americas announced that onchocerciasis only remained in a remote region on the border of Brazil and Venezuela. The area is home to the Yanomami indigenous people. The first countries to receive verification of elimination were Colombia in 2013, Ecuador in 2014, and Mexico in 2015. Guatemala has submitted a request for verification. The key factor in elimination is mass administration of the antiparasitic drug ivermectin. The initial projection was that the disease would be eliminated from remaining foci in the Americas by 2012.  No vaccine to prevent onchocerciasis infection in humans is available. A vaccine to prevent onchocerciasis infection for cattle is in phase three trials. Cattle injected with a modified and weakened form of "O. ochengi" larvae have developed very high levels of protection against infection. The findings suggest that it could be possible to develop a vaccine that protects people against river blindness using a similar approach. Unfortunately, a vaccine to protect humans is still many years off.

Treatment.

In mass drug administration (MDA) programmes, the treatment for onchocerciasis is ivermectin (trade name: Mectizan); infected people can be treated with two doses of ivermectin, six months apart, repeated every three years. The drug paralyses and kills the microfilariae causing fever, itching, and possibly oedema, arthritis and lymphadenopathy. Intense skin itching is eventually relieved, and the progression towards blindness is halted. In addition, while the drug does not kill the adult worms, it does prevent them for a limited time from producing additional offspring. The drug therefore prevents both morbidity and transmission for up to several months.  Ivermectin treatment is particularly effective because it only needs to be taken once or twice a year, needs no refrigeration, and has a wide margin of safety, with the result that it has been widely given by minimally trained community health workers.

Antibiotics.

For the treatment of individuals, doxycycline is used to kill the "Wolbachia" bacteria that live in adult worms. This adjunct therapy has been shown to significantly lower microfilarial loads in the host, and may kill the adult worms, due to the symbiotic relationship between "Wolbachia" and the worm. In four separate trials over ten years with various dosing regimens of doxycycline for individualized treatment, doxycycline was found to be effective in sterilizing the female worms and reducing their numbers over a period of four to six weeks. Research on other antibiotics, such as rifampicin, has shown it to be effective in animal models at reducing "Wolbachia" both as an alternative and as an adjunct to doxycycline. However, doxycycline treatment requires daily dosing for at least four to six weeks, making it more difficult to administer in the affected areas.

Ivermectin.

Ivermectin kills the parasite by interfering with the nervous system and muscle function, in particular, by enhancing inhibitory neurotransmission. The drug binds to and activates glutamate-gated chloride channels. These channels, present in neurons and myocytes, are not invertebrate-specific, but are protected in vertebrates from the action of ivermectin by the blood–brain barrier. Ivermectin is thought to irreversibly activate these channel receptors in the worm, eventually causing an inhibitory postsynaptic potential. The chance of a future action potential occurring in synapses between neurons decreases and the nematodes experience flaccid paralysis followed by death.  Ivermectin is directly effective against the larval stage microfilariae of "O. volvulus"; they are paralyzed and can be killed by eosinophils and macrophages. It does not kill adult females (macrofilariae), but does cause them to cease releasing microfilariae, perhaps by paralyzing the reproductive tract. Ivermectin is very effective in reducing microfilarial load and reducing number of punctate opacities in individuals with onchocerciasis.

Moxidectin.

Moxidectin was approved for onchocerciasis in 2018 for people over the age of 11 in the United States. The safety of multiple doses is unclear.

Epidemiology.

About 21 million people were infected with this parasite in 2017; about 1.2 million of those had vision loss. As of 2017, about 99% of onchocerciasis cases occurred in Africa. Onchocerciasis is currently relatively common in 31 African countries, Yemen, and isolated regions of South America. Over 85 million people live in endemic areas, and half of these reside in Nigeria. Another 120 million people are at risk for contracting the disease. Due to the vector’s breeding habitat, the disease is more severe along the major rivers in the northern and central areas of the continent, and severity declines in villages farther from rivers. Onchocerciasis was eliminated in the northern focus in Chiapas, Mexico, and the focus in Oaxaca, Mexico, where "Onchocerca volvulus" existed, was determined, after several years of treatment with ivermectin, as free of the transmission of the parasite.  According to a 2002 WHO report, onchocerciasis has not caused a single death, but its global burden is 987,000 disability adjusted life years (DALYs). The severe pruritus alone accounts for 60% of the DALYs. Infection reduces the host’s immunity and resistance to other diseases, which results in an estimated reduction in life expectancy of 13 years.

History.

Onchocerca originated in Africa and was exported to the Americas by the slave trade, as part of the Columbian exchange that introduced other old world diseases such as yellow fever into the New World. Findings of a phylogenetic study in the mid-90s are consistent with an introduction to the New World in this manner. DNA sequences of savannah and rainforest strains in Africa differ, while American strains are identical to savannah strains in western Africa. The microfilarial parasite that causes the disease was first identified in 1874 by an Irish naval surgeon, John O’Neill, who was seeking to identify the cause of a common skin disease along the west coast of Africa, known as “craw-craw”. Rudolf Leuckart, a German zoologist, later examined specimens of the same filarial worm sent from Africa by a German missionary doctor in 1890 and named the organism "Filaria volvulus".  Rodolfo Robles and Rafael Pacheco in Guatemala first mentioned the ocular form of the disease in the Americas about 1915. They described a tropical worm infection with adult Onchocerca that included inflammation of the skin, especially the face (‘erisipela de la costa’), and eyes. The disease, commonly called the “filarial blinding disease”, and later referred to as “Robles disease”, was common among coffee plantation workers. Manifestations included subcutaneous nodules, anterior eye lesions, and dermatitis. Robles sent specimens to Émile Brumpt, a French parasitologist, who named it "O. caecutiens" in 1919, indicating the parasite caused blindness (Latin “caecus” meaning blind). The disease was also reported as being common in Mexico. By the early 1920s, it was generally agreed that the filaria in Africa and Central America were morphologically indistinguishable and the same as that described by O’Neill 50 years earlier.  Robles hypothesized that the vector of the disease was the day-biting black fly, "Simulium". Scottish physician Donald Blacklock of the Liverpool School of Tropical Medicine confirmed this mode of transmission in studies in Sierra Leone. Blacklock’s experiments included the re-infection of Simulium flies exposed to portions of the skin of infected subjects on which nodules were present, which led to elucidation of the life cycle of the Onchocerca parasite. Blacklock and others could find no evidence of eye disease in Africa. Jean Hissette, a Belgian ophthalmologist, discovered in 1930 that the organism was the cause of a “river blindness” in the Belgian Congo. Some of the patients reported seeing tangled threads or worms in their vision, which were microfilariae moving freely in the aqueous humor of the anterior chamber of the eye. Blacklock and Strong had thought the African worm did not affect the eyes, but Hissette reported that 50% of patients with onchocerciasis near the Sankuru river in the Belgian Congo had eye disease and 20% were blind. Hisette Isolated the microfilariae from an enucleated eye and described the typical chorioretinal scarring, later called the “Hissette-Ridley fundus” after another ophthalmologist, Harold Ridley, who also made extensive observations on onchocerciasis patients in north west Ghana, publishing his findings in 1945. Ridley first postulated that the disease was brought by the slave trade. The international scientific community was initially skeptical of Hisette’s findings, but they were confirmed by the Harvard African Expedition of 1934, led by Richard P. Strong, an American physician of tropical medicine.

Society and culture.

Since 1987, ivermectin has been provided free of charge for use in humans by Merck through the Mectizan donation program (MDP). The MDP works together with ministries of health and nongovernmental development organisations, such as the World Health Organization, to provide free ivermectin to those who need it in endemic areas.  In 2015 William C. Campbell and Satoshi Ōmura were co-awarded half of that year's Nobel Prize in Physiology or Medicine for the discovery of the avermectin family of compounds, the forerunner of ivermectin. The latter has come to decrease the occurrence of lymphatic filariasis and onchoceriasis.  Uganda's government, working with the Carter Center river blindness program since 1996, switched strategies for distribution of Mectizan. The male-dominated volunteer distribution system had failed to take advantage of traditional kinship structures and roles. The program switched in 2014 from village health teams to community distributors, primarily selecting women with the goal of assuring that everyone in the circle of their family and friends received river blindness information and Mectizan.

Research.

Animal models for the disease are somewhat limited, as the parasite only lives in primates, but there are close parallels. "Litomosoides sigmodontis ", which will naturally infect cotton rats, has been found to fully develop in BALB/c mice. "Onchocerca ochengi", the closest relative of "O. volvulus", lives in intradermal cavities in cattle, and is also spread by black flies. Both systems are useful, but not exact, animal models.  A study of 2501 people in Ghana showed the prevalence rate doubled between 2000 and 2005 despite treatment, suggesting the parasite is developing resistance to the drug. A clinical trial of another antiparasitic agent, moxidectin (manufactured by Wyeth), began on July 1, 2009 (NCT00790998).  A Cochrane review compared outcomes of people treated with ivermectin alone versus doxycycline plus ivermectin. While there were no differences in most vision-related outcomes between the two treatments, there was low quality evidence suggesting treatment with doxycycline plus ivermectine showed improvement in iridocyclitis and punctate keratitis, over those treated with ivermectine alone.

Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm "Onchocerca volvulus". Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindness due to infection, after trachoma. The parasite worm is spread by the bites of a black fly of the "Simulium" type. Usually, many bites are required before infection occurs. These flies live near rivers, hence the common name of the disease. Once inside a person, the worms create larvae that make their way out to the skin, where they can infect the next black fly that bites the person. There are a number of ways to make the diagnosis, including: placing a biopsy of the skin in normal saline and watching for the larva to come out, looking in the eye for larvae, and looking within the bumps under the skin for adult worms. A vaccine against the disease does not exist. Prevention is by avoiding being bitten by flies. This may include the use of insect repellent and proper clothing. Other efforts include those to decrease the fly population by spraying insecticides. Efforts to eradicate the disease by treating entire groups of people twice a year are ongoing in a number of areas of the world. Treatment of those infected is with the medication ivermectin every six to twelve months. This treatment kills the larvae but not the adult worms. The antibiotic doxycycline weakens the worms by killing an associated bacterium called "Wolbachia", and is recommended by some as well. The lumps under the skin may also be removed by surgery. About 15.5 million people are infected with river blindness. Approximately 0.8 million have some amount of loss of vision from the infection. Most infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas of Central and South America. In 1915, the physician Rodolfo Robles first linked the worm to eye disease. It is listed by the World Health Organization (WHO) as a neglected tropical disease.

L’onchocercose ou cécité des rivières est une filariose cutanée, due à un nématode parasite "Onchocerca volvulus", lequel peut vivre jusqu'à quinze années dans le corps humain.


History.

The paper was established on 15 June 1948 and was published in Pingshan, Hebei, until its offices were moved to Beijing in March 1949. Ever since its founding, the "People's Daily" has been under direct control of the Party's top leadership. Deng Tuo and Wu Lengxi served as editor-in-chief from 1948–1958 and 1958–1966, respectively, but the paper was in fact controlled by Mao's personal secretary Hu Qiaomu.  During the Cultural Revolution, the "People's Daily" was one of the few sources of information from which either foreigners or Chinese could figure out what the Chinese government was doing or planning to do. During this period, an editorial in the "People's Daily" would be considered an authoritative statement of government policy, was studied and reproduced nationwide, and analyzed globally for insight into the Party's plans. The most important editorials were jointly published by "People's Daily", "People's Liberation Army Daily" and "Red Flag", from 1967 to 1978, so called "Two newspapers and one journal" (), directly representing the highest voice of Chinese Communist Party.  Newspaper articles in the "People's Daily" are often not read for content so much as placement. A large number of articles devoted to a political figure or idea is often taken as a sign that the mentioned official or subject is rising. Likewise with articles on geographical areas foreign or domestic; recently increased interest in Latin America has been shown.  Editorials in the "People's Daily" are regarded both by foreign observers and Chinese readers as authoritative statements of official government policy, and are therefore studied with care. Distinction is made between editorials, commentaries, and opinions. Although all must be government approved, they differ sharply on the amount of official authoritativeness they contain by design – from the top. For example, although an opinion piece is unlikely to contain views opposed to those of the government, it may express a viewpoint, or it may contain a debate that is under consideration and reflect only the opinions of the writer: an editorial trial balloon to assess internal public opinion. By contrast, an official editorial, which is rather infrequent, means that the government has reached a final decision on an issue.  During the Tiananmen Square protests of 1989, the "People's Daily" editorial of 26 April, which condemned "unlawful parades and demonstrations," marked a significant moment in the newspaper's history. The editorial increased tension between the government and protesters, and top CPC leaders argued about whether to revise it. An article that compiles the most important editorials was released by the "People's Daily" during the student movement.  Since the mid-1990s, the "People's Daily" has faced a decline of governmental subsidies combined with increasing competition from international news sources and Chinese tabloids. As part of its effort to modernize, it began an online edition in 1997, and the web bulletin forums, such as the Strengthening Nation Forum in the Chinese edition, has been known for their surprisingly candid content.  An analysis of the wording of all the issues of the "People's Daily" from 1995 to 2000 was used in the writing of "The First Series of Standardized Forms of Words with Non-standardized Variant Forms".  The "People's Daily" is also responsible for the publication "Global Times", and hosts the Strengthening Nation Forum on its website.

Writing practices.

The "People's Daily" employs "writing task groups" () of various staff to compose editorial pieces to signal the significance of certain pieces or their relationship to the official views of the Communist Party. These groups are published under pen names that may correspond with the topic and weight of a piece, and what specific government or Communist Party body is backing it, often with homophonous references to their purpose. They may be used frequently over many years or only for a few specific pieces.

Online version.

The "People's Daily" also maintains a multilingual internet presence; and established the "People's Daily Online" (人民网) in 1997.  The internet website of "People's Daily" includes pages in Arabic, French, Russian, Spanish, Japanese and English. In comparison to the original Chinese version, the foreign-language version offers less in-depth discussion of domestic policies and affairs and more editorial about China's foreign policies and motives, often explaining China's positive intentions.  In 2014 the newspaper launched a Chinese-language application which was followed on October 15, 2017 by an English-language version.

Overseas media platforms.

"People's Daily" in recent years has been expanding its publicity on the overseas social media platforms. It has tens of millions followers on its Facebook page, Twitter account, Instagram account, and YouTube account. However, an unusually high proportion of its followers are virtually inactive and likely to be fake users, according to the study of Committee to Protect Journalists.  There have been calls for the "People's Daily" to register as a foreign agent under the Foreign Agents Registration Act in U.S. In 2020, the United States Department of State designated the "People's Daily" a "foreign mission," thereby requiring it to disclose more information about its operations in the U.S.

The People's Daily () is the largest newspaper group in China. The paper is an official newspaper of the Central Committee of the Communist Party of China, published worldwide with a circulation of 3 million. In addition to its main Chinese-language edition, it has editions in English, Spanish, Japanese, French, Russian, Portuguese, Arabic, Tibetan, Kazakh, Uyghur, Zhuang, Mongolian, and other minority languages in China. The newspaper provides direct information on the policies and viewpoints of the Communist Party.

Le Quotidien du Peuple (en chinois 人民日报, hanyu pinyin : "Rénmín Ribao") est l'organe de presse officiel du Comité central du Parti communiste chinois. Avec son tirage de trois millions d'exemplaires en 2012, le journal est classé par l'Unesco parmi les dix plus grands du monde.


History.

The issue of representation for French nationals abroad was first addressed in the French Fourth Republic (1946–1958). Three seats were allocated to the Council of the Republic (the then-upper house of Parliament), representing citizens residing in Europe, America and Asia-Oceania. In addition, there were four agencies based in Paris also representing French interests abroad: the Union of French Chambers of Commerce Abroad, the Federation of French Teachers Abroad, the Federation of French Veterans Residing Outside France, and the Union of French Citizens Abroad (UFE). The conflict between these organization and the National Assembly in appointing the three members of the Council of the Republic led to the decision to form an entirely new body to represent French citizens abroad.  Foreign minister Georges Bidault signed the decree establishing the High Council of French Citizens Abroad (, CSFE) in July 1948. The CSFE consisted of 55 members: the three Councillors of the Republic representing French nationals abroad, the presidents of the four organizations above, 42 elected members, and five members appointed by the Minister of Foreign Affairs. The first elections were held in 1970 in 70 countries.  Turnout in these elections suffered a decline from 1997, which prompted efforts to extensively reform the CSFE. It was renamed the Assembly of French Citizens Abroad. The proportion of elected members was further increased. In addition, the electoral boundaries were revised to account for the changing demographics of French nationals abroad.

Role.

The assembly is tasked with protecting the interests of French citizens abroad on issues such as the teaching of French, rights as citizens, social and economic problems, and taxation. They advise the French government on issues concerning French nationals living outside France and the role of France in overseas developments. The assembly also appoints representatives to various public agencies in France, including the National Stock Exchange, Permanent Commission for Employment and Vocational Training of French Citizens Abroad, etc.  The assembly meets four times a year. Bureau meetings take place in June and December, while plenary sessions are held in March and September.

Organization.

Members.

The AFE is composed of 90 members:

Secretariat.

Day-to-day affairs are run by a general secretariat. The secretary general is appointed by the Minister of Foreign Affairs.

President.

The council is presided over by the Minister of Foreign Affairs. He is the council's president, and is assisted by three vice presidents elected by the council.

Committees.

Members also join committees which prepare reports on specific issues which are submitted to the council's sessions. The permanent committees include:

Elections.

Elections to the assembly are staggered based on geographical location.  The 90 elected seats are distributed among 15 electoral districts proportional to population. The districts are as follows:

Composition.

Members organize themselves into political groups. A minimum of 18 members is required to form a group. The assembly currently consists of four groups.

The Assembly of French Citizens Abroad () is the political body that represents French citizens living outside France. The assembly advises the government on issues involving French nationals living outside France, as well as the role of France in overseas developments. Membership consists of directly elected representatives, senators representing French citizens abroad and officials appointed by the Ministry of Foreign and European Affairs.

LAssemblée des Français de l'étranger (abrégée en AFE) est une des instances politiques consultatives qui représente les Français établis hors de France, l'autre étant le conseil consulaire.


History.

The history of Cahors winemaking go back to the era of Ancient Rome, with vines being planted in the area around 50 BC. Since that time, the vines have remained in the land of Quercy and their history has been combined with that of the region.  The region of Cahors enjoyed a great reputation from the Middle Ages until the late 19th century. Its "black wine" was sold shipped from England to Russia. Similar to many other winemaking regions, Cahors was hit badly by The Great French Wine Blight in the late 19th century, when the vines were attacked in the phylloxera epidemic. In the case of Cahors, this happened in 1883-1885.  In February 1956, Cahors was hit by frosts which wiped out almost all the vineyards of the region, which thus needed to be replanted "en masse". In this replanting, Malbec became more dominant than it had been before. Cahors was awarded AOC status in 1971.  Since 2007, the UIVC (Interprofessional Wine Union of Cahors) has developed an association with Wines of Argentina, the agency in charge of promoting Argentine wines at an international level. The same agency originally created World Malbec Day, which is celebrated on the 17th of April every year.

Soils and climate.

Most of the vineyards are located on the gravel terraces within the meanders formed by the river Lot. The lowest terrace is too close to the river and therefore not suitable for viticulture; vineyards have only been established on the second, third, and fourth terraces. There is increasing interest in the plateau (technically the fourth terrace) for viticulture called "Les Causses".  The climate of Cahors is mainly influenced by the Atlantic Ocean, with hot summers and wet winters. In contrast to Bordeaux, it is also influenced by the Mediterranean Sea. The river Lot is an important factor for the microclimate in the vineyards, especially as the nearby Massif Central may occasionally cause severe frost in winter.

Wineries.

Wineries include Château Rouffiac, Château Bovila, Clos de Gamot, Château de Haute-Serre, Mas del périé Fabien Jouves, Château de Mercuès, Clos La Coutale, Château La Caminade, Château de Lagrézette, Château Saint-Didier-Parnac, Château Haut-Monplaisir, Château Famaey, Château Chambert and Château Lacapelle Cabanac.

Kagor wine.

Kagor is a Moldovan wine made from Cabernet Sauvignon grapes. Its name comes from Cahors, France.

Cahors () is a red wine from grapes grown in or around the town of Cahors, France. Cahors is an "Appellation d'origine contrôlée" (AOC) (Controlled designation of origin) which forms part of the South West France wine region. The dominant grape variety in AOC Cahors wines is Malbec, which must make up a minimum of 70% of the wine, and which is known locally as "Auxerrois” or "Côt". It is supplemented by up to 30% Merlot and Tannat.

Le cahors est un vin rouge français d'appellation d'origine protégée du vignoble du Sud-Ouest de la France. Son vignoble produit exclusivement du vin rouge avec le cépage côt N (appelé aussi malbec ou auxerrois). Il est situé à l'ouest de la ville de Cahors, à cheval sur la vallée du Lot dans le département du même nom et sur les causses du Quercy au sud de cette vallée.


Background.

"Riverdance" is rooted in a three-part suite of baroque-influenced traditional music called "Timedance". "Timedance" was composed, recorded and performed for the 1981 Eurovision Song Contest, which was hosted by Ireland. At the time, Bill Whelan and Dónal Lunny composed the music, augmenting the Irish folk band Planxty with a rock rhythm section of electric bass and drums and a four-piece horn section. The piece was performed, with accompanying ballet dancers, during the interval of the contest, and later released as a Planxty single. Whelan had also produced "EastWind", a 1992 album by Planxty member Andy Irvine with Davy Spillane, which fused Irish and Balkan folk music and influenced the genesis of Riverdance. Thirteen years later, Whelan was invited to do the intermission piece for another Eurovision Song Contest in Dublin, and composed Riverdance. In a book about Planxty ("The Humours of Planxty", by Leagues O'Toole), Whelan says, "It was no mistake of mine to call it Riverdance because it connected absolutely to Timedance".

History.

Eurovision performance and aftermath of interval act (1994).

"Riverdance" was first performed during the seven-minute interval of the 1994 Eurovision Song Contest at the Point Theatre in Dublin on 30 April 1994. The performance was transmitted to an estimated 300 million viewers worldwide and earned a standing ovation from the packed theatre of 4,000 people. The performance is often considered the most well known interval act in Eurovision Song Contest history. Riverdance was later performed as an interval act at both the "" (2005) and "Eurovision Song Contest's Greatest Hits" (2015) events.  As one report put it, lead dancers Michael Flatley and Jean Butler ""transformed the previously chaste and reserved traditional dance form into something else entirely"", and after witnessing the initial enthusiasm for the performance in Ireland, husband and wife production team Moya Doherty and John McColgan decided to invest over $1 million into producing a full-length show.  The song "Riverdance" was released as a single featuring Anúna and the RTÉ Concert Orchestra and entered the Irish Singles Chart at No. 1 right after the Eurovision debut, staying there for 18 weeks—the longest amount of time a song has ever topped the Irish chart. It is currently the second highest-selling single of all time in Ireland, behind only Elton John's 1997 double A-side "Candle in the Wind 1997"/"Something About the Way You Look Tonight".  A video benefiting war-torn Rwanda raised $500,000 for the cause and sold 100,000 copies in a week. On 11 August 1994, in response to the Rwandan genocide of May/June 1994, the RTÉ video 'Riverdance for Rwanda' was launched to help raise money for Irish relief agencies in Rwanda.  In November 1994, Riverdance, the original seven-minute version, was invited to perform in London at the prestigious Royal Variety Performance in the presence of Prince Charles. The act, which took place on 28 November at Dominion Theatre, was introduced on stage by Sir Terry Wogan. Earlier that month, tickets went on sale for "Riverdance: The Show", exceeding IR£1million in three weeks.

Dublin and London (February–July 1995).

"Riverdance: The Show" opened at the Point Theatre in Dublin on 9 February 1995. The five-week run was sold out within three days of the tickets going on sale, with tickets reaching record sales of over 120,000. Behind Doherty and McColgan, and composer Bill Whelan, the show starred Flatley and Butler, and featured many of the original Eurovision dance troupe. In April 1995, video release of Riverdance went straight to No. 1 in the Irish charts.  On 8 May 1995, Riverdance performed at the Royal Gala 50th Anniversary of VE Day celebrations at the special invitation of Prince Charles. The show attracted a television audience of 20 million, introducing Riverdance to a whole new set of fans.  On 5 June 1995, UK video release of Riverdance went straight to the No. 2 position in the UK charts, moving to No. 1 the following week, and holding the No. 1 or No. 2 positions for the next seven months, becoming the all-time best-selling music video in the UK. A day later, Riverdance opened at The Apollo in London for a sell-out four-week run.  On 17 July 1995, Riverdance performed at London's Royal College of Music in the presence of Queen Elizabeth The Queen Mother, Queen Elizabeth II, and Princess Margaret. Later that month, Riverdance returned, by popular demand, to the Point Theatre for a six-week sell-out run.

Flatley's departure and second London run (October 1995).

Despite the show's growing success, cracks were beginning to appear in the relationship between the producers and lead dancer Michael Flatley. Flatley had choreographed many of the numbers in the multicultural spectacle, but after the show took off, the two parties clashed over salary and royalty fees. At the end of September 1995, a contract dispute arose between Flatley and Riverdance. On 29 September, days before the show was due to reopen for a second sell-out run at The Apollo, Flatley's TV appearances suddenly became focused on rumours that he was about to walk out. Flatley claimed the dispute had nothing to do with money, but rather creative control of his own choreography. No contract was ever signed—despite media reports indicating he had—because Flatley and his management would not agree to terms. Negotiations reached a stalemate by 2 October, and with 21 hours to go before the show's opening, Doherty opted to sack her star, replacing him with Colin Dunne, nine-times World Irish Dancing Champion. Dunne, who had only just joined the cast and creative team of Riverdance, was initially invited to choreograph and perform the newly commissioned number "Trading Taps" with Tarik Winston. To make matters worse for the producers, Jean Butler turned up days before opening night with her leg in a cast and on crutches, and was unable to perform. As a result, Dunne paired up with original Eurovision troupe member Eileen Martin for the opening night, as they looked to salvage the show and make a name for themselves.  On 3 October, Riverdance opened for another six-week sell-out run at The Apollo. By overwhelming public demand, the run was extended twice, making a box office record of 151 sold out shows at the venue. During this extended period, Riverdance returned to the Royal Variety Performance at Dominion Theatre, where they performed Dunne's choreographed piece "Trading Taps" in the presence of Queen Elizabeth and Prince Philip on 20 November 1995.

New York City (March 1996).

Following phenomenal success in Dublin and London in 1995, Riverdance travelled to the United States for the first time in March 1996. On 13 March, the show opened at the legendary Radio City Music Hall for the first of eight sold-out performances over five days. Costing about $2 million to bring the show from Ireland, Riverdance broke even in its first New York outing.

Continued success in Ireland and London (March–May 1996).

After returning to Ireland and incurring successful runs in Belfast and Cork, Riverdance made their way back to The Apollo in May 1996 for a three and a half month run; the show saw advance box office sales in excess of UK£5m. The show was later extended until the middle of January 1997.

US tour (October 1996 – February 1997).

On 2 October 1996, Riverdance kicked off its US tour at Radio City Music Hall, christening their new US company the Lee (after Cork's main river), while the company continuing to perform in the UK was dubbed the Liffey (after Dublin's main river). After 23 performances at Radio City between 2 October and 20 October, the Lee company moved on to Chicago, Los Angeles and Boston, as well as Detroit and Minneapolis.

Cast departures.

A number of cast departures occurred following the halcyon period of early 1996. In September 1996, Anúna left the show, which was followed swiftly by Jean Butler's departure in January 1997. Then in June 1998, Colin Dunne left Riverdance to begin work on a new project with Butler – "Dancing on Dangerous Ground".

Early 2000s.

In March 2000, the show moved to Broadway's Gershwin Theatre and featured lead dancers Pat Roddy and Eileen Martin of the Shannon company, and singers Brian Kennedy and Tsidii Le Loka. Colin Dunne briefly returned to Riverdance in July 2002 to perform his original choreographed piece "Trading Taps" at New York City's One World Jam at Radio City Music Hall. In June 2003, Breandán de Gallaí and Joanne Doyle featured as the lead dancers at the Opening Ceremony of the 2003 Special Olympics in Dublin. The Opening Ceremony performance also featured the longest troupe line ever seen in an Irish dance show, with over 100 dancers.

Legacy.

"Riverdance" continues to be performed all over the world, in a diminished format and in smaller venues. Current productions are geared towards smaller theatres, whereas past productions have been performed in large theatres and arenas. Sets have therefore been simplified and some numbers contain fewer performers than in past productions (such as those seen on the Live from New York City (1996) and Live from Geneva (2002) DVDs). Each production company is named after an Irish river: Liffey, Lee, Lagan, Avoca, Shannon, Boyne, Corrib, Foyle, Moy and Bann.  On 21 July 2013, a record was set when a line of 1,693 dancers from 44 countries danced to "Riverdance" on a bridge overlooking the River Liffey, led by Jean Butler and Padraic Moyles.

Musicians.

In the spirit of traditional sessions, the musicians play on stage without sheet music.

Riverdance is a theatrical show consisting mainly of traditional Irish music and dance. With a score composed by Bill Whelan, it originated as an interval performance act during the 1994 Eurovision Song Contest, featuring Irish dancing champions Jean Butler, Michael Flatley and the vocal ensemble Anúna. Shortly afterwards, husband and wife production team John McColgan and Moya Doherty expanded it into a stage show, which opened in Dublin on 9 February 1995. Since then, the show has visited over 450 venues worldwide and been seen by over 25 million people, making it one of the most successful dance productions in the world.

La danse traditionnelle irlandaise se caractérise avant tout par des mouvements rapides deeees jambes, alors que le reste du corps, tronc et bras restent fixes et très rigides. La particularité du spectacle est le fait que plusieurs danseurs (vingt-huit au maximum) restent absolument synchronisés. Le spectacle est considéré d'origine irlandaise, comme "Lord of the Dance".


Biography.

Amyot found his way to the University of Paris, where he supported himself by serving some of the richer students. He was nineteen when he became M.A. at Paris, and later he graduated doctor of civil law at Bourges. Through Jacques Colure (or Colin), abbot of St. Ambrose in Bourges, he obtained a tutorship in the family of a secretary of state. By the secretary he was recommended to Margaret of France, Duchess of Berry, and through her influence was made professor of Greek and Latin at Bourges. Here he translated the "Æthiopica" of Heliodorus (1547), for which he was rewarded by Francis I with the abbey of Bellozane.  He was thus enabled to go to Italy to study the Vatican text of Plutarch, on the translation of whose "Lives" (1559–1565) he had been some time engaged. On the way he turned aside on a mission to the Council of Trent. Returning home, he was appointed tutor to the sons of Henry II, by one of whom (Charles IX) he was afterwards made grand almoner (1561) and by the other (Henry III) was appointed, in spite of his plebeian origin, commander of the Order of the Holy Spirit.  Pius V promoted him to the bishopric of Auxerre in 1570, and here he continued to live in comparative quiet, repairing his cathedral and perfecting his translations, for the rest of his days, though troubled towards the close by the insubordination and revolts of his clergy. He was a devout and conscientious churchman, and had the courage to stand by his principles. It is said that he advised the chaplain of Henry III to refuse absolution to the king after the murder of the Guise princes. He was, nevertheless, suspected of approving the crime. His house was plundered, and he was compelled to leave Auxerre for some time. He died bequeathing, it is said, 1200 crowns to the hospital at Orléans for the twelve "deniers" he received there when "poor and naked" on his way to Paris.  He translated seven books of Diodorus Siculus (1554), the "Daphnis et Chloë" of Longus (1559) and the "Opera Moralia" of Plutarch (1572). His vigorous and idiomatic version of Plutarch, "Vies des hommes illustres", was translated into English by Sir Thomas North, and supplied Shakespeare with materials for his Roman plays. Montaigne said of him, "I give the palm to Jacques Amyot over all our French writers, not only for the simplicity and purity of his language in which he surpasses all others, nor for his constancy to so long an undertaking, nor for his profound learning... but I am grateful to him especially for his wisdom in choosing so valuable a work."  It was indeed to Plutarch that Amyot devoted his attention. His other translations were subsidiary. The version of Diodorus he did not publish, although the manuscript had been discovered by him. Amyot took great pains to find and interpret correctly the best authorities, but the interest of his books today lies in the style. His translation reads like an original work. The personal method of Plutarch appealed to a generation addicted to memoirs and incapable of any general theory of history. Amyot's book, therefore, obtained an immense popularity, and exercised great influence over successive generations of French writers.

Jacques Amyot (; 30 October 15136 February 1593), French Renaissance writer and translator, was born of poor parents, at Melun.

Jacques Amyot, né à Melun le et mort à Auxerre le, est un prélat français et l'un des traducteurs les plus renommés de la Renaissance. Il est inhumé à Auxerre.


1792.

The first formation of this name was initially formed on 4 September 1792 under Anne François Augustin de La Bourdonnaye within the Army of the North and the Army of the Centre - he held its command until 22 September that year. It was reorganised on 21 October 1792 to assist the 'camp sous Paris', suppressed the day before, and given général Berruyer as its new commander. It became the "armée de Réserve" on 1 March 1793 (when command of its right wing retained by Berruyer and command of its subordinate left wing given to général Beaufranchet d'Ayat) then the "armée des côtes de la Rochelle" on 30 April the same year, whilst retaining the same organisation and commanders - général Leigonyer and d'Ayat commanded its right and left wings respectively from 29 April to 27 May as interim commanders. Armand Louis de Gontaut-Biron commanded the unit from 28 May until 16 July 1793. It then had no commander until Jean Antoine Rossignol's appointment on 31 July - for those two weeks général Pilotte commanded its right division and Alexis Chalbos its left division.  Rossignol held command for the rest of the unit's existence, barring 25 to 30 August 1793, when he was temporarily replaced by Antoine Joseph Santerre. On 2 October 1793 the French Convention decreed the merger of the army of Mayence with the part of the "armée des côtes de la Rochelle" operating in the Loire-Inférieure department - this new formation was named the Army of the West.

1795-1796.

The second formation of this name was raised on 12 July 1795 using the forces of the 17th military division of Paris, augmented by those of the Somme, Seine-Maritime and Eure departments. Its main purpose was to keep order in Paris and its region. Its first commander was Jacques-François Menou, previously commander of the 17th Division. It was ordered to gather in a camp just outside Paris by the French Convention on 24 July.  Menou was replaced as commander on 5 October the same year by Paul Barras, with Napoleon Bonaparte as his second in command - on that date it put down the Royalist insurrection of 13 Vendémiaire. The formation was also used to suppress the revolt in the Grenelle camp and supported the French Directory during its Coup of 18 Fructidor. Bonaparte took over its command from Barras on 26 October 1795, holding it until he was put in command of the Army of Italy on 2 March 1796. Bonaparte still remained in command of the Army of the Interior for a few more days and the Directory were unable to replace him until he departed for his new command on 10 March - his replacement was Jacques Maurice Hatry. It was disbanded by decree of 25 August 1796, effective on 22 September.

The Army of the Interior ("Armée de l'Intérieur") was a name given to two field armies of the French Revolutionary Army.

L’armée de l'Intérieur est une dénomination donnée deux fois à une armée de la Révolution française, une première fois en 1792/1793 et une seconde fois en 1795/1796


Functions.

In lipid transport, apolipoproteins function as structural components of lipoprotein particles, ligands for cell-surface receptors and lipid transport proteins, and cofactors for enzymes (e.g. apolipoprotein C-II for lipoprotein lipase and apolipoprotein A-I (apoA1) for lecithin-cholesterol acyltransferase).  Different lipoproteins contain different classes of apolipoproteins, which influence their function. Apolipoprotein A-I (apoA1) is the major structural protein component of high-density lipoproteins (HDL), although it is present in other lipoproteins in smaller amounts. Apolipoprotein A-IV (apoA4) is present in chylomicrons, very-low-density lipoproteins (VLDL), and HDL. It is thought to act primarily in reverse cholesterol transport and intestinal lipid absorption via chylomicron assembly and secretion. ApoA-IV synthesized in hypothalamus is suggested to be a satiating factor which regulate the food intake of the rodent. Apolipoprotein B plays a particularly important role in lipoprotein transport being the primary organizing protein of many lipoproteins. Apolipoprotien C-III (apoC3) plays an important role in lipid metabolism specific in regulating the metabolism of triglyceride-rich lipoproteins (TRLs). Apolipoprotein D (apoD) is a soluble carrier protein of lipophilic molecules in neurons and glial cells within the central and peripheral nervous system and apoD can also modulate the stability and oxidation status of these molecules.  Apolipoprotein E (apoE) plays an important role in the transport and uptake of cholesterol by way of its high affinity interaction with lipoprotein receptors, including the low-density lipoprotein (LDL) receptor. ApoE is the major lipoprotein in the central nervous system. Recent findings with apoA1 and apoE suggest that the tertiary structures of these two members of the human exchangeable apolipoprotein gene family are related. The three-dimensional structure of the LDL receptor-binding domain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be stabilised by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix.  Apolipoprotein F (apoF) is one of the minor apolipoprotein in blood plasma and it is a lipid transfer inhibit protein to inhibit cholesteryl ester transfer protein-mediated transfers of cholesteryl esters and triglycerides. Apolipoprotein M (apoM) participates in the lipid metabolism and exhibit anti‐atherosclerotic functions and it is presented in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).

Classes.

There are multiple classes of apolipoproteins and several sub-classes:  Exchangeable apolipoproteins (apoA, apoC, and apoE) have the same genomic structure and are members of a multi-gene family that probably evolved from a common ancestral gene. ApoA1 and ApoA4 are part of the APOA1/C3/A4/A5 gene cluster on chromosome 11.  Hundreds of genetic polymorphisms of the apolipoproteins have been described, and many of them alter their structure and function.

Synthesis and regulation.

Apolipoprotein synthesis in the intestine is regulated principally by the fat content of the diet.  Apolipoprotein synthesis in the liver is controlled by a host of factors, including dietary composition, hormones (insulin, glucagon, thyroxin, estrogens, androgens), alcohol intake, and various drugs (statins, niacin, and fibric acids). ApoB is an integral apoprotein whereas the others are peripheral apoproteins.  Apolipoprotein synthesis such as apoA4 in hypothalamus involves in the integration of signals for regulation of food intake which is regulated by vagal nerve and cholecystokinin.

Disease.

Apolipoprotein has been suggested to be implicated in several types of diseases and dysfunction in individual.  Apolipoprotein C-I (apoC1) level increases in neuropathic pain and fibromyalgia patients which suggest it play an important role in occurrence of these conditions.  Apolipoprotein C-III (apoC3) is a risk factor of cardiovascular disease. Accumulation of plasma TRLs caused by elevated apoC-III leading to hypertriglyceridaemia.  Apolipoprotein D (apoD) level increases in nervous system with a large number of neurologic disorders inclusive of Alzheimer's disease, schizophrenia, and stroke.  Apolipoprotein E (apoE) has been implicated in dementia and Alzheimer's disease.  Apolipoprtoein(a) (apo(a)) is a component of lipoprotein(a) (Lp(a)) and elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for Atherosclerotic Cardiovascular Disease (ASCVD). The cholesterol-rich apoB-containing lipoproteins are also participate in the pathogenesis of ASCVD.

Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fat and cholesterol) to form lipoproteins. They transport lipids (and fat soluble vitamins) in blood, cerebrospinal fluid and lymph.

Les apolipoprotéines sont des protéines constitutives des lipoprotéines, structures chargées de transporter des molécules hydrophobes (triglycérides, cholestérol) dans le sang, milieu aqueux. Elles assurent la cohésion et la solubilisation des lipoprotéines dans le sang. Elles ont aussi un rôle dans la régulation métabolique (activateur/inhibiteur d'enzymes plasmatiques ou ligands des récepteurs membranaires).


Biography.

Early life.

Despite her mother's efforts to induce a miscarriage by means of riding, Anna Maria Luisa de' Medici, the only daughter and second child of Cosimo III de' Medici, Grand Duke of Tuscany, and his consort, Marguerite Louise d'Orléans, was born in Florence on 11 August 1667. She was named after her maternal aunt Anne Marie Louise d'Orléans, Duchess of Montpensier.  Her parents' relationship was quarrelsome; Marguerite Louise took every chance to humiliate Cosimo. On one documented occasion, she branded him "a poor groom" in the presence of the Papal nuncio. The enmity between them continued until 26 December 1674; after all attempts at conciliation failed, a stressed Cosimo consented to his wife's departure for the Convent of Montmartre, France. The contract created that day revoked her privileges as a "petite fille de France", and declared that upon her death all her assets were to be inherited by her children. Cosimo granted her a pension of 80,000 livres in compensation. She abandoned Tuscany in June 1675; Anna Maria Luisa, who was less than eight years old at that time, never saw her again. Although Cosimo doted on his daughter, she was raised by her paternal grandmother, Vittoria della Rovere.

Electress of the Palatinate.

In 1669, Anna Maria Luisa was considered as a potential bride to Louis, "le Grand Dauphin", the heir-apparent of Louis XIV of France. Cosimo III did not like the idea of a French marriage, and never devoted himself fully to the cause (she was later rejected). Instead, Cosimo offered her to his first choice, Peter II of Portugal. Peter's ministers declined, fearing that Anna Maria Luisa might have inherited her mother's temperament, and may seek to dominate Peter II while being herself intractible to reason. In fact, contemporaries thought her traits to be a combination of those of her father and paternal grandmother, Vittoria della Rovere.  Following refusals from Portugal, France, Spain and Savoy, James II of England put forward his brother-in-law, Francesco II d'Este, Duke of Modena, but the Princess deemed a duke too lowly in terms of protocol for the daughter of a "grand" duke. Finally, it was Leopold I, Holy Roman Emperor who suggested Johann Wilhelm, Elector Palatine. The Elector Palatine obtained the style "Royal Highness" from the Holy Roman Emperor for Cosimo III in February 1691. (Cosimo had hitherto been outranked by the Duke of Savoy — much to his anger—who derived "royal" status from his successful pretendership to the abolished Cypriot throne). Consequently, Johann Wilhelm was ultimately chosen. He and Anna Maria Luisa were married by proxy on 29 April 1691. At the accompanying festivities, a contemporary describes the Electress's physical attributes: "In her person, she is tall, her complexion was fair, her eyes large and expressive, both those and her hair were black; her mouth was small, with a fullness of the lips; her teeth were as white as ivory..." She departed for Düsseldorf, her husband’s capital, on 6 May 1691, accompanied by her younger brother, Gian Gastone. Johann Wilhelm surprised her at Innsbruck, where they officially married. The Palatinate Anna Maria Luisa arrived in was ravaged by the ongoing Nine Years' War, in which Louis XIV assaulted the Palatinate on behalf of his brother, Philippe of France, Duke of Orléans, occupying the city of Philippsburg in the process.  The Electress became pregnant in 1692; however, she miscarried. It is thought that soon after arrival she contracted syphilis from the Elector, which explains why Anna Maria Luisa and Johann Wilhelm failed to produce any children. Anna Maria Luisa and Johann Wilhelm, notwithstanding, shared a harmonious marriage. The Electress spent her time enjoying balls, musical performances and other festivities. He commissioned a theatre for her where the comedies of French playwright Molière were performed. Because Anna Maria Luisa patronised many musicians, the contemporary Palatine court enjoyed regard as an international centre of music. She invited Fortunato Chelleri to court and appointed him "maestro di cappella" ("music teacher"). Agostino Steffani, a polymath, was sponsored by the Electress from his arrival in Düsseldorf, in 1703, until her return to Tuscany; the Conservatorio library in Florence houses two editions of his chamber duets.  Anna Maria Luisa arranged a marriage for her younger brother at the instigation of their father: On 2 July 1697 Gian Gastone de' Medici married Anna Maria Franziska of Saxe-Lauenburg, heiress of the eponymous duchy, in Düsseldorf. Gian Gastone's wife repulsed him, and for that reason, they separated in 1708.  The same year as Gian Gastone's marriage, the Peace of Ryswick ended the Nine Years' War: French troops withdrew from the Electoral Palatinate and Johann Wilhelm received the County of Megen. Following the revocation of the Edict of Nantes, a document which had hitherto given rights to Calvinists, in 1685, 2,000 French Huguenots emigrated to the Electoral Palatinate. Johann Wilhelm, under criticism for his treatment of the Palatine Protestants from the Elector of Brandenburg introduced a "Religionsdeklartion" in 1705, which sanctioned religious freedom.

Tuscan succession.

Cosimo III wished to alter the male-only Tuscan line of succession so as to allow the accession of his daughter, Anna Maria Luisa, in the event of a male-line succession failure. But his plan was met with fierce opposition from the European powers. Charles VI, Holy Roman Emperor, Tuscany's nominal feudal over-lord, subscribed, but only if he should succeed her. Cosimo and herself were at odds with the proposal. Without a concord in sight, the "Tuscan question" became dormant.  Some years later, as the question of the succession became more urgent, Cardinal Francesco Maria de' Medici, Cosimo III's brother, was released from his vows and coerced into marrying the incumbent Duke of Guastalla's elder daughter, Eleanor, in 1709. The Electress urged him to care for his health and "give us the consolation of a little prince." However, two years later, he died without issue, taking with him any hope of an heir.  Following the death of his heir apparent, Ferdinando, in 1713, Cosimo deposited a bill in the Senate, Tuscany's titular legislature, promulgating that if Cosimo and his new heir apparent, Gian Gastone, were to predecease the Electress, she would ascend the throne. Charles VI was furious; he replied that the Grand Duchy was an imperial fief and therefore he alone possessed the prerogative to alter the laws of succession. To complicate things further, Elisabeth Farnese, heiress of the Duchy of Parma, the second wife of Philip V of Spain, as a great-granddaughter of Margherita de' Medici, exercised a claim to Tuscany. In May 1716, Charles VI, who constantly changed his stance on the issue, told Florence that the Electress's succession was unquestioned, but added that Austria and Tuscany must soon reach an agreement regarding which royal house was to follow the Medici.  In June 1717, Cosimo declared his wish that the House of Este should succeed the Electress. Charles VI had previously offered the Grand Duke territorial compensation—in the form of the State of Presidi—if he chose quickly, but reneged. In 1718, Charles VI repudiated Cosimo's decision, declaring a union of Tuscany and Modena (the Este lands) unacceptable. Hereafter, a stalemate existed between them.

Return to Florence.

The Elector Palatine died in June 1716. His widow, Anna Maria Luisa, returned to Florence in October 1717. Dowager Grand Princess Violante Beatrice, her brother Ferdinando's widow, and Anna Maria Luisa did not enjoy an amiable relationship. Upon hearing of Anna Maria Luisa's intention to return, Violante Beatrice prepared to depart for Munich, her brother's capital, but Gian Gastone wished her to stay, so she did. To keep the two ladies from quarrelling over precedence, Cosimo III defined Violante Beatrice's status just before the Electress's arrival by appointing her Governess of Siena.  On 4 April 1718 England, France and the Dutch Republic (and later Austria) selected Don Carlos of Spain, the elder child of Elisabeth Farnese and Philip V of Spain, as the Tuscan heir (with no mention of Anna Maria Luisa). By 1722, the Electress was not even acknowledged as heiress, and Cosimo was reduced to a spectator at the conferences for Tuscany's future. In the midst of this, Marguerite Louise, Anna Maria Luisa's mother, died. Instead of willing her valuables to her children, as prescribed by the 1674 agreement, they went to the Princess of Epinoy, a distant relative.  On 25 October 1723, six days before his death, Cosimo III distributed a final proclamation commanding that Tuscany shall stay independent; Anna Maria Luisa shall succeed uninhibited after Gian Gastone; the Grand Duke reserves the right to choose his successor. Unfortunately for Cosimo, Europe completely ignored it. Gian Gastone, now the Grand Duke, and Anna Maria Luisa were not on good terms. He despised the Electress for engineering his unhappy marriage with Anna Maria Franziska of Saxe-Lauenburg, while she detested his liberal policies: he repealed all of his father's anti-Semitic statutes and revelled in upsetting her. Consequently, the Electress was compelled to abandon her apartment in the left wing of the royal palace, the Pitti, for the Villa La Quiete. She refurbished La Quiete's house and gardens with the assistance of Sebastiano Rapi, the gardener of the Boboli Gardens, and the architects Giovanni Battista Foggini and Paolo Giovanozzi. In the period 1722–1725, the Electress embellished the villa further by commissioning twelve statues of various religious figures. In spite of their mutual dislike, the Electress and Violante Beatrice attempted to improve Gian Gastone's poor public image together. Rumours abounded that the Grand Duke had died; it was a rarity for the public to see him. To dispel the said rumours, the Electress compelled him to make an appearance—his last one—in 1729, on the feast day of the patron saint of Florence, John the Baptist. The "Ruspanti", Gian Gastone's morally corrupt entourage, hated the Electress; and she, them. Violante Beatrice tried to withdraw the Grand Duke from their sphere of influence by organising banquets. His conduct at these literally sent those in attendance scrambling for their carriages: he vomited repeatedly into his napkin, belched and told rude jokes. These distractions ceased upon Violante Beatrice's death in 1731.  In 1736, during the War of the Polish Succession, Don Carlos was banished from Tuscany as part of a territorial swap, and Francis III of Lorraine was made heir in his stead. In January 1737, the Spanish troops, who had occupied Tuscany since 1731, withdrew; 6,000 Austrian soldiers took their place.  Gian Gastone died from "an accumulation of diseases" on 9 July 1737, surrounded by prelates and his sister. Anna Maria Luisa was offered a nominal regency by the Prince de Craon, the Grand Duke's envoy, until Francis III could arrive in Florence, but declined. At Gian Gastone's demise, all the House of Medici's allodial possessions, including £2,000,000 liquid cash, a vast art collection, robes of state and lands in the former Duchy of Urbino, were conferred on Anna Maria Luisa.<ref name="Young502/8">Young, p 502; p 508</ref> In regards to this, her most notable act was the "Patto di Famiglia" ("Family Pact"), signed on 31 October 1737. In collaboration with the Holy Roman Emperor and Francis of Lorraine, she willed all the personal property of the Medici's to the Tuscan state, provided that nothing was ever removed from Florence.

Death and legacy.

The "Lorrainers," as the occupying forces were dubbed, were popularly loathed. The Viceroy, the Prince de Craon, whom the Electress disliked for his "vulgar" court, allowed the Electress to live undisturbed in her own wing of the Pitti, living in virtual seclusion, only on occasion receiving a select-number of guests under a black dais in her silver-clad audience room. She occupied herself financing and overseeing the construction of the Cappella dei Principi—started in 1604 by Ferdinando I de' Medici, Grand Duke of Tuscany—to the tune of 1,000 crowns per week, and she donated much of her fortune to charity: £4,000 per annum. This is equivalent to £ in present-day terms. On 18 February 1743, Anna Maria Luisa de' Medici, Dowager Electress Palatine, died of an "oppression on the breast". Sir Horace Mann, 1st Baronet, a British resident in Florence, recalled in a letter that "The common people are convinced she went off in a hurricane of wind; a most violent one began this morning and lasted for about two hours, and now the sun shines as bright as ever..." The royal line of the House of Medici became extinct with her death. Her will, having been completed just months before, according to Sir Horace Mann, left £500,000 worth of jewellery to the Grand Duke Francis and her lands in the former Duchy of Urbino to the Marquis Rinuccini, her main executor and a minister under her father, Cosimo III. She was interred in the crypt that she helped to complete in San Lorenzo; although not entirely finished at the time of her death, her testament stipulated that part of the revenue of her estate should "be used to continue, finish and perfect...the said famous chapel San Lorenzo".  Anna Maria Luisa's single most enduring act was the "Family Pact". It ensured that all the Medicean art and treasures collected over nearly three centuries of political ascendancy remained in Florence. Cynthia Miller Lawrence, an American art-historian, argues that Anna Maria Luisa thus provisioned for Tuscany's future economy through tourism. Sixteen years after her death, the Uffizi Gallery, built by Cosimo "the Great", the founder of the Grand Duchy, was made open to public viewing.  In 2012 after concern caused by the 1966 Flood of the Arno River, her bones were exhumed. A scientific examination found no traces of syphilis, which she had long been thought to have died from.

Anna Maria Luisa de' Medici (11 August 1667 – 18 February 1743) was a Tuscan noblewoman who was the last lineal descendant of the main branch of the House of Medici. A patron of the arts, she bequeathed the Medici's large art collection, including the contents of the Uffizi, Palazzo Pitti and the Medicean villas, which she inherited upon her brother Gian Gastone's death in 1737, and her Palatine treasures to the Tuscan state, on the condition that no part of it could be removed from "the Capital of the grand ducal State...[and from] the succession of His Serene Grand Duke."

Anne-Marie-Louise de Médicis, née à Florence le et décédée dans la même ville le est la fille de Cosme III de Médicis et de Marguerite-Louise d'Orléans, femme de Jean-Guillaume de Neubourg-Wittelsbach. Elle est la dernière des Médicis.


Publication history.

The Winter Guard first appeared during the Kurt Busiek run of "Iron Man" in issue #9 (Oct 1998), where they had several guest appearances. They would later appear in Busiek's stint on the "Avengers".  The team made infrequent appearance in the Marvel Universe until Jeph Loeb brought them to attention in "Hulk" #1. The Winter Guard soon appeared in "She-Hulk" and "War Machine: Weapon of S.H.I.E.L.D.".  David Gallaher brought the team back in "Hulk: Winter Guard" which first appeared as a Marvel Digital Comic and was later reprinted as a comic book. Gallaher returned to writing the team with a 3-issue limited series called "Darkstar and the Winter Guard" in 2010.

Fictional team history.

The Winter Guard made their debut in "Iron Man" vol. 3, #9, and fought alongside the Avengers during both the "Maximum Security" crossover, and the "Kang War".  They made their return with the addition of Darkstar in "Champions" #7 and again with the introduction of Ursa Major in "Incredible Hulk" #258 under the guise of The Soviet Super Soldiers.  Whilst investigating the murder of the Abomination (who was killed by Red Hulk), Doc Samson, She-Hulk and Thunderbolt Ross encounter the revitalized Winter Guard, consisting of Ursa Major, Red Guardian, Darkstar and the Crimson Dynamo. When She-Hulk points out that Darkstar and Red Guardian were dead, Iron Man tells her that they were replaced with new people. It is unknown if the other members of the team are new as well.  After teaming up with War Machine to fight the Skrulls, the team was later seen clashing with She-Hulk and the Lady Liberators – and again with The Presence and Igor Drenkov. This version of the team uses an old alien ship, from the Dire Wraith race, as a headquarters.  They were mentioned by Storm as possible back-up while Rachel Summers was investigating in Madripoor.  The Winter Guard was apparently destroyed by The Intelligencia, who tested their ultimate weapon The Zero Cannon on the unsuspecting heroes. However they were later seen to have survived.  During the "Monsters Unleashed" storyline, the Winter Guard were seen fighting monsters that were attacking Moscow.  The Winter Guard is later reassembled with Ursa Major, Crimson Dynamo, Red Guardian, Darkstar, Vostok, Perun, Chernobog, and a Red Widow.

Members.

Their current membership is:

The Winter Guard is a fictional team of Russian superheroes appearing in American comic books published by Marvel Comics. The Winter Guard are noted for being "Russia's answer to the Avengers". Several members of the group formerly belonged to the Soviet Super-Soldiers, the People's Protectorate and the Supreme Soviets. Unlike those teams, which were often adversarial towards other costumed superheroes, the Winter Guard is much more heroic and representative in nature.

La Winter Guard (la « Garde hivernale » ou la « Garde d'hiver » en français) est une équipe de super-héros évoluant dans l'univers Marvel de la maison d'édition Marvel Comics. Créée par le scénariste Kurt Busiek et le dessinateur, l'équipe apparaît pour la première fois dans le comic book "Iron Man" () #9 en octobre 1998.