History.

Foundation and golden years: 1920–1950.

The club was established as a football club ("Podosferikos Syllogos Aris Thessalonikis") by a group of 22 young friends in a coffee bar in Votsi area on 25 March 1914 and given the name Aris from Ares, the ancient god of war. Its nickname was inspired by the two Balkan Wars of 1912–1913, when Greece fought against the Ottoman Empire before engaging in a war with Bulgaria. In Greek mythology, Aris was a deity who was in conflict with Heracles, the mythological character after which Aris's rival football team, Iraklis, was named. Aris holds a fierce rivalry with PAOK and Olympiakos. In the beginning the club was based on a near the Arch and Tomb of Galerius, but after the accession of two minor football clubs in 1919 and 1921 the club's base was moved near to Flemming Street of eastern Thessaloniki. The first stadium was built on the site where Mars Field Park currently lies on Stratou Avenue. Quickly the club became very popular and soon new teams apart from football were established.  During this early stage of football in Greece no professional league was established. Instead, three minor leagues [in Macedonia (E.P.S.M.), Athens (E.P.S.A.) and Piraeus (E.P.S.P.)] were created, with the champions of each league competing in a postseason mini tournament to claim the title of the national champion. The first official game was held in 1923 against Megas Alexandros Thessaloniki (Alexander the Great), another Thessalonician team. That year marked the first title, when Aris was named regional champion of Macedonia, something that was repeated next year.  In 1926 the club was renamed "Athletic Club Aris Thessaloniki" to include also other sports than football.  Aris' first major success was between 1927 and 1928 when they won the first Greek Championship, beating finalists Atromitos and Ethnikos Piraeus exploiting the abstention from the championship teams of RECs. In the first race on 24 May, the team of Thessaloniki prevailed 3–1 Atromitos, while three days after losing to Ethnikos Piraeus 3–2. In iterative matches played in June in Thessaloniki, Aris won both of his opponents by 3–1 and thus crowned the first champion of Greece. Coach of the team was the German Thomas Kessler, and prominent players of Aris were, among others, Kostas Vikelidis, Savvas Vogiatzis that emerged and top scorer with six goals, Nikos Aggelakis, scorer of the finals with four goals and Dionysis Caltech.  The following year, it was held the final stage of national championships although Aris won the championship title in Thessaloniki, playing two matches barrage against PAOK. The first took place on 12 May 1929 and ended 1–1, while the second was held on 2 June with Aris to beats 4–3, having Nikos Aggelakis scoring a hat-trick.  On 20 April 1929, the first friendly match took place between Aris and Panathinaikos, the "yellows" to defeat 5–4. The second championship came four years later in 1932, only this time his opponents were Olympiacos, Panathinaikos, AEK, Ethnikos, PAOK and Iraklis. Aris managed to collect 22 points in this mini tournament, four more than the second, Panathinaikos, scoring large wins like 7–0 against Panathinaikos, 7–3 against Iraklis and 3–0 versus AEK and Olympiacos in Athens, also new star players emerged, Kitsios, Aggelakis, Bogdanos, Gigopoulos, while Belgian manager De Valer guided effectively the club.  Four years after winning the first Panhellenic title, the "yellows" won the championship. Aris became champion amassing a total of 22 points, four more than second Panathinaikos and scoring big wins like 7–0 against Panathinaikos with four goals Maywood, 6–1 on Apollon Athens with six goals in the Aggelakis' first home appearance with the first group of Kleanthis Vikelidis, 7–3 vs Iraklis with four goals Kitsos and away 0–3 over Olympiacos, PAOK and AEK. Leading scorer of the league emerged Nikos Kitsos with 15 goals and Nikos Aggelakis to 14.  Big stars of that team were Kitsos, Aggelakis, Caltech, and Vogdanou Gkikopoulos while coach De Valera.  That same year, the EPO instituted for the first time the Greek Cup, Mars crashing Panathinaikos 7–2 in the quarterfinal. This was followed by victory over Apollon Athens, to reach the final where they lost 5–3 from AEK Athens, losing the chance to win the first doubles.  Aris won their third title in 1946, playing against two teams, AEK from Athens and Olympiacos from Piraeus, champions of the other two minor domestic leagues. Aris beat Olympiacos twice, scoring two goals and conceding none; came to a draw with AEK in Athens and defeated them in PAOK's stadium in Thessaloniki (score 4–1). Aris has not won a championship since the establishment of the First Division (1959).  Up to 1959, when the united First Division was created, Aris managed to finish first 14 times in the Macedonian division.

Modern times (1950–1981).

Aris' status remained high during this period, which was marked by the construction of the club's homeground, the Kleanthis Vikelides Stadium, named after the legendary homonymous player. Before World War II, Aris' homeground was located in the center of the city, near the Thessaloniki International Fair, but was abandoned in 1936 in order for the "Pedion tou Areos" park ("Mars Field") to be created. The club managed to buy some land during 1951 in a quarter of the city named Charilaou, where the new Stadium was slowly built.  Also in 1959, the tripartite minor league system was abandoned and a new, unified Championship was created.  The club's accomplishments during these years were significant. It was one of the first teams in Greece to qualify for European tournaments. Under the leadership of Alexandros Alexiades, Giorgos Pantziaras and Takis Loukanidis.

1970 Cup Winners.

Aris earned high placings in the League during the 1960s and 1970s, with apex the 1970 Hellenic Cup Title against the club's fierce rival, PAOK, in Kaftanzoglio Stadium.  In the 1970s, Aris was reorganized and a vast number of young players from Thessaloniki, including Kouis, Foiros, Drambis, Zindros and Papafloratos led the club. Its most important achievements during that period included a successful 1980 UEFA campaign when Aris eliminated Benfica and Perugia. Aris was also the first Greek club to score a victory both in Italy and Portugal. At home, the team shared first place with Olympiacos at the end of the 1980 campaign, though it lost the title 2–0 in a tie-breaker against the Piraeus club in Volos National Stadium.

Stone years (1981–2006).

After the mid-1980s and the retirement of the club's honored old guard, Aris entered in a slow decline, rarely reaching European league qualification or notable Greek League position, which—in combination with appreciable financial troubles that left the club near bankruptcy—led to the club's relegation to the Second Division in 1997 and 2005. Both times though Aris managed to resume its place in the first division.

Aris Members' Society era (2006–2014).

In recent years, specially after the creation of an Aris Members' Society that controls the club's fortunes, Aris has qualified several times for the UEFA Europa League, finished fourth in the Superleague three times, and has reached in the Greek Cup Final four times, losing in 2003, 2005, 2008 and 2010, when 25,000 Aris fans went to Athens in the biggest ever move of fans in Greece. In 2008 and 2010 Aris made it through to the UEFA Europa League group stage after eliminating Real Zaragoza and Austria Wien respectively during the Cup's play-off rounds. During the 2010–11 UEFA Europa League they managed to play for the first time in club's history in Europe after Christmas, after a very good appearance in the group stage where they won 1–0 at home and 2–3 away and eliminated the title holders Atlético Madrid. Recent developments include the interest from the club's board to construct a new, modern stadium in eastern Thessaloniki Metropolitan Area to replace the obsolete Kleanthis Vikelidis Stadium and the modernization and expansion of the club's training facilities in Neo Rysio, Thessaloniki. Also, in a unique move for Greek standards, the board decided in December 2009 to establish a radio station, "Aris FM 92.8" in order to promote the communication between Aris fans around the country and the coverage of the clubs activities. In 2014, due to financial problems Aris was relegated to the third tier of Greek football.

Relegation.

After their relegation many were wondering who was going to take care of the team. American business man Alex Kalas emerged the first season with him in charge of the football department while they failed to gain promotion to the Football League. In summer 2015 where the next elections for the role of head of football department Kalas won again and promised to put more money into the club. Kalas also made a number of signings, Honduran legend Carlos Costly, Sierra Leone international John Kamara, Spaniard Guillermo Pérez Moreno, Portuguese footballer Fábio Ruben Moreira Tavares, defender Paschalis Melissas and defender Stavros Petavrakis. Due to Aris failing to get into the second division Kalas was sacked despite only being there for a month. Aris would have to play another year in Gamma Ethniki. While in the Gamma Ethniki, the team demanded that the Hellenic Football Federation allow them to be promoted to a higher level of Greek football. The federation declined to do this and several appeals against the decision were rejected. As a result, 10,000 fans took to the streets on the 26 and 31 August 2015 in Thessaloniki to protest the decision. These protests caused clashes between the police and the fans that led to arrests and Aris didn't manage to get promoted to the professional divisions.

Karipidis era.

Although after the Aris election Arvanitidis became leader of the football department, Theodoros Karipidis was named the head of football department the day afterwards. He signed many players in a few days including former Greek footballer of the club Andreas Tatos, former Real Madrid defender Raul Bravo club legend Sergio Koke, as well as many Super League quality players like Kostas Kaznaferis, Vasilios Rovas, Nikos Tsoumanis, Giannis Siderakis as well as many others. Theodoros Karipidis appointed Nikos Anastopoulos as the manager. During the 2015–16 season Aris managed to be promoted to the second division of Greece with a 21-point difference from the second club. Finally, Irene Karipidis became the major shareholder with overwhelming proportion over 89%.

Supporters.

Aris' fan base is spread across all the economic classes in the city of Thessaloniki and all over Greece. Their rivalry is against clubs such as arch-rival PAOK, but also against the biggest clubs of Athens Olympiacos, Panathinaikos and AEK Athens. Matches against PAOK are local derbies and an event that splits Thessaloniki and Northern Greece in two. Aris' main fan club is called "Super 3" and has symbol a bulldog. It exist since 1988 with 50 more Super 3 clubs spread all over Greece and Europe. There are over 12,000 Super 3 members. In the rest of Europe there are also some organized Aris' fan clubs in countries such as Germany, Italy and Sweden. According to some polls Aris is the 5th most popular team in Greece with around a million fans, an amount quite big considering the lack of titles for many decades.  Against Panathinaikos in the 2010 Greek Cup final, 30,000 Aris fans descended to Athens to what has been described as "the biggest football fans move in Greece".  The club's anthem ("Aris Victorious") was written in 1926.

Crest and colours.

Crest evolution.

A company of young Thessalonians inspired the name of the club by Ares, the ancient Olympian "God of War", after the successful military operations of the Kingdom of Greece during the Balkan Wars, and the liberation of Thessaloniki in 1912 from the Ottoman empire. The emblem of the team is a resting Ares (Greek: Άρης), as depicted in the Ludovisi Ares sculpture. This emblem was chosen in the late 1970s to replace an older and simpler logo which was used since 1914. Also, during the 2000s, a scheme of meander was added to the crest.  The colors of the team are yellow or gold of glory, dominant colour in the culture of Macedonia, and black. Alternative colours also used include white or even dark red uniforms. During the 2000s, the club introduced also a shade of lime.

Kit evolution.

First  Alternative

Shirt and sponsors history.

The following table shows in detail Aris kit manufacturers and shirt sponsors by year:

Facilities.

Stadium.

The stadium of Aris Thessaloniki is named "Kleanthis Vikelides" after the club's legendary player. It is located at 69 Alkminis, Charilaou; 54249 Thessaloniki, and was built in 1951. In 1972, it got a new roof, in 1975 a new north stand, and in 2004, it was fully renovated. Its current total capacity is 22,800 spectators.

Training facilities.

Since the late 1970s, Aris Thessaloniki has created its own training grounds in Neo Rysio (Dasigenio Sports Center), just outside Thessaloniki near the International Airport covering three hectares and including football fields, hosting area with gym, pool and sauna, press room, offices, restaurant and locker rooms. The facilities were rebuilt in September 2010 after a demand placed by manager Héctor Cúper. The facilities were renovated again in 2018 and the grass was ultimately changed in 2019.

Honours.

Domestic.

Super League Greece  Second Division Greece Third Division Greece Greek Football Cup Greater Greece Cup

Regional.

Macedonia FCA Championship* Thessaloniki FCA Championship  "Until 1959–60 the top teams of the regional leagues were qualified for the national championship play-offs."*

Seasons in the 21st Century.

Best position in bold.  Key: 3R = Third Round, 4R = Fourth Round, 5R = Fifth Round, GS = Group Stage, QF = Quarter-finals, SF = Semi-finals, RU = Runner-up.

Aris Thessaloniki in Europe.

Aris is one of the most successful Greek clubs in European competitions and to date has not lost a home game in UEFA competitions, having a record of 27 (14 13 0) home games undefeated.

External links.

Official websites News sites Media

Aris Football Club () is a Greek professional football club based in the city of Thessaloniki, Macedonia, Greece, part of the multi-sports club A.C. Aris Thessaloniki. Aris is one of Greece's most successful clubs, having won the fourth most Super League titles after Olympiacos, Panathinaikos and AEK Athens, while they are tied with PAOK. Created in 1914 as "Aris Thessaloniki Football Club", the club was a founding member of the Macedonian Football Clubs Association, as well as the Hellenic Football Federation. The colours of the club are golden/yellow, a dominant colour in the culture of Macedonia and reminiscent of the Byzantine heritage of Thessaloniki, and black. It is named after Ares, the ancient Olympian "God of War," associated also with courage and masculinity, whose image is portrayed on the club's logo as depicted in the Ludovisi Ares sculpture.

Aris Soluň (řecký: Π.Α.Ε. Άρης) je fotbalový klub který hraje nejvyšší domácí soutěž – Super League.Klub byl založen 25. března 1914 v makedonském městě Soluň jako první řecký klub po získaní nezávislosti na Turecku. Týmové barvy, žlutá a černá, návazují na tradici Byzantské říše. Název klubu je odvozen od řeckého boha války Arése, jehož vyobrazení je na logu klubu..Během své dlouhé historie Aris třikrát vyhrál domácí ligu a jednou pohár bez toho, aby angažoval špičkové manažery a fotbalisty.


Plot.

Every emperor penguin sings a unique song called a "heartsong" to attract a mate. If the male penguin's heartsong matches the female's song, the two penguins mate. Norma Jean, a female penguin, falls for Memphis, a male penguin and they become mates. They lay an egg, which is left in Memphis' care, while Norma Jean leaves with the other females to fish. While the males struggle through the harsh winter, Memphis briefly drops the egg. The resulting chick, Mumble, is unable to sing but can tap dance. Nevertheless, he is enamored with Gloria, a female penguin who is regarded as the most talented of her age. One day, Mumble encounters a group of hostile skua, with a leader who is tagged with a yellow band, which he says is from an alien abduction. Mumble narrowly escapes the hungry birds by falling into a crevice.  Now a young adult, Mumble is frequently ridiculed by the elders. After escaping from a leopard seal attack, Mumble befriends a group of Adelie penguins called "the Amigos", who embrace Mumble's dance moves and assimilate him into their group. After seeing a hidden human excavator in an avalanche, they opt to ask Lovelace, a rockhopper penguin, about its origin. Lovelace has the plastic rings of a six pack entangled around his neck, saying that they have been bestowed upon him by mystic beings.  For the emperor penguins, it is mating season and Gloria is the center of attention. Ramón, one of the Amigos, attempts to help Mumble win her affection by singing a Spanish version of "My Way", with Mumble lip syncing, to no avail. In desperation, Mumble begins tap dancing in synch with her song. She falls for him and the youthful penguins join in for singing and dancing to "Boogie Wonderland". The elders are appalled by Mumble's conduct, which they see as the reason for their lean fishing season. Memphis begs Mumble to stop dancing, for his own sake, but when Mumble refuses, he is exiled.  Mumble and the Amigos return to Lovelace, only to find him being choked by the plastic rings. Lovelace confesses they were snagged on him while swimming off the forbidden shores, beyond the land of the elephant seals. Not long into their journey, they are met by Gloria, who wishes to join with Mumble as his mate. Fearing for her safety, he ridicules Gloria, driving her away.  At the forbidden shore, the group finds a fishing boat. Mumble pursues it solo to the brink of exhaustion. He is eventually washed up on the shore of Australia, where he is rescued and kept at Marine World with Magellanic penguins. After a long and secluded confinement in addition to fruitlessly trying to communicate with the humans, he nearly succumbs to madness. When a girl attempts to interact with Mumble by tapping the glass, he starts dancing, which attracts a large crowd. He is released back into the wild, with a tracking device attached to his back. He returns to his colony and challenges the will of the elders. Memphis reconciles with him, just as a research team arrives, proving the statements of the existence of "aliens" to be true. The whole of the colony, even Noah the leader of the elders, engages in dance.  The research team returns their expedition footage, prompting a worldwide debate. The governments realize they are overfishing, leading to the banning of all Antarctic fishing. At this, the emperor penguins and the Amigos celebrate.

Production.

George Miller cites as an initial inspiration for the film an encounter with a grizzled old cameraman, whose father was Frank Hurley of the Shackleton expeditions, during the shooting of "Mad Max 2": "We were sitting in this bar, having a milkshake, and he looked across at me and said, ‘Antarctica.’ He'd shot a documentary there. He said, ‘You’ve got to make a film in Antarctica. It’s just like out here, in the wasteland. It’s spectacular.’ And that always stuck in my head.”  "Happy Feet" was also partially inspired by earlier documentaries such as the BBC's "Life in the Freezer". In 2001, during an otherwise non-sequitur meeting, Doug Mitchell impulsively presented Warner Bros., studio president Alan Horn with an early rough draft of the film's screenplay, and asked them to read it while he and Miller flew back to Australia. By the time they'd landed, Warner had decided to provide funding on the film. Production was slated to begin sometime after the completion of the fourth "Mad Max" film, "", but geo-political complications pushed "Happy Feet" to the forefront in early 2003.  The animation is invested heavily in motion capture technology, with the dance scenes acted out by human dancers. The tap-dancing for Mumble in particular was provided by Savion Glover who was also co-choreographer for the dance sequences. The dancers went through "Penguin School" to learn how to move like a penguin, and also wore head apparatus to mimic a penguin's beak.  "Happy Feet" needed an enormous group of computers, and Animal Logic worked with IBM to build a server farm with sufficient processing potential. The film took four years to make. Ben Gunsberger, Lighting Supervisor and VFX Department Supervisor, says this was partly because they needed to build new infrastructure and tools. The server farm used IBM BladeCenter framework and BladeCenter HS20 blade servers, which are extremely dense separate computer units each with two Intel Xeon processors. Rendering took up 17 million CPU hours over a nine-month period.  According to Miller, the environmental message was not a major part of the original script, but "In Australia, we're very, very aware of the ozone hole," he said, "and Antarctica is literally the canary in the coal mine for this stuff. So it sort of had to go in that direction." This influence led to a film with a more environmental tone. Miller said, "You can't tell a story about Antarctica and the penguins without giving that dimension."  The film was dedicated to the memory of Nick Enright, Michael Jonson, Robby McNeilly Green, and Steve Irwin.

Music.

"Happy Feet" is a jukebox musical, taking previously recorded songs and working them into the film's soundtrack to fit with the mood of the scene or character. Two soundtrack albums were released for the film; one containing songs from and inspired by the film, and another featuring John Powell's instrumental score. They were released on 31 October 2006 and 19 December 2006, respectively.  Prince's "Song of the Heart" won the Golden Globe Award for Best Original Song. The film won Golden Trailer Award for Best Music. The song was written by Prince specifically for "Happy Feet" shortly after he was given a private screening of the film in order to gain his approval for the use of his song "Kiss" in a musical number. Prince enjoyed the film, gave his approval for the use of "Kiss" and offered to write an original song for the production, which he completed a week later.

Soundtrack.

"Happy Feet: Music from the Motion Picture" is the lyrical soundtrack album from the 2006 animated film "Happy Feet". As of March 2007, the OST has sold over 272,627 copies in the US.

Reception.

Box office.

The film opened at number 1 in the United States on its first weekend of release (17–19 November), grossing $41.6 million and beating "Casino Royale" for the top spot. It remained number 1 for the Thanksgiving weekend, making $51.6 million over the five-day period. In total, the film was the top grosser for three weeks, a 2006 box office feat matched only by "". As of 8 June 2008, "Happy Feet" had grossed $198.0 million in the U.S. and $186.3 million overseas, making about $384.3 million worldwide. "Happy Feet" was the third highest grossing animated film of 2006 in the U.S., behind "Cars" and "". The film was released in about 35 international territories at the close of 2006.  The production budget was $100 million.

Critical reception.

"Happy Feet" received generally positive reviews from critics. On review aggregator site Rotten Tomatoes, the film has a 76% "Certified Fresh" score based on 167 reviews, with an average rating of 6.91/10. The site's consensus reads, "Visually dazzling, with a thoughtful storyline and catchy musical numbers, "Happy Feet" marks a successful animated debut from the makers of "Babe"." Metacritic reports a 77 out of 100 rating, based on 30 critics, indicating "generally favorable reviews".

Analysis.

The film garnered analysis and dissection from various critics. Film critic Yar Habnegnal wrote an essay in "Forum on Contemporary Art and Society" that examines the themes of encroachment presented throughout the film, as well as various other subtexts and themes, such as religious hierarchy and interracial tensions. Vadim Rizov of IFC sees Mumble as just the latest in a long line of cinematic religious mavericks.  On a technical or formal level, the film has also been lauded in some corners for its innovative introduction of Miller's roving style of subjective cinematography into contemporary animation.

Home media.

"Happy Feet" was released on home media on 27 March 2007, in the United States in three formats; DVD (in separate widescreen and pan and scan editions), Blu-ray Disc, and an HD DVD/DVD combo pack.  Among the DVD's special features is a scene that was cut from the film where Mumble meets a blue whale and an albatross. The albatross was Steve Irwin's first voice role in the film before he voiced the elephant seal in the final cut. The scene was finished and included on the DVD in Irwin's memory. This scene is done in Irwin's classic documentary style, with the albatross telling the viewer all about the other characters in the scene, and the impact people are having on their environment.

Accolades.

The film appeared on numerous critics' top ten lists of the best films of 2006.

Video games.

A video game based on the film was developed by A2M and published by Midway Games. It has the same main cast as the film. It was released for the PC, PlayStation 2, GameCube, GBA, NDS, and Wii.  Artificial Life, Inc. has also developed a mobile game for the Japan market.

Legacy.

Sequel.

"Happy Feet Two" was produced at Dr. D Studios and released on 18 November 2011. Wood and Williams reprised their roles for the sequel. Murphy was set to reprise her role and begin recording sometime in 2010, but was replaced by P!nk after Murphy died from pneumonia on 20 December 2009. Matt Damon and Brad Pitt signed on as Bill the Krill and Will the Krill respectively.

4-D attraction.

"Happy Feet 4-D Experience" is a 12-minute 4D film shown at various 4D theaters over the world. It retells the condensed story of "Happy Feet" with the help of 3D projection and sensory effects, including moving seats, wind, mist and scents. Produced by SimEx-Iwerks, the 4D experience premiered in March 2010 at the Drayton Manor Theme Park. Other locations included Sea World (2010–2011), Shedd Aquarium (2010–2012), Moody Gardens (2010–2011), Nickelodeon Suites Resort, and Adventure Aquarium.

Happy Feet is a 2006 computer-animated musical comedy film directed, produced, and co-written by George Miller. It stars the voices of Elijah Wood, Robin Williams, Brittany Murphy, Hugh Jackman, Nicole Kidman, Hugo Weaving, and E.G. Daily. An international co-production between the United States and Australia, the film was produced at Sydney-based visual effects and animation studio Animal Logic for Warner Bros., Village Roadshow Pictures, and Kingdom Feature Productions, and was released in North American theaters on 17 November 2006. It is the first animated film produced by Kennedy Miller and Animal Logic.

Happy Feet je počítačově animovaný film režírovaný Georgem Millerem, který se také podílel na scénáři. Producentem je studio Animal Logic pro Warner Bros., Village Roadshow Pictures a Kingdom Feature Productions. V Severní Americe měl premiéru 17. listopadu 2006, v České republice se promítal od 7. prosince téhož roku. Zároveň byla vydána verze pro IMAX 2D formát, o 3D se uvažovalo, ale nakonec se kvůli napjatým financím záměr neprovedl. 108 minut dlouhý Happy Feet získal Oskara za nejlepší animovaný snímek a nominaci na Annie Award ve stejné kategorii.


Early life.

Joseph Saxton was born in Huntingdon, Pennsylvania and first entered as an apprentice to a watchmaker when he was twelve years old. Saxon was the son of a Mr. Saxton, a mechanic, and Elizabeth Ashbaugh, daughter of John Ashbaugh Sr. This information comes from the book "Pioneer period and Pioneer People of Fairfield, Ohio" by C.M.L. Wiseman. https://archive.org/details/pioneerperiodpio00wise_0/page/n387

Career.

Philadelphia.

In 1817, aged 18, Joseph Saxton moved to Philadelphia where he found employment as a watchmaker, engraver, and apprentice machinist. During this time, he made his first inventions: a machine for cutting the teeth of marine chronometer wheels and an escapement and compensating pendulum for clocks. He also constructed a clock for the newly-rebuilt steeple of the Independence Hall.

England.

Looking to further his education, Joseph Saxton traveled to London, England in 1828 and resided there nine years. For most of his stay he was employed by the Adelaide Gallery of Practical Science, a museum for the public that demonstrated new inventions and scientific principles. While working for the gallery, Saxton invented the magneto-electric machine, an apparatus for measuring the velocity of vessels, a device for measuring the height of water in a steam boiler, the riflescope, and the fountain pen prototype.

Return to the US.

After almost a decade abroad, Saxton returned to Philadelphia in 1837 and accepted a position at the Philadelphia Mint, first as superintended the making of machinery and then as curator of weights and measures, accurate sets of which were furnished to national and State governments. Among his inventions of this time may be mentioned a mirror comparator for comparing standards of length and a new form of dividing engine; a self-registering tide gauge, and an immersed hydrometer.  In the fall of 1839, Saxton used a daguerreotype to take what is generally considered to be the first known photograph taken in the U.S. The image was taken from the window of his office at the Philadelphia Mint and captured the cupola of Central High School and a portion of the State Armory building. It was taken on a sheet of polished metal. A seidlitz powder box with a few flakes of iodine answered for a coating box, while a cigar box and burning glass were improvised for a camera. An iron spoon served to heat the mercury to develop the plate. The picture which was produced is owned by the Historical Society of Pennsylvania.  Fellow photographic pioneer Robert Cornelius, the author of the first photographic portrait ever taken, designed the photographic plate of the image.  The first reference to the photograph appeared on 24 October 1839 in the "United States Gazette". An 1897 publication about public schools of Philadelphia indicates it was taken on October 16, 1839, the day after the definite account of Daguerre's process was published in Philadelphia.

Later life.

From 1843 until his death, three decades later, he was superintendent of weights and measures for the United States Coast Survey. He died in Washington, D.C. on 26 October 1873.  He was a member of the American Philosophical Society, the Franklin Institute and the National Academy of Sciences. In 1843 he was awarded the John Scott Legacy Medal and Premium by the Franklin Institute for the invention of his reflecting pyrometer.

Joseph Saxton (March 22, 1799 – October 26, 1873) was an American inventor, watchmaker, machinist, and photographer from Pennsylvania. Saxton is considered to be the first known American photographer for taking the oldest known photograph in the United States in 1839.

Joseph Saxton (22. března 1799 Huntingdon - 26. října 1873 Washington, USA) byl americký vynálezce a fotograf narozený v Huntingdonu v Pensylvánii. Je autorem několika vynálezů, ale také první pořízené fotografie na americkém území.


Description.

The cranial remains of stegosaurids, like all stegosaurians, are rarely discovered. Hence, a significant portion of the knowledge of their skull morphology comes from few complete skulls discovered of "Stegosaurus" and fragmentary remains of other stegosaurids. In general, stegosaurids have proportionally long, low and narrow snouts with a deep mandible, compared to that of "Huayangosaurus". Stegosaurids also lack premaxillary teeth.  Among stegosaurids, only "Kentrosaurus" has been found with parascapular spines, which project posteriorly out of the lower part of the shoulder plates. These spines are long, rounded and comma-shaped in lateral view and have an enlarged base. "Loricatosaurus" was also believed to have a parascapular spine, but Maidment et al. (2008) observed that the discovered specimen, from which the spine is described, has a completely different morphology than the parascapular spine specimens of other stegosaurs. They suggest it may be a fragmentary tail spine instead. The genuine absence of parascapular spines in other stegosaurids is considered a secondary loss since many basal stegosaurs like "Gigantspinosaurus" and "Huayangosaurus" have been discovered with them.  Stegosaurids also lack lateral scute rows that run longitudinally on either side of the trunk in huayangosaurids and ankylosaurs, indicating yet another secondary loss of a plesiomorphic characters. However, the absence of lateral scutes as well as pre-maxillary teeth mentioned above are not specifically diagnostic of stegosaurids, since these features are also present in other non-huayangosaurid stegosaurs, whose phylogenetic relations within Stegosauria are unclear.

Plates and spikes.

Stegosaurids exhibit the characteristic dorsal osteoderms, found in all stegosaurs, in the form of erect plates and spines. Stegosaurid plates have a thick base and central portion, but are transversely thin elsewhere. The plates become remarkably large and thin in "Stegosaurus". They are found in varying sizes along the dorsum, with the central region of the back usually having the largest and tallest plates. The arrangement of these parasagittal dorsal plates has been intensely debated in the past. Marsh suggested a single median row of plates running post-cranially along the longitudinal axis and Lull argued in favour of bilaterally paired arrangement throughout the series. Current scientific consensus lies in the arrangement proposed by Gilmore - two parasagittal rows of staggered alternates, after the discovery of an almost complete skeleton preserved in this manner in rock. Furthermore, no two plates share the same size and shape, making the possibility of bilaterally paired rows even less likely. Plates are usually found with distinct vascular grooves on their lateral surfaces, suggesting the presence of a circulatory network. Stegosaurids also have osteoderms on the throat in the form of small depressed ossicles and two pairs of elongated spike-like tail-spines.  In an ontogenetic histological analysis of "Stegosaurus" plates and spikes, Hayashi et al. (2012) examined their structure and function through juveniles to old adults. They found that throughout the ontogeny, the dorsal osteoderms are composed of dense ossified collagen fibres in both the cortical and cancellous sections of the bone, suggesting that plates and spikes are formed from the direct mineralization of already existing fibrous networks in the skin. However, the many structural features, seen in the spikes and plates of old adults specimens, are acquired at different stages of development. Extensive vascular networks form in the plates during the change from juveniles to young adults and persist in old adults but spikes acquire a thick cortex with a large axial vascular channel only in old adults. Hayashi et al. argue that the formation of nourishing vascular networks in young adults supported the growth of large plates. This would have enhanced the size of the animal, which may have helped attract mates and deter rivals. Furthermore, the presence of the vascular networks in the plates of the young adult indicate a secondary use of the plates as a thermoregulatory device for heat loss much like the elephant ear, toucan bill or alligator osteoderms. The thickening of the cortical section of the bone and the compaction of bone in the terminal tail-spikes in old adults suggest that they were used as defence weapons, but not until an ontogenetically late stage. The development of the large axial channel in old adults from small canals in young adults, facilitated the further enlargement of the spikes by increasing the amount of nourishment supplied. On the other hand, plates do not show a similar degree of bone compaction or cortical thickening indicating they would not be capable of taking much weight from above. This suggests they were not as important as spikes in active defense.  The protective nature of dorsal plates has also been questioned in the past Davitashvili (1961) noted that narrow dorsal location of the plates still left the sides vulnerable. Since the pattern of plates and spines vary between species, he suggested it could be important for intraspecific recognition and as a display for sexual selection. This is corroborated by Spassov's (1982) observations that the plates are arranged for maximum visible effect when viewed laterally during non-aggressive agonistic behaviour, as opposed to from a head-on aggressive stance.  The discovery of an impression of the skin covering the dorsal plates has implications for all possible functions of stegosaurian plates. Christiansen and Tschopp (2010) found that the skin was smooth with long, parallel, shallow grooves indicating a keratinous structure covering the plates. The addition of beta-keratin, a strong protein, would indeed allow the plates to bear more weight, suggesting they may have been used for active defense. A keratinous covering would also allow greater surface area for the plates to be uses as a mating display structures, which could be potentially coloured like the beaks of modern birds. At the same time this finding implies that the use of plates for thermo-regulation may be less likely because the keratinous covering would make heat transfer from the bone highly ineffective.

Classification.

In 1877, Othniel Marsh discovered and named "Stegosaurus armatus", from which the name of the family ‘Stegosauridae’ was erected in 1880. In comparison to Huayangosauridae, notable synapomorphies of Stegosauridae include a large antitrochanter (supracetabular process) in the ilium, a long prepubic process and long femur relative to the length of the humerus. Furthermore, stegosaurid sacral ribs are T-shaped in parasagittal cross-section and the dorsal vertebrae have an elongated neural arch.  Stegosaurid specimens originally described under the genera "Wuerhosaurus" and "Hesperosaurus" were referred to the genus "Stegosaurus", under the names "Stegosaurus" "homheni" and "Stegosaurus" "mjosi", respectively, by Maidment et al. (2010). Furthermore, many "Stegosaurus" specimens that were previously believed to from different species, within the genus, were all assigned to "Stegosaurus" "armatus." This reclassification of the specimens occurred after finding that all differences between specimens could be explained by intraspecific variation.  The structure of the stegosaurid family tree has been debated for a while. However, in two of the most extensive cladistics analyses of Stegosauria conducted to date, both Mateus et al. (2009) and Maidment (2010) present similar phylogenetic relationships within Stegosauridae (shown below). The well-resolved phylogenies place the newly discovered long-necked stegosaurid "Miragaia" as sister taxa to "Dacentrurus" forming the clade Dacentrurinae. Mateus et al. note that in both "Miragaia" and "Dacentrurus," the cervical rib projects posteriorly and the anterior pubic process is dorsoventrally deep and bears a dorsal projection at its anterior tip in lateral view. Their phylogeny also points to a sister-group relationship between the new clade Dacentrurinae and the genus "Stegosaurus", supported by the shared presence of postzygapophyses on cervical vertebrae that are elongate and project posterior to the posterior centrum facet. "Dacentrurus" was previously considered to be a basal stegosaurid, but the discovery and observation of "Miragaia" has suggested that it is a derived taxon.

Paleobiology.

Posture.

A digital articulation and manipulation of digital scans of specimen material of "Kentrosaurus" inferred that stegosaurids may have used an erect limb posture, like that of most mammals, for habitual locomotion while using a sprawled crocodilian pose for defensive behavior. The sprawled pose would allow them to tolerate the large lateral forces used in swinging the spiked-tailed against predators as a clubbing device.

Feeding.

In order to explore the feeding habits of stegosaurids, Reichel (2010) created a 3-D model of "Stegosaurus" teeth using the software ZBrush. The model finds that the bite forces of "Stegosaurus" was significantly weaker than that of Labradors, wolves and humans. The finding suggests that these dinosaurs would be capable of breaking smaller branches and leaves with their teeth, but would not be able to bite through a thick object (12mm or more in diameter). Parrish et al.’s (2004) description of Jurassic flora in the stegosaurid-rich Morrison Formation supports this finding. The flora during this time-period was dominated by seasonal small, fast-growing herbaceous plants, which stegosaurids could consume easily if Reichel's reconstruction is accurate.  Mallison (2010) suggested that "Kentrosaurus" may have used a tripodal stance on their hindlimbs and tail to double the foraging height from the general low browsing height under one metre for stegosaurids. This challenged the view that stegosaurs are primarily low vegetation feeders because of their small heads, short necks and short forelimbs, since the tripodal stance would also give them access to young trees and high bushes.  Another piece of evidence suggesting that some stegosaurids may have consumed more than just low vegetation was the discovery of the long-necked stegosaurid "Miragaia" "longicollum". This dinosaur's neck has at least 17 cervical vertebrae achieved through the transformation of thoracic vertebrae into cervical vertebrae and possible lengthening of the centrum. This is more than most sauropod dinosaurs, which also achieved the elongation of the neck through similar mechanisms and had access to fodder higher off the ground.

Sexual dimorphism.

There have been several findings of possible sexual dimorphism in stegosaurids. Saitta (2015) presents evidence of two morphs of "Hesperosaurus" dorsal plates, with one morph having a wide, oval plate with a surface area 45% larger than the narrow, tall morph. Considering that dorsal plates most likely functioned as display structures and that the wide oval shape allowed a broad continuous display, Saitta assigns the wider morph with larger surface area as male.  Kevin Padian, a paleontologist at the University of California, Berkeley, remarked that Saitta had misidentified features in his specimen's bone tissue sections and said “there’s no evidence the animal has stopped growing”. Paidan also expressed ethical concerns about the use of private specimens in the study.  "Kentrosaurus", "Dacentrurus" and "Stegosaurus" are also suggested to have exhibited dimorphism in the form of three extra sacral ribs in the females.

Stegosauridae is a clade of thyreophoran dinosaurs (armoured dinosaurs) within the suborder Stegosauria. The clade is defined as all species of dinosaurs more closely related to "Stegosaurus" than "Huayangosaurus". The name ‘Stegosauridae’ is thus a stem-based name taken from the well-represented genus – "Stegosaurus" (meaning ‘roofed lizard’). Fossil evidence of stegosaurids, dating from the Middle Jurassic through the Early Cretaceous, have been recovered from North America, Eurasia and Africa. On the other hand, Stegosauridae's sister clade, huayangosaurids, can be traced only to the Middle Jurassic.

Stegosauridi ("zastřešení ještěři") byla čeleď býložravých ptakopánvých dinosaurů ze skupiny Thyreophora. Vyskytovali se v období střední jury až spodní křídy (před 165 až 125 miliony let) na území několika kontinentů. Poslední známí zástupci, jako byl pochybný čínský rod "Stegosaurides", mohli žít ještě později, zhruba před 115 miliony let.


Discovery and naming.

It was named by Wu Wen-hao, Pascal Godefroit and Hu Dong-yu in 2010 and the type species is "Bolong yixianensis". The genus name is derived from the names of the brothers Bo Hai-chen and Bo Xue, who helped uncover it, and the Mandarin word 龍 "lóng" "dragon". The specific name refers to the Yixian Formation which is where is Liaoning it was found.  The holotype fossil, YHZ-001, consists of a skull with lower jaws from which a middle portion is missing. The fossil was highly compressed.  In 2013 a second specimen was described, ZMNH-M8812, consisting of an almost complete skeleton of a very young animal. It was found by a farmer in the village of Xitaizhi.

Description.

"Bolong" was a relatively small animal with an estimated length of four meters and a weight of 200 kilograms. The head is convex and fairly stocky with powerful mandibles. The teeth are relatively large. Different autapomorphies (unique derived traits) that can be established are: a cavity at the interface of the lacrimal bone, the maxilla, the backwards branch of the prefrontal bone, consisting of a front-to-rear depth cavity above the edges of the eye socket, the lower protrusion of the predentarium extending rearwardly parallel to the lower edge, the interface of the predentarium that occupies less than two-thirds of the height of the dentarium so that the front tip of the dentarium protrudes a third above the predentarium, and that the teeth in the maxilla have dental crowns of which the main ridge bends at the tip of the tooth.  The second specimen showed a different autapomorphy: the inside of the maxillary teeth are thickened and enclosed from the front and rear cutting edges and is divided in half by a striking vertical ledge.

Phylogeny.

The describers placed "Bolong" in Hadrosauroidea. It would have been one of the most basal hadrosauroids found in Asia.

Bolong (meaning "Bo's dragon") is a genus of iguanodontian dinosaur known from the Early Cretaceous-age Yixian Formation of western Liaoning Province, China. It lived about 125 million years ago in the earliest Aptian.

Bolong ("drak objevitelů fosilií Bo Hai-Chena a Bo Xueho") byl rod ornitopodního dinosaura, který žil v období spodní křídy na území dnešní čínské provincie Liao-ning. Jednalo se o velmi primitivního zástupce iguanodontů. Zkameněliny tohoto čtyřnohého býložravce byly objeveny na západě provincie v souvrství Yixian. Autory vědeckého popisu jsou paleontologové Wu Wen-hao, Pascal Godefroit a Hu Dong-yu, kteří dali v roce 2010 dinosaurovi jméno "Bolong yixianensis". Přesné rozměry tohoto dinosaura nejsou známé.


Composition.

Wagner read von Eschenbach's poem "Parzival" while taking the waters at Marienbad in 1845. After encountering Arthur Schopenhauer's writings in 1854, Wagner became interested in Asian philosophies, especially Buddhism. Out of this interest came "Die Sieger" ("The Victors", 1856), a sketch Wagner wrote for an opera based on a story from the life of Buddha. The themes which were later explored in "Parsifal" of self-renunciation, reincarnation, compassion, and even exclusive social groups (castes in ', the Knights of the Grail in Parsifal) were first introduced in '.  According to his autobiography ', Wagner conceived "Parsifal" on Good Friday morning, April 1857, in the'(German: "Asylum"), the small cottage on Otto Wesendonck's estate in the Zürich suburb of Enge, which Wesendonck – a wealthy silk merchant and generous patron of the arts – had placed at Wagner's disposal, through the good offices of his wife Mathilde Wesendonck. The composer and his wife Minna had moved into the cottage on 28 April: However, as his second wife Cosima Wagner later reported on 22 April 1879, this account had been colored by a certain amount of poetic licence: The work may indeed have been conceived at Wesendonck's cottage in the last week of April 1857, but Good Friday that year fell on 10 April, when the Wagners were still living at Zeltweg 13 in Zürich. If the prose sketch which Wagner mentions in "" was accurately dated (and most of Wagner's surviving papers are dated), it could settle the issue once and for all, but unfortunately it has not survived.  Wagner did not resume work on "Parsifal" for eight years, during which time he completed "Tristan und Isolde" and began "Die Meistersinger von Nürnberg". Then, between 27 and 30 August 1865, he took up "Parsifal" again and made a prose

Performance history.

The premiere.

On 12 November 1880, Wagner conducted a private performance of the prelude for his patron Ludwig II of Bavaria at the Court Theatre in Munich. The premiere of the entire work was given in the Festspielhaus at Bayreuth on 26 July 1882 under the baton of the Jewish-German conductor Hermann Levi. Stage designs were by Max Brückner and Paul von Joukowsky who took their lead from Wagner himself. The Grail hall was based on the interior of Siena Cathedral which Wagner had visited in 1880, while Klingsor's magic garden was modelled on those at the Palazzo Rufolo

Ban outside Bayreuth.

For the first twenty years of its existence, the only staged performances of "Parsifal" took place in the Bayreuth Festspielhaus, the venue for which Wagner conceived the work (except eight private performances for Ludwig II at Munich in 1884 and 1885). Wagner had two reasons for wanting to keep "Parsifal" exclusively for the Bayreuth stage. Firstly, he wanted to prevent it from degenerating into'mere amusement' for an opera-going public. Only at Bayreuth could his last work be presented in the way envisaged by him—a tradition maintained by his wife, Cosima, long after his death. Secondly, he thought that the opera would provide an income for his family after his death if Bayreuth had the monopoly on its performance.  The Bayreuth authorities allowed unstaged performances to take place in

Applause.

At Bayreuth performances audiences do not applaud at the end of the first act. This tradition is the result of a misunderstanding arising from Wagner's desire at the premiere to maintain the serious mood of the opera. After much applause following the first and second acts, Wagner spoke to the audience and said that the cast would take no curtain calls until the end of the performance. This confused the audience, who remained silent at the end of the opera until Wagner addressed them again, saying that he did not

Post-war performances.

"Parsifal" is one of the Wagner operas regularly presented at the Bayreuth Festival to this day. Among the more significant post-war productions was that directed in 1951 by Wieland Wagner, the composer's grandson. At the first Bayreuth Festival after World War II he presented a radical move away from literal representation of the Hall of the Grail or the Flowermaiden's bower. Instead, lighting effects and the bare minimum of scenery were used to complement Wagner's music. This production was heavily influenced by the ideas of the Swiss stage designer Adolphe Appia. The reaction to this production was extreme: Ernest Newman, Richard Wagner's biographer described it as "not only the best "Parsifal" I have ever seen and heard, but one of

Synopsis.

Place: Near the seat of the Grail

Act 1.

In a forest near the home of the Grail and its Knights, Gurnemanz, eldest Knight of the Grail, wakes his young squires and leads them in prayer. He sees Amfortas, King of the Grail Knights, and his entourage approaching. Amfortas has been injured by his own Holy Spear, and the wound will not heal.  Musical introduction to the work with a duration of c. 9–13 minutes.  Scene 1  Gurnemanz asks the lead Knight for news of the King's health. The Knight says the King has suffered during the night and is going early to bathe in the holy lake. The squires ask Gurnemanz to explain how the King's injury can be healed, but he evades their question and a wild woman – Kundry – bursts in. She gives Gurnemanz a vial of balsam, brought from Arabia, to ease the King's pain and then collapses, exhausted.  Amfortas arrives, borne on a stretcher by Knights of the Grail. He calls out for Gawain, whose attempt at relieving the King's pain had failed. He is told that Gawain has left again, seeking a better remedy. Raising

Act 2.

Musical introduction of c. 2–3 minutes.  Scene 1  Klingsor's magic castle. Klingsor conjures up Kundry, waking her from her sleep. He calls her by many names: First Sorceress (), Hell's Rose (), Herodias, Gundryggia and, lastly, Kundry. She is now transformed into an incredibly alluring woman, as when she once seduced Amfortas. She mocks Klingsor's mutilated condition by sarcastically inquiring if he is chaste (""), but she cannot resist his power. Klingsor observes that Parsifal is approaching and summons his enchanted knights to fight the boy. Klingsor watches

Act 3.

Musical introduction of c. 4–6 minutes.  Scene 1  The scene is the same as that of the opening of the opera, in the domain of the Grail, but many years later. Gurnemanz is now aged and bent. It is Good Friday. He hears moaning near his hermit's hut and discovers Kundry unconscious in the brush, as he had many years before ("Sie! Wieder da!"). He revives her using water from the Holy Spring, but she will only speak the word "serve" ("Dienen"). Gurnemanz wonders if there

Reactions.

Since "Parsifal" could initially only be seen at the Bayreuth Festival, the first presentation in 1882 was attended by many notable figures. Reaction was varied. Some thought that "Parsifal" marked a weakening of Wagner's abilities. The critic Eduard Hanslick gave his opinion that "The Third act may be counted the most unified and the most atmospheric. It is not the richest musically," going on to note "And Wagner's creative powers? For a man of his age and his method they are astounding... [but] It would be foolishness to declare that Wagner's fantasy, and specifically his musical invention, has retained the freshness and facility of yore. One cannot help but discern sterility and prosaicism, together with increasing longwindedness."  The conductor Felix Weingartner found that: "The Flowermaidens' costumes showed extraordinary lack of taste, but the singing was incomparable... When the curtain had been rung down on the final scene and we were walking down the hill, I seemed to hear the words of Goethe 'and you can say you were present.' The "Parsifal" performances of 1882 were artistic events of supreme interest and it is my pride and joy that I participated in them."  Hugo Wolf was a student at the time of the 1882 Festival, yet still managed to find money for tickets to see "Parsifal" twice. He emerged overwhelmed: "Colossal – Wagner's most inspired, sublimest creation." He reiterated this view in a postcard from Bayreuth in 1883: ""Parsifal" is without doubt by far the most beautiful and sublime work in the whole field of Art." Gustav Mahler was also present in 1883 and he wrote to a friend; "I can hardly describe my present state

Criticism and influence.

As Wagner's last opera, "Parsifal" has been both influential and controversial. The use of Christian symbols in "Parsifal" (the Grail, the Spear, references to the Redeemer) together with its restriction to Bayreuth for almost 30 years sometimes led to performances being regarded almost as a religious rite. However, Wagner never actually refers to Jesus Christ by name in the opera, only to "The Redeemer". In his essay "Religion and Art" Wagner himself described the use of Christian imagery thus:  The critic Eduard Hanslick objected to the religious air surrounding "Parsifal" even at the premiere: "The question of whether "Parsifal" should really be withheld from all theatres and limited to... Bayreuth was naturally on all tongues... I must state here that the church scenes in "Parsifal" did not make the offensive impression on me that others and I had been led to expect from reading the libretto. They are religious situations – but for all their earnest dignity they are not in the style of the church, but completely in the style of the opera. "Parsifal" is an opera, call it a'stage festival' or 'consecrational stage festival' if you will."

Schopenhauer.

Wagner had been greatly impressed with his reading of Arthur Schopenhauer in 1854, and this deeply affected his thoughts and practice on music and art. Some writers (e.g. Bryan Magee) see "Parsifal" as Wagner's last great espousal of Schopenhauerian philosophy. Parsifal can heal Amfortas and redeem Kundry because he shows compassion, which Schopenhauer saw as the highest form of human morality. Moreover, he displays compassion

Nietzsche.

Friedrich Nietzsche, who was originally one of Wagner's champions, chose to use "Parsifal" as the grounds for his breach with Wagner; an extended critique of "Parsifal" opens the third essay ("What Is the Meaning of Ascetic Ideals?") of "On the

Racism debate.

Some writers see in the opera the promotion of racism or anti-semitism. One line of argument suggests that "Parsifal" was written in support of the ideas of Arthur de Gobineau who advocated Aryanism. Parsifal is proposed as the "pure-blooded" (i.e. Aryan) hero who overcomes Klingsor, who is perceived as a Jewish stereotype, particularly since he opposes the quasi-Christian Knights of the Grail. Such claims remain heavily debated, since there is nothing explicit in the libretto to support them. Wagner never mentions such ideas in his many writings, and Cosima Wagner's diaries, which relate in great detail Wagner's thoughts over the last 14 years of his life (including the period covering the composition and first performance of "Parsifal") never mention any such intention. Wagner first met Gobineau very briefly in 1876, but it was only in 1880 that he read Gobineau's "An Essay on the Inequality of the Human Races". However, Wagner had completed the libretto for "Parsifal" by 1877, and the original drafts of the story date back to 1857. Despite this chronological evidence, Gobineau is frequently cited as a major inspiration for "Parsifal".  The related question of whether the opera contains a specifically anti-Semitic message is

Music.

Leitmotifs.

A "leitmotif" is a recurring musical theme within a particular piece of music, associated with a particular person, place or idea. Wagner is the composer most often associated with leitmotifs, and "Parsifal" makes liberal use of them. Wagner did not specifically identify or name leitmotifs in the score of "Parsifal" (any more than he did in any other of his scores), although his wife Cosima mentions statements he made about some of them in her diary. However, Wagner's followers (notably Hans von Wolzogen whose guide to "Parsifal"

Chromaticism.

Many music theorists have used "Parsifal" to explore difficulties in analyzing the chromaticism of late 19th century music. Theorists such as David Lewin and Richard Cohn have explored

Notable excerpts.

As is common in mature Wagner operas, "Parsifal" was composed such that each act was a continuous flow of music; hence there are no free-standing arias in the work. However a number of orchestral excerpts from the opera were arranged

Parsifal Suite.

In 2019 Schott Music published a 45-minute suite of orchestral music from the opera entitled "Parsifal Suite", constructed

Instrumentation.

The score for "Parsifal" calls for three flutes, three oboes, one English horn, three clarinets in B-flat and A, one bass clarinet in B-flat and A, three bassoons, one contrabassoon; four horns in F, three trumpets in F, three trombones, one tuba, 6 onstage trumpets in F, 6 onstage trombones; a percussion section that includes four timpani (requiring two players), tenor drums, 4 onstage church bells, one onstage thunder machine; two harps and strings. "Parsifal" is one of only two works by Wagner in which he used the contrabassoon.

Recordings.

"Parsifal" was expressly composed for the stage at Bayreuth and many of the most famous recordings of the opera come from live performances on that stage. In the pre-LP era, Karl Muck conducted excerpts from the opera at Bayreuth. These are still considered some of the best performances of the opera on disc. They also contain the only sound evidence of the bells constructed for the work's premiere, which were melted down for scrap during World War II.  Hans Knappertsbusch was the conductor most closely associated with "Parsifal" at Bayreuth in the post-war years, and the performances under his baton in 1951 marked the re-opening of the Bayreuth Festival after World War II. These historic performances were recorded and are available on the Teldec label in mono sound. Knappertsbusch recorded

Filmed versions.

In addition to a number of staged performances available on DVD, "Parsifal" was adapted for the screen by film director Hans-Jürgen Syberberg. There is also a 1998 documentary directed by Tony Palmer titled: "Parsifal – The Search for the Grail". It was recorded in various European theaters, including the Mariinsky Theatre, the Ravello

Parsifal (WWV 111) is an opera in three acts by German composer Richard Wagner. It is loosely based on "Parzival" by Wolfram von Eschenbach, a 13th-century epic poem of the Arthurian knight Parzival (Percival) and his quest for the Holy Grail (12th century).

Parsifal je opera Richarda Wagnera z roku 1882. Opera má tři jednání a čerpá ze středověkých legend o Svatém grálu. Premiéra "Parsifala", Wagnerova posledního díla, se uskutečnila 26. července 1882 ve Festivalovém divadle v Bayreuthu v rámci druhých Hudebních slavností v Bayreuthu. O několik měsíců později Wagner zemřel.


Subunit composition.

Eukaryotic types.

Many eukaryotic cells possess two different types of condensin complexes, known as condensin I and condensin II, each of which is composed of five subunits (Figure 2). Condensins I and II share the same pair of core subunits, SMC2 and SMC4, both belonging to a large family of chromosomal ATPases, known as SMC proteins (SMC stands for Structural Maintenance of Chromosomes). Each of the complexes contains a distinct set of non-SMC regulatory subunits (a kleisin subunit and a pair of HEAT repeat subunits). Both complexes are large, having a total molecular mass of 650-700 kDa.  The core subunits condensins (SMC2 and SMC4) are conserved among all eukaryotic species that have been studied to date. The non-SMC subunits unique to condensin I are also conserved among eukaryotes, but the occurrence of the non-SMC subunits unique to condensin II is highly variable among species.

Prokaryotic types.

Prokaryotic species also have condensin-like complexes that play an important role in chromosome (nucleoid) organization and segregation. The prokaryotic condensins can be classified into two types: SMC-ScpAB and MukBEF. Many eubacterial and archaeal species have SMC-ScpAB, whereas a subgroup of eubacteria (known as γ-proteobacteria) including "Escherichia coli" has MukBEF. ScpA and MukF belong to a family of proteins called "kleisins", whereas ScpB and MukF have recently been classified into a new family of proteins named "kite".  Despite highly divergent primary structures of their corresponding subunits between SMC-ScpAB and MukBEF, it is reasonable to consider that the two complexes play similar if not identical functions in prokaryotic chromosome organization and dynamics, based on their molecular architecture and their defective cellular phenotypes. Both complexes are therefore often called prokaryotic (or bacterial) condensins. Recent studies report the occurrence of a third complex related to MukBEF (termed MksBEF) in some bacterial species.

Molecular mechanisms.

Molecular structures.

SMC dimers that act as the core subunits of condensins display a highly characteristic V-shape, each arm of which is composed of anti-parallel coiled-coils (Figure 3; see SMC proteins for details). The length of each coiled-coil arm reaches ~50 nm, which corresponds to the length of ~150 bp of double-stranded DNA (dsDNA). In eukaryotic condensin I and II complexes, a kleisin subunit bridges the two head domains of an SMC dimer, and binds to two HEAT repeat subunits (Figure 1).  Early studies elucidated the structure of parts of bacterial condensins, such as MukBEF and SMC-ScpA. In eukaryotic complexes, several structures of subcomplexes and subdomains have been reported, including the hinge and arm domains of an SMC2-SMC4 dimer, a CAP-G(ycg1)/CAP-H(brn1) subcomplex, and a CAP-D2(ycs4)/CAP-H(brn1) subcomplex. On the other hand, fast-speed atomic force microscopy has demonstrated that the arms of an SMC dimer is far more flexible than was expected.

Molecular activities.

Condensin I purified from "Xenopus" egg extracts is a DNA-stimulated ATPase and displays the ability to introduce positive superhelical tension into dsDNA in an ATP-hydrolysis-dependent manner (positive supercoiling activity). Similar activities have been detected in condensins from other organisms. The positive supercoiling activity is activated "in vitro" by Cdk1 phosphorylation, suggesting that it is likely one of the physiological activities directly involved in mitotic chromosome assembly. It is postulated that this activity of condensin I helps fold DNA and promotes topoisomerase II-mediated resolution of sister chromatids. Early single-DNA-molecule experiments also demonstrated in real time that condensin I is able to compact DNA in an ATP-hydrolysis dependent manner.  Most recently, single-molecule experiments have demonstrated that budding yeast condensin I is able to translocate along dsDNA (motor activity) and to "extrude" DNA loops (loop extrusion activity) in an ATP hydrolysis-dependent manner. In the latter experiments, the activity of individual condensin complexes on DNA was visualized by real-time fluorescence imaging, revealing that condensin I indeed is a fast loop-extruding motor and that a single condensin I complex can extrude 1,500 bp of DNA per second in a strictly ATP-dependent manner. It has been proposed that condensin I anchors DNA between Ycg1-Brn1 subunits and pulls DNA asymmetrically to form large loops. Moreover, it has been shown that condensin complexes can traverse each other, forming dynamic loop structures and changing their sizes.  It is unknown how condensins might act on nucleosomal DNA. Recent development of a reconstitution system has identified the histone chaperone FACT as an essential component of condensin I-mediated chromosome assembly "in vitro", providing an important clue to this problem. It has also been shown that condensins can assemble chromosome-like structures in cell-free extracts even under the condition where nucleosome assembly is largely suppressed. This observation indicates that condensins can work at least in part on non-nucleosomal DNA in a physiological setting.  Only limited information is currently available as to the functional contribution of individual subunits of condensins to their activities. An SMC2-SMC4 dimer has an ability to reanneal complementary single-stranded DNA. This activity does not require ATP. For eukaryotic complexes, it has been reported that HEAT repeat subunits contribute to part of DNA binding and to the assembly of chromosome axes. Flexible and extendable nature of HEAT repeats could underlie the dynamic action of condensins and the architecture of mitotic chromosomes.

Mathematical modeling.

Several attempts on mathematical modeling and computer simulation of mitotic chromosome assembly, based on molecular activities of condensins, have been reported. Representative ones include modeling based on loop extrusion, stochastic pairwise contacts and a combination of looping and inter-condensin attractions.

Functions in chromosome assembly and segregation.

Mitosis.

In human tissue culture cells, the two condensin complexes are regulated differently during the mitotic cell cycle (Figure 4). Condensin II is present within the cell nucleus during interphase and participates in an early stage of chromosome condensation within the prophase nucleus. On the other hand, condensin I is present in the cytoplasm during interphase, and gains access to chromosomes only after the nuclear envelope breaks down (NEBD) at the end of prophase. During prometaphase and metaphase, condensin I and condensin II cooperate to assemble rod-shaped chromosomes, in which two sister chromatids are fully resolved. Such differential dynamics of the two complexes is observed in "Xenopus" egg extracts, mouse oocytes, and neural stem cells, indicating that it is part of a fundamental regulatory mechanism conserved among different organisms and cell types. It is most likely that this mechanism ensures the ordered action of the two complexes, namely, condensin II first and condensin I later.  On metaphase chromosomes, condensins I and II are both enriched in the central axis in a non-overlapping fashion (Figure 5). Depletion experiments "in vivo" and immunodepletion experiments in "Xenopus" egg extracts demonstrate that the two complexes have distinct functions in assembling metaphase chromosomes. Cells deficient in condensin functions are not arrested at a specific stage of cell cycle, displaying chromosome segregation defects (i.e., anaphase bridges) and progressing through abnormal cytokinesis.  The relative contribution of condensins I and II to mitosis varies among different eukaryotic species. For instance, each of condensins I and II plays an essential role in embryonic development in mice. They have both overlapping and non-overlapping functions during the mitotic cell cycle. On the other hand, condensin II is non-essential for mitosis in the primitive alga "C. merolae" and the land plant "A. thaliana". Curiously, condensin II plays a dominant role over condensin I in the "C. elegans" early embryos. This peculiarity could be due to the fact that "C. elegans" has a specialized chromosome structure known as holocentric chromosomes. Fungi, such as "S. cerevisiae" and "S. pombe" have no condensin II from the first. These differences among eukaryotic species provide important implications in the evolution of chromosome architecture (see the section of "Evolutionary implications" below).  It has recently become possible that cell cycle-dependent structural changes of chromosomes are monitored by a genomics-based method known as Hi-C (High-throughput chromosome conformation capture). The impact of condensin deficiency on chromosome conformation has been addressed in budding yeast, fission yeast, and the chicken DT40 cells. The outcome of these studies strongly supports the notion that condensins play crucial roles in mitotic chromosome assembly and that condensin I and II have distinct functions in this process. Moreover, quantitative imaging analyses allow researchers to count the number of condensin complexes present on human metaphase chromosomes.

Meiosis.

Condensins also play important roles in chromosome assembly and segregation in meiosis. Genetic studies have been reported in "S. cerevisiae," "D. melanogaster," and "C. elegans". In mice, requirements for condensin subunits in meiosis have been addressed by antibody-mediated blocking experiments and conditional gene knockout analyses. In mammalian meiosis I, the functional contribution of condensin II appears bigger than that of condensin I. As has been shown in mitosis, however, the two condensin complexes have both overlapping and non-overlapping functions, too, in meiosis. Unlike cohesin, no meiosis-specific subunits of condensins have been identified so far.

Chromosomal functions outside of mitosis or meiosis.

Recent studies have shown that condensins participate in a wide variety of chromosome functions outside of mitosis or meiosis.

Posttranslational modifications.

Condensin subunits are subjected to various posttranslational modifications in a cell cycle-dependent manner. Among them, the best-studied example is phosphorylation. For instance, Cdk1 (Cyclin-dependent kinase 1) activates condensin I, whereas CK2 (Casein kinase 2) negatively regulate its activity.  It has been reported that, in "D. melanogaster", the CAP-H2 subunit of condensin II is degraded through the action of SCF ubiquitin ligase.

Relevance to diseases.

It was demonstrated that MCPH1, one of the proteins responsible for human primary microcephaly, has the ability to negatively regulate condensin II. In "mcph1" patient cells, condensin II (but not condensin I) is hyperactivated, leading to premature chromosome condensation in G2 phase (i.e., before entering mitosis). There is no evidence, however, that misregulation of condensin II is directly related to the etiology of "mcph1" microcephaly. More recently, it has been reported that hypomorphic mutations in condensin I or II subunits cause microcephaly in humans. In mice, hypomorphic mutations in condensin II subunits cause specific defects in T cell development, leading to T cell lymphoma. It is interesting to note that cell types with specialized cell division modes, such as neural stem cells and T cells, are particularly susceptible to mutations in condensin subunits.

Evolutionary implications.

Prokaryotes have primitive types of condensins, indicating that the evolutionary origin of condensins precede that of histones. The fact that condensins I and II are widely conserved among extant eukaryotic species strongly implicates that the last eukaryotic common ancestor (LECA) had both complexes. It is therefore reasonable to speculate that some species such as fungi have lost condensin II during evolution.  Then why do many eukaryotes have two different condensin complexes? As discussed above, the relative contribution of condensins I and II to mitosis varies among different organisms. They play equally important roles in mammalian mitosis, whereas condensin I has a predominant role over condensin II in many other species. In those species, condensin II might have been adapted for various non-essential functions other than mitosis. Although there is no apparent relationship between the occurrence of condensin II and the size of genomes, it seems that the functional contribution of condensin II becomes big as the genome size increases. The relative contribution of the two condensin complexes to mitotic chromosome architecture also change during development, making an impact on the morphology of mitotic chromosomes. Thus, the balancing act of condensins I and II is apparently fine-tuned in both evolution and development.

Relatives.

Eukaryotic cells have two additional classes of SMC protein complexes. Cohesin contains SMC1 and SMC3 and is involved in sister chromatid cohesion. The SMC5/6 complex contains SMC5 and SMC6 and is implicated in recombinational repair.

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis (Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in "Xenopus" egg extracts.

Kondenzin je bílkovinný komplex vyskytující se v jádře a složený ze dvou SMC proteinů (SMC2 a SMC4) a tří dalších pomocných podjednotek. Je stavbou podobný kohezinům. Účastní se kondenzace chromozomů, ačkoliv je známo, že ty mohou do jisté míry kondenzovat i tehdy, není-li kondenzin přítomen. Svou funkci plní během mitózy, kdy se v jádře vyskytuje jeden kondenzinový komplex na každých 10 000 nukleotidů.


Signs and symptoms.

Symptom onset is usually rapid, often occurring within minutes of elevated serotonin levels. Serotonin syndrome encompasses a wide range of clinical findings. Mild symptoms may consist of increased heart rate, shivering, sweating, dilated pupils, myoclonus (intermittent jerking or twitching), as well as overresponsive reflexes. However, many of these symptoms may be side effects of the drug or drug interaction causing excessive levels of serotonin; not an effect of elevated serotonin itself. Tremor is a common side effect of MDMA's action on dopamine, whereas hyperreflexia is symptomatic of exposure to serotonin agonists. Moderate intoxication includes additional abnormalities such as hyperactive bowel sounds, high blood pressure and hyperthermia; a temperature as high as. The overactive reflexes and clonus in moderate cases may be greater in the lower limbs than in the upper limbs. Mental changes include hypervigilance or insomnia and agitation. Severe symptoms include severe increases in heart rate and blood pressure that may lead to shock. Temperature may rise to above in life-threatening cases. Other abnormalities include metabolic acidosis, rhabdomyolysis, seizures, kidney failure, and disseminated intravascular coagulation; these effects usually arising as a consequence of hyperthermia.  The symptoms are often described as a clinical triad of abnormalities:

Cause.

A large number of medications and street drugs can cause serotonin syndrome when taken alone at high doses or in combination with other serotonergic drugs. The table below lists some of these drugs. Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. It may also occur due to an overdose of a single serotonergic agent. The combination of MAOIs with precursors such as L-tryptophan or 5-HTP pose a particularly acute risk of life-threatening serotonin syndrome. The case of combination of MAOIs with tryptamine agonists (commonly known as ayahuasca) can present similar dangers as their combination with precursors, but this phenomenon has been described in general terms as the "cheese effect". Many MAOIs irreversibly inhibit monoamine oxidase. It can take at least four weeks for this enzyme to be replaced by the body in the instance of irreversible inhibitors. With respect to tricyclic antidepressants only clomipramine and imipramine have a risk of causing SS.  Many medications may have been incorrectly thought to cause serotonin syndrome. For example, some case reports have implicated atypical antipsychotics in serotonin syndrome, but it appears based on their pharmacology that they are unlikely to cause the syndrome. It has also been suggested that mirtazapine has no significant serotonergic effects, and is therefore not a dual action drug. Bupropion has also been suggested to cause serotonin syndrome, although as there is no evidence that it has any significant serotonergic activity, it is thought unlikely to produce the syndrome. In 2006 the United States Food and Drug Administration issued an alert suggesting that the combined use of SSRIs or SNRIs and triptan medications or sibutramine could potentially lead to severe cases of serotonin syndrome. This has been disputed by other researchers as none of the cases reported by the FDA met the Hunter criteria for serotonin syndrome. The condition has however occurred in surprising clinical situations, and because of phenotypic variations among individuals, it has been associated with unexpected drugs, including mirtazapine.  The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. Serotonin syndrome has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure. The serotonergic toxicity of SSRIs increases with dose, but even in over-dose it is insufficient to cause fatalities from serotonin syndrome in healthy adults. Elevations of central nervous system serotonin will typically only reach potentially fatal levels when drugs with different mechanisms of action are mixed together. Various drugs, other than SSRIs, also have clinically significant potency as serotonin reuptake inhibitors, (e.g. tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome.

Pathophysiology.

Serotonin is a neurotransmitter involved in multiple biologically complex processes including aggression, pain, sleep, appetite, anxiety, depression, migraine, and vomiting. In humans the effects of excess serotonin were first noted in 1960 in patients receiving a monoamine oxidase inhibitor (MAOI) and tryptophan. The syndrome is caused by increased serotonin in the central nervous system. It was originally suspected that agonism of 5-HT receptors in central grey nuclei and the medulla was responsible for the development of the syndrome. Further study has determined that overstimulation of primarily the 5-HT receptors appears to contribute substantially to the condition. The 5-HT receptor may still contribute through a pharmacodynamic interaction in which increased synaptic concentrations of a serotonin agonist saturate all receptor subtypes. Additionally, noradrenergic CNS hyperactivity may play a role as CNS norepinephrine concentrations are increased in serotonin syndrome and levels appear to correlate with the clinical outcome. Other neurotransmitters may also play a role; NMDA receptor antagonists and GABA have been suggested as affecting the development of the syndrome. Serotonin toxicity is more pronounced following supra-therapeutic doses and overdoses, and they merge in a continuum with the toxic effects of overdose.

Spectrum concept.

A postulated "spectrum concept" of serotonin toxicity emphasises the role that progressively increasing serotonin levels play in mediating the clinical picture as side effects merge into toxicity. The dose-effect relationship is the effects of progressive elevation of serotonin, either by raising the dose of one drug, or combining it with another serotonergic drug which may produce large elevations in serotonin levels. Some experts prefer the terms serotonin toxicity or serotonin toxidrome, to more accurately reflect that it is a form of poisoning.

Diagnosis.

There is no specific test for serotonin syndrome. Diagnosis is by symptom observation and investigation of the person's history. Several criteria have been proposed. The first evaluated criteria were introduced in 1991 by Harvey Sternbach. Researchers later developed the Hunter Toxicity Criteria Decision Rules, which have better sensitivity and specificity, 84% and 97%, respectively, when compared with the gold standard of diagnosis by a medical toxicologist. As of 2007, Sternbach's criteria were still the most commonly used.  The most important symptoms for diagnosing serotonin syndrome are tremor, extreme aggressiveness, akathisia, or clonus (spontaneous, inducible and ocular). Physical examination of the patient should include assessment of deep-tendon reflexes and muscle rigidity, the dryness of the mucosa of the mouth, the size and reactivity of the pupils, the intensity of bowel sounds, skin color, and the presence or absence of sweating. The patient's history also plays an important role in diagnosis, investigations should include inquiries about the use of prescription and over-the-counter drugs, illicit substances, and dietary supplements, as all these agents have been implicated in the development of serotonin syndrome. To fulfill the Hunter Criteria, a patient must have taken a serotonergic agent and meet one of the following conditions:

Differential diagnosis.

Serotonin toxicity has a characteristic picture which is generally hard to confuse with other medical conditions, but in some situations it may go unrecognized because it may be mistaken for a viral illness, anxiety disorders, neurological disorder, anticholinergic poisoning, sympathomimetic toxicity, or worsening psychiatric condition. The condition most often confused with serotonin syndrome is neuroleptic malignant syndrome (NMS). The clinical features of neuroleptic malignant syndrome and serotonin syndrome share some features which can make differentiating them difficult. In both conditions, autonomic dysfunction and altered mental status develop. However, they are actually very different conditions with different underlying dysfunction (serotonin excess vs dopamine blockade). Both the time course and the clinical features of NMS differ significantly from those of serotonin toxicity. Serotonin toxicity has a rapid onset after the administration of a serotonergic drug and responds to serotonin blockade such as drugs like chlorpromazine and cyproheptadine. Dopamine receptor blockade (NMS) has a slow onset, typically evolves over several days after administration of a neuroleptic drug, and responds to dopamine agonists such as bromocriptine.  Differential diagnosis may become difficult in patients recently exposed to both serotonergic and neuroleptic drugs. Bradykinesia and extrapyramidal "lead pipe" rigidity are classically present in NMS, whereas serotonin syndrome causes hyperkinesia and clonus; these distinct symptoms can aid in differentiation.

Management.

Management is based primarily on stopping the usage of the precipitating drugs, the administration of serotonin antagonists such as cyproheptadine, and supportive care including the control of agitation, the control of autonomic instability, and the control of hyperthermia. Additionally, those who ingest large doses of serotonergic agents may benefit from gastrointestinal decontamination with activated charcoal if it can be administered within an hour of overdose. The intensity of therapy depends on the severity of symptoms. If the symptoms are mild, treatment may only consist of discontinuation of the offending medication or medications, offering supportive measures, giving benzodiazepines for myoclonus, and waiting for the symptoms to resolve. Moderate cases should have all thermal and cardiorespiratory abnormalities corrected and can benefit from serotonin antagonists. The serotonin antagonist cyproheptadine is the recommended initial therapy, although there have been no controlled trials demonstrating its efficacy for serotonin syndrome. Despite the absence of controlled trials, there are a number of case reports detailing apparent improvement after people have been administered cyproheptadine. Animal experiments also suggest a benefit from serotonin antagonists. Cyproheptadine is only available as tablets and therefore can only be administered orally or via a nasogastric tube; it is unlikely to be effective in people administered activated charcoal and has limited use in severe cases. Cyproheptadine can be stopped when the person is no longer experiencing symptoms and the half life of serotonergic medications already passed.  Additional pharmacological treatment for severe case includes administering atypical antipsychotic drugs with serotonin antagonist activity such as olanzapine. Critically ill people should receive the above therapies as well as sedation or neuromuscular paralysis. People who have autonomic instability such as low blood pressure require treatment with direct-acting sympathomimetics such as epinephrine, norepinephrine, or phenylephrine. Conversely, hypertension or tachycardia can be treated with short-acting antihypertensive drugs such as nitroprusside or esmolol; longer acting drugs such as propranolol should be avoided as they may lead to hypotension and shock. The cause of serotonin toxicity or accumulation is an important factor in determining the course of treatment. Serotonin is catabolized by monoamine oxidase A in the presence of oxygen, so if care is taken to prevent an unsafe spike in body temperature or metabolic acidosis, oxygenation will assist in dispatching the excess serotonin. The same principle applies to alcohol intoxication. In cases of serotonin syndrome caused by monoamine oxidase inhibitors oxygenation will not help to dispatch serotonin. In such instances, hydration is the main concern until the enzyme is regenerated.

Agitation.

Specific treatment for some symptoms may be required. One of the most important treatments is the control of agitation due to the extreme possibility of injury to the person themselves or caregivers, benzodiazepines should be administered at first sign of this. Physical restraints are not recommended for agitation or delirium as they may contribute to mortality by enforcing isometric muscle contractions that are associated with severe lactic acidosis and hyperthermia. If physical restraints are necessary for severe agitation they must be rapidly replaced with pharmacological sedation. The agitation can cause a large amount of muscle breakdown. This breakdown can cause severe damage to the kidneys through a condition called rhabdomyolysis.

Hyperthermia.

Treatment for hyperthermia includes reducing muscle overactivity via sedation with a benzodiazepine. More severe cases may require muscular paralysis with vecuronium, intubation, and artificial ventilation. Suxamethonium is not recommended for muscular paralysis as it may increase the risk of cardiac dysrhythmia from hyperkalemia associated with rhabdomyolysis. Antipyretic agents are not recommended as the increase in body temperature is due to muscular activity, not a hypothalamic temperature set point abnormality.

Prognosis.

Upon the discontinuation of serotonergic drugs, most cases of serotonin syndrome resolve within 24 hours, although in some cases delirium may persist for a number of days. Symptoms typically persist for a longer time frame in patients taking drugs which have a long elimination half-life, active metabolites, or a protracted duration of action.  Cases have reported muscle pain and weakness persisting for months, and antidepressant discontinuation may contribute to ongoing features. Following appropriate medical management, serotonin syndrome is generally associated with a favorable prognosis.

Epidemiology.

Epidemiological studies of serotonin syndrome are difficult as many physicians are unaware of the diagnosis or they may miss the syndrome due to its variable manifestations. In 1998 a survey conducted in England found that 85% of the general practitioners that had prescribed the antidepressant nefazodone were unaware of serotonin syndrome. The incidence may be increasing as a larger number of pro-serotonergic drugs (drugs which increase serotonin levels) are now being used in clinical practice. One postmarketing surveillance study identified an incidence of 0.4 cases per 1000 patient-months for patients who were taking nefazodone. Additionally, around 14 to 16 percent of persons who overdose on SSRIs are thought to develop serotonin syndrome.

Notable cases.

The most widely recognized example of serotonin syndrome was the death of Libby Zion in 1984. Zion was a freshman at Bennington College at her death on March 5, 1984, at age 18. She died within 8 hours of her emergency admission to the New York Hospital Cornell Medical Center. She had an ongoing history of depression, and came to the Manhattan hospital on the evening of March 4, 1984, with a fever, agitation and "strange jerking motions" of her body. She also seemed disoriented at times. The emergency room physicians were unable to diagnose her condition definitively but admitted her for hydration and observation. Her death was caused by a combination of pethidine and phenelzine. A medical intern prescribed the pethidine. The case influenced graduate medical education and residency work hours. Limits were set on working hours for medical postgraduates, commonly referred to as interns or residents, in hospital training programs, and they also now require closer senior physician supervision.

Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases body temperature can increase to greater than. Complications may include seizures and extensive muscle breakdown. Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-HTP, St. John's wort, triptans, ecstasy (MDMA), metoclopramide, ondansetron, or cocaine. It occurs in about 15% of SSRI overdoses. It is a predictable consequence of excess serotonin on the central nervous system (CNS). Onset of symptoms is typically within a day of the extra serotonin. Diagnosis is based on a person's symptoms and history of medication use. Other conditions that can produce similar symptoms such as neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic toxicity, heat stroke, and meningitis should be ruled out. No laboratory tests can confirm the diagnosis. Initial treatment consists of discontinuing medications which may be contributing. In those who are agitated, benzodiazepines may be used. If this is not sufficient, a serotonin antagonist such as cyproheptadine may be used. In those with a high body temperature active cooling measures may be needed. The number of cases of serotonin syndrome that occur each year is unclear. With appropriate treatment the risk of death is less than one percent. The high-profile case of Libby Zion, who is generally accepted to have died from serotonin syndrome, resulted in changes to graduate medical education in New York State.

Serotoninový syndrom je potenciálně život ohrožující stav způsobený nadměrně zvýšenou hladinou serotoninu v důsledku nepříznivé reakce na léky, která může nastat po léčebné aplikaci léků, jejich náhodné interakci nebo předávkováním. Serotoninový syndrom není idiosynkratická reakce na léky; je předvidatelným důsledkem nadměrné serotonergické aktivity centrální nervové soustavy (CNS) a periferních serotoninových receptorů. Z toho důvodu někteří odborníci preferují názvy serotoninová toxicita či serotoninový toxidrom, neboť přesněji vyjadřují skutečnost, že jde o druh otravy. Jiné názvy používané k označení tohoto syndromu je serotoninová bouře, hyperserotonemie či serotonergický syndrom.