title: Vaudeville

text: At its height, vaudeville played across multiple strata of economic class and auditorium size. On the vaudeville circuit, it was said that if an act would succeed in Peoria, Illinois, it would work anywhere. The question "Will it play in Peoria?" has now become a metaphor for whether something appeals to the American mainstream public. The three most common levels were the "small time" (lower-paying contracts for more frequent performances in rougher, often converted theatres), the "medium time" (moderate wages for two performances each day in purpose-built theatres), and the "big time" (possible remuneration of several thousand dollars per week in large, urban theatres largely patronized by the middle and upper-middle classes). As performers rose in renown and established regional and national followings, they worked their way into the less arduous working conditions and better pay of the big time. The capital of the big time was New York City's Palace Theatre (or just "The Palace" in the slang of vaudevillians), built by Martin Beck in 1913 and operated by Keith. Featuring a bill stocked with inventive novelty acts, national celebrities, and acknowledged masters of vaudeville performance (such as comedian and trick roper Will Rogers), the Palace provided what many vaudevillians considered the apotheosis of remarkable careers. A standard show bill would begin with a sketch, follow with a single (an individual male or female performer); next would be an alley-oop (an acrobatic act); then another single, followed by yet another sketch such as a blackface comedy. The acts that followed these for the rest of the show would vary from musicals to jugglers to song-and-dance singles and end with a final extravaganza – either musical or drama – with the full company. These shows would feature such stars as ragtime and jazz pianist Eubie Blake, the famous and magical Harry Houdini, and child star Baby Rose Marie. In the "New-York Tribune"s article about Vaudeville, it is said that at any given time, Vaudeville was employing over twelve thousand different people throughout its entire industry. Each entertainer would be on the road 42 weeks at a time while working a particular "Circuit" – or an individual theatre chain of a major company.


title: Vaudeville

text: While the neighborhood character of vaudeville attendance had always promoted a tendency to tailor fare to specific audiences, mature vaudeville grew to feature houses and circuits specifically aimed at certain demographic groups. Black patrons, often segregated into the rear of the second gallery in white-oriented theatres, had their own smaller circuits, as did speakers of Italian and Yiddish. (For a brief discussion of Black vaudeville, see Theatre Owners Booking Association.) This foreign addition combined with comedy produced such acts as "minstrel shows of antebellum America" and Yiddish theatre. Many ethnic families joined in on this entertainment business, and for them, this traveling lifestyle was simply a continuation of the circumstances that brought them to America. Through these acts, they were able to assimilate themselves into their new home while also bringing bits of their own culture into this new world. White-oriented regional circuits, such as New England's "Peanut Circuit", also provided essential training grounds for new artists while allowing established acts to experiment with and polish new material. At its height, vaudeville was rivaled only by churches and public schools among the nation's premiere public gathering places.


title: Vaudeville

text: Another slightly different aspect of Vaudeville was an increasing interest in the female figure. The previously mentioned ominous idea of "the blue envelopes" led to the phrase "blue" material, which described the provocative subject matter present in many Vaudeville acts of the time. Many managers even saw this scandalous material as a marketing strategy to attract many different audiences. As stated in Andrew Erdman's book "Blue Vaudeville", the Vaudeville stage was "a highly sexualized space ... where unclad bodies, provocative dancers, and singers of 'blue' lyrics all vied for attention." Such performances highlighted and objectified the female body as a "sexual delight", but more than that, historians think that Vaudeville marked a time in which the female body became its own "sexual spectacle". This sexual image began sprouting everywhere an American went: the shops, a restaurant, the grocery store, etc. The more this image brought in the highest revenue, the more Vaudeville focused on acts involving women. Even acts that were as innocent as a sister act were higher sellers than a good brother act. Consequently, Erdman adds that female Vaudeville performers such as Julie Mackey and Gibson's Bathing Girls began to focus less on talent and more on physical appeal through their figure, tight gowns, and other revealing attire. It eventually came as a surprise to audience members when such beautiful women actually possessed talent in addition to their appealing looks. This element of surprise colored much of the reaction to the female entertainment of this time.


title: Vaudeville

text: In the 1920s, announcements seeking all-girl bands for vaudeville performances appeared in industry publications like "Billboard", "Variety" and in newspapers. Bands like The Ingenues and The Dixie Sweethearts were well-publicized, while other groups were simply described as "all-girl Revue". According to Feminist Theory, similar trends in theater and film objectified women, an example of male gaze, as women's role in public life was expanding. These expectations for women in the 19th century played a big role in the compelling aspects of vaudeville. Through vaudeville, many women were allowed to join their male counterparts on the stage and found success in their acts.


title: Vaudeville

text: Leila Marie Koerber, later Marie Dressler, was a Canadian actress who specialized in vaudeville comedy, and eventually won an Academy Award for Best Actress later in her career. Being the daughter of a musician, she moved to the United States of America in her childhood. At just fourteen years old, she left home to begin her career, lying about her age and sending her mother half of her paycheck. Dressler found great success and was known for her comedic timing and physical comedy, like carrying her male co-stars. She eventually worked on Broadway, where she had a great desire to become a serious actress but was advised to remain in comedy. She went on to star in a few films but again returned to vaudeville, her original career.


title: Vaudeville

text: Another famous vaudevillian actress was Trixi Friganza, originally born Delia O’Callaghan. She had a famous catchphrase; "You know Trixi with her bag of tricks." She began her career in opera, performing to help provide for her family. The oldest of three daughters, she wanted to help her family financially but had to do it secretly, as female performers were frowned on at the time. She worked largely in comedy and gained acclaim and success due to her willingness to step into other's roles who had fallen ill, and were otherwise unable to perform. In her acts, she often emphasized her plus-size figure, calling herself the "perfect forty-six". Friganza was also a poet and writer. She used many of her performances as ways to raise money to support the poor or disenfranchised and went on record publicly numerous times to support these social causes. Friganza also spent much of her life fighting for women’s equality and pushing for self-acceptance for women, both publicly and within themselves, as well as their rights in comparison to men.


title: Vaudeville

text: Another famous comedienne, one who brought in thousands of audience members with her signature improvisational skills, was May Irwin. She worked from about 1875 to 1914. Originally born Ada Campbell, she began her life on the stage at thirteen years old following the death of her father. She and her older sister created a singing act called the "Irwin Sisters". Many years later, their act had taken off and with performances in both vaudeville and burlesque at famous music halls, until Irwin decided to continue her career on her own. She then changed her approach to vaudeville, performing African-American-influenced songs, even later writing her songs. She introduced her signature in vaudeville, "The Bully Song", which was performed in a Broadway show. This is when she began experimenting with improvisational comedy and quickly found her unique success, even taking her performances global with acts in the U.K.


title: Vaudeville

text: In addition to vaudeville's prominence as a form of American entertainment, it reflected the newly evolving urban inner-city culture and interaction of its operators and audience. Making up a large portion of immigration to the United States in the mid-19th century, Irish Americans interacted with established Americans, with the Irish becoming subject to discrimination due to their ethnic physical and cultural characteristics. The ethnic stereotypes of Irish through their greenhorn depiction alluded to their newly arrived status as immigrant Americans, with the stereotype portrayed in avenues of entertainment.


title: Vaudeville

text: Following the Irish immigration wave, several waves followed in which new immigrants from different backgrounds came in contact with the Irish in America's urban centers. Already settled and being native English speakers, Irish Americans took hold of these advantages and began to assert their positions in the immigrant racial hierarchy based on skin tone and assimilation status, cementing job positions that were previously unavailable to them as recently arrived immigrants. As a result, Irish Americans became prominent in vaudeville entertainment as curators and actors, creating a unique ethnic interplay between Irish American use of self-deprecation as humor and their diverse inner city surroundings.


title: Vaudeville

text: The interactions between newly arrived immigrants and settled immigrants within the backdrop of the unknown American urban landscape allowed vaudeville to be utilized as an avenue for expression and understanding. The often hostile immigrant experience in their new country was now used for comic relief on the vaudeville stage, where stereotypes of different ethnic groups were perpetuated. The crude stereotypes that emerged were easily identifiable not only by their distinct ethnic cultural attributes, but how those attributes differed from the mainstream established American culture and identity.


title: Vaudeville

text: Coupled with their historical presence on the English stage for comic relief, and as operators and actors of the vaudeville stage, Irish Americans became interpreters of immigrant cultural images in American popular culture. New arrivals found their ethnic group status defined within the immigrant population and in their new country as a whole by the Irish on stage. Unfortunately, the same interactions between ethnic groups within the close living conditions of cities also created racial tensions which were reflected in vaudeville. Conflict between Irish and African Americans saw the promotion of black-face minstrelsy on the stage, purposefully used to place African Americans beneath the Irish in the racial and social urban hierarchy.


title: Vaudeville

text: Although the Irish had a strong Celtic presence in vaudeville and in the promotion of ethnic stereotypes, the ethnic groups that they were characterizing also utilized the same humor. As the Irish donned their ethnic costumes, groups such as the Chinese, Italians, Germans and Jews utilized ethnic caricatures to understand themselves as well as the Irish. The urban diversity within the vaudeville stage and audience also reflected their societal status, with the working class constituting two-thirds of the typical vaudeville audience.


title: Vaudeville

text: The ethnic caricatures that now comprised American humor reflected the positive and negative interactions between ethnic groups in America's cities. The caricatures served as a method of understanding different groups and their societal positions within their cities. The use of the greenhorn immigrant for comedic effect showcased how immigrants were viewed as new arrivals, but also what they could aspire to be. In addition to interpreting visual ethnic caricatures, the Irish American ideal of transitioning from the shanty to the lace curtain became a model of economic upward mobility for immigrant groups.


title: Vaudeville

text: The continued growth of the lower-priced cinema in the early 1910s dealt the heaviest blow to vaudeville. This was similar to the advent of free broadcast television's diminishing the cultural and economic strength of the cinema. Cinema was first regularly commercially presented in the US in vaudeville halls. The first public showing of movies projected on a screen took place at Koster and Bial's Music Hall in 1896. Lured by greater salaries and less arduous working conditions, many performers and personalities, such as Al Jolson, W. C. Fields, Mae West, Buster Keaton, the Marx Brothers, Jimmy Durante, Bill "Bojangles" Robinson, Edgar Bergen, Fanny Brice, Burns and Allen, and Eddie Cantor, used the prominence gained in live variety performance to vault into the new medium of cinema. In doing so, such performers often exhausted in a few moments of screen time the novelty of an act that might have kept them on tour for several years. Other performers who entered in vaudeville's later years, including Jack Benny, Abbott and Costello, Kate Smith, Cary Grant, Bob Hope, Milton Berle, Judy Garland, Rose Marie, Sammy Davis Jr., Red Skelton, Larry Storch and The Three Stooges, used vaudeville only as a launching pad for later careers. They left live performance before achieving the national celebrity of earlier vaudeville stars, and found fame in new venues.


title: Vaudeville

text: The line between live and filmed performances was blurred by the number of vaudeville entrepreneurs who made more or less successful forays into the movie business. For example, Alexander Pantages quickly realized the importance of motion pictures as a form of entertainment. He incorporated them in his shows as early as 1902. Later, he entered into a partnership with the Famous Players-Lasky, a major Hollywood production company and an affiliate of Paramount Pictures.


title: Vaudeville

text: By the late 1920s, most vaudeville shows included a healthy selection of cinema. Earlier in the century, many vaudevillians, cognizant of the threat represented by cinema, held out hope that the silent nature of the "flickering shadow sweethearts" would preclude their usurpation of the paramount place in the public's affection. With the introduction of talking pictures in 1926, the burgeoning film studios removed what had remained the chief difference in favor of live theatrical performance: spoken dialogue. Historian John Kenrick wrote:


title: Vaudeville

text: Top vaudeville stars filmed their acts for one-time pay-offs, inadvertently helping to speed the death of vaudeville. After all, when "small time" theatres could offer "big time" performers on screen at a nickel a seat, who could ask audiences to pay higher amounts for less impressive live talent? The RKO studios took over the famed Orpheum vaudeville circuit and swiftly turned it into a chain of full-time movie theatres. The half-century tradition of vaudeville was effectively wiped out within less than four years.


title: Vaudeville

text: Inevitably, managers further trimmed costs by eliminating the last of the live performances. Vaudeville also suffered due to the rise of broadcast radio following the greater availability of inexpensive receiver sets later in the decade. Even the hardiest in the vaudeville industry realized the form was in decline; the perceptive understood the condition to be terminal. The standardized film distribution and talking pictures of the 1930s confirmed the end of vaudeville. By 1930, the vast majority of formerly live theatres had been wired for sound, and none of the major studios were producing silent pictures. For a time, the most luxurious theatres continued to offer live entertainment, but most theatres were forced by the Great Depression to economize.


title: Vaudeville

text: Some in the industry blamed cinema's drain of talent from the vaudeville circuits for the medium's demise. Others argued that vaudeville had allowed its performances to become too familiar to its famously loyal, now seemingly fickle audiences.


title: Vaudeville

text: There was no abrupt end to vaudeville, though the form was clearly sagging by the late 1920s. Joseph Kennedy Sr. in a hostile buyout, acquired the Keith-Albee-Orpheum Theatres Corporation (KAO), which had more than 700 vaudeville theatres across the United States which had begun showing movies. The shift of New York City's Palace Theatre, vaudeville's center, to an exclusively cinema presentation on 16 November 1932, is often considered to have been the death knell of vaudeville.


title: Vaudeville

text: Though talk of its resurrection was heard during the 1930s and later, the demise of the supporting apparatus of the circuits and the higher cost of live performance made any large-scale renewal of vaudeville unrealistic.


title: Vaudeville

text: The most striking examples of Gilded Age theatre architecture were commissioned by the big time vaudeville magnates and stood as monuments of their wealth and ambition. Examples of such architecture are the theatres built by impresario Alexander Pantages. Pantages often used architect B. Marcus Priteca (1881–1971), who in turn regularly worked with muralist Anthony Heinsbergen. Priteca devised an exotic, neo-classical style that his employer called "Pantages Greek".


title: Vaudeville

text: Though classic vaudeville reached a zenith of capitalization and sophistication in urban areas dominated by national chains and commodious theatres, small-time vaudeville included countless more intimate and locally controlled houses. Small-time houses were often converted saloons, rough-hewn theatres, or multi-purpose halls, together catering to a wide range of clientele. Many small towns had purpose-built theatres. A small yet interesting example might include what is called Grange Halls in northern New England, still being used. These are old-fashioned, wooden buildings with creaky, dimly-lit, wooden stages all of which is which is meant to offset the isolation of a farming lifestyle. These stages can offer anything from child performers to something called contra-dances to visits by Santa to local, musical talent, to homemade foods such as whoopee pies.


title: Vaudeville

text: Some of the most prominent vaudevillians successfully made the transition to cinema, though others were not as successful. Some performers such as Bert Lahr fashioned careers out of combining live performance with radio and film roles. Many others later appeared in the Catskill resorts that constituted the "Borscht Belt".


title: Vaudeville

text: Vaudeville was instrumental in the success of the newer media of film, radio, and television. Comedies of the new era adopted many of the dramatic and musical tropes of classic vaudeville acts. Film comedies of the 1920s through the 1940s used talent from the vaudeville stage and followed a vaudeville aesthetic of variety entertainment, both in Hollywood and in Asia, including China.


title: Vaudeville

text: The rich repertoire of the vaudeville tradition was mined for prominent prime-time radio variety shows such as "The Rudy Vallée Show". The structure of a single host introducing a series of acts became a popular television style and can be seen consistently in the development of television, from "The Milton Berle Show" in 1948 to "Late Night with David Letterman" in the 1980s. The multi-act format had renewed success in shows such as "Your Show of Shows" with Sid Caesar and "The Ed Sullivan Show". Today, performers such as Bill Irwin, a MacArthur Fellow and Tony Award-winning actor, are frequently lauded as "New Vaudevillians".


title: Vaudeville

text: References to vaudeville and the use of its distinctive argot continue throughout Western popular culture. Words such as "flop" and "gag" were terms created from the vaudeville era and have entered the American idiom. Though not credited often, vaudevillian techniques can commonly be witnessed on television and in movies, remarkably in the recent, worldwide phenomenon of tv shows such as America’s Got Talent.


title: Vaudeville

text: In 2018, noted film director Christopher Annino, maker of a new silent feature film, "Silent Times", founded Vaudeville Con, a gathering to celebrate the history of vaudeville. The first meeting was held in Pawcatuck, Connecticut.


title: Vaudeville

text: The records of the Tivoli Theatre are housed at the State Library of Victoria, Melbourne, Australia, with additional personal papers of vaudevillian performers from the Tivoli Theatre, including extensive costume and set design holdings, held by the Performing Arts Collection, Arts Centre Melbourne.


title: Vaudeville

text: The American Vaudeville Museum, one of the largest collections of vaudeville memorabilia, is located at the University of Arizona.


title: Vaudeville

text: The Elgin and Winter Garden Theatres in Toronto houses the world's largest collection of vaudeville props and scenery.


title: Vaudeville

text: The Benjamin Franklin Keith and Edward F. Albee Collection housed at the University of Iowa includes a large collection of managers' report books recording and commenting on the lineup and quality of the acts each night.


title: Serotonin syndrome

text: 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, including a potentiality of death. 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.


title: Serotonin syndrome

text: 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, 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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 rather than 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. 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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 US 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.


title: Serotonin syndrome

text: 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, (such as tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome.


title: Serotonin syndrome

text: Although the most significant health risk associated with opioid overdoses is respiratory depression, it is still possible for an individual to develop serotonin syndrome from certain opioids without the loss of consciousness. However, most cases of opioid-related serotonin syndrome involve the concurrent use of a serotergenic drug such as antidepressants. Nonetheless, it is not uncommon for individuals taking opioids to also be taking antidepressants due to the comorbidity of pain and depression.


title: Serotonin syndrome

text: Cases where opioids alone are the cause of serotonin syndrome are typically seen with tramadol, because of its dual mechanism as a serotonin-norepinephrine reuptake inhibitor. Serotonin syndrome caused by tramadol can be particularly problematic if an individual taking the drug is unaware of the risks associated with it and attempts to self-medicate symptoms such as headache, agitation, and tremors with more opioids, further exacerbating the condition.


title: Serotonin syndrome

text: Serotonin is a neurotransmitter involved in multiple complex biological 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 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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:


title: Serotonin syndrome

text: 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


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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 MAOIs oxygenation will not help to dispatch serotonin. In such instances, hydration is the main concern until the enzyme is regenerated.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: Cases have reported persisting chronic symptoms, and antidepressant discontinuation may contribute to ongoing features. Following appropriate medical management, serotonin syndrome is generally associated with a favorable prognosis.


title: Serotonin syndrome

text: 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.


title: Serotonin syndrome

text: 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.


title: Yara Shahidi

text: Yara Sayeh Shahidi (born February 10, 2000) is an American actress and model. She gained recognition for her starring role as the oldest daughter Zoey Johnson on the sitcom "Black-ish" (2014–2022) and its spin-off series "Grown-ish" (2018–present). Her film credits include "Imagine That" (2009), "Smallfoot" (2018), and the lead role in "The Sun Is Also a Star" (2019). "Time" included her on "The 30 Most Influential Teens of 2016" list.


title: Yara Shahidi

text: Yara Sayeh Shahidi was born in Minneapolis, Minnesota, to Keri Salter Shahidi and Afshin Shahidi, a photographer. Her mother, Keri Salter, is of African-American and Choctaw heritage, whereas her father Afshin is Iranian. Afshin was one of the principal photographers for musician Prince until his death in 2016. Prince also kept a signed photo of Yara in his editing suit at Paisley Park, which can be seen on the VIP Tour. The family moved to California for Afshin's work when Yara was 4 years old. She is the older sister of child actor and model Sayeed Shahidi and they have a younger brother, Ehsan. The rapper Nas is a cousin.


title: Yara Shahidi

text: Her mother Keri states her daughter's first name "Yara" means "Someone who is close to your heart" in Persian . Shahidi is also a common surname in Iran, of Muslim origin.


title: Yara Shahidi

text: Shahidi graduated in 2017 from Dwight Global Online School. Starting in 2018, Shahidi began college at Harvard University with a plan to major in Interdisciplinary Sociology and African American Studies.


title: Yara Shahidi

text: Shahidi began her career when she was 6 years old, appearing in television commercials and print advertisements for companies such as McDonald's, Ralph Lauren, Target, GapKids, Disney, Guess Kids and The Children's Place. She frequently worked with her mother and younger brother in various print and broadcast campaigns.


title: Yara Shahidi

text: Shahidi made her cinematic debut in 2009, starring opposite Eddie Murphy in Paramount Pictures' "Imagine That", for which she received a Young Artist Award nomination for the best performance in a feature film category. She also appeared in the Angelina Jolie action film "Salt" in 2010 as a next door neighbor. In 2012, she played Chloe Johnson, the daughter of President William Johnson, in the TV series "The First Family".


title: Yara Shahidi

text: Starting in September 2014, Shahidi began her role in ABC's prime-time comedy "Black-ish" as 14-year-old Zoey Johnson. In December 2014 she won an NAACP Image Award in the category of 'Best Supporting Actress in a Comedy'.


title: Yara Shahidi

text: In 2016, she signed to model with New York's Women Management modeling agency, in hopes of providing a platform to see more women of color in diverse roles.


title: Yara Shahidi

text: ABC announced in 2017 that Shahidi would be headlining a "Black-ish" spinoff, titled "Grown-ish", on its sister network Freeform. The series premiered on January 3, 2018.


title: Yara Shahidi

text: She was one of fifteen women selected to appear on the cover of the September 2019 issue of "British Vogue", by guest editor Meghan, Duchess of Sussex.


title: Yara Shahidi

text: In 2020, Shahidi and her mother launched their production company 7th Sun and signed a deal with ABC Studios to produce shows. She was cast as Tinker Bell in the upcoming "Peter Pan" remake "Peter Pan & Wendy". and will appear in the Apple TV+ anthology series "Extrapolations".


title: Yara Shahidi

text: Shahidi founded Eighteen x 18 with social news publisher NowThis, which "will be a platform to encourage [her] peers to vote for the very first time in our upcoming midterm elections." Her other organizations include Yara's Club a partnership with Young Women's Leadership Network (YWLN) of New York, which provides online mentorship in hopes to end poverty through education.


title: Yara Shahidi

text: Shahidi's activism was noticed by former first lady Michelle Obama, who wrote her a letter of recommendation to Harvard University. She was also given the opportunity by "Teen Vogue" to interview Hillary Clinton in 2017.


title: Uncharted: The Lost Legacy

text: Uncharted: The Lost Legacy is a 2017 action-adventure game developed by Naughty Dog and published by Sony Interactive Entertainment. It is a standalone expansion to "". Players control Chloe Frazer, who seeks the Tusk of Ganesh in the Western Ghats mountain ranges of India, with the help of ex-mercenary Nadine Ross, and prevent a ruthless warlord and his army of insurgents from igniting a civil war in the country. It is the first "Uncharted" game not to feature series protagonist Nathan Drake.


title: Uncharted: The Lost Legacy

text: Like other "Uncharted" games, "The Lost Legacy" is played from a third-person perspective; players use firearms and can use melee combat and stealth to defend against enemies. Players solve puzzles, incorporating several platformer elements to advance the narrative, and navigate the game world on foot or by vehicle. Development of "The Lost Legacy" began soon after the release of "Uncharted 4: A Thief's End" in May 2016. It builds upon gameplay elements established in previous "Uncharted" titles with its more open-ended gameplay. Chloe, a supporting character who appeared in previous "Uncharted" games as a friend, love interest, and associate to Nathan Drake, is the focus of the game, with the story, design, and gameplay elements reflecting her character. Claudia Black, Laura Bailey and Troy Baker reprised their roles as Chloe, Nadine and Sam respectively, through voice and motion capture, and assisted writer Josh Scherr and creative director Shaun Escayg with the development of the characters and story.


title: Uncharted: The Lost Legacy

text: "The Lost Legacy" was released for PlayStation 4 in August 2017; a remastered version was released for PlayStation 5 in January 2022, and for Windows in October 2022. The critical response to the game was positive.


title: Uncharted: The Lost Legacy

text: "Uncharted: The Lost Legacy" is an action-adventure game played from a third-person perspective, with platform game elements. Players control Chloe Frazer—a treasure hunter who is physically adept and can jump, sprint, climb, swim, swing, and perform other acrobatic actions. Players traverse several environments, moving through locations including towns, buildings, and temples to advance through the game's story. Players use firearms, melee combat, and stealth to defend against the hostile enemies, and also drive vehicles during some gameplay segments.


title: Uncharted: The Lost Legacy

text: In combat, players can use long-ranged weapons, such as rifles and shotguns, and short-barreled guns such as pistols and revolvers; handheld explosives such as grenades and C4 are also available. Though players can attack enemies directly, they have the option to use stealth tactics to attack undetected or sneak by them; the game introduces silenced weapons. While the game is linear, environments feature multiple paths for players to explore; maps are larger than those in "". The game features an artificial intelligence system in which hostile enemies react to any combat situation they are placed in; they respond to players' actions, coordinate tactics, and cooperate with each other. Players' companions are also controlled by artificial intelligence and can assist in combat by throwing objects at threats to stun them, announcing the location of unseen enemies, or using weapons to attack enemies. The game features periods without combat, often involving conversation between the characters. Players also can decide the outcome of some conversations through a dialogue tree.


title: Uncharted: The Lost Legacy

text: The game gives access to the multiplayer of "Uncharted 4", with additional content tied into "The Lost Legacy".


title: Uncharted: The Lost Legacy

text: In India, treasure hunter Chloe Frazer (Claudia Black) searches for the legendary tusk of Ganesh, the son of Hindu god Shiva, who lost the tusk while defending his father's temple. Chloe's father was killed by bandits while searching for the tusk. Chloe slips past insurgents and meets up with mercenary Nadine Ross (Laura Bailey). They sneak into the office of the insurgents' leader, Asav (Usman Ally) a former acquaintance of Nadine, who wants to use the tusk to rally India into a civil war. Chloe and Nadine steal a map pointing toward the tusk within the ancient Hoysala Empire and a disc that acts as a key.


title: Uncharted: The Lost Legacy

text: In India's Western Ghats, Chloe and Nadine follow the trail of several towers emblazoned with Hindu weapons: Ganesh's trident, Shiva's bow, and the axe of Parashurama, who used the axe to remove the tusk. The trail leads them to one of Hoysala's two capitals, Halebidu, whose last emperor left to be conquered by the Persians seemingly out of vanity. They realize the emperor left a false trail; the tusk is at the older capital, Belur. On the way there, they escape Asav and his men but lose the disc. While spying on Asav's forces, Nadine sees her old enemy Samuel Drake (Troy Baker); she realizes he is Asav's expert. When she expresses her intention to kill Sam, primarily due to the , Chloe reveals she was working with him before he was abducted. Feeling angry and betrayed, Nadine separates from Chloe, but they make amends.


title: Uncharted: The Lost Legacy

text: At Belur, they navigate several puzzles before being captured by Asav, who has realized that Sam is no expert and was misleading them the whole time, forcing Chloe to use the disc to reveal the tusk. In the process, she discovers that Ganesh allowed Parashurama to cut off his tusk; as Shiva gave the axe to him, Ganesh did not want to shame his father by proving the axe useless. Asav triggers a trap and leaves Chloe, Nadine & Sam to drown. Chloe picks the locks on their handcuffs and they escape. Despite tensions between Nadine and Sam, the three chase after Asav to take back the tusk. Nadine is enraged to find that Asav is working with Shoreline, the mercenary group she used to run and from which she was ousted.


title: Uncharted: The Lost Legacy

text: Asav trades the tusk to Orca (Gideon Emery), Nadine's former lieutenant, who now runs Shoreline. Chloe, Nadine & Sam down Orca's helicopter and learn that Asav traded the tusk for a bomb he plans to detonate in the capital and trigger a civil war. Orca pulls a gun on Nadine, but Sam saves her, allowing her to shoot Orca dead. Commandeering a jeep, the three catch up to the train carrying the bomb. The women board the train and fight through Asav's men. Chloe and Sam switch the tracks, redirecting the train away from the city. In the engine car, Chloe and Nadine fight Asav, whose leg becomes trapped under the bomb. They jump to safety before the train falls from a collapsed bridge and explodes, killing Asav. Chloe and Nadine decide to partner up, while Sam reacts with horror at their intentions to donate the valuable tusk to the Ministry of Culture.


title: Uncharted: The Lost Legacy

text: Naughty Dog began developing "The Lost Legacy" following the release of "Uncharted 4" in May 2016, initially exploring narrative ideas. Kurt Margenau and Shaun Escayg were chosen to lead development as game director and creative director, respectively. Margenau was selected for his knowledge of programming and passion for gaming and interactivity, while Escayg was chosen for his understanding of narrative structure. The game's original score was written by Henry Jackman, who previously composed "Uncharted 4". While the development team initially contemplated creating "Uncharted 5", they opted to create downloadable content (DLC) for "Uncharted 4", as the simultaneous development of "The Last of Us Part II" led them to favor a more condensed story for a sooner release.


title: Uncharted: The Lost Legacy

text: "The Lost Legacy" was announced at the PlayStation Experience event on December 4, 2016, alongside its debut gameplay trailer. A gameplay video was released in April 2017, revealing the release date and announcing the pre-order bonus: the original "", emulated on PlayStation 4. A story trailer was also shown at E3 in June. The game was released for PlayStation 4 on August 22, 2017 in North America, and August 23 in Europe. The standalone version of "The Lost Legacy" was removed from the PlayStation Store in December 2021; with the game available only in a digital bundle with "Uncharted 4". A remastered version for PlayStation 5 was released on January 28, 2022 alongside "Uncharted 4" as "Uncharted: Legacy of Thieves Collection". The Windows version, developed in collaboration with Iron Galaxy, was released on October 19, 2022.


title: Uncharted: The Lost Legacy

text: The team experimented with using Nathan Drake, the protagonist of previous "Uncharted" games, as a secondary character, but found that it "felt superfluous". Several other characters were also considered as protagonists, including Charlie Cutter, Nathan's daughter Cassie, Nathan's brother Sam Drake and friend Victor Sullivan; the team felt Sullivan's age would hinder gameplay. They decided to follow Chloe Frazer and Nadine Ross, who first appeared in "" (2009) and "Uncharted 4", respectively. The team opted to focus on new relationships with established secondary characters in the "Uncharted" series, a departure from "" (2014), the downloadable content (DLC) for "The Last of Us" (2013), which instead focused on a "missing chunk of the story". They originally envisioned the length of "The Lost Legacy" to be similar to "Left Behind"; as development progressed, they realized the game would be larger, and it became a standalone title instead of DLC, with an estimated length of over 10 hours.


title: Uncharted: The Lost Legacy

text: Claudia Black and Laura Bailey portrayed Chloe and Nadine, respectively, in "The Lost Legacy", reprising their roles from previous entries in the series. The actors' performances were mostly recorded using motion capture, with the remaining audio elements recorded later in a studio. Video recording also captures the actors' faces, for animators to later construct. The game's actors regularly contributed to the development of the characters; co-writer Josh Scherr found that the actors were more familiar with the character motivations, and made changes to the script throughout production. The game was built around Chloe's character, with the narrative and art design reflecting her darker, grounded mindset. When returning to the character, Black was intrigued by the events that took place in her life between "Uncharted 3" and "The Lost Legacy".


title: Uncharted: The Lost Legacy

text: The team placed particular importance on Chloe's design in "The Lost Legacy", maintaining familiar elements like her ponytail, but displaying minor signs of aging, including wrinkles. Her design and fighting style is different from Nathan Drake's, and her animations were altered as a result. The team found Chloe's character interesting as her moral compass is a "little bit less directed" than Nathan's; while she would previously seek artifacts for the reward, she is interested in the history of the Tusk of Ganesh due to its relevance to her family, and Scherr found this interesting to explore. They were also interested in exploring Chloe's coping mechanism from previous games: while she would previously escape a dangerous situation to save herself, in "The Lost Legacy" she is forced to persevere due to her leadership. The team felt that Chloe would require a partner with military expertise, and Nadine would be desperate for more work following "Uncharted 4". The pairing of the characters interested the team due to their vast differences: Chloe is "spontaneous and impulsive", whereas Nadine is structured, and they need to overcome their differences to work together. The writers felt that the banter between the characters required subtlety over previous series entries; during development, they sometimes found that the dialogue was "too friendly", and altered the script as a result.


title: Uncharted: The Lost Legacy

text: The game's antagonist, Asav, is portrayed by Usman Ally. When preparing for the role, Ally met with Escayg to discuss experiences with "despotic regimes that had their roots in what was perceived as a noble cause". Escayg compared Asav to Mexican medical surgeon José Manuel Mireles, having seen the documentary "Cartel Land" (2015); Ally described Mireles as "someone who had the charisma and belief in his people to rise and lead a revolution of sorts", noting that Asav possesses a similar mindset and weaknesses. Ally found that relating to historical revolutionaries allowed him to better understand the character's logic.


title: Uncharted: The Lost Legacy

text: Scherr and Escayg wrote the game's story. While previous "Uncharted" games followed specific historic figures, such as Marco Polo and Henry Avery, "The Lost Legacy" instead focuses on the region, and the surrounding philosophy and culture, due to the shorter development time allowing less intensive research. The writers particularly focused on Hinduism and the surrounding mythology when researching for the story. With "The Lost Legacy", the team aimed to include the "slightly more fantastical feel" from the first three "Uncharted" games, which was absent from "Uncharted 4" due to the grounded story. Escayg found that the game's smaller scope allowed a better opportunity to explore each character, and their stories and viewpoints. He also attempted to demonstrate the characters' emotional state through gameplay. The story of "The Lost Legacy" allowed the team to explore gameplay elements scrapped from "Uncharted 4".


title: Uncharted: The Lost Legacy

text: While some of the large open areas of "Uncharted 4" were limited by the game's development schedule, Naughty Dog updated the production process to allow up to five teams to develop one location at a time for "The Lost Legacy". The natural diversity of the Western Ghats area also allowed the team to explore different settings, including jungles, mountains, temples, and large urban environments. The iconography and deities of India were also appealing to the team.


title: Uncharted: The Lost Legacy

text: The team reworked the combat mechanics of "Uncharted" to better fit Chloe's size and fighting style; while Nathan fought like a brawler, Chloe utilizes more martial arts techniques. While players can control the character and camera in the game, the team orchestrates gameplay elements to construct specific shots. Art director Tate Mosesian said that "there's very little that's random". The team sought to "take advantage" of color when composing shots in the game. The team purchased a lock picking set during development, to assist with the implementation of the in-game lock-picking mechanics.


title: Uncharted: The Lost Legacy

text: "Uncharted: The Lost Legacy" received "generally favorable" reviews, according to review aggregator Metacritic. "Eurogamer" ranked the game 18th on their list of the "Top 50 Games of 2017", "GamesRadar+" ranked it tenth on their list of the 25 Best Games of 2017, and EGMNow ranked it 21st in their list of the 25 Best Games of 2017, while "Polygon" ranked it 47th on their list of the 50 best games of 2017. The game was nominated for "Best PlayStation 4 Game", "Best Action-Adventure Game", "Best Graphics" and "Best Story" in IGN's Best of 2017 Awards; and won the award for "Best Graphics" in "Game Informer"s 2017 Action Game of the Year Awards.


title: Uncharted: The Lost Legacy

text: "Uncharted: The Lost Legacy" sold 23,131 copies on PlayStation 4 within its first week on sale in Japan, which placed it at number four on the all-format sales chart. On the week of its release, "Lost Legacy" topped the UK video game sales chart, later selling 48,000 digital copies within 5 weeks of its release.


title: Sucrose

text: Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula .


title: Sucrose

text: For human consumption, sucrose is extracted and refined from either sugarcane or sugar beet. Sugar mills – typically located in tropical regions near where sugarcane is grown – crush the cane and produce raw sugar which is shipped to other factories for refining into pure sucrose. Sugar beet factories are located in temperate climates where the beet is grown, and process the beets directly into refined sugar. The sugar-refining process involves washing the raw sugar crystals before dissolving them into a sugar syrup which is filtered and then passed over carbon to remove any residual colour. The sugar syrup is then concentrated by boiling under a vacuum and crystallized as the final purification process to produce crystals of pure sucrose that are clear, odorless, and sweet.


title: Sucrose

text: Sugar is often an added ingredient in food production and recipes. About 185 million tonnes of sugar were produced worldwide in 2017.


title: Sucrose

text: Sucrose is particularly dangerous as a risk factor for tooth decay because "Streptococcus mutans" bacteria convert it into a sticky, extracellular, dextran-based polysaccharide that allows them to cohere, forming plaque. Sucrose is the only sugar that bacteria can use to form this sticky polysaccharide.


title: Sucrose

text: The word "sucrose" was coined in 1857, by the English chemist William Miller from the French ("sugar") and the generic chemical suffix for sugars "-ose". The abbreviated term "Suc" is often used for "sucrose" in scientific literature.


title: Sucrose

text: The name "saccharose" was coined in 1860 by the French chemist Marcellin Berthelot. Saccharose is an obsolete name for sugars in general, especially sucrose.


title: Sucrose

text: In sucrose, the monomers glucose and fructose are linked via an ether bond between C1 on the glucosyl subunit and C2 on the fructosyl unit. The bond is called a glycosidic linkage. Glucose exists predominantly as a mixture of α and β "pyranose" anomers, but sucrose has only the α form. Fructose exists as a mixture of five tautomers but sucrose has only the β--fructofuranose form. Unlike most disaccharides, the glycosidic bond in sucrose is formed between the reducing ends of both glucose and fructose, and not between the reducing end of one and the non-reducing end of the other. This linkage inhibits further bonding to other saccharide units, and prevents sucrose from spontaneously reacting with cellular and circulatory macromolecules in the manner that glucose and other reducing sugars do. Since sucrose contains no anomeric hydroxyl groups, it is classified as a non-reducing sugar.


title: Sucrose

text: Sucrose crystallizes in the monoclinic space group P2 with room-temperature lattice parameters "a" = 1.08631 nm, "b" = 0.87044 nm, "c" = 0.77624 nm, β = 102.938°.


title: Sucrose

text: The purity of sucrose is measured by polarimetry, through the rotation of plane-polarized light by a sugar solution. The specific rotation at using yellow "sodium-D" light (589 nm) is +66.47°. Commercial samples of sugar are assayed using this parameter. Sucrose does not deteriorate at ambient conditions.


title: Sucrose

text: Sucrose does not melt at high temperatures. Instead, it decomposes at to form caramel. Like other carbohydrates, it combusts to carbon dioxide and water. Mixing sucrose with the oxidizer potassium nitrate produces the fuel known as rocket candy that is used to propel amateur rocket motors.


title: Sucrose

text: This reaction is somewhat simplified though. Some of the carbon does get fully oxidized to carbon dioxide, and other reactions, such as the water-gas shift reaction also take place. A more accurate theoretical equation is:


title: Sucrose

text: Sucrose can be dehydrated with sulfuric acid to form a black, carbon-rich solid, as indicated in the following idealized equation:


title: Sucrose

text: The formula for sucrose's decomposition can be represented as a two-step reaction: the first simplified reaction is dehydration of sucrose to pure carbon and water, and then carbon oxidises to with from air.


title: Sucrose

text: Hydrolysis breaks the glycosidic bond converting sucrose into glucose and fructose. Hydrolysis is, however, so slow that solutions of sucrose can sit for years with negligible change. If the enzyme sucrase is added, however, the reaction will proceed rapidly. Hydrolysis can also be accelerated with acids, such as cream of tartar or lemon juice, both weak acids. Likewise, gastric acidity converts sucrose to glucose and fructose during digestion, the bond between them being an acetal bond which can be broken by an acid.


title: Sucrose

text: Given (higher) heats of combustion of 1349.6 kcal/mol for sucrose, 673.0 for glucose, and 675.6 for fructose, hydrolysis releases about per mole of sucrose, or about 3 small calories per gram of product.


title: Sucrose

text: The biosynthesis of sucrose proceeds via the precursors UDP-glucose and fructose 6-phosphate, catalyzed by the enzyme sucrose-6-phosphate synthase. The energy for the reaction is gained by the cleavage of uridine diphosphate (UDP).


title: Sucrose

text: Sucrose is formed by plants, algae and cyanobacteria but not by other organisms. Sucrose is the end product of photosynthesis and is found naturally in many food plants along with the monosaccharide fructose. In many fruits, such as pineapple and apricot, sucrose is the main sugar. In others, such as grapes and pears, fructose is the main sugar.


title: Sucrose

text: After numerous unsuccessful attempts by others, Raymond Lemieux and George Huber succeeded in synthesizing sucrose from acetylated glucose and fructose in 1953.


title: Sucrose

text: In nature, sucrose is present in many plants, and in particular their roots, fruits and nectars, because it serves as a way to store energy, primarily from photosynthesis. Many mammals, birds, insects and bacteria accumulate and feed on the sucrose in plants and for some it is their main food source. Although honeybees consume sucrose, the honey they produce consists primarily of fructose and glucose, with only trace amounts of sucrose.


title: Sucrose

text: As fruits ripen, their sucrose content usually rises sharply, but some fruits contain almost no sucrose at all. This includes grapes, cherries, blueberries, blackberries, figs, pomegranates, tomatoes, avocados, lemons and limes.


title: Sucrose

text: Sucrose is a naturally occurring sugar, but with the advent of industrialization, it has been increasingly refined and consumed in all kinds of processed foods.


title: Sucrose

text: The production of table sugar has a long history. Some scholars claim Indians discovered how to crystallize sugar during the Gupta dynasty, around AD 350.


title: Sucrose

text: Other scholars point to the ancient manuscripts of China, dated to the 8th century BC, where one of the earliest historical mentions of sugar cane is included along with the fact that their knowledge of sugar cane was derived from India. By about 500 BC, residents of modern-day India began making sugar syrup, cooling it in large flat bowls to produce raw sugar crystals that were easier to store and transport. In the local Indian language, these crystals were called (), which is the source of the word "candy".


title: Sucrose

text: The army of Alexander the Great was halted on the banks of river Indus by the refusal of his troops to go further east. They saw people in the Indian subcontinent growing sugarcane and making "granulated, salt-like sweet powder", locally called (), pronounced as () in Greek (Modern Greek, , ). On their return journey, the Greek soldiers carried back some of the "honey-bearing reeds". Sugarcane remained a limited crop for over a millennium. Sugar was a rare commodity and traders of sugar became wealthy. Venice, at the height of its financial power, was the chief sugar-distributing center of Europe. Arabs started producing it in Sicily and Spain. Only after the Crusades did it begin to rival honey as a sweetener in Europe. The Spanish began cultivating sugarcane in the West Indies in 1506 (Cuba in 1523). The Portuguese first cultivated sugarcane in Brazil in 1532.


title: Sucrose

text: Sugar remained a luxury in much of the world until the 18th century. Only the wealthy could afford it. In the 18th century, the demand for table sugar boomed in Europe and by the 19th century it had become regarded as a human necessity. The use of sugar grew from use in tea, to cakes, confectionery and chocolates. Suppliers marketed sugar in novel forms, such as solid cones, which required consumers to use a sugar nip, a pliers-like tool, in order to break off pieces.


title: Sucrose

text: The demand for cheaper table sugar drove, in part, colonization of tropical islands and nations where labor-intensive sugarcane plantations and table sugar manufacturing could thrive. Growing sugar cane crop in hot humid climates, and producing table sugar in high temperature sugar mills was harsh, inhumane work. The demand for cheap labor for this work, in part, first drove slave trade from Africa (in particular West Africa), followed by indentured labor trade from South Asia (in particular India). Millions of slaves, followed by millions of indentured laborers were brought into the Caribbean, Indian Ocean, Pacific Islands, East Africa, Natal, north and eastern parts of South America, and southeast Asia. The modern ethnic mix of many nations, settled in the last two centuries, has been influenced by table sugar.


title: Sucrose

text: Beginning in the late 18th century, the production of sugar became increasingly mechanized. The steam engine first powered a sugar mill in Jamaica in 1768, and, soon after, steam replaced direct firing as the source of process heat. During the same century, Europeans began experimenting with sugar production from other crops. Andreas Marggraf identified sucrose in beet root and his student Franz Achard built a sugar beet processing factory in Silesia (Prussia). The beet-sugar industry took off during the Napoleonic Wars, when France and the continent were cut off from Caribbean sugar. In 2009, about 20 percent of the world's sugar was produced from beets.


title: Sucrose

text: Today, a large beet refinery producing around 1,500 tonnes of sugar a day needs a permanent workforce of about 150 for 24-hour production.


title: Sucrose

text: Table sugar (sucrose) comes from plant sources. Two important sugar crops predominate: sugarcane ("Saccharum spp.") and sugar beets ("Beta vulgaris"), in which sugar can account for 12% to 20% of the plant's dry weight. Minor commercial sugar crops include the date palm ("Phoenix dactylifera"), sorghum ("Sorghum vulgare"), and the sugar maple ("Acer saccharum"). Sucrose is obtained by extraction of these crops with hot water; concentration of the extract gives syrups, from which solid sucrose can be crystallized. In 2017, worldwide production of table sugar amounted to 185 million tonnes.


title: Sucrose

text: Most cane sugar comes from countries with warm climates, because sugarcane does not tolerate frost. Sugar beets, on the other hand, grow only in cooler temperate regions and do not tolerate extreme heat. About 80 percent of sucrose is derived from sugarcane, the rest almost all from sugar beets.


title: Sucrose

text: In mid-2018, India and Brazil had about the same production of sugar – 34 million tonnes – followed by the European Union, Thailand, and China as the major producers. India, the European Union, and China were the leading domestic consumers of sugar in 2018.


title: Sucrose

text: Beet sugar comes from regions with cooler climates: northwest and eastern Europe, northern Japan, plus some areas in the United States (including California). In the northern hemisphere, the beet-growing season ends with the start of harvesting around September. Harvesting and processing continues until March in some cases. The availability of processing plant capacity and the weather both influence the duration of harvesting and processing – the industry can store harvested beets until processed, but a frost-damaged beet becomes effectively unprocessable.


title: Sucrose

text: The United States sets high sugar prices to support its producers, with the effect that many former purchasers of sugar have switched to corn syrup (beverage manufacturers) or moved out of the country (candy manufacturers).


title: Sucrose

text: The low prices of glucose syrups produced from wheat and corn (maize) threaten the traditional sugar market. Used in combination with artificial sweeteners, they can allow drink manufacturers to produce very low-cost goods.


title: Sucrose

text: High-fructose corn syrup (HFCS) is significantly cheaper as a sweetener for food and beverage manufacturing than refined sucrose. This has led to sucrose being partially displaced in U.S. industrial food production by HFCS and other non-sucrose natural sweeteners.


title: Sucrose

text: Reports in public media have regarded HFCS as less safe than sucrose. However, the most common forms of HFCS contain either 42 percent fructose, mainly used in processed foods, or 55 percent fructose, mainly used in soft drinks, as compared to sucrose, which is 50 percent fructose. Given approximately equal glucose and fructose content, there does not appear to be a significant difference in safety. That said, clinical dietitians, medical professionals, and the U.S. Food and Drug Administration (FDA) agree that dietary sugars are a source of empty calories associated with certain health problems, and recommend limiting the overall consumption of sugar-based sweeteners.


title: Sucrose

text: Since the 6th century BC, cane sugar producers have crushed the harvested vegetable material from sugarcane in order to collect and filter the juice. They then treat the liquid, often with lime (calcium oxide), to remove impurities and then neutralize it. Boiling the juice then allows the sediment to settle to the bottom for dredging out, while the scum rises to the surface for skimming off. In cooling, the liquid crystallizes, usually in the process of stirring, to produce sugar crystals. Centrifuges usually remove the uncrystallized syrup. The producers can then either sell the sugar product for use as is, or process it further to produce lighter grades. The later processing may take place in another factory in another country.


title: Sucrose

text: Sugarcane is a major component of Brazilian agriculture; the country is the world's largest producer of sugarcane and its derivative products, such as crystallized sugar and ethanol (ethanol fuel).


title: Sucrose

text: Beet sugar producers slice the washed beets, then extract the sugar with hot water in a "diffuser". An alkaline solution ("milk of lime" and carbon dioxide from the lime kiln) then serves to precipitate impurities (see carbonatation). After filtration, evaporation concentrates the juice to a content of about 70% solids, and controlled crystallisation extracts the sugar. A centrifuge removes the sugar crystals from the liquid, which gets recycled in the crystalliser stages. When economic constraints prevent the removal of more sugar, the manufacturer discards the remaining liquid, now known as molasses, or sells it on to producers of animal feed.


title: Sucrose

text: It is difficult to distinguish between fully refined sugar produced from beet and cane. One way is by isotope analysis of carbon. Cane uses C4 carbon fixation, and beet uses C3 carbon fixation, resulting in a different ratio of C and C isotopes in the sucrose. Tests are used to detect fraudulent abuse of European Union subsidies or to aid in the detection of adulterated fruit juice.


title: Sucrose

text: Sugar cane tolerates hot climates better, but the production of sugar cane needs approximately four times as much water as the production of sugar beet. As a result, some countries that traditionally produced cane sugar (such as Egypt) have built new beet sugar factories since about 2008. Some sugar factories process both sugar cane and sugar beets and extend their processing period in that way.


title: Sucrose

text: The production of sugar leaves residues that differ substantially depending on the raw materials used and on the place of production. While cane molasses is often used in food preparation, humans find molasses from sugar beets unpalatable, and it consequently ends up mostly as industrial fermentation feedstock (for example in alcohol distilleries), or as animal feed. Once dried, either type of molasses can serve as fuel for burning.


title: Sucrose

text: Pure beet sugar is difficult to find, so labelled, in the marketplace. Although some makers label their product clearly as "pure cane sugar", beet sugar is almost always labeled simply as sugar or pure sugar. Interviews with the 5 major beet sugar-producing companies revealed that many store brands or "private label" sugar products are pure beet sugar. The lot code can be used to identify the company and the plant from which the sugar came, enabling beet sugar to be identified if the codes are known.


title: Sucrose

text: Mill white, also called plantation white, crystal sugar or superior sugar is produced from raw sugar. It is exposed to sulfur dioxide during the production to reduce the concentration of color compounds and helps prevent further color development during the crystallization process. Although common to sugarcane-growing areas, this product does not store or ship well. After a few weeks, its impurities tend to promote discoloration and clumping; therefore this type of sugar is generally limited to local consumption.


title: Sucrose

text: Blanco directo, a white sugar common in India and other south Asian countries, is produced by precipitating many impurities out of cane juice using phosphoric acid and calcium hydroxide, similar to the carbonatation technique used in beet sugar refining. Blanco directo is more pure than mill white sugar, but less pure than white refined.


title: Sucrose

text: White refined is the most common form of sugar in North America and Europe. Refined sugar is made by dissolving and purifying raw sugar using phosphoric acid similar to the method used for blanco directo, a carbonatation process involving calcium hydroxide and carbon dioxide, or by various filtration strategies. It is then further purified by filtration through a bed of activated carbon or bone char. Beet sugar refineries produce refined white sugar directly without an intermediate raw stage.


title: Sucrose

text: White refined sugar is typically sold as granulated sugar, which has been dried to prevent clumping and comes in various crystal sizes for home and industrial use:


title: Sucrose

text: Brown sugar comes either from the late stages of cane sugar refining, when sugar forms fine crystals with significant molasses content, or from coating white refined sugar with a cane molasses syrup (blackstrap molasses). Brown sugar's color and taste becomes stronger with increasing molasses content, as do its moisture-retaining properties. Brown sugars also tend to harden if exposed to the atmosphere, although proper handling can reverse this.


title: Sucrose

text: Scientists and the sugar industry use degrees Brix (symbol °Bx), introduced by Adolf Brix, as units of measurement of the mass ratio of dissolved substance to water in a liquid. A 25 °Bx sucrose solution has 25 grams of sucrose per 100 grams of liquid; or, to put it another way, 25 grams of sucrose sugar and 75 grams of water exist in the 100 grams of solution.


title: Sucrose

text: The Brix degrees are measured using an infrared sensor. This measurement does not equate to Brix degrees from a density or refractive index measurement, because it will specifically measure dissolved sugar concentration instead of all dissolved solids. When using a refractometer, one should report the result as "refractometric dried substance" (RDS). One might speak of a liquid as having 20 °Bx RDS. This refers to a measure of percent by weight of "total" dried solids and, although not technically the same as Brix degrees determined through an infrared method, renders an accurate measurement of sucrose content, since sucrose in fact forms the majority of dried solids. The advent of in-line infrared Brix measurement sensors has made measuring the amount of dissolved sugar in products economical using a direct measurement.


title: Sucrose

text: Refined sugar was a luxury before the 18th century. It became widely popular in the 18th century, then graduated to becoming a necessary food in the 19th century. This evolution of taste and demand for sugar as an essential food ingredient unleashed major economic and social changes. Eventually, table sugar became sufficiently cheap and common enough to influence standard cuisine and flavored drinks.


title: Sucrose

text: Sucrose forms a major element in confectionery and desserts. Cooks use it for sweetening. It can also act as a food preservative when used in sufficient concentrations. Sucrose is important to the structure of many foods, including biscuits and cookies, cakes and pies, candy, and ice cream and sorbets. It is a common ingredient in many processed and so-called "junk foods".


title: Sucrose

text: Fully refined sugar is 99.9% sucrose, thus providing only carbohydrate as dietary nutrient and 390 kilocalories per 100 g serving (USDA data, right table). There are no micronutrients of significance in fully refined sugar (right table).


title: Sucrose

text: In humans and other mammals, sucrose is broken down into its constituent monosaccharides, glucose and fructose, by sucrase or isomaltase glycoside hydrolases, which are located in the membrane of the microvilli lining the duodenum. The resulting glucose and fructose molecules are then rapidly absorbed into the bloodstream. In bacteria and some animals, sucrose is digested by the enzyme invertase. Sucrose is an easily assimilated macronutrient that provides a quick source of energy, provoking a rapid rise in blood glucose upon ingestion. Sucrose, as a pure carbohydrate, has an energy content of 3.94 kilocalories per gram (or 17 kilojoules per gram).


title: Sucrose

text: If consumed excessively, sucrose may contribute to the development of metabolic syndrome, including increased risk for type 2 diabetes, weight gain and obesity in adults and children.


title: Sucrose

text: Tooth decay (dental caries) has become a pronounced health hazard associated with the consumption of sugars, especially sucrose. Oral bacteria such as "Streptococcus mutans" live in dental plaque and metabolize "any" free sugars (not just sucrose, but also glucose, lactose, fructose, and cooked starches) into lactic acid. The resultant lactic acid lowers the pH of the tooth's surface, stripping it of minerals in the process known as tooth decay.


title: Sucrose

text: All 6-carbon sugars and disaccharides based on 6-carbon sugars can be converted by dental plaque bacteria into acid that demineralizes teeth, but sucrose may be uniquely useful to "Streptococcus sanguinis" (formerly "Streptococcus sanguis") and "Streptococcus mutans". Sucrose is the only dietary sugar that can be converted to sticky glucans (dextran-like polysaccharides) by extracellular enzymes. These glucans allow the bacteria to adhere to the tooth surface and to build up thick layers of plaque. The anaerobic conditions deep in the plaque encourage the formation of acids, which leads to carious lesions. Thus, sucrose could enable "S. mutans", "S. sanguinis" and many other species of bacteria to adhere strongly and resist natural removal, e.g. by flow of saliva, although they are easily removed by brushing. The glucans and levans (fructose polysaccharides) produced by the plaque bacteria also act as a reserve food supply for the bacteria.


title: Sucrose

text: Such a special role of sucrose in the formation of tooth decay is much more significant in light of the almost universal use of sucrose as the most desirable sweetening agent. Widespread replacement of sucrose by high-fructose corn syrup (HFCS) has not diminished the danger from sucrose. If smaller amounts of sucrose are present in the diet, they will still be sufficient for the development of thick, anaerobic plaque and plaque bacteria will metabolise other sugars in the diet, such as the glucose and fructose in HFCS.


title: Sucrose

text: Sucrose is a disaccharide made up of 50% glucose and 50% fructose and has a glycemic index of 65. Sucrose is digested rapidly, but has a relatively low glycemic index due to its content of fructose, which has a minimal effect on blood glucose.


title: Sucrose

text: As with other sugars, sucrose is digested into its components via the enzyme sucrase to glucose (blood sugar). The glucose component is transported into the blood where it serves immediate metabolic demands, or is converted and reserved in the liver as glycogen.


title: Sucrose

text: The occurrence of gout is connected with an excess production of uric acid. A diet rich in sucrose may lead to gout as it raises the level of insulin, which prevents excretion of uric acid from the body. As the concentration of uric acid in the body increases, so does the concentration of uric acid in the joint liquid and beyond a critical concentration, the uric acid begins to precipitate into crystals. Researchers have implicated sugary drinks high in fructose in a surge in cases of gout.


title: Sucrose

text: In 2015, the World Health Organization published a new guideline on sugars intake for adults and children, as a result of an extensive review of the available scientific evidence by a multidisciplinary group of experts. The guideline recommends that both adults and children ensure their intake of free sugars (monosaccharides and disaccharides added to foods and beverages by the manufacturer, cook or consumer, and sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates) is less than 10% of total energy intake. A level below 5% of total energy intake brings additional health benefits, especially with regards to dental caries.


title: Sucrose

text: The sugar refining industry often uses bone char (calcinated animal bones) for decolorizing. About 25% of sugar produced in the U.S. is processed using bone char as a filter, the remainder being processed with activated carbon. As bone char does not seem to remain in finished sugar, Jewish religious leaders consider sugar filtered through it to be pareve, meaning that it is neither meat nor dairy and may be used with either type of food. However, the bone char must source to a kosher animal (e.g. cow, sheep) for the sugar to be kosher.


title: Sucrose

text: One of the most widely traded commodities in the world throughout history, sugar accounts for around 2% of the global dry cargo market. International sugar prices show great volatility, ranging from around 3 cents to over 60 cents per pound in the 50 years. About 100 of the world's 180 countries produce sugar from beet or cane, a few more refine raw sugar to produce white sugar, and all countries consume sugar. Consumption of sugar ranges from around 3 kilograms (7 lb) per person per annum in Ethiopia to around 40 kg (90 lb) in Belgium. Consumption per capita rises with income per capita until it reaches a plateau of around 35 kg (75 lb) per person per year in middle income countries.


title: Sucrose

text: Many countries subsidize sugar production heavily. The European Union, the United States, Japan, and many developing countries subsidize domestic production and maintain high tariffs on imports. Sugar prices in these countries have often up to triple the prices on the international market; , with world market sugar futures prices strong, such prices were typically double world prices.


title: Sucrose

text: Within international trade bodies, especially in the World Trade Organization (WTO), the "G20" countries led by Brazil have long argued that, because these sugar markets in essence exclude cane sugar imports, the G20 sugar producers receive lower prices than they would under free trade. While both the European Union and United States maintain trade agreements whereby certain developing and least developed countries (LDCs) can sell certain quantities of sugar into their markets, free of the usual import tariffs, countries outside these preferred trade régimes have complained that these arrangements violate the "most favoured nation" principle of international trade. This has led to numerous tariffs and levies in the past.


title: Sucrose

text: In 2004, the WTO sided with a group of cane sugar exporting nations (led by Brazil and Australia) and ruled illegal the EU sugar-régime and the accompanying "ACP-EU Sugar Protocol", that granted a group of African, Caribbean, and Pacific countries receive preferential access to the European sugar market. In response to this and to other rulings of the WTO, and owing to internal pressures against the EU sugar-régime, the European Commission proposed on 22 June 2005 a radical reform of the EU sugar-régime that cut prices by 39% and eliminated all EU sugar exports.


title: Sucrose

text: The African, Caribbean, Pacific and LDC sugar exporters reacted with dismay to the EU sugar proposals. On 25 November 2005, the EC agreed to cut EU sugar prices by 36% as from 2009.


title: Sucrose

text: In 2007, it seemed that the U.S. Sugar Program could become the next target for reform. However, some commentators expected heavy lobbying from the U.S. sugar industry, which donated $2.7 million to U.S. House and Senate incumbents in the 2006 U.S. election, more than any other group of U.S. food-growers. Especially prominent among sugar lobbyists were the Fanjul Brothers, so-called "sugar barons" who made the single individual contributions of soft money to both the Democratic and Republican parties in the U.S. political system.


title: Sucrose

text: Small quantities of sugar, especially specialty grades of sugar, reach the market as 'fair trade' commodities; the fair trade system produces and sells these products with the understanding that a larger-than-usual fraction of the revenue will support small farmers in the developing world. However, whilst the Fairtrade Foundation offers a premium of $60.00 per tonne to small farmers for sugar branded as "Fairtrade", government schemes such as the U.S. Sugar Program and the ACP-EU Sugar Protocol offer premiums of around $400.00 per tonne above world market prices. However, the EU announced on 14 September 2007 that it had offered "to eliminate all duties and quotas on the import of sugar into the EU".


title: Sucrose

text: The U.S. Sugar Association subsequently launched a campaign to promote sugar over artificial substitutes. The Association aggressively contradicts many common beliefs regarding negative side-effects of sugar consumption. The campaign aired a high-profile television commercial during the 2007 Primetime Emmy Awards on FOX Television.


title: Biotechnology

text: Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term "biotechnology" was first used by Károly Ereky in 1919, meaning the production of products from raw materials with the aid of living organisms.


title: Biotechnology

text: The concept of biotechnology encompasses a wide range of procedures for modifying living organisms according to human purposes, going back to domestication of animals, cultivation of the plants, and "improvements" to these through breeding programs that employ artificial selection and hybridization. Modern usage also includes genetic engineering as well as cell and tissue culture technologies. The American Chemical Society defines biotechnology as the application of biological organisms, systems, or processes by various industries to learning about the science of life and the improvement of the value of materials and organisms such as pharmaceuticals, crops, and livestock. As per the European Federation of Biotechnology, biotechnology is the integration of natural science and organisms, cells, parts thereof, and molecular analogues for products and services. Biotechnology is based on the basic biological sciences (e.g., molecular biology, biochemistry, cell biology, embryology, genetics, microbiology) and conversely provides methods to support and perform basic research in biology.


title: Biotechnology

text: Biotechnology is the research and development in the laboratory using bioinformatics for exploration, extraction, exploitation, and production from any living organisms and any source of biomass by means of biochemical engineering where high value-added products could be planned (reproduced by biosynthesis, for example), forecasted, formulated, developed, manufactured, and marketed for the purpose of sustainable operations (for the return from bottomless initial investment on R & D) and gaining durable patents rights (for exclusives rights for sales, and prior to this to receive national and international approval from the results on animal experiment and human experiment, especially on the pharmaceutical branch of biotechnology to prevent any undetected side-effects or safety concerns by using the products). The utilization of biological processes, organisms or systems to produce products that are anticipated to improve human lives is termed biotechnology.


title: Biotechnology

text: By contrast, bioengineering is generally thought of as a related field that more heavily emphasizes higher systems approaches (not necessarily the altering or using of biological materials "directly") for interfacing with and utilizing living things. Bioengineering is the application of the principles of engineering and natural sciences to tissues, cells, and molecules. This can be considered as the use of knowledge from working with and manipulating biology to achieve a result that can improve functions in plants and animals. Relatedly, biomedical engineering is an overlapping field that often draws upon and applies "biotechnology" (by various definitions), especially in certain sub-fields of biomedical or chemical engineering such as tissue engineering, biopharmaceutical engineering, and genetic engineering.


title: Biotechnology

text: Although not normally what first comes to mind, many forms of human-derived agriculture clearly fit the broad definition of "'utilizing a biotechnological system to make products". Indeed, the cultivation of plants may be viewed as the earliest biotechnological enterprise.


title: Biotechnology

text: Agriculture has been theorized to have become the dominant way of producing food since the Neolithic Revolution. Through early biotechnology, the earliest farmers selected and bred the best-suited crops (e.g., those with the highest yields) to produce enough food to support a growing population. As crops and fields became increasingly large and difficult to maintain, it was discovered that specific organisms and their by-products could effectively fertilize, restore nitrogen, and control pests. Throughout the history of agriculture, farmers have inadvertently altered the genetics of their crops through introducing them to new environments and breeding them with other plants — one of the first forms of biotechnology.


title: Biotechnology

text: These processes also were included in early fermentation of beer. These processes were introduced in early Mesopotamia, Egypt, China and India, and still use the same basic biological methods. In brewing, malted grains (containing enzymes) convert starch from grains into sugar and then adding specific yeasts to produce beer. In this process, carbohydrates in the grains broke down into alcohols, such as ethanol. Later, other cultures produced the process of lactic acid fermentation, which produced other preserved foods, such as soy sauce. Fermentation was also used in this time period to produce leavened bread. Although the process of fermentation was not fully understood until Louis Pasteur's work in 1857, it is still the first use of biotechnology to convert a food source into another form.


title: Biotechnology

text: Before the time of Charles Darwin's work and life, animal and plant scientists had already used selective breeding. Darwin added to that body of work with his scientific observations about the ability of science to change species. These accounts contributed to Darwin's theory of natural selection.


title: Biotechnology

text: For thousands of years, humans have used selective breeding to improve the production of crops and livestock to use them for food. In selective breeding, organisms with desirable characteristics are mated to produce offspring with the same characteristics. For example, this technique was used with corn to produce the largest and sweetest crops.


title: Biotechnology

text: In the early twentieth century scientists gained a greater understanding of microbiology and explored ways of manufacturing specific products. In 1917, Chaim Weizmann first used a pure microbiological culture in an industrial process, that of manufacturing corn starch using "Clostridium acetobutylicum," to produce acetone, which the United Kingdom desperately needed to manufacture explosives during World War I.


title: Biotechnology

text: Biotechnology has also led to the development of antibiotics. In 1928, Alexander Fleming discovered the mold "Penicillium". His work led to the purification of the antibiotic compound formed by the mold by Howard Florey, Ernst Boris Chain and Norman Heatley – to form what we today know as penicillin. In 1940, penicillin became available for medicinal use to treat bacterial infections in humans.