World Series

The World Series is the annual championship series of Major League Baseball in North America, contested since 1903 between the American League champion team and the National League champion team. The winner of the World Series championship is determined through a best-of-seven playoff, the winning team is awarded the Commissioner's Trophy; as the series is played during the fall season in North America, it is sometimes referred to as the Fall Classic. Since 2017, it has been known as the World Series presented by YouTube TV for sponsorship reasons. Prior to 1969, the team with the best regular-season win-loss record in each league automatically advanced to the World Series; the World Series has been contested 115 times as of 2019, with the AL winning 66 and the NL winning 49. Until the formation of the American Association in 1882 as a second major league, the National Association of Professional Base Ball Players and the National League represented the top level of organized baseball in the United States.

All championships were awarded to the team with the best record at the end of the season, without a postseason series being played. From 1884 to 1890, the National League and the American Association faced each other in a series of games at the end of the season to determine an overall champion; these series were disorganized in comparison to the modern World Series, with the terms arranged through negotiation of the owners of the championship teams beforehand. The number of games played ranged from as few as three in 1884, to a high of fifteen in 1887. Both the 1885 and 1890 Series ended in each team having won three games with one tie game; the series was promoted and referred to as "The Championship of the United States", "World's Championship Series", or "World's Series" for short. In his book Krakatoa: The Day the World Exploded: August 27, 1883, Simon Winchester mentions in passing that the World Series was named for the New York World newspaper, but this view is disputed; the 19th-century competitions are, not recognized as part of World Series history by Major League Baseball, as it considers 19th-century baseball to be a prologue to the modern baseball era.

Until about 1960, some sources treated the 19th-century Series on an equal basis with the post-19th-century series. After about 1930, many authorities list the start of the World Series in 1903 and discuss the earlier contests separately. Following the collapse of the American Association after the 1891 season, the National League was again the only major league; the league championship was awarded in 1892 by a playoff between half-season champions. This scheme was abandoned after one season. Beginning in 1893—and continuing until divisional play was introduced in 1969—the pennant was awarded to the first-place club in the standings at the end of the season. For four seasons, 1894–1897, the league champions played the runners-up in the post season championship series called the Temple Cup. A second attempt at this format was the Chronicle-Telegraph Cup series, played only once, in 1900. In 1901, the American League was formed as a second major league. No championship series were played in 1901 or 1902 as the National and American Leagues fought each other for business supremacy.

After two years of bitter competition and player raiding, the National and American Leagues made peace and, as part of the accord, several pairs of teams squared off for interleague exhibition games after the 1903 season. These series were arranged by the participating clubs. One of them matched the two pennant winners, Pittsburgh Pirates of the NL and Boston Americans of the AL, it had been arranged well in advance by the two owners, as both teams were league leaders by large margins. Boston upset Pittsburgh by five games to three, winning with pitching depth behind Cy Young and Bill Dinneen and with the support of the band of Royal Rooters; the Series brought much civic pride to Boston and proved the new American League could beat the Nationals. The 1904 Series, if it had been held, would have been between the AL's Boston Americans and the NL's New York Giants. At that point there was no governing body for the World Series nor any requirement that a Series be played, thus the Giants' owner John T.

Brush refused to allow his team to participate in such an event, citing the "inferiority" of the upstart American League. John McGraw, the Giants' manager went so far as to say that his Giants were "world champions" since they were the champions of the "only real major league". At the time of the announcement, their new cross-town rivals, the New York Highlanders, were leading the AL, the prospect of facing the Highlanders did not please Giants management. Boston won on the last day of the season, the leagues had agreed to hold a World's Championship Series in 1904, but it was not binding, Brush stuck to his original decision. In addition t

Evolutionary models of human drug use

The use of psychoactive substances is one of the most perplexing human behaviors. Psychoactive drugs can relieve the symptoms of mental disorders or cause harm to individuals and societies. Psychoactive drugs can induce pleasure, increase energy, relieve pain, or can impose a large social burden in the form of chronic illness and be a cause of mortality. Why do humans seek out and at times develop addictions to drugs that harm them? A number of attempts have been made to understand drug use and addiction from an evolutionary perspective. Evolutionary models of drug use are unique in that they emphasize the effect drugs had on fitness over human evolution; the dominant paradigm of drug abuse focuses on human neurobiology and suggests that drug use is the result of reward-related behavior and that drug addiction is a consequence of drug interference with natural reward systems. This tradition postulates that the chemical compounds humans seek out increase brain dopamine levels and thereby usurp the mesolimbic pathway, a system intended to motivate/reward fitness enhancing behaviors such as those that increase access to food and sex.

Ideas concerning the neural bases of motivation and reinforcement in behavior can be traced back to the 1950s. In 1953, Olds and Milner published findings implicating a brain region a cluster of dopamine neurons, with reward-based learning. Drugs of abuse were discovered to increase dopamine in the region of the brain associated with reward-based-learning. Research on the molecular pathways of addiction suggests that drugs of abuse, despite their diverse chemical substrates, converge on a common circuitry in the brain's limbic system. Drugs are thought to activate the mesolimbic dopamine pathway, facilitating dopamine transmission in the nucleus accumbens, via disinhibition, uptake blockade, etc. to produce a dopamine-like, yet dopamine independent effect. The hijack model of drug abuse explains that drugs that elicit positive emotion mediate incentive motivation in the nucleus accumbens of the brain. Put another way, drugs of abuse act on ancient and evolutionarily conserved neural mechanisms associated with positive emotions that evolved to mediate incentive behavior.

Psychoactive drugs induce emotions. Positive emotions such as euphoria and excitation are tools chosen by natural selection to help direct the behavior and physiology of an individual towards an increase in Darwinian fitness. For example, in the environment of evolutionary adaptation, humans would feel positive euphoric emotions in response to a successful foraging session or in the event of a successful breeding. Many psychoactive substances yet do not produce fitness benefits. Researchers have shown how emotional disposition is correlated with problematic use of alcohol, wherein if the reason for alcohol consumption is positive, the user is thought to drink to enhance positive feelings with greater control of the substance than if the user's emotional disposition prior to alcoholic consumption was negative. In these cases, the individual is drinking to cope and is shown to have less control over his/her own use. Alcohol mediates negative feelings by their suppression but encourages the habituated continuance of positive emotion.

Recovering alcoholics report that the reason for relapse is related to the impulse to compensate for negative feelings, resulting in a motivation to cope and therefore drink. Despite being harmful, drugs such as nicotine, alcohol, THC, opium artificially stimulate the emotions and neural circuits involved in the mesolimbic reward system thus encouraging drug consumption. Drugs of abuse are harmful, why do they increase dopamine like sugar and sex do? The hijack hypothesis suggests that drugs are effective hijackers of neural reward circuitry because they are evolutionarily novel. Proposing that modern-day drug concentrations, methods of delivery, the existence of certain drugs themselves were not available until on an evolutionary time scale, thus human biology has been slow to adapt and is presently mismatched and susceptible. To explain how drugs increase dopamine and cause positive emotions while at the same time lowering reproductive fitness, researchers posited that evolutionarily novel drugs hijack the brain's mesolimbic dopamine system and generate a false positive signal of a fitness benefit as well as inhibiting negative effects, to signal a lack of negative fitness consequences.

Modern drug addiction fundamentally indicates a false increase of fitness, leading to increasing drug abuse to continue gain if the gain is realized as being false. That these drugs create a signal in the brain that indicates, the arrival of a huge fitness benefit which changes behavioral propensities so that drug seeking increases in frequency and displaces adaptive behaviors. Proponents of the hijack hypothesis suggest that the paradox of drug reward is due to this evolutionary mismatch, that extant access to psychoactive drug concentrations and products are unmatched by those that existed in the past. Why do humans seek out and consume drugs that harm them? The paradox of drug reward refers to the puzzling ability of drugs to induce both aversive and rewarding effects. Despite contention on the particulars of dopamine induced reward and behavior, there is agreement that dopamine plays an instrumental role in the processing of reward-related stimuli and that drug induced dopamine stimulation explains at least some part of drug abuse phenomena.

And still all major recreation

Panton–Valentine leukocidin

Panton–Valentine leukocidin is a cytotoxin—one of the β-pore-forming toxins. The presence of PVL is associated with increased virulence of certain strains of Staphylococcus aureus, it is present in the majority of community-associated Methicillin-resistant Staphylococcus aureus isolates studied and is the cause of necrotic lesions involving the skin or mucosa, including necrotic hemorrhagic pneumonia. PVL creates pores in the membranes of infected cells. PVL is produced from the genetic material of a bacteriophage that infects Staphylococcus aureus, making it more virulent, it was discovered by Van deVelde in 1894 due to its ability to lyse leukocytes. It was named after Sir Philip Noel Panton and Francis Valentine when they associated it with soft tissue infections in 1932. Exotoxins such as PVL constitute essential components of the virulence mechanisms of S. aureus. Nearly all strains secrete lethal factors that convert host tissues into nutrients required for bacterial growth. PVL is a member of the synergohymenotropic toxin family that induces pores in the membranes of cells.

The PVL factor is encoded in a prophage—designated as Φ-PVL—which is a virus integrated into the S. aureus bacterial chromosome. Its genes secrete two proteins -- toxins designated 33 and 34 kDa in size; the structures of both proteins have been solved in the soluble forms, are present in the PDB as ID codes 1t5r and 1pvl respectively. See the PDBe article for more information on these structures. LukS-PV and LukF-PV act together as subunits, assembling in the membrane of host defense cells, in particular, white blood cells and macrophages; the subunits fit together and form a ring with a central pore through which cell contents leak and which acts as a superantigen. Other authors contribute the differential response of MRSA subtypes to phenol-soluble modulin peptides and not to PVL. PVL causes leukocyte destruction and necrotizing pneumonia, an aggressive condition that can kill up to 75% of patients. Comparing cases of staphylococcal necrotizing pneumonia, 85% of community-acquired cases were PVL-positive, while none of the hospital-acquired cases were.

CAP afflicted younger and healthier patients and yet had a worse outcome It has played a role in a number of outbreaks of fatal bacterial infections. PVL may increase the expression of staphylococcal protein A, a key pro-inflammatory factor for pneumonia. Panton–Valentine leukocidin is one of many toxins associated with S. aureus infection. Because it can be found in all CA-MRSA strains that cause soft-tissue infections, it was long described as a key virulence factor, allowing the bacteria to target and kill specific white blood cells known as neutrophils; this view was challenged, when it was shown that removal of PVL from the two major epidemic CA-MRSA strains resulted in no loss of infectivity or destruction of neutrophils in a mouse model. Genetic analysis shows that PVL CA-MRSA has emerged several times, on different continents, rather than being the worldwide spread of a single clone. Panton-Valentine+leukocidin at the US National Library of Medicine Medical Subject Headings A deadly toxin with a romantic name