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In the early 1990s, critics began to question Alzheimer's findings and form their own hypotheses based on Alzheimer's notes and papers. Amaducci and colleagues hypothesized that Auguste Deter had metachromatic leukodystrophy, a rare condition in which accumulations of fats affect the cells that produce myelin. Claire O'Brien, meanwhile, hypothesized that Auguste Deter actually had a vascular dementing disease.
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Aedile
Aedile ( , , from , "temple edifice") was an elected office of the Roman Republic. Based in Rome, the aediles were responsible for maintenance of public buildings () and regulation of public festivals. They also had powers to enforce public order and duties to ensure the city of Rome was well supplied and its civil infrastructure well maintained, akin to modern local government.
There were two pairs of aediles: the first were the "plebeian aediles" (Latin: "aediles plebis") and possession of this office was limited to plebeians; the other two were "curule aediles" (Latin: "aediles curules"), open to both plebeians and patricians, in alternating years. An "aedilis curulis" was classified as a "magister curulis".
The office of the aedilis was generally held by young men intending to follow the "cursus honorum" to high political office, traditionally after their quaestorship but before their praetorship. It was not a compulsory part of the cursus, and hence a former quaestor could be elected to the praetorship without having held the position of aedile. However, it was an advantageous position to hold because it demonstrated the aspiring politician's commitment to public service, as well as giving him the opportunity to hold public festivals and games, an excellent way to increase his name recognition and popularity.
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History of the office.
Plebeian aediles.
The plebeian aediles were created in the same year as the tribune of the plebs (494 BC). Originally intended as assistants to the tribunes, they guarded the rights of the plebeians with respect to their headquarters, the Temple of Ceres. Subsequently, they assumed responsibility for maintenance of the city's buildings as a whole. Their duties at first were simply ministerial. They were the assistants to the tribunes in whatever matters that the tribunes might entrust to them, although most matters with which they were entrusted were of minimal importance.
Around 446 BC, they were given the authority to care for the decrees of the Senate. When a "senatus consultum" was passed, it would be transcribed into a document and deposited in the public treasury, the "Aerarium". They were given this power because the consuls, who had held this power before, arbitrarily suppressed and altered the documents. They also maintained the acts of the Plebeian Council (People's Assembly), the "plebiscites". Plebiscites, once passed, were also transcribed into a physical document for storage. While their powers grew over time, it is not always easy to distinguish the difference between their powers, and those of the censors. Occasionally, if a censor was unable to carry out one of his tasks, an aedile would perform the task instead.
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Curule aediles.
According to Livy (vi. 42), after the passing of the Licinian rogations in 367 BC, an extra day was added to the Roman games; the plebeian aediles refused to bear the additional expense, whereupon the patricians offered to undertake it, on condition that they were admitted to the aedileship. The plebeians accepted the offer, and accordingly two curule aediles were appointed—at first from the patricians alone, then from patricians and plebeians in turn, lastly, from either—at the Tribal Assembly under the presidency of the consul. Curule aediles, as formal magistrates, held certain honors that plebeian aediles (who were not technically magistrates), did not hold.
Besides having the right to sit on a curule seat ("sella curulis") and to wear a toga praetexta, the curule aediles also held the power to issue edicts ("jus edicendi"). These edicts often pertained to matters such as the regulation of the public markets, or what we might call "economic regulation". Livy suggests, perhaps incorrectly, that both curule as well as plebeian Aediles were sacrosanct. Although the curule aediles always ranked higher than the plebeian, their functions gradually approximated and became practically identical. Within five days after the beginning of their terms, the four aediles (two plebeian, two curule) were required to determine, by lot or by agreement among themselves, what parts of the city each should hold jurisdiction over.
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Differences between the two.
There was a distinction between the two sets of aediles when it came to public festivals. Some festivals were plebeian in nature, and thus were under the superintendence of plebeian aediles. Other festivals were supervised exclusively by the curule aediles, and it was often with these festivals that the aediles would spend lavishly. This was often done to secure voters' support in future elections. Because aediles were not reimbursed for public expenditures, most individuals seeking the office were independently wealthy. Since this office was a stepping stone to higher office and the Senate, it helped to ensure that only wealthy individuals (mostly landowners) would win election to high office. These extravagant expenditures began shortly after the end of Second Punic War, and increased as the spoils returned from Rome's new eastern conquests. Even the decadence of the emperors rarely surpassed that of the aediles under the Republic, as could have been seen during Julius Caesar's aedileship.
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Election to the office.
Plebeian aediles and Curule aediles were elected by the Tribal Assembly. Since the plebeian aediles were elected by the plebeians rather than by all of the people of Rome (plebeians as well as patricians), they were not technically magistrates. Before the passage of the "Lex Villia Annalis", individuals could run for the aedileship by the time they turned twenty-seven. After the passage of this law in 180 BC, a higher age was set, probably thirty-six. By the 1st century BC, aediles were elected in July, and took office on the first day in January.
Powers of the office.
Cicero (Legg. iii. 3, 7) divides these functions under three heads:
(1) Care of the city:
the repair and preservation of temples, sewers and aqueducts; street cleansing and paving; regulations regarding traffic, dangerous animals and dilapidated buildings; precautions against fire; superintendence of baths and taverns; enforcement of sumptuary laws; punishment of gamblers and usurers; the care of public morals generally, including the prevention of foreign superstitions and the registration of meretrices. They also punished those who had too large a share of the "ager publicus", or kept too many cattle on the state pastures.
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(2) Care of provisions:
investigation of the quality of the articles supplied and the correctness of weights and measures; the purchase of grain for disposal at a low price in case of necessity.
(3) Care of the games:
superintendence and organization of the public games, as well as of those given by themselves and private individuals (e.g., at funerals) at their own expense.
Ambitious persons often spent enormous sums in this manner to win the popular favor with a view to official advancement.
Under the Empire.
In 44 BC, Julius Caesar added two plebeian aediles called "cereales", whose special duty was the care of the cereal (grain) supply. Under Augustus the office lost much of its importance, its judicial functions and the care of the games being transferred to the praetor, while its city responsibilities were limited by the appointment of an urban prefect. Augustus took for himself its powers over various religious duties. By stripping it of its powers over temples, he effectively destroyed the office, by taking from it its original function. After this point, few people were willing to hold such a powerless office, and Augustus was even known to compel individuals into holding the office. He accomplished this by randomly selecting former tribunes and quaestors for the office. Future emperors would continue to dilute the power of the office by transferring its powers to newly created offices. However, the office did retain some powers over licentiousness and disorder, in particular over the baths and brothels, as well as the registration of prostitutes. In the 3rd century, it disappeared altogether.
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Under the Empire, Roman colonies and cities often had officials with powers similar to those of the republican aediles, although their powers widely varied. It seems as though they were usually chosen annually.
Modern day.
Examples of modern use of the term "edil" include:
Shakespeare.
In his play "Coriolanus", Shakespeare references the aediles. However, they are minor characters, and their chief role is to serve as policemen.
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American Airlines
American Airlines, Inc. is a major airline in the United States headquartered in Fort Worth, Texas, within the Dallas–Fort Worth metroplex, and is the largest airline in the world in terms of passengers carried and daily flights. American, along with its regional subsidiaries and contractors operating under the brand name American Eagle, operate an extensive international and domestic network with almost 6,800 flights per day to nearly 350 destinations in 48 countries. The airline is also a founding member of the Oneworld alliance, one of the world's three major airline alliances.
American Airlines and American Eagle operate out of ten hubs, with Dallas/Fort Worth International Airport (DFW) being the largest. The airline serves more than 200 million passengers annually, and averages more than 500,000 daily. , the company employs 103,440 staff members.
History.
American Airlines was started in 1930 as a union of more than eighty small airlines. The two organizations from which American Airlines originated were Robertson Aircraft Corporation and Colonial Air Transport. The former was first created in Missouri in 1921, with both being merged in 1929 into holding company The Aviation Corporation. This, in turn, was made in 1930 into an operating company and rebranded as American Airways. In 1934, when new laws and attrition of mail contracts forced many airlines to reorganize, the corporation redid its routes into a connected system and was renamed American Airlines. The airline fully developed its international business between 1970 and 2000. It purchased Trans World Airlines in 2001.
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American had a direct role in the development of the Douglas DC-3, which resulted from a marathon telephone call from American Airlines CEO C. R. Smith to Douglas Aircraft Company founder Donald Wills Douglas Sr., when Smith persuaded a reluctant Douglas to design a sleeper aircraft based on the DC-2 to replace American's Curtiss Condor II biplanes. (The existing DC-2's cabin was wide, too narrow for side-by-side berths.) Douglas agreed to proceed with development only after Smith informed him of American Airline's intention to purchase 20 aircraft. The prototype DST (Douglas Sleeper Transport) first flew on December 17, 1935, the 32nd anniversary of the Wright Brothers' flight at Kitty Hawk, North Carolina. Its cabin was wide, and a version with 21 seats instead of the 14–16 sleeping berths of the DST was given the designation DC-3. There was no prototype DC-3; the first DC-3 built followed seven DSTs off the production line and was delivered to American Airlines. American Airlines inaugurated passenger service on June 26, 1936, with simultaneous flights from Newark, New Jersey, and Chicago, Illinois.
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American also had a direct role in the development of the DC-10, which resulted from a specification from American Airlines to manufacturers in 1966 to offer a widebody aircraft that was smaller than the Boeing 747, but capable of flying similar long-range routes from airports with shorter runways. McDonnell Douglas responded with the DC-10 trijet shortly after the two companies' merger. On February 19, 1968, the president of American Airlines, George A. Spater, and James S. McDonnell of McDonnell Douglas announced American's intention to acquire the DC-10. American Airlines ordered 25 DC-10s in its first order. The DC-10 made its first flight on August 29, 1970, and received its type certificate from the FAA on July 29, 1971. On August 5, 1971, the DC-10 entered commercial service with American Airlines on a round-trip flight between Los Angeles and Chicago.
In 2011, due to a downturn in the airline industry, American Airlines' parent company, the AMR Corporation, filed for bankruptcy protection. In 2013, American Airlines merged with US Airways but kept the American Airlines name, as it was the better-recognized brand internationally; the combination of the two airlines resulted in the creation of the largest airline in the United States, and ultimately the world.
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In December 2023, the company was added to the Dow Jones Sustainability World Index.
Network.
Hubs.
American currently operates ten hubs.
Alliance and codeshare agreements.
American Airlines is a member of the Oneworld alliance and has codeshares with the following airlines:
Joint ventures.
American Airlines has established three joint ventures with fellow Oneworld alliance members, expanding beyond basic codesharing to include coordinated route planning, scheduling, and revenue sharing on jointly operated routes. The Atlantic Joint Business covers transatlantic flights with Aer Lingus, British Airways, Finnair and Iberia. The Pacific Joint Business encompasses transpacific flights with Japan Airlines. A joint venture with Qantas covers routes between the United States, Australia, and New Zealand.
Cabins.
Flagship First is American's international and transcontinental first class product. It is offered only on Boeing 777-300ERs and select Airbus A321s, which American designates "A321T". The seats are fully lie-flat and offer direct aisle access with only one on each side of the aisle in each row. As with the airline's other premium cabins, Flagship First offers wider food and beverage options, larger seats, and lounge access at certain airports. American offers domestic Flagship First service on transcontinental routes between New York–JFK and Los Angeles, New York–JFK and San Francisco, New York-JFK and Santa Ana, Boston and Los Angeles, and Miami and Los Angeles, as well as on the standard domestic route between New York-JFK and Boston. The airline will debut new Flagship Suite premium seats and a revamped aircraft interior for its long-haul fleet with fresh deliveries of its Airbus A321XLR and Boeing 787-9 aircraft, beginning in 2024.
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Flagship Business is American's international and transcontinental business class product. It is offered on all Boeing 777-200ERs, Boeing 777-300ERs, Boeing 787-8s, and Boeing 787-9s, as well as select Airbus A321s. All Flagship Business seats are fully lie-flat. The amenities in Flagship Business include complimentary alcoholic/non-alcoholic beverages, multi-course meals, and lounge access.
First class is the highest class of service on domestically configured aircraft. When such aircraft are used on international services this cabin is branded as business class. Seats range from in width and have of pitch. Dining options include complimentary alcoholic and non-alcoholic beverages on all flights as well as standard economy snack offerings, enhanced snack basket selections on flights over , and meals on flights or longer.
Premium Economy is American's economy plus product. It is offered on all widebody aircraft. The cabin debuted on the airline's Boeing 787-9s in late 2016 and is also available on Boeing 777-200s and -300s, and Boeing 787-8s. Premium Economy seats are wider than seats in the main cabin (American's economy cabin) and provide more amenities: Premium Economy customers get two free checked bags, priority boarding, and enhanced food and drink service, including free alcohol. This product made American Airlines the first U.S. carrier to offer a four-cabin aircraft.
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Main Cabin (economy class) is American's economy product found on all mainline and regional aircraft in its fleet. Seats range from in width and have of pitch. American markets several rows within the main cabin immediately behind Main Cabin Extra as "Main Cabin Preferred", which requires an extra charge to select for those without status.
Main Cabin Extra seats are located in the front few rows and exit rows of the economy cabin on all aircraft and have additional pitch, complimentary alcoholic beverages and boarding one group ahead of the main cabin. It is available on all of the mainline fleet and American Eagle aircraft.
American also offers Basic Economy, the airline's lowest main cabin fare on many routes. Basic Economy consists of a Main Cabin ticket with numerous restrictions, including waiting until check-in for a seat assignment, no upgrades or refunds, and boarding in the last group. Originally Basic Economy passengers could only carry a personal item. Later, American revised their Basic Economy policies to allow for a carry-on bag.
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In May 2017, American announced it would add more seats to some of its Boeing 737 MAX 8 jets and reduce overall legroom in the basic economy class. The last three rows were to lose , going from the current . The remainder of the main cabin was to have of legroom. This "Project Oasis" seating configuration has since been expanded to all 737 MAX 8s as well as standard Boeing 737-800 and non-transcontinental Airbus A321 jets. New Airbus A321neo jets have been delivered with the same configuration. This configuration has been considered unpopular with passengers, especially American's frequent flyers, as the new seats have less padding, less legroom, and no seatback entertainment.
Reward programs.
AAdvantage.
AAdvantage is the frequent flyer program for American Airlines. It was launched on May 1, 1981, and remains the largest frequent flyer program, with over 115 million members as of 2021. Miles accumulated in the program allow members to redeem tickets, upgrade service class, or obtain free or discounted car rentals, hotel stays, merchandise, or other products and services through partners. The most active members, based on the accumulation of Loyalty Points with American Airlines, are designated AAdvantage Gold, AAdvantage Platinum, AAdvantage Platinum Pro, and AAdvantage Executive Platinum elite members, with privileges such as separate check-in, priority upgrade, and standby processing, or free upgrades. AAdvantage status corresponds with Oneworld status levels allowing elites to receive reciprocal benefits from American's Oneworld partner airlines.
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AAdvantage co-branded credit cards are also available and offer other benefits. The cards are issued by CitiCards, a subsidiary of Citigroup, Barclaycard, and Bilt card in the United States, by several banks including Butterfield Bank and Scotiabank in the Caribbean, and by Banco Santander in Brazil. In December 2024, it was announced that American would be cutting ties with Barclays and would instead be rolling members into its partnership with Citigroup starting in 2026.
AAdvantage allows one-way redemption, starting at 7,500 miles.
Admirals Club.
The Admirals Club was conceived by AA president C.R. Smith as a marketing promotion shortly after he was made an honorary Texas Ranger. Inspired by the Kentucky colonels and other honorary title designations, Smith decided to make particularly valued passengers "admirals" of the "Flagship fleet" (AA called its aircraft "Flagships" at the time). The list of admirals included many celebrities, politicians, and other VIPs, as well as more "ordinary" customers who had been particularly loyal to the airline.
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There was no physical Admirals Club until shortly after the opening of LaGuardia Airport. During the airport's construction, New York Mayor Fiorello LaGuardia had an upper-level lounge for press conferences and business meetings. At one such press conference, he noted that the entire terminal was being offered for lease to airline tenants; after a reporter asked whether the lounge would be leased as well, LaGuardia replied that it would, and a vice president of AA immediately offered to lease the premises. The airline then procured a liquor license and began operating the lounge as the "Admirals Club" in 1939.
The second Admirals Club opened at Washington National Airport. Because it was illegal to sell alcohol in Virginia at the time, the club contained refrigerators for the use of its members so they could store their liquor at the airport. For many years, membership in the Admirals Club (and most other airline lounges) was by the airline's invitation. After a passenger sued for discrimination, the club switched to a paid membership program in 1974.
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Flagship Lounge.
Though affiliated with the Admirals Club and staffed by many of the same employees, the Flagship Lounge is a separate lounge designed explicitly for customers flying in first class and business class on international flights and transcontinental domestic flights.
Corporate affairs.
Business trends.
The key trends for American Airlines are (as of the financial year ending 31 December):
Ownership and structure.
American Airlines, Inc., is publicly traded through its parent company, American Airlines Group Inc., under NASDAQ: AAL , with a market capitalization of about $11 billion as of 2024, and is included in the S&P 500 index.
American Eagle is a network of six regional carriers that operate under a codeshare and service agreement with American, operating flights to destinations in the United States, Canada, the Caribbean, and Mexico. Three of these carriers are independent, and three are subsidiaries of American Airlines Group: Envoy Air Inc., Piedmont Airlines, Inc., and PSA Airlines Inc.
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Headquarters.
American Airlines is headquartered across several buildings in Fort Worth, Texas that it calls the "Robert L. Crandall Campus" in honor of former president and CEO Robert Crandall. The , five-building office complex called was designed by Pelli Clarke Pelli Architects. The campus is located on 300 acres, adjacent to Dallas/Fort Worth International Airport, American's fortress hub.
Before it was headquartered in Texas, American Airlines was headquartered at 633 Third Avenue in the Murray Hill area of Midtown Manhattan, New York City. In 1979, American moved its headquarters to a site at Dallas/Fort Worth International Airport, which affected up to 1,300 jobs. Mayor of New York City Ed Koch described the move as a "betrayal" of New York City. American moved to two leased office buildings in Grand Prairie, Texas. On January 17, 1983, the airline finished moving into a $150 million ($ when adjusted for inflation), facility in Fort Worth; $147 million (about $ when adjusted for inflation) in Dallas/Fort Worth International Airport bonds financed the headquarters. The airline began leasing the facility from the airport, which owns the facility. Following the merger of US Airways and American Airlines, the new company consolidated its corporate headquarters in Fort Worth, abandoning the US Airways headquarters in Phoenix, AZ.
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As of 2015, American Airlines is the corporation with the most significant presence in Fort Worth.
In 2015, American announced it would build a new headquarters in Fort Worth. Groundbreaking began in the spring of 2016, and occupancy was completed in September 2019. The airline plans to house 5,000 new workers in the building.
It will be located on a property adjacent to the airline's flight academy and conference and training center, west of Texas State Highway 360, west from the current headquarters. The airline will lease from Dallas–Fort Worth International Airport, and this area will include the headquarters. Construction of the new headquarters began after the demolition of the Sabre facility, previously on the site.
The airline considered developing a new headquarters in Irving, Texas, on the old Texas Stadium site, before deciding to keep the headquarters in Fort Worth.
Corporate identity.
Logo.
In 1931, an American employee, Goodrich Murphy designed the AA logo as an entry in a logo contest. The eagle in the logo was copied from a Scottish hotel brochure. The logo was redesigned by Massimo Vignelli in 1967. Thirty years later, in 1997, American Airlines was able to make its logo Internet-compatible by buying the domain AA.com. "AA" is also American's two-letter IATA airline designator.
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On January 17, 2013, American launched a new rebranding and marketing campaign with FutureBrand dubbed "A New American". This included a new logo, which includes elements of the 1967 logo.
American Airlines faced difficulty obtaining copyright registration for their 2013 logo. On June 3, 2016, American Airlines sought to register it with the United States Copyright Office, but in October of that year, the Copyright Office ruled that the logo was ineligible for copyright protection, as it did not pass the threshold of originality, and was thus in the public domain. American requested that the Copyright Office reconsider. Still, on January 8, 2018, the Copyright Office affirmed its initial determination. After American Airlines submitted additional materials, the Copyright Office reversed its decision on December 7, 2018, and ruled that the logo contained enough creativity to merit copyright protection.
Aircraft livery.
American's early liveries varied widely, but a standard livery was adopted in the 1930s, featuring an eagle painted on the fuselage. The eagle became a symbol of the company and inspired the name of American Eagle Airlines. Propeller aircraft featured an international orange lightning bolt running down the length of the fuselage, which was replaced by a simpler orange stripe with the introduction of jets.
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In the late 1960s, American commissioned designer Massimo Vignelli to develop a new livery. The original design called for a red, white, and blue stripe on the fuselage and a simple "AA" logo, without an eagle, on the tail; instead, Vignelli created a highly stylized eagle, which remained the company's logo until January 16, 2013.
On January 17, 2013, American unveiled a new livery. Before then, American had been the only major U.S. airline to leave most of its aircraft surfaces unpainted. This was because C. R. Smith would not say he liked painted aircraft and refused to use any liveries that involved painting the entire plane. Robert "Bob" Crandall later justified the distinctive natural metal finish by noting that less paint reduced the aircraft's weight, thus saving fuel costs.
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In the end, American let their employees decide the new livery's fate. On an internal website for employees, American posted two options, one the new livery and one a modified version of the old livery. All of the American Airlines Group employees (including US Airways and other affiliates) were able to vote. American ultimately decided to keep the new look. Parker announced that American would keep a US Airways and America West heritage aircraft in the fleet, with plans to add a heritage TWA aircraft and a heritage American plane with the old livery. As of September 2019, American has heritage aircraft for Piedmont, PSA, America West, US Airways, Reno Air, TWA, and AirCal in their fleet. They also have two AA branded heritage 737-800 aircraft, an AstroJet N905NN, and the polished aluminum livery used from 1967 to 2013, N921NN.
Customer Service.
American, both before and after the merger with US Airways, has consistently performed poorly in rankings. The Wall Street Journal's annual airline rankings have ranked American as the worst or second-worst U.S. carrier for ten of the past twelve years, and in the bottom three of U.S. Airlines for at least the past twelve years. The airline has persistently performed poorly in the areas of losing checked luggage and bumping passengers due to oversold flights.
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Worker relations.
The main representatives of key groups of employees are:
Subsidiary companies.
Sky Chefs.
In 1942, American Airlines established Sky Chefs, a wholly-owned subsidiary, as a catering company to serve their fleet. In 1986, Sky Chefs was sold to Toronto-based Onex Capital Corporation for $170 million. Since 2001, it has been fully owned by the LSG Group.
Flagship Hotels / Americana Hotels.
In the late-1960s, American Airlines established the Flagship Hotels chain as a subsidiary of Sky Chefs. On July 21, 1972, American Airlines leased four hotels from the Loews Corporation, three of them branded as Americana Hotels, for a period of thirty years. American merged the hotels with their Flagship Hotels, and rebranded the entire chain as Americana Hotels. In 1980, American Airlines sold Americana Hotels to Bass Brothers Enterprises of Fort Worth, Texas.
Concerns and conflicts.
Environmental violations.
Between October 1993 to July 1998, American Airlines was repeatedly cited for using high-sulfur fuel in motor vehicles at 10 major airports around the country, a violation of the Clean Air Act.
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Lifetime AAirpass.
In 1981, as a means of creating revenue in a period of loss-making, American Airlines offered a lifetime pass of unlimited travel for the initial cost of $250,000. This entitled the pass holder to fly anywhere in the world. Twenty-eight were sold. However, after some time, the airline realized they were making losses on the tickets, with the ticketholders costing them up to $1 million each. Ticketholders were booking large numbers of flights with some ticketholders flying interstate for lunch or flying to London multiple times a month. AA raised the cost of the lifetime pass to $3 million, and then finally stopped offering it in 2003. AA then used litigation to cancel two of the lifetime offers, saying the passes "had been terminated due to fraudulent activity".
Discrimination complaints.
On October 24, 2017, the NAACP issued a travel advisory for American Airlines urging African Americans to "exercise caution" when traveling with the airline. The NAACP issued the advisory after four incidents. In one incident, a black woman was moved from first class to coach while her white traveling companion was allowed to remain in first class. In another incident, a black man was forced to give up his seats after being confronted by two unruly white passengers. According to the NAACP, while they did receive complaints on other airlines, most of their complaints in the year before their advisory were on American Airlines. In July 2018, the NAACP lifted their travel advisory saying that American has made improvements to mitigate discrimination and unsafe treatment of African Americans.
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Carbon footprint.
American Airlines reported total CO2e emissions (direct and indirect) for the twelve months ending December 31, 2020, at 20,092 Kt (-21,347 /-51.5% y-o-y). The company aims to achieve net zero carbon emissions by 2050. In November 2023, American Airlines purchased the first carbon credit contract (for 10,000 metric tons of sequestered at $100 per ton) from Graphyte, a carbon removal startup company invested in by Breakthrough Energy that compresses sawdust, tree bark, rice hulls, plant stalks, and other agricultural waste into biomass bricks wrapped in a polymer barrier to prevent decomposition that are stored underground.
Notes and references.
Notes
References
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Antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexual dysfunction, and emotional blunting. There is an increased risk of suicidal thinking and behavior when taken by children, adolescents, and young adults. Discontinuation syndrome, which resembles recurrent depression in the case of the SSRI class, may occur after stopping the intake of any antidepressant
Research regarding the effectiveness of antidepressants for depression in adults is controversial and has found both benefits and drawbacks. Meanwhile, evidence of benefit in children and adolescents is unclear, even though antidepressant use has considerably increased in children and adolescents in the 2000s. While a 2018 study found that the 21 most commonly prescribed antidepressant medications were slightly more effective than placebos for the short-term (acute) treatments of adults with major depressive disorder, other research has found that the placebo effect may account for most or all of the drugs' observed efficacy.
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Research on the effectiveness of antidepressants is generally done on people who have severe symptoms, a population that exhibits much weaker placebo responses, meaning that the results may not be extrapolated to the general population that has not (or has not yet) been diagnosed with anxiety or depression.
Medical uses.
Antidepressants are prescribed to treat major depressive disorder (MDD), anxiety disorders, chronic pain, and some addictions. Antidepressants are often used in combination with one another.
Despite its longstanding prominence in pharmaceutical advertising, the idea that low serotonin levels cause depression is not supported by scientific evidence. Proponents of the monoamine hypothesis of depression recommend choosing an antidepressant which impacts the most prominent symptoms. Under this practice, for example, a person with MDD who is also anxious or irritable would be treated with selective serotonin reuptake inhibitors (SSRIs) or norepinephrine reuptake inhibitors, while a person suffering from loss of energy and enjoyment of life would take a norepinephrine–dopamine reuptake inhibitor.
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Major depressive disorder.
The UK National Institute for Health and Care Excellence (NICE)'s 2022 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, "unless that is the person's preference". The guidelines recommended that antidepressant treatment be considered:
The guidelines further note that in most cases, antidepressants should be used in combination with psychosocial interventions and should be continued for at least six months to reduce the risk of relapse and that SSRIs are typically better tolerated than other antidepressants.
American Psychiatric Association (APA) treatment guidelines recommend that initial treatment be individually tailored based on factors including the severity of symptoms, co-existing disorders, prior treatment experience, and the person's preference. Options may include antidepressants, psychotherapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or light therapy. The APA recommends antidepressant medication as an initial treatment choice in people with mild, moderate, or severe major depression, and that should be given to all people with severe depression unless ECT is planned.
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Reviews of antidepressants generally find that they benefit adults with depression. On the other hand, some contend that most studies on antidepressant medication are confounded by several biases: the lack of an active placebo, which means that many people in the placebo arm of a double-blind study may deduce that they are not getting any true treatment, thus destroying double-blindness; a short follow up after termination of treatment; non-systematic recording of adverse effects; very strict exclusion criteria in samples of patients; studies being paid for by the industry; selective publication of results. This means that the small beneficial effects that are found may not be statistically significant.
Among the 21 most commonly prescribed antidepressants, the most effective and well-tolerated are escitalopram, paroxetine, sertraline, agomelatine, and mirtazapine. For children and adolescents with moderate to severe depressive disorder, some evidence suggests fluoxetine (either with or without cognitive behavioral therapy) is the best treatment, but more research is needed to be certain. Sertraline, escitalopram, and duloxetine may also help reduce symptoms.
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A 2023 systematic review and meta-analysis of randomized controlled trials of antidepressants for major depressive disorder found that the medications provided only small or doubtful benefits in terms of quality of life. Likewise, a 2022 systematic review and meta-analysis of randomized controlled trials of antidepressants for major depressive disorder in children and adolescents found small improvements in quality of life. Quality of life as an outcome measure is often selectively reported in trials of antidepressants.
Anxiety disorders.
For children and adolescents, fluvoxamine and escitalopram are effective in treating a range of anxiety disorders. Fluoxetine, sertraline, and paroxetine can also help with managing various forms of anxiety in children and adolescents.
Meta-analyses of published and unpublished trials have found that antidepressants have a placebo-subtracted effect size (standardized mean difference or SMD) in the treatment of anxiety disorders of around 0.3, which equates to a small improvement and is roughly the same magnitude of benefit as their effectiveness in the treatment of depression. The effect size (SMD) for improvement with placebo in trials of antidepressants for anxiety disorders is approximately 1.0, which is a large improvement in terms of effect size definitions. In relation to this, most of the benefit of antidepressants for anxiety disorders is attributable to placebo responses rather than to the effects of the antidepressants themselves.
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Generalized anxiety disorder.
Antidepressants are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder in which the central feature is excessively worrying about numerous events. Key symptoms include excessive anxiety about events and issues going on around them and difficulty controlling worrisome thoughts that persists for at least 6 months.
Antidepressants provide a modest to moderate reduction in anxiety in GAD. The efficacy of different antidepressants is similar.
Social anxiety disorder.
Some antidepressants are used as a treatment for social anxiety disorder, but their efficacy is not entirely convincing, as only a small proportion of antidepressants showed some effectiveness for this condition. Paroxetine was the first drug to be FDA-approved for this disorder. Its efficacy is considered beneficial, although not everyone responds favorably to the drug.
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Paroxetine was the first drug to be FDA-approved for this disorder. Its efficacy is considered beneficial, although not everyone responds favorably to the drug. Sertraline and fluvoxamine extended-release were later approved for it as well, while escitalopram is used off-label with acceptable efficiency. However, there is not enough evidence to support Citalopram for treating social anxiety disorder, and fluoxetine was no better than a placebo in clinical trials. SSRIs are used as a first-line treatment for social anxiety, but they do not work for everyone. One alternative would be venlafaxine, an SNRI, which has shown benefits for social phobia in five clinical trials against a placebo, while the other SNRIs are not considered particularly useful for this disorder as many of them did not undergo testing for it. , it is unclear if duloxetine and desvenlafaxine can provide benefits for people with social anxiety. However, another class of antidepressants called MAOIs are considered effective for social anxiety, but they come with many unwanted side effects and are rarely used.
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However, another class of antidepressants called MAOIs are considered effective for social anxiety, but they come with many unwanted side effects and are rarely used. Phenelzine was shown to be a good treatment option, but its use is limited by dietary restrictions. Moclobemide is a RIMA and showed mixed results, but still received approval in some European countries for social anxiety disorder. TCA antidepressants, such as clomipramine and imipramine, are not considered effective for this anxiety disorder in particular. This leaves out SSRIs such as paroxetine, sertraline, and fluvoxamine CR as acceptable and tolerated treatment options for this disorder.
Obsessive–compulsive disorder.
SSRIs are a second-line treatment for adult obsessive–compulsive disorder (OCD) with mild functional impairment, and a first-line treatment for those with moderate or severe impairment.
In children, SSRIs are considered as a second-line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects. Sertraline and fluoxetine are effective in treating OCD for children and adolescents.
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Clomipramine, a TCA drug, is considered effective and useful for OCD. However, it is used as a second-line treatment because it is less well-tolerated than SSRIs. Despite this, it has not shown superiority to fluvoxamine in trials. All SSRIs can be used effectively for OCD. SNRI use may also be attempted, though no SNRIs have been approved for the treatment of OCD. Despite these treatment options, many patients remain symptomatic after initiating the medication, and less than half achieve remission.
Placebo responses are a large component of the benefit of antidepressants in the treatment of depression and anxiety. However, placebo responses with antidepressants are lower in magnitude in the treatment of OCD compared to depression and anxiety. A 2019 meta-analysis found placebo improvement effect sizes (SMD) of about 1.2 for depression, 1.0 for anxiety disorders, and 0.6 for OCD with antidepressants.
Post–traumatic stress disorder.
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Panic disorder.
Panic disorder is treated relatively well with medications compared to other disorders. Several classes of antidepressants have shown efficacy for this disorder, with SSRIs and SNRIs used first-line. Paroxetine, sertraline, and fluoxetine are FDA-approved for panic disorder, while fluvoxamine, escitalopram, and citalopram are also considered effective for them. SNRI venlafaxine is also approved for this condition. Unlike social anxiety and PTSD, some TCAs antidepressants, like clomipramine and imipramine, have shown efficacy for panic disorder. Moreover, the MAOI phenelzine is also considered useful. Panic disorder has many drugs for its treatment. However, the starting dose must be lower than the one used for major depressive disorder because people have reported an increase in anxiety as a result of starting the medication. In conclusion, while panic disorder's treatment options seem acceptable and useful for this condition, many people are still symptomatic after treatment with residual symptoms.
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Eating disorders.
Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa. SSRIs (fluoxetine in particular) are preferred over other antidepressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized. Bupropion is not recommended for the treatment of eating disorders, due to an increased risk of seizure.
Similar recommendations apply to binge eating disorder. SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.
Clinical trials have generated mostly negative results for the use of SSRIs in the treatment of anorexia nervosa. Treatment guidelines from the National Institute of Health and Care Excellence (NICE) recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association (APA) note that SSRIs confer no advantage regarding weight gain, but may be used for the treatment of co-existing depressive, anxiety, or obsessive–compulsive disorders.
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Pain.
Fibromyalgia.
A 2012 meta-analysis concluded that antidepressant treatment favorably affects pain, health-related quality of life, depression, and sleep in fibromyalgia syndrome. Tricyclics appear to be the most effective class, with moderate effects on pain and sleep, and small effects on fatigue and health-related quality of life. The fraction of people experiencing a 30% pain reduction on tricyclics was 48%, versus 28% on placebo. For SSRIs and SNRIs, the fractions of people experiencing a 30% pain reduction were 36% (20% in the placebo comparator arms) and 42% (32% in the corresponding placebo comparator arms) respectively. Discontinuation of treatment due to side effects was common. Antidepressants including amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole are recommended by the European League Against Rheumatism (EULAR) for the treatment of fibromyalgia based on "limited evidence".
Neuropathic pain.
A 2014 meta-analysis from the Cochrane Collaboration found the antidepressant duloxetine to be effective for the treatment of pain resulting from diabetic neuropathy. The same group reviewed data for amitriptyline in the treatment of neuropathic pain and found limited useful randomized clinical trial data. They concluded that the long history of successful use in the community for the treatment of fibromyalgia and neuropathic pain justified its continued use. The group was concerned about the potential overestimation of the amount of pain relief provided by amitriptyline, and highlighted that only a small number of people will experience significant pain relief by taking this medication.
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Other uses.
Antidepressants may be modestly helpful for treating people who have both depression and alcohol dependence, however, the evidence supporting this association is of low quality. Bupropion is used to help people stop smoking. Antidepressants are also used to control some symptoms of narcolepsy. Antidepressants may be used to relieve pain in people with active rheumatoid arthritis. However, further research is required. Antidepressants have been shown to be superior to placebo in treating depression in individuals with physical illness, although reporting bias may have exaggerated this finding. Antidepressants have been shown to improve some parts of cognitive functioning for depressed users, such as memory, attention, and processing speed.
Certain antidepressants acting as serotonin 5-HT2A receptor antagonists, such as trazodone and mirtazapine, have been used as hallucinogen antidotes or "trip killers" to block the effects of serotonergic psychedelics like psilocybin and lysergic acid diethylamide (LSD).
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Limitations and strategies.
Among individuals treated with a given antidepressant, between 30% and 50% do not show a response. Approximately one-third of people achieve a full remission, one-third experience a response, and one-third are non-responders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, anxiety, sleep disturbance, fatigue, and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates three to six times higher in people with residual symptoms than in those, who experience full remission. In addition, antidepressant drugs tend to lose efficacy throughout long-term maintenance therapy. According to data from the Centers for Disease Control and Prevention, less than one-third of Americans taking one antidepressant medication have seen a mental health professional in the previous year. Several strategies are used in clinical practice to try to overcome these limits and variations. They include switching medication, augmentation, and combination.
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There is controversy amongst researchers regarding the efficacy and risk-benefit ratio of antidepressants. Although antidepressants consistently out-perform a placebo in meta-analyses, the difference is modest and it is not clear that their statistical superiority results in clinical efficacy. The aggregate effect of antidepressants typically results in changes below the threshold of clinical significance on depression rating scales. Proponents of antidepressants counter that the most common scale, the HDRS, is not suitable for assessing drug action, that the threshold for clinical significance is arbitrary, and that antidepressants consistently result in significantly raised scores on the mood item of the scale. Assessments of antidepressants using alternative, more sensitive scales, such as the MADRS, do not result in marked difference from the HDRS and likewise only find a marginal clinical benefit. Another hypothesis proposed to explain the poor performance of antidepressants in clinical trials is a high treatment response heterogeneity. Some patients, that differ strongly in their response to antidepressants, could influence the average response, while the heterogeneity could itself be obscured by the averaging. Studies have not supported this hypothesis, but it is very difficult to measure treatment effect heterogeneity. Poor and complex clinical trial design might also account for the small effects seen for antidepressants. The randomized controlled trials used to approve drugs are short, and may not capture the full effect of antidepressants. Additionally, the placebo effect might be inflated in these trials by frequent clinical consultation, lowering the comparative performance of antidepressants. Critics agree that current clinical trials are poorly-designed, which limits the knowledge on antidepressants. More naturalistic studies, such as STAR*D, have produced results, which suggest that antidepressants may be less effective in clinical practice than in randomized controlled trials.
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Critics of antidepressants maintain that the superiority of antidepressants over placebo is the result of systemic flaws in clinical trials and the research literature. Trials conducted with industry involvement tend to produce more favorable results, and accordingly many of the trials included in meta-analyses are at high risk of bias. Additionally, meta-analyses co-authored by industry employees find more favorable results for antidepressants. The results of antidepressant trials are significantly more likely to be published if they are favorable, and unfavorable results are very often left unpublished or misreported, a phenomenon called publication bias or selective publication. Although this issue has diminished with time, it remains an obstacle to accurately assessing the efficacy of antidepressants. Misreporting of clinical trial outcomes and of serious adverse events, such as suicide, is common. Ghostwriting of antidepressant trials is widespread, a practice in which prominent researchers, or so-called key opinion leaders, attach their names to studies actually written by pharmaceutical company employees or consultants. A particular concern is that the psychoactive effects of antidepressants may lead to the unblinding of participants or researchers, enhancing the placebo effect and biasing results. Some have therefore maintained that antidepressants may only be active placebos. When these and other flaws in the research literature are not taken into account, meta-analyses may find inflated results on the basis of poor evidence.
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Critics contend that antidepressants have not been proven sufficiently effective by RCTs or in clinical practice and that the widespread use of antidepressants is not evidence-based. They also note that adverse effects, including withdrawal difficulties, are likely underreported, skewing clinicians' ability to make risk-benefit judgements. Accordingly, they believe antidepressants are overused, particularly for non-severe depression and conditions in which they are not indicated. Critics charge that the widespread use and public acceptance of antidepressants is the result of pharmaceutical advertising, research manipulation, and misinformation.
Current mainstream psychiatric opinion recognizes the limitations of antidepressants but recommends their use in adults with more severe depression as a first-line treatment.
Switching antidepressants.
The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved within the following six to eight weeks of treatment with an antidepressant, switch to an antidepressant in the same class, and then to a different class. A 2006 meta-analysis review found wide variation in the findings of prior studies: for people who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug. However, the more antidepressants an individual had previously tried, the less likely they were to benefit from a new antidepressant trial. However, a later meta-analysis found no difference between switching to a new drug and staying on the old medication: although 34% of treatment-resistant people responded when switched to the new drug, 40% responded without being switched.
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Augmentation and combination.
For a partial response, the American Psychiatric Association (APA) guidelines suggest augmentation or adding a drug from a different class. These include lithium and thyroid augmentation, dopamine agonists, sex steroids, NRIs, glucocorticoid-specific agents, or the newer anticonvulsants.
A combination strategy involves adding another antidepressant, usually from a different class to affect other mechanisms. Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy. Other tests conducted include the use of psychostimulants as an augmentation therapy. Several studies have shown the efficacy of combining modafinil for treatment-resistant people. It has been used to help combat SSRI-associated fatigue.
Long-term use and stopping.
The effects of antidepressants typically do not continue once the course of medication ends. This results in a high rate of relapse. In 2003, a meta-analysis found that 18% of people who had responded to an antidepressant relapsed while still taking it, compared to 41% whose antidepressant was switched for a placebo.
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A gradual loss of therapeutic benefit occurs in a minority of people during the course of treatment. A strategy involving the use of pharmacotherapy in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies. For patients who wish to stop their antidepressants, engaging in brief psychological interventions such as Preventive Cognitive Therapy or mindfulness-based cognitive therapy while tapering down has been found to diminish the risk for relapse.
Adverse effects.
Antidepressants can cause various adverse effects, depending on the individual and the drug in question.
Almost any medication involved with serotonin regulation has the potential to cause serotonin toxicity (also known as "serotonin syndrome") – an excess of serotonin that can induce mania, restlessness, agitation, emotional lability, insomnia, and confusion as its primary symptoms. Although the condition is serious, it is not particularly common, generally only appearing at high doses or while on other medications. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal. Antidepressants appear to increase the risk of diabetes by about 1.3-fold.
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MAOIs tend to have pronounced (sometimes fatal) interactions with a wide variety of medications and over-the-counter drugs. If taken with foods that contain very high levels of tyramine (e.g., mature cheese, cured meats, or yeast extracts), they may cause a potentially lethal hypertensive crisis. At lower doses, the person may only experience a headache due to an increase in blood pressure.
In response to these adverse effects, a different type of MAOI, the class of reversible inhibitor of monoamine oxidase A (RIMA), has been developed. The primary advantage of RIMAs is that they do not require the person to follow a special diet while being purportedly effective as SSRIs and tricyclics in treating depressive disorders.
Tricyclics and SSRI can cause the so-called drug-induced QT prolongation, especially in older adults; this condition can degenerate into a specific type of abnormal heart rhythm called Torsades de points, which can potentially lead to sudden cardiac arrest.
Some antidepressants are also believed to increase thoughts of suicidal ideation.
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Antidepressants have been associated with an increased risk of dementia in older adults.
Researchers have developed a tool that allows people to rate their concern about common side effects of antidepressants. The tool ranks potential treatment options in a visual display that highlights the drugs with side effects of least concern to an individual.
Pregnancy.
SSRI use in pregnancy has been associated with a variety of risks with varying degrees of proof of causation. As depression is independently associated with negative pregnancy outcomes, determining the extent to which observed associations between antidepressant use and specific adverse outcomes reflect a causative relationship has been difficult in some cases. In other cases, the attribution of adverse outcomes to antidepressant exposure seems fairly clear.
SSRI use in pregnancy is associated with an increased risk of spontaneous abortion of about 1.7-fold, and is associated with preterm birth and low birth weight.
A systematic review of the risk of major birth defects in antidepressant-exposed pregnancies found a small increase (3% to 24%) in the risk of major malformations and a risk of cardiovascular birth defects that did not differ from non-exposed pregnancies. A study of fluoxetine-exposed pregnancies found a 12% increase in the risk of major malformations that did not reach statistical significance. Other studies have found an increased risk of cardiovascular birth defects among depressed mothers not undergoing SSRI treatment, suggesting the possibility of ascertainment bias, e.g. that worried mothers may pursue more aggressive testing of their infants. Another study found no increase in cardiovascular birth defects and a 27% increased risk of major malformations in SSRI exposed pregnancies. The FDA advises for the risk of birth defects with the use of paroxetine and the MAOI should be avoided.
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A 2013 systematic review and meta-analysis found that antidepressant use during pregnancy was statistically significantly associated with some pregnancy outcomes, such as gestational age and preterm birth, but not with other outcomes. The same review cautioned that because differences between the exposed and unexposed groups were small, it was doubtful whether they were clinically significant.
A neonate (infant less than 28 days old) may experience a withdrawal syndrome from abrupt discontinuation of the antidepressant at birth. Antidepressants can be present in varying amounts in breast milk, but their effects on infants are currently unknown.
Moreover, SSRIs inhibit nitric oxide synthesis, which plays an important role in setting the vascular tone. Several studies have pointed to an increased risk of prematurity associated with SSRI use, and this association may be due to an increased risk of pre-eclampsia during pregnancy.
Antidepressant-induced mania.
Another possible problem with antidepressants is the chance of antidepressant-induced mania or hypomania in people with or without a diagnosis of bipolar disorder. Many cases of bipolar depression are very similar to those of unipolar depression. Therefore, the person can be misdiagnosed with unipolar depression and be given antidepressants. Studies have shown that antidepressant-induced mania can occur in 20–40% of people with bipolar disorder. For bipolar depression, antidepressants (most frequently SSRIs) can exacerbate or trigger symptoms of hypomania and mania. Bupropion has been associated with a lower risk of mood switch than other antidepressants.
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Suicide.
Studies have shown that the use of antidepressants is correlated with an increased risk of suicidal behavior and thinking (suicidality) in those aged under 25 years old. This problem has been serious enough to warrant government intervention by the US Food and Drug Administration (FDA) to warn of the increased risk of suicidality during antidepressant treatment. According to the FDA, the heightened risk of suicidality occurs within the first one to two months of treatment. The National Institute for Health and Care Excellence (NICE) places the excess risk in the "early stages of treatment". A meta-analysis suggests that the relationship between antidepressant use and suicidal behavior or thoughts is age-dependent. Compared with placebo, the use of antidepressants is associated with an increase in suicidal behavior or thoughts among those 25 years old or younger (OR=1.62). A review of RCTs and epidemiological studies by Healy and Whitaker found an increase in suicidal acts by a factor of 2.4. There is no effect or possibly a mild protective effect among those aged 25 to 64 (OR=0.79). Antidepressant treatment has a protective effect against suicidality among those aged 65 and over (OR=0.37).
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Sexual dysfunction.
Sexual side effects are also common with SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction. Although usually reversible, these sexual side-effects can, in rare cases, continue after the drug has been completely withdrawn.
In a study of 1,022 outpatients, overall sexual dysfunction with all antidepressants averaged 59.1% with SSRI values between 57% and 73%, mirtazapine 24%, nefazodone 8%, amineptine 7%, and moclobemide 4%. Moclobemide, a selective reversible MAO-A inhibitor, does not cause sexual dysfunction and can lead to an improvement in all aspects of sexual function.
Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting 5-HT2 and 5-HT3 receptors; decreased dopamine; decreased norepinephrine; blockade of cholinergic and α1adrenergic receptors; inhibition of nitric oxide synthetase; and elevation of prolactin levels. Mirtazapine is reported to have fewer sexual side effects, most likely because it antagonizes 5-HT2 and 5-HT3 receptors and may, in some cases, reverse sexual dysfunction induced by SSRIs by the same mechanism.
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Bupropion, a weak NDRI and nicotinic antagonist, may be useful in treating reduced libido as a result of SSRI treatment.
Emotional blunting.
Certain antidepressants may cause emotional blunting, characterized by a reduced intensity of both positive and negative emotions as well as symptoms of apathy, indifference, and amotivation. It may be experienced as either beneficial or detrimental depending on the situation. This side effect has been particularly associated with serotonergic antidepressants like SSRIs and SNRIs but may be less with atypical antidepressants like bupropion, agomelatine, and vortioxetine. Higher doses of antidepressants seem to be more likely to produce emotional blunting than lower doses. Emotional blunting can be decreased by reducing dosage, discontinuing the medication, or switching to a different antidepressant that may have less propensity for causing this side effect.
Changes in weight.
Changes in appetite or weight are common among antidepressants but are largely drug-dependent and related to which neurotransmitters they affect. Mirtazapine and paroxetine, for example, may be associated with weight gain and/or increased appetite, while others (such as bupropion and venlafaxine) achieve the opposite effect.
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The antihistaminic properties of certain TCA- and TeCA-class antidepressants have been shown to contribute to the common side effects of increased appetite and weight gain associated with these classes of medication.
Bone loss.
A 2021 nationwide cohort study in South Korea observed a link between SSRI use and bone loss, particularly in recent users. The study also stressed the need of further research to better understand these effects. A 2012 review found that SSRIs along with tricyclic antidepressants were associated with a significant increase in the risk of osteoporotic fractures, peaking in the months after initiation, and moving back towards baseline during the year after treatment was stopped. These effects exhibited a dose–response relationship within SSRIs which varied between different drugs of that class. A 2018 meta-analysis of 11 small studies found a reduction in bone density of the lumbar spine in SSRI users which affected older people the most.
Risk of death.
A 2017 meta-analysis found that antidepressants were associated with a significantly increased risk of death (+33%) and new cardiovascular complications (+14%) in the general population. Conversely, risks were not greater in people with existing cardiovascular disease.
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Discontinuation syndrome.
Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication. The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, and anxiety. The problem usually begins within three days and may last for several months. Rarely psychosis may occur.
A discontinuation syndrome can occur after stopping any antidepressant including selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). The risk is greater among those who have taken the medication for longer and when the medication in question has a short half-life. The underlying reason for its occurrence is unclear. The diagnosis is based on the symptoms.
Methods of prevention include gradually decreasing the dose among those who wish to stop, though it is possible for symptoms to occur with tapering. Treatment may include restarting the medication and slowly decreasing the dose. People may also be switched to the long-acting antidepressant fluoxetine, which can then be gradually decreased.
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Approximately 20–50% of people who suddenly stop an antidepressant develop an antidepressant discontinuation syndrome. The condition is generally not serious. Though about half of people with symptoms describe them as severe. Some restart antidepressants due to the severity of the symptoms.
Pharmacology.
Antidepressants act via a large number of different mechanisms of action. This includes serotonin reuptake inhibition (SSRIs, SNRIs, TCAs, vilazodone, vortioxetine), norepinephrine reuptake inhibition (NRIs, SNRIs, TCAs), dopamine reuptake inhibition (bupropion, amineptine, nomifensine), direct modulation of monoamine receptors (vilazodone, vortioxetine, SARIs, agomelatine, TCAs, TeCAs, antipsychotics), monoamine oxidase inhibition (MAOIs), and NMDA receptor antagonism (ketamine, esketamine, dextromethorphan), among others (e.g., brexanolone, tianeptine). Some antidepressants also have additional actions, like sigma receptor modulation (certain SSRIs, TCAs, dextromethorphan) and antagonism of histamine H1 and muscarinic acetylcholine receptors (TCAs, TeCAs).
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The earliest and most widely known scientific theory of antidepressant action is the monoamine hypothesis, which can be traced back to the 1950s and 1960s. This theory states that depression is due to an imbalance, most often a deficiency, of the monoamine neurotransmitters, namely serotonin, norepinephrine, and/or dopamine. However, serotonin in particular has been implicated, as in the serotonin hypothesis of depression. The monoamine hypothesis was originally proposed based on observations that reserpine, a drug which depletes the monoamine neurotransmitters, produced depressive effects in people, and that certain hydrazine antituberculosis agents like iproniazid, which prevent the breakdown of monoamine neurotransmitters, produced apparent antidepressant effects. Most currently marketed antidepressants, which are monoaminergic in their actions, are theoretically consistent with the monoamine hypothesis. Despite the widespread nature of the monoamine hypothesis, it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, many people with depression do not respond to monoaminergic antidepressants. A number of alternative hypotheses have been proposed, including hypotheses involving glutamate, neurogenesis, epigenetics, cortisol hypersecretion, and inflammation, among others.
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In 2022, a major systematic umbrella review by Joanna Moncrieff and colleagues showed that the serotonin theory of depression was not supported by evidence from a wide variety of areas. The authors concluded that there is no association between serotonin and depression, and that there is no evidence that strongly supports the theory that depression is caused by low serotonin activity or concentrations. Other literature had described the lack of support for the theory previously. In many of the expert responses to the review, it was stated that the monoamine hypothesis had already long been abandoned by psychiatry. This is in spite of about 90% of the general public in Western countries believing the theory to be true and many in the field of psychiatry continuing to promote the theory up to recent times. In addition to the serotonin umbrella review, reviews have found that reserpine, a drug that depletes the monoamine neurotransmitters—including serotonin, norepinephrine, and dopamine—shows no consistent evidence of producing depressive effects. Instead, findings of reserpine and mood are highly mixed, with similar proportions of studies finding that it has no influence on mood, produces depressive effects, or actually has antidepressant effects. In relation to this, the general monoamine hypothesis, as opposed to only the serotonin theory of depression, likewise does not appear to be well-supported by evidence.
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The serotonin and monoamine hypotheses of depression have been heavily promoted by the pharmaceutical industry (e.g., in advertisements) and by the psychiatric profession at large despite the lack of evidence in support of them. In the case of the pharmaceutical industry, this can be attributed to obvious financial incentives, with the theory creating a bias against non-pharmacological treatments for depression.
An alternative theory for antidepressant action proposed by certain academics such as Irving Kirsch and Joanna Moncrieff is that they work largely or entirely via placebo mechanisms. This is supported by meta-analyses of randomized controlled trials of antidepressants for depression, which consistently show that placebo groups in trials improve about 80 to 90% as much as antidepressant groups on average and that antidepressants are only marginally more effective for depression than placebos. The difference between antidepressants and placebo corresponds to an effect size (SMD) of about 0.3, which in turn equates to about a 2- to 3-point additional improvement on the 0–52-point (HRSD) and 0–60-point (MADRS) depression rating scales used in trials.
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The difference between antidepressants and placebo corresponds to an effect size (SMD) of about 0.3, which in turn equates to about a 2- to 3-point additional improvement on the 0–52-point (HRSD) and 0–60-point (MADRS) depression rating scales used in trials. Differences in effectiveness between different antidepressants are small and not clinically meaningful. The small advantage of antidepressants over placebo is often statistically significant and is the basis for their regulatory approval, but is sufficiently modest that its clinical significance is doubtful. Moreover, the small advantage of antidepressants over placebo may simply be a methodological artifact caused by unblinding due to the psychoactive effects and side effects of antidepressants, in turn resulting in enhanced placebo effects and apparent antidepressant efficacy. Placebos have been found to modify the activity of several brain regions and to increase levels of dopamine and endogenous opioids in the reward pathways.
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The placebo response, or the improvement in scores in the placebo group in clinical trials, is not only due to the placebo effect, but is also due to other phenomena such as spontaneous remission and regression to the mean. Depression tends to have an episodic course, with people eventually recovering even with no medical intervention, and people tend to seek treatment, as well as enroll in clinical trials, when they are feeling their worst. In meta-analyses of trials of depression therapies, Kirsch estimated based on improvement in untreated waiting-list controls that spontaneous remission and regression to the mean only account for about 25% of the improvement in depression scores with antidepressant therapy. However, another academic, Michael P. Hengartner, has argued and presented evidence that spontaneous remission and regression to the mean might actually account for most of the improvement in depression scores with antidepressants, and that the substantial placebo effect observed in clinical trials might largely be a methodological artifact. This suggests that antidepressants may be associated with much less genuine treatment benefit, whether due to the placebo effect or to the antidepressant itself, than has been traditionally assumed.
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It has been proposed that psychedelics used for therapeutic purposes may act as active "super placebos".
Types.
Selective serotonin reuptake inhibitors.
Selective serotonin reuptake inhibitors (SSRIs) are believed to increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the norepinephrine and dopamine transporters.
SSRIs are the most widely prescribed antidepressants in many countries. The efficacy of SSRIs in mild or moderate cases of depression has been disputed.
Serotonin–norepinephrine reuptake inhibitors.
Serotonin–norepinephrine reuptake inhibitors (SNRIs) are potent inhibitors of the reuptake of serotonin and norepinephrine. These neurotransmitters are known to play an important role in mood. SNRIs can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act mostly upon serotonin alone.
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The human serotonin transporter (SERT) and norepinephrine transporter (NET) are membrane proteins that are responsible for the reuptake of serotonin and norepinephrine. Balanced dual inhibition of monoamine reuptake may offer advantages over other antidepressants drugs by treating a wider range of symptoms.
SNRIs are sometimes also used to treat anxiety disorders, obsessive–compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), chronic neuropathic pain, and fibromyalgia syndrome (FMS), and for the relief of menopausal symptoms.
Serotonin modulators and stimulators.
Serotonin modulator and stimulators (SMSs), sometimes referred to more simply as "serotonin modulators", are a type of drug with a multimodal action specific to the serotonin neurotransmitter system. To be precise, SMSs simultaneously modulate one or more serotonin receptors and inhibit the reuptake of serotonin. The term was coined in reference to the mechanism of action of the serotonergic antidepressant vortioxetine, which acts as a serotonin reuptake inhibitor (SRI), a partial agonist of the 5-HT1A receptor, and antagonist of the 5-HT3 and 5-HT7 receptors. However, it can also technically be applied to vilazodone, which is an antidepressant as well and acts as an SRI and 5-HT1A receptor partial agonist.
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An alternative term is serotonin partial agonist/reuptake inhibitor (SPARI), which can be applied only to vilazodone.
Serotonin antagonists and reuptake inhibitors.
Serotonin antagonist and reuptake inhibitors (SARIs) while mainly used as antidepressants are also anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also act as α1-adrenergic receptor antagonists. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds. They include trazodone and nefazodone.
Tricyclic antidepressants.
The majority of the tricyclic antidepressants (TCAs) act primarily as serotonin–norepinephrine reuptake inhibitors (SNRIs) by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), respectively, which results in an elevation of the synaptic concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission. Notably, with the sole exception of amineptine, the TCAs have weak affinity for the dopamine transporter (DAT), and therefore have low efficacy as dopamine reuptake inhibitors (DRIs).
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Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and norepinephrine reuptake inhibitors (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs.
Tetracyclic antidepressants.
Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their chemical structure, which contains four rings of atoms, and are closely related to tricyclic antidepressants (TCAs), which contain three rings of atoms.
Monoamine oxidase inhibitors.
Monoamine oxidase inhibitors (MAOIs) are chemicals that inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression. They are also used in the treatment of Parkinson's disease and several other disorders.
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Because of potentially lethal dietary and drug interactions, MAOIs have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.
MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOIs appear to be particularly effective in the management of bipolar depression according to a retrospective-analysis. There are reports of MAOI efficacy in obsessive–compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports.
MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety disorders.
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NMDA receptor antagonists.
NMDA receptor antagonists like ketamine and esketamine are rapid-acting antidepressants and seem to work via blockade of the ionotropic glutamate NMDA receptor. Other NMDA antagonists may also play a role in treating depression. The combination medication dextromethorphan/bupropion (Auvelity), which contains the NMDA receptor antagonist dextromethorphan, was approved in the United States in 2022 for treating major depressive disorder.
Others.
See the list of antidepressants and management of depression for other drugs that are not specifically characterized.
Adjuncts.
Adjunct medications are an umbrella category of substances that increase the potency or "enhance" antidepressants. They work by affecting variables very close to the antidepressant, sometimes affecting a completely different mechanism of action. This may be attempted when depression treatments have not been successful in the past.
Common types of adjunct medication techniques generally fall into the following categories:
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It is unknown if undergoing psychological therapy at the same time as taking anti-depressants enhances the anti-depressive effect of the medication.
Less common adjuncts.
Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, Lithium dramatically decreases the suicide risk in recurrent depression. There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function.
Psychopharmacologists have also tried adding a stimulant, in particular, D-amphetamine. However, the use of stimulants in cases of treatment-resistant depression is relatively controversial. A review article published in 2007 found psychostimulants may be effective in treatment-resistant depression with concomitant antidepressant therapy, but a more certain conclusion could not be drawn due to substantial deficiencies in the studies available for consideration, and the somewhat contradictory nature of their results.
History.
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The idea of an antidepressant, if melancholy is thought synonymous with depression, existed at least as early as the 1599 pamphlet "A pil to purge melancholie or, A preprative to a pvrgation: or, Topping, copping, and capping: take either or whether: or, Mash them, and squash them, and dash them, and diddle come derrie come daw them, all together..". Thomas d'Urfey's "Wit and Mirth: Or Pills to Purge Melancholy", the title of a large collection of songs, was published between 1698 and 1720.
Before the 1950s, opioids and amphetamines were commonly used as antidepressants. Amphetamine has been described as the first antidepressant. Use of opioids and amphetamines for depression was later restricted due to their addictive nature and side effects. Extracts from the herb St John's wort have been used as a "nerve tonic" to alleviate depression.
St John's wort fell out of favor in most countries through the 19th and 20th centuries, except in Germany, where "Hypericum" extracts were eventually licensed, packaged, and prescribed. Small-scale efficacy trials were carried out in the 1970s and 1980s, and attention grew in the 1990s following a meta-analysis. It remains an over-the-counter (OTC) supplement in most countries. Lead contamination associated with its usage has been seen as concerning, as lead levels in women in the United States taking St. John's wort are elevated by about 20% on average. Research continues to investigate its active component hyperforin, and to further understand its mode of action.
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Isoniazid, iproniazid, and imipramine.
In 1951, Irving Selikoff and Edward H. Robitzek, working out of Sea View Hospital on Staten Island, began clinical trials on two new anti-tuberculosis agents developed by Hoffman-LaRoche, isoniazid, and iproniazid. Only patients with a poor prognosis were initially treated. Nevertheless, their condition improved dramatically. Selikoff and Robitzek noted "a subtle general stimulation ... the patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems." The promise of a cure for tuberculosis in the Sea View Hospital trials was excitedly discussed in the mainstream press.
In 1952, learning of the stimulating side effects of isoniazid, the Cincinnati psychiatrist Max Lurie tried it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved depression in two-thirds of their patients, so they then coined the term "antidepressant" to refer to its action. A similar incident took place in Paris, where Jean Delay, head of psychiatry at Sainte-Anne Hospital, heard of this effect from his pulmonology colleagues at Cochin Hospital. In 1952 (before Lurie and Salzer), Delay, with the resident Jean-Francois Buisson, reported the positive effect of isoniazid on depressed patients. The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of diamine oxidase, coupled with a weak inhibition of monoamine oxidase A.
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Selikoff and Robitzek also experimented with another anti-tuberculosis drug, iproniazid; it showed a greater psychostimulant effect, but more pronounced toxicity. Later, Jackson Smith, Gordon Kamman, George E. Crane, and Frank Ayd, described the psychiatric applications of iproniazid. Ernst Zeller found iproniazid to be a potent monoamine oxidase inhibitor. Nevertheless, iproniazid remained relatively obscure until Nathan S. Kline, the influential head of research at Rockland State Hospital, began to popularize it in the medical and popular press as a "psychic energizer". Roche put a significant marketing effort behind iproniazid. Its sales grew until it was recalled in 1961, due to reports of lethal hepatotoxicity.
The antidepressant effect of a tricyclic antidepressant, a three-ringed compound, was first discovered in 1957 by Roland Kuhn in a Swiss psychiatric hospital. Antihistamine derivatives were used to treat surgical shock and later as neuroleptics. Although in 1955, reserpine was shown to be more effective than a placebo in alleviating anxious depression, neuroleptics were being developed as sedatives and antipsychotics.
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Attempting to improve the effectiveness of chlorpromazine, Kuhn in conjunction with the Geigy Pharmaceutical Company discovered the compound "G 22355", later renamed imipramine. Imipramine had a beneficial effect on patients with depression who showed mental and motor retardation. Kuhn described his new compound as a "thymoleptic" "taking hold of the emotions," in contrast with neuroleptics, "taking hold of the nerves" in 1955–56. These gradually became established, resulting in the patent and manufacture in the US in 1951 by Häfliger and SchinderA.
Antidepressants became prescription drugs in the 1950s. It was estimated that no more than fifty to one hundred individuals per million had the kind of depression that these new drugs would treat, and pharmaceutical companies were not enthusiastic about marketing for this small market. Sales through the 1960s remained poor compared to the sales of tranquilizers, which were being marketed for different uses. Imipramine remained in common use and numerous successors were introduced. The use of monoamine oxidase inhibitors (MAOI) increased after the development and introduction of "reversible" forms affecting only the MAO-A subtype of inhibitors, making this drug safer to use.
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By the 1960s, it was thought that the mode of action of tricyclics was to inhibit norepinephrine reuptake. However, norepinephrine reuptake became associated with stimulating effects. Later tricyclics were thought to affect serotonin as proposed in 1969 by Carlsson and Lindqvist as well as Lapin and Oxenkrug.
Second-generation antidepressants.
Researchers began a process of rational drug design to isolate antihistamine-derived compounds that would selectively target these systems. The first such compound to be patented was zimelidine in 1971, while the first released clinically was indalpine. Fluoxetine was approved for commercial use by the US Food and Drug Administration (FDA) in 1988, becoming the first blockbuster SSRI. Fluoxetine was developed at Eli Lilly and Company in the early 1970s by Bryan Molloy, Klaus Schmiegel, David T. Wong, and others. SSRIs became known as "novel antidepressants" along with other newer drugs such as SNRIs and NRIs with various selective effects.
Rapid-acting antidepressants.
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Esketamine (brand name Spravato), the first rapid-acting antidepressant to be approved for clinical treatment of depression, was introduced for this indication in March 2019 in the United States.
Research.
A 2016 randomized controlled trial evaluated the rapid antidepressant effects of the psychedelic Ayahuasca in treatment-resistant depression with a positive outcome. In 2018, the FDA granted Breakthrough Therapy Designation for psilocybin-assisted therapy for treatment-resistant depression and in 2019, the FDA granted Breakthrough Therapy Designation for psilocybin therapy treating major depressive disorder.
Publication bias and aged research.
A 2018 systematic review published in The Lancet comparing the efficacy of 21 different first and second generation antidepressants found that antidepressant drugs tended to perform better and cause less adverse events when they were novel or experimental treatments compared to when they were evaluated again years later. Unpublished data was also associated with smaller positive effect sizes. However, the review did not find evidence of bias associated with industry funded research.
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Society and culture.
Prescription trends.
United Kingdom.
In the UK, figures reported in 2010 indicated that the number of antidepressants prescribed by the National Health Service (NHS) almost doubled over a decade. Further analysis published in 2014 showed that number of antidepressants dispensed annually in the community went up by 25 million in the 14 years between 1998 and 2012, rising from 15 million to 40 million. Nearly 50% of this rise occurred in the four years after the Great Recession, during which time the annual increase in prescriptions rose from 6.7% to 8.5%. These sources also suggest that aside from the recession, other factors that may influence changes in prescribing rates may include: improvements in diagnosis, a reduction of the stigma surrounding mental health, broader prescribing trends, GP characteristics, geographical location, and housing status. Another factor that may contribute to increasing consumption of antidepressants is the fact that these medications now are used for other conditions including social anxiety and post-traumatic stress disorder.
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Between 2005 and 2017, the number of adolescents (12 to 17 years) in England who were prescribed antidepressants has doubled. On the other hand, antidepressant prescriptions for children aged 5–11 in England decreased between 1999 and 2017. From April 2015, prescriptions increased for both age groups (for people aged 0 to 17) and peaked during the first COVID lockdown in March 2020.
According to National Institute for Health and Care Excellence (NICE) guidelines, antidepressants for children and adolescents with depression and obsessive-compulsive disorder (OCD) should be prescribed together with therapy and after being assessed by a child and adolescent psychiatrist. However, between 2006 and 2017, only 1 in 4 of 12–17 year-olds who were prescribed an SSRI by their GP had seen a specialist psychiatrist and 1 in 6 has seen a pediatrician. Half of these prescriptions were for depression and 16% for anxiety, the latter not being licensed for treatment with antidepressants. Among the suggested possible reasons why GPs are not following the guidelines are the difficulties of accessing talking therapies, long waiting lists, and the urgency of treatment. According to some researchers, strict adherence to treatment guidelines would limit access to effective medication for young people with mental health problems.
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United States.
In the United States, antidepressants were the most commonly prescribed medication in 2013. Of the estimated 16 million "long term" (over 24 months) users, roughly 70 percent are female. , about 16.5% of white people in the United States took antidepressants compared with 5.6% of black people in the United States.
United States: The most commonly prescribed antidepressants in the US retail market in 2010 were:
Netherlands: In the Netherlands, paroxetine is the most prescribed antidepressant, followed by amitriptyline, citalopram and venlafaxine.
Adherence.
, worldwide, 30% to 60% of people did not follow their practitioner's instructions about taking their antidepressants, and in the US, it appeared that around 50% of people did not take their antidepressants as directed by their practitioner.
When people fail to take their antidepressants, there is a greater risk that the drug will not help, that symptoms get worse, that they miss work or are less productive at work, and that the person may be hospitalized.
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Social science perspective.
Some academics have highlighted the need to examine the use of antidepressants and other medical treatments in cross-cultural terms, because various cultures prescribe and observe different manifestations, symptoms, meanings, and associations of depression and other medical conditions within their populations. These cross-cultural discrepancies, it has been argued, then have implications on the perceived efficacy and use of antidepressants and other strategies in the treatment of depression in these different cultures. In India, antidepressants are largely seen as tools to combat marginality, promising the individual the ability to reintegrate into society through their use—a view and association not observed in the West.
Environmental impacts.
Because most antidepressants function by inhibiting the reuptake of neurotransmitters serotonin, dopamine, and norepinephrine these drugs can interfere with natural neurotransmitter levels in other organisms impacted by indirect exposure. Antidepressants fluoxetine and sertraline have been detected in aquatic organisms residing in effluent-dominated streams. The presence of antidepressants in surface waters and aquatic organisms has caused concern because ecotoxicological effects on aquatic organisms due to fluoxetine exposure have been demonstrated.
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Coral reef fish have been demonstrated to modulate aggressive behavior through serotonin. Artificially increasing serotonin levels in crustaceans can temporarily reverse social status and turn subordinates into aggressive and territorial dominant males.
Exposure to Fluoxetine has been demonstrated to increase serotonergic activity in fish, subsequently reducing aggressive behavior. Perinatal exposure to Fluoxetine at relevant environmental concentrations has been shown to lead to significant modifications of memory processing in 1-month-old cuttlefish. This impairment may disadvantage cuttlefish and decrease their survival. Somewhat less than 10% of orally administered Fluoxetine is excreted from humans unchanged or as glucuronide.
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Auger effect
The Auger effect (; ) or Auger−Meitner effect is a physical phenomenon in which atoms eject electrons. It occurs when an inner-shell vacancy in an atom is filled by an electron, releasing energy that causes the emission of another electron from a different shell of the same atom.
When a core electron is removed, leaving a vacancy, an electron from a higher energy level may fall into the vacancy, resulting in a release of energy. For light atoms (Z<12), this energy is most often transferred to a valence electron which is subsequently ejected from the atom. This second ejected electron is called an Auger electron. For heavier atomic nuclei, the release of the energy in the form of an emitted photon becomes gradually more probable.
Effect.
Upon ejection, the kinetic energy of the Auger electron corresponds to the difference between the energy of the initial electronic transition into the vacancy and the ionization energy for the electron shell from which the Auger electron was ejected. These energy levels depend on the type of atom and the chemical environment in which the atom was located.
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Auger electron spectroscopy involves the emission of Auger electrons by bombarding a sample with either X-rays or energetic electrons and measures the intensity of Auger electrons that result as a function of the Auger electron energy. The resulting spectra can be used to determine the identity of the emitting atoms and some information about their environment.
Auger recombination is a similar Auger effect which occurs in semiconductors. An electron and electron hole (electron-hole pair) can recombine giving up their energy to an electron in the conduction band, increasing its energy. The reverse effect is known as impact ionization.
The Auger effect can impact biological molecules such as DNA. Following the K-shell ionization of the component atoms of DNA, Auger electrons are ejected leading to damage of its sugar-phosphate backbone.
Discovery.
The Auger emission process was observed and published in 1922 by Lise Meitner, an Austrian-Swedish physicist, as a side effect in her competitive search for the nuclear beta electrons with the British physicist Charles Drummond Ellis.
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The French physicist Pierre Victor Auger independently discovered it in 1923 upon analysis of a Wilson cloud chamber experiment and it became the central part of his PhD work. High-energy X-rays were applied to ionize gas particles and observe photoelectric electrons. The observation of electron tracks that were independent of the frequency of the incident photon suggested a mechanism for electron ionization that was caused from an internal conversion of energy from a radiationless transition. Further investigation, and theoretical work using elementary quantum mechanics and transition rate/transition probability calculations, showed that the effect was a radiationless effect more than an internal conversion effect.
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Akio Morita
was a Japanese entrepreneur and co-founder of Sony along with Masaru Ibuka.
Early life.
Akio Morita was born in Nagoya. Morita's family was involved in sake, miso and soy sauce production in the village of Kosugaya (currently a part of Tokoname City) on the western coast of Chita Peninsula in Aichi Prefecture since 1665. He was the oldest of four siblings and his father Kyuzaemon trained him as a child to take over the family business. Akio, however, found his true calling in mathematics and physics, and in 1944 he graduated from Osaka Imperial University with a degree in physics. He was later commissioned as a sub-lieutenant in the Imperial Japanese Navy, and served in World War II. During his service, Morita met his future business partner Masaru Ibuka at a study group for developing infrared-guided bombs (Ke-Go) in the Navy's Wartime Research Committee.
Sony.
In September 1945, Ibuka founded a radio repair shop in the bombed out Shirokiya Department Store in Nihonbashi, Tokyo. Morita saw a newspaper article about Ibuka's new venture and, after some correspondence, chose to join him in Tokyo. With funding from Morita's father, they co-founded "Tokyo Tsushin Kogyo Kabushiki Kaisha" (Tokyo Telecommunications Engineering Corporation, the forerunner of Sony Corporation) in 1946 with about 20 employees and initial capital of ¥190,000.
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In 1949, the company developed magnetic recording tape and, in 1950, sold the first tape recorder in Japan. Ibuka was instrumental in securing the licensing of transistor technology from Bell Labs to Sony in the 1950s, thus making Sony one of the first companies to apply transistor technology to non-military uses. In 1957, the company produced a pocket-sized radio (the first to be fully transistorized), and in 1958, Morita and Ibuka decided to rename their company Sony (derived from "sonus"—Latin for "sound"—and "sonny", a then-common American expression). Morita was an advocate for all the products made by Sony. However, since the radio was slightly too big to fit in a shirt pocket, Morita made his employees wear shirts with slightly larger pockets to give the radio a "pocket sized" appearance.
Morita founded Sony Corporation of America (SONAM, currently abbreviated as SCA) in 1960. In the process, he was struck by the mobility of employees between American companies, which was unheard of in Japan at that time. When he returned to Japan, he encouraged experienced, middle-aged employees of other companies to reevaluate their careers and consider joining Sony. The company filled many positions in this manner, and inspired other Japanese companies to do the same. In 1961, Sony Corporation was the first Japanese company to be listed on the New York Stock Exchange, in the form of American depositary receipts (ADRs).
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In March 1968, Morita set up a joint venture in Japan between Sony and CBS Records, with him as president, to manufacture "software" for Sony's hardware.
Morita became president of Sony in 1971, taking over from Ibuka who had served from 1950 to 1971. In 1975, Sony released the first Betamax home videocassette recorder, a year before the VHS format came out.
Ibuka retired in 1976 and Morita was named chairman of the company. In 1979, the Walkman was introduced, making it one of the world's first portable music players and in 1982, Sony launched the world's first compact disc player, the Sony CDP-101, with a compact disc (CD) itself, a new data storage format Sony and Philips co-developed. In that year, a 3.5-inch floppy disk structure was introduced by Sony, and it soon became the defacto standard. In 1984, Sony launched the Discman series, which extended their Walkman brand to portable CD products.
Under the vision of Morita, the company aggressively expanded into new businesses. Part of its motivation for doing so was the pursuit of "convergence", linking film, music and digital electronics. Twenty years after setting up a joint venture with CBS Records in Japan, Sony bought CBS Records Group which consisted of Columbia Records, Epic Records and other CBS labels. In 1989, they acquired Columbia Pictures Entertainment (Columbia Pictures, TriStar Pictures and others).
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Norio Ohga, who had joined the company in the 1950s after sending Morita a letter denouncing the poor quality of the company's tape recorders, succeeded Morita as chief executive officer in 1989.
Morita suffered a cerebral hemorrhage in 1993 while playing tennis and on November 25, 1994, stepped down as Sony chairman to be succeeded by Ohga.
Other affiliations.
Morita was vice chairman of the Japan Business Federation (Japan Federation of Economic Organizations), and was a member of the Japan-U.S. Economic Relations Group, also known as the "Wise Men's Group". He helped General Motors with its acquisition of an interest in Isuzu in 1972. He was the third Japanese chairman of the Trilateral Commission. His amateur radio call sign is JP1DPJ.
Publications.
In 1966, Morita wrote a book called "Gakureki Muyō Ron" (学歴無用論, Never Mind School Records), where he stresses that school records are not important to success or one's business skills. In 1986, Morita wrote an autobiography titled "Made in Japan". He co-authored the 1991 book "The Japan That Can Say No" with politician Shintaro Ishihara, where they criticized American business practices and encouraged Japanese to take a more independent role in business and foreign affairs. (Actually, Morita had no intention to criticize American practices at that time.) The book was translated into English and caused controversy in the United States, and Morita later had his chapters removed from the English version and distanced himself from the book.
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Awards and honours.
In 1972, Morita received the Golden Plate Award of the American Academy of Achievement. Morita was awarded the Albert Medal by the United Kingdom's Royal Society of Arts in 1982, the first Japanese to receive the honor. Two years later, he received the prestigious Legion of Honour, and in 1991, was awarded the First Class Order of the Sacred Treasure from the Emperor of Japan. He was elected to the American Philosophical Society in 1992 and the American Academy of Arts and Sciences in 1993. That same year, he was awarded an honorary British knighthood (KBE). Morita received the International Distinguished Entrepreneur Award from the University of Manitoba in 1987. In 1998, he was the only Asian person on "Time" magazine's list of the 20 most influential business people of the 20th century as part of their . He was posthumously awarded the Grand Cordon of the Order of the Rising Sun in 1999. In 2003, Anaheim University's Graduate School of Business was renamed the Akio Morita School of Business in his honor. The Morita family's support for the program led to the growth of the Anaheim University Akio Morita School of Business in Tokyo, Japan.
Death.
Morita, who loved to play golf and tennis, suffered a stroke in 1993, during a game of tennis. The stroke weakened him and left him in a wheelchair. On November 25, 1994, he stepped down as Sony chairman. On October 3, 1999, Morita died of pneumonia at the age of 78 in a Tokyo hospital, where he had been admitted since August 1999.
External links.
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Anode
An anode usually is an electrode of a polarized electrical device through which conventional current enters the device. This contrasts with a cathode, which is usually an electrode of the device through which conventional current leaves the device. A common mnemonic is ACID, for "anode current into device". The direction of conventional current (the flow of positive charges) in a circuit is opposite to the direction of electron flow, so (negatively charged) electrons flow from the anode of a galvanic cell, into an outside or external circuit connected to the cell. For example, the end of a household battery marked with a "+" is the cathode (while discharging).
In both a galvanic cell and an electrolytic cell, the anode is the electrode at which the oxidation reaction occurs. In a galvanic cell the anode is the wire or plate having excess negative charge as a result of the oxidation reaction. In an electrolytic cell, the anode is the wire or plate upon which excess positive charge is imposed. As a result of this, anions will tend to move towards the anode where they will undergo oxidation.
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Historically, the anode of a galvanic cell was also known as the zincode because it was usually composed of zinc.
Charge flow.
The terms anode and cathode are not defined by the voltage polarity of electrodes, but are usually defined by the direction of current through the electrode. An anode usually is the electrode of a device through which conventional current (positive charge) flows into the device from an external circuit, while a cathode usually is the electrode through which conventional current flows out of the device.
In general, if the current through the electrodes reverses direction, as occurs for example in a rechargeable battery when it is being charged, the roles of the electrodes as anode and cathode are reversed. However, the definition of anode and cathode is different for electrical devices such as diodes and vacuum tubes where the electrode naming is fixed and does not depend on the actual charge flow (current). These devices usually allow substantial current flow in one direction but negligible current in the other direction. Therefore, the electrodes are named based on the direction of this "forward" current. In a diode the anode is the terminal through which current enters and the cathode is the terminal through which current leaves, when the diode is forward biased. The names of the electrodes do not change in cases where reverse current flows through the device. Similarly, in a vacuum tube only one electrode can thermionically emit electrons into the evacuated tube, so electrons can only enter the device from the external circuit through the heated electrode. Therefore, this electrode is permanently named the cathode, and the electrode through which the electrons exit the tube is named the anode.
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Conventional current depends not only on the direction the charge carriers move, but also the carriers' electric charge. The currents outside the device are usually carried by electrons in a metal conductor. Since electrons have a negative charge, the direction of electron flow is opposite to the direction of conventional current. Consequently, electrons leave the device through the anode and enter the device through the cathode.
Examples.
The polarity of voltage on an anode with respect to an associated cathode varies depending on the device type and on its operating mode. In the following examples, the anode is negative in a device that provides power, and positive in a device that consumes power:
In a discharging battery or galvanic cell (diagram on left), the anode is the negative terminal: it is where conventional current flows into the cell. This inward current is carried externally by electrons moving outwards.
In a recharging battery, or an electrolytic cell, the anode is the positive terminal imposed by an external source of potential difference. The current through a recharging battery is opposite to the direction of current during discharge; in other words, the electrode which was the cathode during battery discharge becomes the anode while the battery is recharging.
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In battery engineering, it is common to designate one electrode of a rechargeable battery the anode and the other the cathode according to the roles the electrodes play when the battery is discharged. This is despite the fact that the roles are reversed when the battery is charged. When this is done, "anode" simply designates the negative terminal of the battery and "cathode" designates the positive terminal.
In a diode, the anode is the terminal represented by the tail of the arrow symbol (flat side of the triangle), where conventional current flows into the device. Note the electrode naming for diodes is always based on the direction of the forward current (that of the arrow, in which the current flows "most easily"), even for types such as Zener diodes or solar cells where the current of interest is the reverse current.
In vacuum tubes or gas-filled tubes, the anode is the terminal where current enters the tube.
Etymology.
The word was coined in 1834 from the Greek ἄνοδος ("anodos"), 'ascent', by William Whewell, who had been consulted by Michael Faraday over some new names needed to complete a paper on the recently discovered process of electrolysis. In that paper Faraday explained that when an electrolytic cell is oriented so that electric current traverses the "decomposing body" (electrolyte) in a direction "from East to West, or, which will strengthen this help to the memory, that in which the sun appears to move", the anode is where the current enters the electrolyte, on the East side: ""ano" upwards, "odos" a way; the way which the sun rises".
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The use of 'East' to mean the 'in' direction (actually 'in' → 'East' → 'sunrise' → 'up') may appear contrived. Previously, as related in the first reference cited above, Faraday had used the more straightforward term "eisode" (the doorway where the current enters). His motivation for changing it to something meaning 'the East electrode' (other candidates had been "eastode", "oriode" and "anatolode") was to make it immune to a possible later change in the direction convention for current, whose exact nature was not known at the time. The reference he used to this effect was the Earth's magnetic field direction, which at that time was believed to be invariant. He fundamentally defined his arbitrary orientation for the cell as being that in which the internal current would run parallel to and in the same direction as a hypothetical magnetizing current loop around the local line of latitude which would induce a magnetic dipole field oriented like the Earth's. This made the internal current East to West as previously mentioned, but in the event of a later convention change it would have become West to East, so that the East electrode would not have been the 'way in' any more. Therefore, "eisode" would have become inappropriate, whereas "anode" meaning 'East electrode' would have remained correct with respect to the unchanged direction of the actual phenomenon underlying the current, then unknown but, he thought, unambiguously defined by the magnetic reference. In retrospect the name change was unfortunate, not only because the Greek roots alone do not reveal the anode's function any more, but more importantly because as we now know, the Earth's magnetic field direction on which the "anode" term is based is subject to reversals whereas the current direction convention on which the "eisode" term was based has no reason to change in the future.
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Since the later discovery of the electron, an easier to remember and more durably correct technically although historically false, etymology has been suggested: anode, from the Greek "anodos", 'way up', 'the way (up) out of the cell (or other device) for electrons'.
Electrolytic anode.
In electrochemistry, the "anode" is where oxidation occurs and is the positive polarity contact in an electrolytic cell. At the anode, anions (negative ions) are forced by the electrical potential to react chemically and give off electrons (oxidation) which then flow up and into the driving circuit. Mnemonics: LEO Red Cat (Loss of Electrons is Oxidation, Reduction occurs at the Cathode), or AnOx Red Cat (Anode Oxidation, Reduction Cathode), or OIL RIG (Oxidation is Loss, Reduction is Gain of electrons), or Roman Catholic and Orthodox (Reduction – Cathode, anode – Oxidation), or LEO the lion says GER (Losing electrons is Oxidation, Gaining electrons is Reduction).
This process is widely used in metals refining. For example, in copper refining, copper anodes, an intermediate product from the furnaces, are electrolysed in an appropriate solution (such as sulfuric acid) to yield high purity (99.99%) cathodes. Copper cathodes produced using this method are also described as electrolytic copper.
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Historically, when non-reactive anodes were desired for electrolysis, graphite (called plumbago in Faraday's time) or platinum were chosen. They were found to be some of the least reactive materials for anodes. Platinum erodes very slowly compared to other materials, and graphite crumbles and can produce carbon dioxide in aqueous solutions but otherwise does not participate in the reaction.
Battery or galvanic cell anode.
In a battery or galvanic cell, the anode is the negative electrode from which electrons flow out towards the external part of the circuit. Internally the positively charged cations are flowing away from the anode (even though it is negative and therefore would be expected to attract them, this is due to electrode potential relative to the electrolyte solution being different for the anode and cathode metal/electrolyte systems); but, external to the cell in the circuit, electrons are being pushed out through the negative contact and thus through the circuit by the voltage potential as would be expected.
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Battery manufacturers may regard the negative electrode as the anode, particularly in their technical literature. Though from an electrochemical viewpoint incorrect, it does resolve the problem of which electrode is the anode in a secondary (or rechargeable) cell. Using the traditional definition, the anode switches ends between charge and discharge cycles.
Vacuum tube anode.
In electronic vacuum devices such as a cathode-ray tube, the anode is the positively charged electron collector. In a tube, the anode is a charged positive plate that collects the electrons emitted by the cathode through electric attraction. It also accelerates the flow of these electrons.
Diode anode.
In a semiconductor diode, the anode is the P-doped layer which initially supplies holes to the junction. In the junction region, the holes supplied by the anode combine with electrons supplied from the N-doped region, creating a depleted zone. As the P-doped layer supplies holes to the depleted region, negative dopant ions are left behind in the P-doped layer ('P' for positive charge-carrier ions). This creates a base negative charge on the anode. When a positive voltage is applied to anode of the diode from the circuit, more holes are able to be transferred to the depleted region, and this causes the diode to become conductive, allowing current to flow through the circuit. The terms anode and cathode should not be applied to a Zener diode, since it allows flow in either direction, depending on the polarity of the applied potential (i.e. voltage).
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Sacrificial anode.
In cathodic protection, a metal anode that is more reactive to the corrosive environment than the metal system to be protected is electrically linked to the protected system. As a result, the metal anode partially corrodes or dissolves instead of the metal system. As an example, an iron or steel ship's hull may be protected by a zinc sacrificial anode, which will dissolve into the seawater and prevent the hull from being corroded. Sacrificial anodes are particularly needed for systems where a static charge is generated by the action of flowing liquids, such as pipelines and watercraft. Sacrificial anodes are also generally used in tank-type water heaters.
In 1824 to reduce the impact of this destructive electrolytic action on ships hulls, their fastenings and underwater equipment, the scientist-engineer Humphry Davy developed the first and still most widely used marine electrolysis protection system. Davy installed sacrificial anodes made from a more electrically reactive (less noble) metal attached to the vessel hull and electrically connected to form a cathodic protection circuit.
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A less obvious example of this type of protection is the process of galvanising iron. This process coats iron structures (such as fencing) with a coating of zinc metal. As long as the zinc remains intact, the iron is protected from the effects of corrosion. Inevitably, the zinc coating becomes breached, either by cracking or physical damage. Once this occurs, corrosive elements act as an electrolyte and the zinc/iron combination as electrodes. The resultant current ensures that the zinc coating is sacrificed but that the base iron does not corrode. Such a coating can protect an iron structure for a few decades, but once the protecting coating is consumed, the iron rapidly corrodes.
If, conversely, tin is used to coat steel, when a breach of the coating occurs it actually accelerates oxidation of the iron.
Impressed current anode.
Another cathodic protection is used on the impressed current anode. It is made from titanium and covered with mixed metal oxide. Unlike the sacrificial anode rod, the impressed current anode does not sacrifice its structure. This technology uses an external current provided by a DC source to create the cathodic protection. Impressed current anodes are used in larger structures like pipelines, boats, city water tower, water heaters and more.
Related antonym.
The opposite of an anode is a cathode. When the current through the device is reversed, the electrodes switch functions, so the anode becomes the cathode and the cathode becomes anode, as long as the reversed current is applied. The exception is diodes where electrode naming is always based on the forward current direction.
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Analog television
Analog television is the original television technology that uses analog signals to transmit video and audio. In an analog television broadcast, the brightness, colors and sound are represented by amplitude, phase and frequency of an analog signal.
Analog signals vary over a continuous range of possible values which means that electronic noise and interference may be introduced. Thus with analog, a moderately weak signal becomes snowy and subject to interference. In contrast, picture quality from a digital television (DTV) signal remains good until the signal level drops below a threshold where reception is no longer possible or becomes intermittent.
Analog television may be wireless (terrestrial television and satellite television) or can be distributed over a cable network as cable television.
All broadcast television systems used analog signals before the arrival of DTV. Motivated by the lower bandwidth requirements of compressed digital signals, beginning just after the year 2000, a digital television transition is proceeding in most countries of the world, with different deadlines for the cessation of analog broadcasts. Several countries have made the switch already, with the remaining countries still in progress mostly in Africa, Asia, and South America.
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Development.
The earliest systems of analog television were mechanical television systems that used spinning disks with patterns of holes punched into the disc to scan an image. A similar disk reconstructed the image at the receiver. Synchronization of the receiver disc rotation was handled through sync pulses broadcast with the image information. Camera systems used similar spinning discs and required intensely bright illumination of the subject for the light detector to work. The reproduced images from these mechanical systems were dim, very low resolution and flickered severely.
Analog television did not begin in earnest as an industry until the development of the cathode-ray tube (CRT), which uses a focused electron beam to trace lines across a phosphor coated surface. The electron beam could be swept across the screen much faster than any mechanical disc system, allowing for more closely spaced scan lines and much higher image resolution. Also, far less maintenance was required of an all-electronic system compared to a mechanical spinning disc system. All-electronic systems became popular with households after World War II.
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Standards.
Broadcasters of analog television encode their signal using different systems. The official systems of transmission were defined by the ITU in 1961 as: A, B, C, D, E, F, G, H, I, K, K1, L, M and N. These systems determine the number of scan lines, frame rate, channel width, video bandwidth, video-audio separation, and so on. A color encoding scheme (NTSC, PAL, or SECAM) could be added to the base monochrome signal. Using RF modulation the signal is then modulated onto a very high frequency (VHF) or ultra high frequency (UHF) carrier wave. Each frame of a television image is composed of scan lines drawn on the screen. The lines are of varying brightness; the whole set of lines is drawn quickly enough that the human eye perceives it as one image. The process repeats and the next sequential frame is displayed, allowing the depiction of motion. The analog television signal contains timing and synchronization information so that the receiver can reconstruct a two-dimensional moving image from a one-dimensional time-varying signal.
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The first commercial television systems were black-and-white; the beginning of color television was in the 1950s.
A practical television system needs to take luminance, chrominance (in a color system), synchronization (horizontal and vertical), and audio signals, and broadcast them over a radio transmission. The transmission system must include a means of television channel selection.
Analog broadcast television systems come in a variety of frame rates and resolutions. Further differences exist in the frequency and modulation of the audio carrier. The monochrome combinations still existing in the 1950s were standardized by the International Telecommunication Union (ITU) as capital letters A through N. When color television was introduced, the chrominance information was added to the monochrome signals in a way that black and white televisions ignore. In this way backward compatibility was achieved.
There are three standards for the way the additional color information can be encoded and transmitted. The first was the American NTSC system. The European and Australian PAL and the French and former Soviet Union SECAM standards were developed later and attempt to cure certain defects of the NTSC system. PAL's color encoding is similar to the NTSC systems. SECAM, though, uses a different modulation approach than PAL or NTSC. PAL had a late evolution called PALplus, allowing widescreen broadcasts while remaining fully compatible with existing PAL equipment.
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In principle, all three color encoding systems can be used with any scan line/frame rate combination. Therefore, in order to describe a given signal completely, it is necessary to quote the color system plus the broadcast standard as a capital letter. For example, the United States, Canada, Mexico and South Korea used (or use) NTSC-M, Japan used NTSC-J, the UK used PAL-I, France used SECAM-L, much of Western Europe and Australia used (or use) PAL-B/G, most of Eastern Europe uses SECAM-D/K or PAL-D/K and so on.
Not all of the possible combinations exist. NTSC is only used with system M, even though there were experiments with NTSC-A (405 line) in the UK and NTSC-N (625 line) in part of South America. PAL is used with a variety of 625-line standards (B, G, D, K, I, N) but also with the North American 525-line standard, accordingly named PAL-M. Likewise, SECAM is used with a variety of 625-line standards.
For this reason, many people refer to any 625/25 type signal as "PAL" and to any 525/30 signal as "NTSC", even when referring to digital signals; for example, on DVD-Video, which does not contain any analog color encoding, and thus no PAL or NTSC signals at all.
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