title: It Happened One Night

text: It has garnered critical acclaim and is widely hailed one of the greatest films ever made". It Happened One Night" is the first of only three films (along with "One Flew Over the Cuckoo's Nest" and "The Silence of the Lambs") to win all five major Academy Awards: Best Picture, Best Director, Best Actor, Best Actress, and Best Adapted Screenplay. In 1993, it was selected for preservation in the US National Film Registry by the Library of Congress, being deemed "culturally, historically, or aesthetically significant". In 2013, the film underwent an extensive restoration by Sony Pictures.


title: It Happened One Night

text: Spoiled heiress Ellen "Ellie" Andrews has eloped with pilot and fortune-hunter King Westley against the wishes of her extremely wealthy father, Alexander Andrews, who wants to have the marriage annulled because he knows that Westley is really interested only in Ellie's money. Jumping ship in Florida, Ellie runs away and boards a Greyhound bus to New York City to reunite with her husband. She meets fellow passenger Peter Warne, a newspaper reporter who recently lost his job. Soon, Peter recognizes her and gives her a choice. If she gives him an exclusive on her story, he will help her reunite with Westley. If not, he will tell her father where she is. Ellie agrees to help.


title: It Happened One Night

text: As they go through several adventures, Ellie loses her initial disdain for Peter and they begin to fall in love. When the bus breaks down and they begin hitchhiking, they fail to secure a ride until Ellie displays a shapely leg to Danker, the next driver. When they stop en route, Danker tries to steal their luggage but Peter chases him down and seizes his Model T. Near the end of their journey, Ellie confesses her love to Peter. The owners of the motel in which they stay notice that Peter's car is gone and then expel Ellie. Believing Peter has deserted her, Ellie telephones her father, who agrees to let her marry Westley. Meanwhile, Peter has obtained money from his editor to marry Ellie but he misses her on the road. Although Ellie has no desire to be with Westley, she believes that Peter has betrayed her for the reward money and so agrees to have a second, formal wedding with Westley.


title: It Happened One Night

text: On the wedding day, she finally reveals the whole story to her father. When Peter comes to Ellie's home, Andrews offers him the reward money, but Peter insists on being paid only his expenses, a paltry $39.60 for items that he had been forced to sell to buy gasoline. When Andrews presses Peter for an explanation of his odd behavior and demands to know if he loves her, Peter first tries to dodge the questions but then admits that he loves Ellie and storms out. Westley arrives for his wedding via an autogyro, but at the ceremony, Andrews reveals to his daughter about Peter's refusal of the reward money and tells her that her car is waiting by the back gate in case she changes her mind. At the last minute, just before she says "I do", she decides not to go through with the wedding. Ellie dumps Westley at the altar, bolts for her car, and drives away as the newsreel cameras crank.


title: It Happened One Night

text: A few days later, Andrews is working at his desk when Westley calls to tell him that he will take the financial settlement and not contest the annulment. His executive assistant brings him a telegram from Peter: "What's holding up the annulment, you slowpoke? The walls of Jericho are toppling!" That is a reference to a makeshift wall made of a blanket hung over a rope that was tied across the rooms separating the beds they had slept in, in order to give them each privacy while traveling together. With the annulment in hand, Andrews sends the reply, "Let 'em topple."


title: It Happened One Night

text: The last scene has Peter's battered Model T parked in a motor court in Glen Falls, Michigan. The mom-and-pop owners talk and wonder why, on such a warm night, the newlyweds (he had seen the marriage license) wanted a clothesline, an extra blanket, and the little tin trumpet that he had gotten for them. As they look at the cabin, the toy trumpet sounds a fanfare, the blanket falls to the floor, and the lights in the cabin go out.


title: It Happened One Night

text: Neither Gable nor Colbert was the first choice to play the lead roles. Miriam Hopkins rejected the part of Ellie. Robert Montgomery and Myrna Loy were then offered the roles, but both turned down the script. Loy later noted that the final story as filmed bore little resemblance to the script that she and Montgomery had been given. Margaret Sullavan also rejected the part. Constance Bennett was willing to accept the role if she could produce the film herself but Columbia Pictures would not agree to that condition. Bette Davis then wanted the role but she was under contract with Warner Brothers and Jack L. Warner refused to lend her. Carole Lombard was unable to accept because Columbia's proposed filming schedule would conflict with her work on "Bolero" at Paramount. Loretta Young also turned it down.


title: It Happened One Night

text: Harry Cohn suggested Colbert, who initially turned down the role. Her first film, "For the Love of Mike" (1927), had been directed by Capra and was such a disaster that neither wanted to work with the other again. Later, she agreed to the role only if her salary was doubled to $50,000 and if her scenes were completed in four weeks so that she could take a planned vacation.


title: It Happened One Night

text: According to Hollywood legend, Gable was lent to Columbia Pictures, then considered a minor studio, as punishment for refusing a role at his own studio. That tale has been partially refuted by more recent biographies. Metro-Goldwyn-Mayer did not have a project ready for Gable and the studio was paying him his contracted salary of $2,000 per week whether he worked or not. Louis B. Mayer lent him to Columbia for $2,500 per week, hence netting MGM $500 per week while he was gone. Capra, however, insisted that Gable was a reluctant participant in the film.


title: It Happened One Night

text: Filming began in a tense atmosphere as Gable and Colbert were dissatisfied with the quality of the script. Capra understood their dissatisfaction and let screenwriter Robert Riskin rewrite it. Colbert continued to show her displeasure on the set. She also initially balked at pulling up her skirt to entice a passing driver to provide a ride, complaining that it was unladylike. Upon seeing the chorus girl who was brought in as her body double, an outraged Colbert told the director, "Get her out of here. I'll do it. That's not my leg!" Capra claimed that Colbert "had many little tantrums, motivated by her antipathy toward me," however, "she was wonderful in the part." Part of the film was made on Thousand Oaks Boulevard in Thousand Oaks, California.


title: It Happened One Night

text: In 2013 "It Happened One Night" was digitally restored. A new wet-gate master was produced by Sony Colorworks for scanning at 4K. The images were digitally treated at Prasad Corporation to remove dirt, tears, scratches, and other artifacts. Care was taken to preserve the original look of the film.


title: It Happened One Night

text: After filming was done, Colbert complained to her friend, "I just finished the worst picture in the world". Columbia appeared to have low expectations for the film and did not mount much of an advertising campaign for it. Initial reviews were generally positive, Mordaunt Hall of "The New York Times" called it "a good piece of fiction, which, with all its feverish stunts, is blessed with bright dialogue and a good quota of relatively restrained scenes". Hall described Colbert's performance as "engaging and lively" and Gable as "excellent". "Variety" reported that it was "without a particularly strong plot" but "manages to come through in a big way, due to the acting, dialog, situations and directing". "Film Daily" praised it as "a lively yarn, fast-moving, plenty humorous, racy enough to be tantalizing, and yet perfectly decorous". The "New York Herald Tribune" called it "lively and amusing". John Mosher of "The New Yorker" panned it as "pretty much nonsense and quite dreary" which was probably the review Capra had in mind when he recalled in his autobiography that "sophisticated" critics had dismissed the film. Despite the positive reviews, the film was only moderately successful in its initial run. After it was released to secondary movie houses, ticket sales became brisk, especially in smaller towns where the film's characters and simple romance struck a chord with moviegoers who were not surrounded by luxury. It turned out to be a major box office smash, easily Columbia's biggest hit until the late 1980's. During its initial release, the film earned $1 million in theater rentals from the United States and Canada.


title: It Happened One Night

text: Rotten Tomatoes compiled 95 reviews of the film to form a 99% "Certified Fresh" score and an average rating of 9.2/10. The consensus reads, "Capturing its stars and director at their finest, "It Happened One Night" remains unsurpassed by the countless romantic comedies it has inspired". In 1935, after her Academy Award nomination, Colbert decided not to attend the ceremony since she felt she would not win and planned to take a cross-country railroad trip. After she was named the winner, studio chief Harry Cohn sent someone to "drag her off" the train, which had not departed, to take her to the ceremony. Colbert arrived wearing a two-piece traveling suit which she had had the Paramount Pictures costume designer, Travis Banton, make for her trip.


title: It Happened One Night

text: The film won all five of the Academy Awards for which it was nominated at the 7th Academy Awards for 1934:


title: It Happened One Night

text: "It Happened One Night" was the first film to win the "Big Five" Academy Awards (Best Picture, Best Director, Best Actor, Best Actress and Best Writing). , only two other films have achieved this feat: "One Flew Over the Cuckoo's Nest" in 1975 and "The Silence of the Lambs" in 1991. "It Happened One Night" was also the last film to win both lead acting Academy Awards until "One Flew Over the Cuckoo's Nest" in 1975.


title: It Happened One Night

text: On December 15, 1996, Gable's Oscar was auctioned off to Steven Spielberg for $607,500, who donated the statuette to the Motion Picture Academy. On June 9 of the following year, Colbert's Oscar was offered for auction by Christie's but attracted no bids.


title: It Happened One Night

text: "It Happened One Night" made an immediate impact on the public. In one scene, Gable undresses for bed, taking off his shirt to reveal that he is bare-chested. An urban legend claims that, as a result, sales of men's undershirts declined noticeably. The movie also prominently features a Greyhound bus in the story, spurring interest in bus travel nationwide.


title: It Happened One Night

text: The unpublished memoirs of animator Friz Freleng mention that this was one of his favorite films. "It Happened One Night" has a few interesting parallels with, and may have even inspired certain characteristics of, the cartoon character Bugs Bunny, who made his first appearance six years later, and who Freleng helped develop. In the film, a minor character, Oscar Shapely, continually calls the Gable character "Doc," an imaginary character named "Bugs Dooley" is mentioned once in order to frighten Shapely, and there is also a scene in which Gable eats carrots while talking quickly with his mouth full, as Bugs does.


title: It Happened One Night

text: The film has inspired a number of remakes, including the musicals "Eve Knew Her Apples" (1945) starring Ann Miller and "You Can't Run Away from It" (1956) starring June Allyson and Jack Lemmon, which was directed and produced by Dick Powell.


title: It Happened One Night

text: "It Happened One Night" was adapted as a one-hour radio play on the March 20, 1939 broadcast of "Lux Radio Theatre", with Colbert and Gable reprising their roles. The screenplay was also adapted as a radio play for the January 28, 1940, broadcast of "The Campbell Playhouse", starring Orson Welles (Mr. Andrews), William Powell (Peter Grant) and Miriam Hopkins (Ellie Andrews).


title: It Happened One Night

text: "It Happened One Night" has been adapted into numerous Indian films. These include three Hindi adaptations: "Chori Chori" (1956), "Nau Do Gyarah" (1957) and "Dil Hai Ke Manta Nahin" (1991), one Bengali adaptation "Chaoa Paoa" (1959), two Tamil adaptations: "Chandrodayam" (1966) and "Kadhal Rojavae" (2000), and one Kannada adaptation "Hudugaata" (2007).


title: It Happened One Night

text: The 1937 Laurel and Hardy comedy "Way Out West" parodied the famous hitchhiking scene with Stan Laurel managing to stop a stage coach using the same technique. Mel Brooks's film "Spaceballs" (1987) parodies the wedding scene. As she walks down the aisle to wed Prince Valium, Princess Vespa (Daphne Zuniga) is told by King Roland (Dick Van Patten) that Lone Starr (Bill Pullman) forsook the reward for the princess's return and only asked to be reimbursed for the cost of the trip.


title: It Happened One Night

text: Other films have used familiar plot points from "It Happened One Night". In "Bandits" (2001), Joe Blake (Bruce Willis) erects a blanket partition between motel room beds out of respect for Kate Wheeler's (Cate Blanchett's) privacy. He remarks that he saw people do the same thing in an old movie. In "Sex and the City 2", Carrie and Mr. Big watch the film (specifically the hitchhiking scene) in a hotel; later in the film Carrie uses the idea which she got from the film to get a taxi in the Middle East.


title: It Happened One Night

text: In "The Bogman of Letchmoor Heath", the second episode of the horror/comedy television series "She-Wolf of London" (1990–1991), lead characters Randi Wallace (Kate Hodge) and Ian Matheson (Neil Dickson) rent a motel room, and, uncomfortable with the lack of privacy afforded, Ian stretches a bed sheet like a curtain between the two beds. Ian makes reference to "It Happened One Night" but Randi is unfamiliar with the film, remarking that she would rather "read a book".


title: It Happened One Night

text: Beginning in January 2014, the comic "9 Chickweed Lane" tied a story arc to "It Happened One Night" when one of the characters, Lt. William O'Malley, is injured during World War II and believes himself to be Peter Warne. As he sneaks through German-occupied France, several plot points run parallel to that of "It Happened One Night" and he believes his French contact to be Ellen Andrews.


title: Molar concentration

text: Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solution. In chemistry, the most commonly used unit for molarity is the number of moles per liter, having the unit symbol mol/L or mol/dm in SI unit. A solution with a concentration of 1 mol/L is said to be 1 molar, commonly designated as 1 M.


title: Molar concentration

text: Molar concentration or molarity is most commonly expressed in units of moles of solute per litre of solution. For use in broader applications, it is defined as amount of substance of solute per unit volume of solution, or per unit volume available to the species, represented by lowercase formula_1:


title: Molar concentration

text: Here, formula_3 is the amount of the solute in moles, formula_4 is the number of constituent particles present in volume formula_5 (in litres) of the solution, and formula_6 is the Avogadro constant, since 2019 defined as exactly . The ratio formula_7 is the number density formula_8.


title: Molar concentration

text: In thermodynamics the use of molar concentration is often not convenient because the volume of most solutions slightly depends on temperature due to thermal expansion. This problem is usually resolved by introducing temperature correction factors, or by using a temperature-independent measure of concentration such as molality.


title: Molar concentration

text: The reciprocal quantity represents the dilution (volume) which can appear in Ostwald's law of dilution.


title: Molar concentration

text: If a molecular entity dissociates in solution, the concentration refers to the original chemical formula in solution, the molar concentration is sometimes called formal concentration or formality ("F") or analytical concentration ("c"). For example, if a sodium carbonate solution () has a formal concentration of "c"() = 1 mol/L, the molar concentrations are "c"() = 2 mol/L and "c"() = 1 mol/L because the salt dissociates into these ions.


title: Molar concentration

text: In the International System of Units (SI) the coherent unit for molar concentration is mol/m. However, this is inconvenient for most laboratory purposes and most chemical literature traditionally uses mol/dm, which is the same as mol/L. This traditional unit is often called a molar and denoted by the letter M, for example:


title: Molar concentration

text: To avoid confusion with SI prefix mega, which has the same abbreviation, small caps ᴍ or italicized "M" are also used in journals and textbooks.


title: Molar concentration

text: where formula_18 is the average molar mass of the solution, formula_19 is the density of the solution.


title: Molar concentration

text: A simpler relation can be obtained by considering the total molar concentration, namely, the sum of molar concentrations of all the components of the mixture:


title: Molar concentration

text: The sum of molar concentrations gives the total molar concentration, namely the density of the mixture divided by the molar mass of the mixture or by another name the reciprocal of the molar volume of the mixture. In an ionic solution, ionic strength is proportional to the sum of the molar concentration of salts.


title: Molar concentration

text: The molar concentration depends on the variation of the volume of the solution due mainly to thermal expansion. On small intervals of temperature, the dependence is


title: Molar concentration

text: where formula_28 is the molar concentration at a reference temperature, formula_29 is the thermal expansion coefficient of the mixture.


title: Mafia III

text: Mafia III is a 2016 action-adventure video game developed by Hangar 13 and published by 2K Games. It was released in October 2016 for PlayStation 4, Windows, and Xbox One, in May 2017 for macOS, and in October 2021 for Google Stadia. It is the sequel to "Mafia II" and the third installment in the "Mafia" series. Set within the fictional city of New Bordeaux (based on New Orleans) in 1968, the story follows former criminal and Vietnam veteran Lincoln Clay, who is forced to return to a life of crime to help his adoptive family settle problems with the local branch of the Mafia. After the Mafia betray and murder his family, Lincoln embarks on a quest for revenge while slowly building a criminal empire and seizing power from other criminal organisations in the city.


title: Mafia III

text: The development of "Mafia III" began soon after "Mafia II"s release, but initially had problems. 2K Czech, the developer of the series' first installments, oversaw restructure, with much of the development team assigned to the company's new studio, Hangar 13. After deciding on recreating New Orleans in 1968, the development team drew influence from the series' previous projects, and designed the game around Clay to replicate the core structure of its predecessors. Much of the development work constituted the open world's creation, and several team members conducted field research around Louisiana to capture footage for the design team. The game's soundtrack features several licensed songs composed by various musicians who were active during the time period.


title: Mafia III

text: Upon release, the game received mixed reviews, with praise directed at its story, characters, darker themes, and soundtrack. However, some of the gameplay mechanics and the presence of technical issues drew criticism. The game was a commercial success, selling seven million copies worldwide. On May 19, 2020, to coincide with the of the first "Mafia" game, 2K Games released a version of "Mafia III" comprised with all downloadable content packs titled Mafia III: Definitive Edition. This "Definitive Edition" was later included in the "Mafia: Trilogy" pack, released on September 25, 2020.


title: Mafia III

text: "Mafia III" is an action-adventure game set in an open world environment and played from a third-person perspective, in which the player assume control of Lincoln Clay, a Vietnam War veteran on a quest to seek revenge for his adopted family, who are murdered by local mobs. The game is set in 1968 New Bordeaux, a re-imagined version of New Orleans, with the game world being larger than the "Mafia" and "Mafia II" maps combined. "Mafia III"s map is made up of ten districts: Bayou Fantom, Delray Hollow, Barclay Mills, Frisco Fields, Pointe Verdun, Tickfaw Harbor, Southdowns, River Row, Downtown, and the French Ward. Players can complete objectives using a variety of approaches. For example, players can use the weapons provided in the game, like shotguns and revolvers, to eliminate enemies, or call for allies, who arrive in a van and assist players.


title: Mafia III

text: Alternatively, they can make use of stealth tactics throughout the entire mission without being noticed by enemies. The core gameplay revolves around gunplay. In addition, players can also perform executing moves and engage in melee-combat. The game features a cover system, allowing players to take cover behind objects to avoid enemy gunfire or detection. Players can interrogate non-playable characters after defeating them in order to gain more information on their objectives, like scaring them while driving a car. Players can attack and overrun locations owned by the Italian mob, and assign one of their lieutenants to operate around the local area. The game allows players to drive cars from the era with realistic driving mechanics and sounds.


title: Mafia III

text: Set nearly two decades after its predecessor, "Mafia III" takes place during the late 1960s, within the fictional U.S. city of New Bordeaux. Situated within America's southern states and coastline, the city is composed of island districts, industrial complexes and ports, high-rise offices and apartments, slums, suburban housing, and historical districts, interconnected by railroads and an extensive road network, with a large swampland separating the city from the coast. The city consists of a mixture of cultures including African-Americans, Irish, Italians and Haitians, and is mostly controlled by one Mafia crime family – the Marcano family – alongside smaller organisations like the Irish Mob, the Haitian Mob, the "Black Mob", and the Southern Union, a group of white supremacists.


title: Mafia III

text: The city's design, including its architectural styles, cultures and lifestyles, were influenced by the real-life aspects of the southern United States during the time period, primarily the city of New Orleans. The game's story focuses primarily within this setting, while its downloadable content expands the setting with additional locations around New Bordeaux.


title: Mafia III

text: In 1968, Vietnam veteran Lincoln Clay returns home to New Bordeaux and reunites with his surrogate father and Black Mob leader Sammy Robinson, his adoptive brother Ellis, and his friend, Father James Ballard. While initially planning to leave for California, Lincoln agrees to stay and help Sammy, who is facing problems from the Haitian Mob and is indebted to mob boss Sal Marcano. Lincoln ends the conflict with the Haitians by killing their leader and meets with Marcano to see how he can cover Sammy's debts. Although Lincoln declines his suggestion to take over the Black Mob from Sammy, Marcano nonetheless recruits him and Ellis to help his son Giorgi rob the city's branch of the Federal Reserve during the local Mardi Gras celebrations. Aided by their friend Danny Burke, whose father is also looking to settle matters with Marcano after a previous falling out, the group carries out the heist with little complications, but the Marcanos turn on them afterward, killing Sammy, Ellis, and Danny before setting Sammy's bar on fire. Lincoln is also shot and left to die but is rescued by James.


title: Mafia III

text: After recovering, Lincoln contacts his former CIA handler John Donovan, who agrees to help for unknown reasons and assists him by locating three crime bosses that also seek revenge against Marcano: new Haitian leader Cassandra, eyeing Delray Hollow, which was taken over by the Dixie Mafia; Danny's father and Irish Mob boss Thomas Burke, whose turf was also given to a rival by Marcano; and exiled Sicilian mafioso Vito Scaletta, who joined Marcano's ranks as part of a deal made with the Commission, but was eventually betrayed and left for dead after Marcano's nephew took over. After reclaiming their respective territories, Lincoln begins violently undoing the Marcano family, taking over their rackets and turf and assigning them to his allies, who slowly come to respect his skill. In the event any are neglected and eventually abandon him, Lincoln must eliminate them.


title: Mafia III

text: While dismantling the Marcano family's operations and attacking Marcano's lieutenants, Lincoln learns that Marcano has recently begun building a new casino with the intention of becoming independent of the Commission, and the main intent of the heist was to steal money plates. Lincoln proceeds to attack Marcano's three capos who were tasked with obtaining real estate, counterfeiting money to cover mounting expenses, and getting politicians to legalize gambling. After all three capos are dealt with, Lincoln attacks the casino, killing Marcano's remaining men and Giorgi, before confronting Marcano himself. Accepting his fate, he shares a drink with Lincoln while explaining that, although he doesn't regret his actions, he had only tried to improve New Bordeaux and get himself and his family out of the life of crime before anything bad happened to them. After killing Marcano or letting him commit suicide, Lincoln leaves the casino and is greeted by Commission consigliere Leo Galante, sent to investigate the attacks against Marcano. Satisfied that Lincoln's vendetta is over, Galante informs him that he can take over the New Bordeaux underworld provided the Commission receives a cut of the profits.


title: Mafia III

text: After Lincoln informs James and Donovan of Marcano's death, the latter leaves the city and advises him to take over, while the former, appalled with such a concept, reminds Lincoln that his goal was to remove Marcano, not replace him, and implores him to stick with his original plan of getting a job in California. At this point, the player must choose Lincoln's fate. The game has multiple endings dependent on Lincoln's choice, determining whether his empire flourishes or collapses under Lincoln's or one of his surviving lieutenants' leadership, and whether Lincoln abandons the criminal lifestyle, succumbs to its vices, or is assassinated by a remorseful James with a car bomb.


title: Mafia III

text: Regardless of the outcome, Lincoln's actions in New Bordeaux spawn an investigation by the FBI, led by Jonathan Maguire, who is later interviewed for a documentary on Lincoln's life, as is James and a few others who knew him. In 1971, Donovan is brought before a Senate committee to explain his role in Lincoln's crimes. The meeting ends with Donovan revealing he had helped Lincoln because he wanted to investigate Marcano's link as one of the conspirators behind John F. Kennedy's assassination, and shooting a senator who was named in Marcano's files as a co-conspirator, while promising to track down and kill everyone else responsible for President Kennedy's death.


title: Mafia III

text: The game was first rumored in August 2011. In November 2012, 2K Czech, the developer of the original "Mafia" and "Mafia II", announced that the company was working on a "top secret, AAA game". However, the company was later restructured on January 10, 2014, and the main studio in Prague was shuttered, with resources being allocated to a new headquarters in Novato, California. A new studio called Hangar 13 was established by 2K Games in Novato in the same year. Rod Fergusson, who had just left 2K's Irrational Games after completing "BioShock Infinite", had originally been in charge of Hangar 13, but later left as a result of creative differences with how he wanted to take the game. Instead, Haden Blackman, who had previously worked with LucasArts, was named as the lead to oversee the project.


title: Mafia III

text: Hangar 13 and 2K Games wanted to stay true to the quality that many users expected over the previous games. The game uses the graphics software Simplygon. The development team were interested in creating a world based on New Orleans, and eventually decided on setting the game in 1968. The team used a collection of old photographs to recreate the world. Various alterations to the world were made to suit the narrative: the bayou and the city have been positioned at close proximity, despite being at a further distance in real Louisiana; the Superdome stadium was being constructed in 1968, but is excluded from the game. The team intended the world to be accessible for high-speed chases. The team also wanted to move away from the stereotypical Italian mafia scene and represent a different side of gang-related crime scenarios. Another aspect of setting a special tone and atmosphere in the game has been the choice of licensed music. Haden Blackman indicated that "Mafia III" will include a "ton of great music" from the sixties.


title: Mafia III

text: American rapper Ice Cube collaborated with producer DJ Shadow to create the song "Nobody Wants to Die" for the game's promotion.


title: Mafia III

text: The game was officially teased by 2K on July 28, 2015, and was formally revealed at Gamescom 2015 with a cinematic trailer. "Mafia III" was released on October 7, 2016, for PlayStation 4, Windows, and Xbox One. Players who pre-ordered the game received a downloadable content pack titled "Family Kick-Back Pack" which introduced several new weapons and vehicles to the game. Players can also purchase the Limited Deluxe Edition and the Limited Collector's Edition. The Limited Deluxe Edition's content include the base game and the season pass, while the Limited Collector's Edition added additional content such as the game's original soundtrack and art book.


title: Mafia III

text: A mobile game entitled "Mafia III Rivals" was also released to tie in with the main game, developed by Cat Daddy Games for Android and iOS. "Rivals" is presented as a role-playing game with turn-based combat mechanics. A free demo of "Mafia III" was released on March 28, 2017, the same day as the first downloadable content pack of the game.


title: Mafia III

text: Following the game's initial release, several pieces of story-based downloadable content (DLC) were released. Besides the story and optional side missions (which occur simultaneously with the base game's events), each DLC adds new vehicle upgrades, weapons, and gameplay mechanics which can also be used in the base game. After eliminating the main villain of each DLC, Lincoln will be given additional missions which feature a character he met during the main objective.


title: Mafia III

text: "Mafia III" received "mixed or average" reviews from critics, according to review aggregator Metacritic. Critics praised the story, characters, and darker themes, but criticized the repetitive gameplay and the presence of numerous technical issues.


title: Mafia III

text: Alex Donaldson of VG247 gave the game a mixed review, writing, ""Mafia III" features one of my [favorite] video game stories of the year, some gorgeous presentation, an amazing soundtrack and an interesting world. Sadly it also has by-the-numbers mission design and dubious performance." In his 2/5 star review, Sam White of "The Guardian" wrote, "To say "Mafia III" is a disappointment is an understatement. It has all of the surface components to form a great game: the writing and acting are superb, its direction and style are great, but its mechanical underpinnings are archaic and desperately unimaginative."


title: Mafia III

text: Marty Sliva for IGN gave the game a score of 7.5 out of 10, summarizing his review with: ""Mafia 3"s strong characters and confident storytelling kept me engaged, even if the gameplay rarely delivered anything but bog-standard and repetitive open-world action. That's a bummer, because Lincoln is an incredible protagonist and New Bordeaux is a fantastic setting thematically, and it would've been great to see them put to better use." Brian Mazique of "Forbes" gave the game an 8.1/10, saying, "This might not be everyone's cup of tea, but if you love a good character study and aren't in search of gameplay mechanics that break new ground in innovation and control, this is one you should own."


title: Mafia III

text: "Mafia III" was the second best-selling retail game in the UK in its week of release, behind "FIFA 17". "Mafia III" sold 58.7% more than that of "Mafia II" in the UK. It debuted at number 9 on the Japanese sales charts, with 15,838 copies sold. On November 2, 2016, Take-Two Interactive announced that the game shipped in 4.5 million in it first week, setting a new launch record for 2K Games. On February 7, 2017, Take-Two Interactive announced that the game has now shipped 5 million copies. By the end of March 2020, the game had sold more than 7 million copies.


title: Mafia III

text: On release, it was found that the PC version was locked to 30 FPS; a patch to unlock the 30 FPS cap and address other issues in-game has since been released.


title: Mafia III

text: In 2017, development at Hangar 13 reportedly split into two groups, one focused on downloadable content for "Mafia III", and one building the concepts for "Mafia IV". Early ideas set the game in 1970s Las Vegas, with the "glitz and glamour of mob-controlled Sin City." Plans for "Mafia IV" didn't last long as Hangar 13 chose to create their own original video game instead, though Hangar 13 reassured fans that they still own the series and would not forget about it.


title: Mafia III

text: In August 2019, Take-Two Interactive (parent company of 2K and Hangar 13) registered three trademarks in relation to the Mafia franchise. Two of the trademarks are for ""Mafia"" and their respective text-based logos only differ in typography. The first one is identical to the font used for the first two installments in the franchise. The second one is different and without any description. The third trademark directly mentions "Mafia 2" and features the same silhouette logo from 2010.


title: Mafia III

text: On May 13, 2020, 2K announced the "Mafia: Trilogy" pack, which includes a remake of the first "Mafia" game (titled ""), a remaster of "Mafia II", and a version of "Mafia III" comprised with all additional content packs. The collection was released on September 25 for the PlayStation 4, Windows, and Xbox One. The "Definitive Editions" of "Mafia II" and "III" were made available separately on May 19, 2020.


title: Spix's macaw

text: Spix's macaw (Cyanopsitta spixii), also known as the little blue macaw, is a macaw species that was endemic to Brazil. It is a member of tribe Arini in the subfamily Arinae (Neotropical parrots), part of the family Psittacidae (the true parrots). It was first described by German naturalist Georg Marcgrave, when he was working in the State of Pernambuco, Brazil in 1638 and it is named for German naturalist Johann Baptist von Spix, who collected a specimen in 1819 on the bank of the Rio São Francisco in northeast Bahia in Brazil. This bird has been completely extirpated from its natural range, and following a several-year survey, the IUCN officially declared it extinct in the wild in 2019.


title: Spix's macaw

text: The bird is a medium-size parrot weighing about , smaller than most of the large macaws. Its appearance is various shades of blue, with a grey-blue head, light blue underparts, and vivid blue upperparts. Males and females are almost identical in appearance; however, the females are slightly smaller.


title: Spix's macaw

text: The species inhabited riparian Caraibeira ("Tabebuia aurea") woodland galleries in the drainage basin of the Rio São Francisco within the Caatinga dry forest climate of interior northeastern Brazil. It had a very restricted natural habitat due to its dependence on the tree for nesting, feeding and roosting. It feeds primarily on seeds and nuts of Caraiba and various "Euphorbiaceae" (spurge) shrubs, the dominant vegetation of the Caatinga. Due to deforestation in its limited range and specialized habitat, the bird was rare in the wild throughout the twentieth century. It has always been very rare in captivity, partly due to the remoteness of its natural range.


title: Spix's macaw

text: It is listed on CITES Appendix I, which makes international trade prohibited except for legitimate conservation, scientific or educational purposes. The IUCN regard the Spix's macaw as extinct in the wild. Its last known stronghold in the wild was in northeastern Bahia, Brazil and sightings were very rare. After a 2000 sighting of a male bird, the next and last sighting was in 2016.


title: Spix's macaw

text: The species is now maintained through a captive breeding program at several conservation organizations under the aegis of the Brazilian government. One of these organizations, the Association for the Conservation of Threatened Parrots (ACTP) moved birds back from Germany to Brazil in 2020 as part of their plan to release Spix's macaws back into the wild. The Brazilian Chico Mendes Institute for Biodiversity Conservation (ICMBio) is conducting a project "Ararinha-Azul" with an associated plan to restore the species to the wild as soon as sufficient breeding birds and restored habitat are available.


title: Spix's macaw

text: Spix's macaw is the only known species of the genus "Cyanopsitta". The genus name is derived from the Ancient Greek "kuanos" meaning "blue" and "psittakos" meaning "parrot". The species name "spixii" is a Latinized form of the surname "von Spix", hence "Cyanopsitta spixii" means "blue parrot of Spix". The genus "Cyanopsitta" is one of six genera of Central and South American macaws in the tribe Arini, which also includes all the other long-tailed New World parrots. Tribe Arini together with the short-tailed Amazon and allied parrots and a few miscellaneous genera make up subfamily Arinae of Neotropical parrots in family Psittacidae of true parrots.


title: Spix's macaw

text: In 1638 Georg Marcgrave was the first European naturalist to observe and describe the species; however, it is named for Johann Baptist von Spix, who collected the type specimen in April 1819 in Brazil, but gave it the misnomer "Arara hyacinthinus" not realizing till later that the name collided with "Psittacus hyacinthinus", the name assigned to the hyacinth macaw described by John Lathan in 1790. Spix's mistake was noticed in 1832 by German Professor of Zoology Johann Wagler, who realized that the 1819 specimen was smaller and a different color than the hyacinth macaw and he designated the new species as ""Sittace spixii"". It wasn't until 1854 that naturalist Prince Charles Bonaparte properly placed it in its own genus, designating the bird "Cyanopsitta spixi", based on important morphological differences between it and the other blue macaws. It was listed as "Cyanopsittacus spixi" by Italian zoologist Tommaso Salvadori in his 1891 "Catalog of the Birds in the British Museum".


title: Spix's macaw

text: Naturalists have noted the Spix's similarity to other smaller members of tribe Arini based on general morphology as long ago as Rev. F.G. Dutton, president of the Avicultural Society U.K. in 1900: "it's more like a conure" ('conure' is not a defined taxon – in Dutton's time, it referred to the archaic genus "Conurus"; today those would be among the smaller non-macaw parakeets in "Arini"). Brazilian ornithologist Helmut Sick stated in 1981: ""Cyanopsitta spixii"...is not a real macaw". (Sick's remark was in the context of an article on "Lear's macaw", a larger blue macaw. He recognized, as Spix had not 150 years before, that "C. spixii" is notably different from the larger macaws).


title: Spix's macaw

text: The morphology-based taxonomy of "C. spixii", intermediate between the macaws and the smaller Arini, has been confirmed by recent molecular phylogenetic studies. In a 2008 molecular phylogenetic study of 69 parrot genera, the clade diagrams indicate that "C. spixii" split from the ancestral parakeets before the differentiation of the modern macaws. However, not all of the macaw genera were represented in the study. The study also states that diversification of the Neotropical parrot lineages occurred starting 33 mya, a period roughly coinciding with the separation of South America from West Antarctica. The author notes that the study challenges the classification of British ornithologist Nigel Collar in the encyclopedic "Handbook of the Birds of the World", volume 4 (1997). A 2011 study by the same authors which includes key genera of macaws further elucidates the macaw taxonomy: the clade diagram of that study places "C. spixii" in a clade including the macaw genera which is sister to a clade containing the "Aratinga"s and other smaller parakeets. Within the macaw clade, "C. spixii" was the first taxon to diverge from the ancestral macaws; its nearest relatives are the red-bellied macaw ("Orthopsittaca manilata") and the blue-headed macaw ("Primolius couloni").


title: Spix's macaw

text: Spix's macaw is easy to identify being the only small blue macaw and also by the bare grey facial skin of its lores and eyerings. It is about long including tail length of . It has a wing length of . The external appearance of adult male and female are identical; however, the average weight of captive males is about and captive females average about . Its plumage is grey-blue on the head, pale blue on the underparts, and vivid blue on the upperparts, wings and tail. The legs and feet are brownish-black. In adults the bare facial skin is grey, the beak is entirely dark grey, and the irises are yellow. Juveniles are similar to adults, but they have pale grey bare facial skin, brown irises, and a white stripe along the top-center of their beaks (along the culmen).


title: Spix's macaw

text: In the wild, the most common seeds and nuts consumed by Spix's were from Pinhão ("Jatropha pohliana" var. "mollissima") and Favela ("Cnidoscolus phyllacanthus"). However these trees are colonizers, not native to the bird's habitat, so they could not have been historical staples of the diet.


title: Spix's macaw

text: Its diet also included seeds and nuts from Joazeiro ("Ziziphus Joazeiro"), Baraúna ("Schinopsis brasiliensis"), Imburana ("Commiphora leptophloeos" or "Bursera leptophloeos"), Facheiro ("Pilosocereus piauhyensis)", "Phoradendron" species, Caraibeira ("Tabebuia caraiba"), Angico ("Anadenanthera macrocarpa"), Umbu ("Spondias tuberosa") and Unha-de-gato ("Acacia paniculata"). Reports from previous Spix's macaw researchers seem to add another two plants to the list: "Maytenus rigida" and "Geoffroea spinosa". "Combretum leprosum" may also be a possibility.


title: Spix's macaw

text: Captive bred Spix's macaws reach sexual maturity at seven years of age. A paired female born at the Loro Parque Fundación laid eggs at the age of five years, but these were infertile. It is suspected that late maturity in captivity may be due to inbreeding or other artificial environmental factors, as other parrots of similar size reach sexual maturity in two to four years. In the wild, mating involves elaborate courtship rituals, like feeding each other and flying together. This process is known to possibly take several seasons in other large parrots, and it may also be the case for the Spix's. They make their nests in the hollows of large mature Caraibeira trees, and reuse the nest year after year. The breeding season is November to March, with most eggs hatching in January to coincide with the start of the Caatinga January to April rainy season. In the wild, Spix's were believed to lay three eggs per clutch; in captivity, the average number is four eggs, and can range from one to seven. Incubation period is 25–28 days and only the female performs incubation duties. The chicks fledge in 70 days and are independent in 100–130 days.


title: Spix's macaw

text: The mating call of Spix's macaw can be described as the sound "whichaka". The sound is made by creating a low rumble in the abdomen bringing the sound up to a high pitch. Its voice is a repeated short grating. It also makes squawking noises.


title: Spix's macaw

text: Its lifespan in the wild is unknown; the only documented bird (the last wild male), was older than 20 years. The eldest bird in captivity died at age 34 years.


title: Spix's macaw

text: Various accounts relate that the birds were more common in Pernambuco than in Bahia through the 1960s but not later. Spix's macaw was most recently (1974–1987) known in the Río São Francisco valley, in northeastern Brazil, principally in the basins on the south side of the river in the State of Bahia. In 1974, ornithologist Helmut Sick, based on information from traders and trappers, extended the possible range of the Spix's macaw to embrace the northeastern part of the state of Goias and the southern part of the state of Maranhao. Other ornithologists reporting the bird in various parts of the state of Piaui further extended the range to a vast area of the dry interior of northeast Brazil.


title: Spix's macaw

text: Study of the lone bird discovered at Melância creek in 1990 revealed substantive information about its habitat. It had been previously assumed that the Spix's macaw had a vast range in the interior of Brazil embracing several different habitat types, including buriti palm swamps, cerrado, and dry Caatinga. But the evidence collected in Melância Creek indicated that the Spix's macaw was a specially adapted inhabitant of the disappearing woodland galleries. Ornithologist Tony Silva mentions that "where Caraibeiras have been felled, as in the Pernambuco side of the São Francisco River, the species has disappeared".


title: Spix's macaw

text: Much remains uncertain about the extent of the bird's original range, because most of its woodland habitat was cleared before naturalists observed either the birds or the Caraiba nesting sites. The historical range is now believed to have encompassed portions of the states of Bahia and Pernambuco in a wide corridor along a stretch of the Rio São Francisco between Juazeiro (or possibly Remanso) and Abaré. Previous observations of the birds from further west are very difficult to explain but conceivably stem from either escaped captive birds or more likely the misidentification of another species such as red-bellied macaw ("Orthopsittaca manilatus").


title: Spix's macaw

text: The Caatinga vegetation of northeastern Bahia (which hosts the Spix habitat) is stunted trees, thorny shrubs and cacti, dominated by plants of the family Euphorbiaceae. This macaw lived in the hottest and driest part of the "Caatinga" within Caraiba, or Caribbean trumpet tree ("Tabebuia caraiba") woodland galleries. The Caraibeira constitutes a microclimate within the Caatinga. The existing galleries are fringes of unique woodland extending a maximum of to either side along a series of seasonal waterways at least 8 m wide in the Rio São Francisco drainage basin. All T. caraiba woodland was recorded in the middle and lower levels of the creek system where fine alluvial deposits were present. The character of the galleries is tall (8m) evenly spaced Caraibeira trees, ten per hundred meters, interspersed with low scrub and desert cacti. Large mature trees of this species (and apparently no other) provided the nesting hollows of Spix's macaws, as well as shelter and their seedpods, food for the species.


title: Spix's macaw

text: Notable among the seasonal waterways are Riacho Melância watershed 30 km south of Curaçá, where the last known wild Spix's macaw nest was located, adjacent Riacho Barra Grande, and Riacho da Vargem ~100 km to the north near Abaré all in the State of Bahia south of Rio São Francisco. In 1990, these were all that remained of what was once believed to be a vast filigree of creekside Caraibeira woodland extending 50 km into the Caatinga on either side of the Rio São Francisco along a significant stretch of its middle reaches. There is also one confirmed site, since cleared, along Brígida Creek on the north shore of Rio São Francisco in Pernambuco.


title: Spix's macaw

text: The species appears to have been seen and described – "MARACANA Brasiliensibus, avis Psittaco planè similis (cuius & species) sed maior, plumae totius ex gryseo subcoerulescunt, clamat ut Psittacus. Fructus amat, Murucuia imprimis. (Translation: "Brazilian parrot, bird very similar to Psittacus [ grey parrot ] but larger, the entire plumage is ashy-bluish, calls like a parrot. Fruit it loves, especially Passionfruit.") – by the German naturalist Georg Marcgrave when he worked in Pernambuco in 1638.


title: Spix's macaw

text: Spix's macaw is named for German naturalist Johann Baptist von Spix, who collected the first specimen in April 1819 near the São Francisco River in the vicinity of Juazeiro Recent authorities cite the type locality as Curaca, but others say the locality can't be known with certainty.. Spix wrote: "habitat gregarius, rarissimus licet, propre Joazeiro in campis riparüs fluminis St. Francisci, voce tenui insignis" ("it lives in flocks, although very rare, near Joazeiro in the region bordering the rio São Francisco, [and is] notable for its thin voice").


title: Spix's macaw

text: The next reported sighting of the bird wasn't for 84 years, in 1903 by Othmar Reiser of the Austrian Academy of Sciences, west of Juazeiro at Lagoa de Parnaguá (lake at Parnagua) in the State of Piaui. (What we now know about its habitat and probable range casts doubt on this observation) Reiser had also seen one in captivity at a railway station in Remanso. These observations resulted in an early supposition of a vast potential range for the species in the dry interior of the northeast.


title: Spix's macaw

text: With the passage of the Brazil Wildlife Protection Act in 1967, Brazil forbade the export of its wildlife, and in 1975 became a party to the CITES treaty. These actions barely affected the illicit bird trade, but Spix owners were forced underground (consequently complicating the later effort to initiate a captive recovery program).


title: Spix's macaw

text: The bird had not been studied in the wild until the 1970s. In 1974, Brazilian ornithologist Helmut Sick observed groups of three and four of the birds near Formosa do Rio Preta in northwest Bahia flying over buriti Palms (Mauritia flexuosa). As recently as 1980, Robert Ridgely (ornithologist) stated that "there is no available evidence indicating a recent decline in numbers." Beginning around 1980, at the very height of the illegal bird trade, traders and trappers removed dozens of Spix's from the wild, and by the early 80s, it was generally believed to be extinct in the wild. Naturalist Dr. Paul Roth conducted field surveys of the bird in the Curacá region from 1985 to 1988. Roth found only 5 birds in 1985, three in 1986, and only two after May 1987.


title: Spix's macaw

text: Two of the birds were captured for trade in 1987. A single male, paired with a female blue-winged macaw, was discovered at the site in 1990. A female Spix's macaw released from captivity at the site in 1995 was killed by collision with a power line after seven weeks. The last wild male disappeared from the site in October 2000; his disappearance was thought to have marked the extinction of this species in the wild. However, wild Spix's macaws may have been sighted in 2016. While the IUCN Red List views its status as Critically Endangered and possibly extinct in the wild, ornithologist Nigel Collar of BirdLife International, the authority for the IUCN Redlist of birds now calls this bird extinct in the wild.


title: Spix's macaw

text: As of June 2022, a flock of eight Spix' macaws has been released back into the wild and appears to be doing well. Another release is planned for December of the same year.


title: Spix's macaw

text: The bird was already rare by the time of Spix's discovery of it in 1819 following 100 years of intensive burning, logging and grazing of the Caatinga. Centuries of deforestation, human encroachment and agricultural development along the Rio Sao Francisco corridor following European colonization of eastern Brazil preceded its precipitous decline in the latter part of the 20th century. Naturalists surveying its known remaining native habitat in the Curaçá region have estimated that it could have supported no more than about 60 birds at any time in the last 100 years.


title: Spix's macaw

text: Contributing factors were the anthropic introduction of invasive and predatory species of black rats, feral cats, mongooses and marmoset monkeys which prey on the eggs and young, and goats, sheep and cattle which destroy the regenerative growth of the woodland trees, particularly the Caraibeira seedlings.


title: Spix's macaw

text: Other recent evidence has shown that anthropic changes that occurred on the northern shore of the São Francisco River, such as a broad scale conversion into agricultural lands and flooding following the construction of Sobradinho Dam starting in 1974, have changed the flora structure and displaced the Spix's macaw away from that portion of its original range.


title: Spix's macaw

text: The decline of the species in the 1970s and early 80s is attributed to hunting and trapping of the birds, unsustainable harvesting of the Caraíba trees for firewood, the construction of the Sobradinho Dam above Juazeiro starting in 1974 that submerged the basin woodlands under an artificial lake, and the northward migration of the Africanized bee, which competes for nesting sites.


title: Spix's macaw

text: Caraiba grows very slowly; most of the trees are 200–300 years old, and there has not been any regenerative growth for the last 50 years. In addition, 45% of the Caatinga dry forest in which the woodland galleries are embedded has been cleared for farms, ranches and plantations. Climate change resulting in desertification of significant parts of the Caatinga has permanently reduced the potential reclaimable habitat.


title: Spix's macaw

text: An analysis in 2018 based on threats, time since last known confirmed records, and patterns of bird extinction suggested that the bird was in all probability extinct in the wild. As of 2019, the IUCN classifies the species as extinct in the wild.


title: Spix's macaw

text: In the middle 1980s, by the time fieldwork to locate and understand the habitat of the Spix was completed, it was apparent that the Spix must be nearing extinction in the wild. Conservationists realized that a captive breeding program would be necessary to preserve the species. At a meeting in 1987 of conservationist groups including IUCN at Loro Parque (one of the original Spix holders) in Tenerife, Canary Islands (Spain), only 17 captive Spix macaws could be located. Without the attendance of most of the captive Spix holders or involvement of the Brazilian government, little was accomplished.


title: Spix's macaw

text: In 1990, the Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis (IBAMA, Brazilian Institute of Environment and Renewable Natural Resources) established the Permanent Committee for the Recovery of Spix's Macaw, called CPRAA, and its "Ararinha Azul" project (Little Blue Macaw project) in order to conserve the species. At that time, the known captive population of Spix's stood at 15, and one in the wild. Early 1990 was the low point for conservation of the Spix. The Permanent Committee was dissolved in 2002 due to irreconcilable differences between the parties involved. In 2004 a committee was re-formed and re-structured under the title of "The Working Group for the Recovery of the Spix's Macaw".


title: Spix's macaw

text: Since 1987, the Loro Parque Foundation financed the field program to protect and study the last wild male, to protect and restore key habitat, and other important actions. In 1997, the Loro Parque Foundation returned the ownership to the Government of Brazil of all the Spix's macaws held in its facilities.


title: Spix's macaw

text: Between 2000 and 2003, most of two large collections of Spix at Birds International in the Philippines and the aviaries of Swiss aviculturist Dr. Hammerli were purchased by Sheikh Saud bin Muhammed bin Ali Al-Thani of Qatar and became Al Wabra Wildlife Preservation. Under the Sheikh were instituted standards of animal keeping, veterinary care, animal husbandry and stud book records for the conservation of the Spix's.


title: Spix's macaw

text: In 2007 and 2008, two farms totalling in Curaçá, State of Bahia, Brazil were purchased by the Lymington Foundation (with contributions from ACTP and Parrots International) and Al Wabra Wildlife Preservation. These compose a small but important part of the natural habitat of the Spix, in the vicinity where the last known wild Spix nest existed. Efforts to clear the habitat of introduced predators and restore the natural Caraibeira seedlings and important creek systems are ongoing on the land.


title: Spix's macaw

text: In May 2012, Brazil's ICMBio formulated and published a 5-year National Action Plan (PAN) for conservation and reestablishment of the species in the wild. Highlights of the plan are to increase the captive population to 150 specimens (expected by 2020), build a breeding facility in Brazil within the Spix's native habitat, acquire and restore additional portions of its range, and prepare for its release into the wild between 2017 and 2021. Pursuant to the plan, in 2012, the Brazilian government established NEST, a private aviary near Avaré, State of Sao Paulo, Brazil as a breeding and staging center for eventual release of the Spix into the wild. Birds formerly housed at the Sao Paulo Zoo as well as Loro Parque Foundation and other conservation organizations were relocated to NEST. The Spix's at NEST are owned by the Brazilian government and managed by Al Wabra Wildlife Preservation.


title: Spix's macaw

text: The existing captive population is descended from just 7 wild caught founder birds, which are believed to


title: Spix's macaw

text: have all come from just two wild nests that existed post 1982: pairs originally owned by Birds International in the Philippines, Dr. Hammerli in Switzerland, and Wolfgang Keissling (Loro Parque), and a male from the São Paulo Zoo.


title: Spix's macaw

text: In the years since 1987 when naturalists, conservationists and later IBAMA/ICMBio started tracking the Spix, only two sets of birds unknown in 1987 have ever been discovered: Dr. Hammerli's in 1991, and a single male bird found in Colorado, U.S. in 2002 named Presley. There is no evidence that any others not known in 1987 still exist (though see a cryptic reference to black market dealing in the birds in 1995.)


title: Spix's macaw

text: As of 2022 there are approximately 177 Spix's macaws in captivity. Eighty-three of these are participating in an international breeding program managed by the Instituto Chico Mendes de Conservação da Biodiversidade (ICMBio), the Natural Heritage Branch of the Brazilian Government. Most of these are managed at Al Wabra Wildlife Preservation (AWWP), which purchased the population of Birds International and most of the birds in Dr. Hammerli's Swiss collection. Other Spixs are located at Loro Parque Foundation, Tenerife, Canary Islands, Association for the Conservation of Threatened Parrots (ACTP) in Berlin, Germany, and NEST in Brazil. At three of these five conservation organizations (AWWP, ACTP and NEST), a captive breeding program is guiding Spix's macaw a step closer to re-establishment back to its natural habitat in Brazil. (The female at Loro Parque Foundation cannot be bred due to health reasons). Both the AWWP and the ACTP have loaned individuals to Jurong Bird Park in Singapore.


title: Spix's macaw

text: The status and locations of 5 Spix's sold to private owners from Dr. Hammerli's Swiss collection in 1999 are unknown but presumed to be still alive; they are the likely source of the approximately 13 Spix's in the hands of private owner(s) in Switzerland.


title: Spix's macaw

text: In July 2015, the number of Spix's macaws held in captivity participating in the ICMBio recovery program reached 110(NEST:12, ACTP:12, AWWP:86). The count does not include an unverifiable number of birds in private hands.


title: Spix's macaw

text: The captive population suffers from very low heterozygosity – the original wild caught founder birds were few, closely related in the wild and intensively inbred in captivity – resulting in infertility, and high rate of embryo deaths (at AWWP, only one in six eggs laid is fertile; only two-thirds of those hatch).


title: Spix's macaw

text: For unknown reasons, originally suspected to be bloodline related, captive specimens seemed to have delayed sexual maturity. The youngest pairs to lay fertile eggs were 10 years of age. Other captive breeding issues are that, possibly because of inbreeding, many more hens than cocks are hatched, at least twice as many.


title: Spix's macaw

text: All or nearly all hatched chicks in the breeding program are hand raised by experienced staff, to reduce the risk of losing a scarce live chick (only about one out of ten viable eggs laid hatch). No chick has been lost through weaning. Non-invasive DNA testing of plucked feathers has been introduced to determine the gender of the chicks. The sex of chicks is not determined until they undergo feather development when they reach one to two months of age.


title: Spix's macaw

text: Spix's macaws choose their own mates independently, so best genetic pairings are not guaranteed. Artificially created "pairs" may groom and associate with each other as if they were a pair, but in fact are not mates, and it may take several seasons to determine this. Another complication is that infected birds cannot be paired with uninfected birds, due to risk of spreading viral diseases.


title: Spix's macaw

text: Newest developments in captive breeding programs of this species involved assisted reproduction techniques in the Spix's macaw:


title: Spix's macaw

text: In the 2009–2010 breeding season, a research collaboration between Loro Parque Fundación of Tenerife, Canary Islands and the University of Giessen in Germany used a new technique developed for semen collection and tested in many other parrot species on the Spix's macaws. However, artificial insemination was not used in this case.


title: Spix's macaw

text: Scientists from the University of Giessen of the working group of Prof. Dr. Michael Lierz, Clinic for Birds, Reptiles, Amphibians and Fish, developed a novel technique for semen collection and artificial insemination in large parrots. The research team used artificial insemination for the first time ever in the Spix's macaw at Al Wabra Wildlife Preservation in 2012.


title: Spix's macaw

text: In the 2013 breeding season veterinarians and scientists from Parrot Reproduction Consulting, a German veterinary practice focused on parrot reproduction medicine, and Al Wabra developed new specific strategies for semen collection and artificial insemination of the Spix's macaw. These resulted in the world's first egg fertilisation and first chicks of the Spix's macaw as a result of assisted reproduction, performed et al-Wabra Wildlife Preservation. Two chicks were produced and the first chick was called "Neumann" after Daniel Neumann, the veterinarian who performed these inseminations.


title: Spix's macaw

text: In 2018, the population of the species numbered approximately 158 individuals and an agreement was signed between the Ministry of the Environment of Brazil and conservation organizations of Belgium (Pairi Daiza Foundation) and Germany (Association for the Conservation of Threatened Parrots) to establish the repatriation of 50 Spix's macaws to Brazil by the first quarter of 2019. The Spix's macaw was reintroduced to the wild in June 2022.


title: Spix's macaw

text: The project of reintroduction of the Spix's macaw in Brazil included the creation of two protected areas in the state of Bahia: the Wildlife Refuge of Spix's Macaw, in Curaçá, and the Environmental Protection Area of Spix's Macaw, in Juazeiro, with a awareness work done with the local population and the construction of a reproduction and readaptation center.


title: Spix's macaw

text: In August 2018, 146 of the 160 Spix's macaws in the world lived in the Association for the Conservation of Threatened Parrots in Rüdersdorf, (Germany). 120 of them came from Qatar, transferred due to the death of the maintainer of the Al Wabra Wildlife Preserve, Sheikh Saud bin Muhammed Al Thani, in 2014, and the economic embargo imposed to Qatar for Saudi Arabia, UAE, Egypt and Bahrain, in 2017. The goal of the Association is to produce about 20 macaws per year.


title: Spix's macaw

text: Between April and July 2021, three Spix's macaw born in the Caatinga region in the state of Bahia in Brazil, twenty years after the declaration of extinction in wild by the Brazilian government. The chicks are from a couple that came from Germany in 2020. The Chico Mendes Institute for Biodiversity Conservation (ICMBio), also declared that the species will be reintroduced into nature in the next years.


title: Spix's macaw

text: One of the earliest records (and one of very few at all) of a Spix's macaw in a public zoo was a dramatic display of "the four blues" including Spix's, glaucous, hyacinth, and Lear's macaws in 1900 at the Berlin Zoo.


title: Spix's macaw

text: The bird was exceedingly rare in aviculture, the few being held by wealthy collectors rather than privately as pets. A trickle of Spix's appeared in captivity starting in the late 1800s. The earliest known specimens were three held by the London Zoological Society between 1878 and 1902.


title: Spix's macaw

text: One of the few accounts of the Spix in captivity was given by Rev. F.G. Dutton, president of the Avicultural Society U.K. in 1900: "I have not yet seen a good-tempered Spix ... My Spix, which is really more a Conure than a Macaw, will not look at sop of any sort, except sponge cake given from one's fingers, only drinks plain water, and lives mainly on sunflower seed. It has hemp, millet, and canary, and peanuts, but I do not think it eats much of any of them. It barks the branches of the tree in which it is loose, and may eat the bark. It would very likely be all the better if it would eat bread and milk, as it might then produce some flight feathers, which it never yet has had. But I expect it would not eat any sop, even if I gave it nothing else."


title: Spix's macaw

text: The bird remained rare and highly coveted. The first captive breeding occurred in the 1950s in Brazil, in the aviaries of the late Alvaro Carvalhaes, an aviculturist from Santos. He hatched numerous chicks, some reports say as many as 24, one of which ended up at the Naples Zoo (Italy), where it remained alive until the late 1980s. Most of his birds died of poisoning in the 1970s. Some of these birds were the likely source of rumored Brazilian Spix owners in the 1960s and 1970s.


title: Spix's macaw

text: Bates and Busenbark say that the bird was intelligent and affectionate, talked some, and had no worse proclivity for screaming than Amazons. They also noted that the Spix were spiteful to other birds.


title: Spix's macaw

text: In October 2002, a Spix named Presley was discovered in Colorado, and repatriated to Brazil. This Spix had not been among those known in 1987. Because all known specimens of the Spix's macaw are now in a conservation program run by the Brazilian government, there are now no sources from which the bird may be obtained for the pet trade. Presley died on 25 June 2014 outside São Paulo, at the approximate age of 40.


title: Spix's macaw

text: What appears to be the last Spix discovered in the wild was found on 18 June 2016 in Curaçá, Brazil, however it is speculated that this may have been a bird released from captivity due to fear of the authorities.


title: Spix's macaw

text: The Spix is one of the "four blues", the four species of all blue macaws formerly seen in captivity together including the hyacinth macaw, Lear's macaw, and glaucous macaw (possibly extinct).


title: Spix's macaw

text: In the animated TV series "Noah's Island", the "Born to be Wild" episode focuses on Noah, the main character, bringing a breeding pair of Spix's macaws to his island from the Amazon rainforest, in the hope that they will breed. At first, the two macaws are both very aggressive and fight with each other, but they eventually make up and fall in love.


title: Spix's macaw

text: In the opener of the Gorgo episode of "Mystery Science Theater 3000", Crow finds that his head crown has become a nesting spot for two Spix's macaw eggs. Later in the episode he reveals that the eggs have been taken away by Egg Protective Services after he accidentally made an omelet in front of them.


title: Spix's macaw

text: In the 2011 animated movie "Rio", the main characters Blu (Jesse Eisenberg) and Jewel (Anne Hathaway) are the supposed last pair of Spix's macaws in the world (although they are referred to as blue macaws). The movie even references their extinct-in-the-wild status and at one point ornithologist Túlio Monteiro mentions the species' scientific name. In its 2014 sequel "Rio 2", it is revealed that they are not the last pair at all, but in actuality other Spix's macaws are thriving secretly in the Amazon rainforest.


title: Spix's macaw

text: In a 2008 episode titled "Wildlife" of "" the bird was included in an international animal smuggling ring. It was found in the purse of a victim who had been mauled by a tiger. References were made to the extreme rarity of the bird and the potential value of it and other endangered species.


title: Spix's macaw

text: On 18 June 2016 one specimen was seen in Curaçá in the Brazilian state of Bahia. On 19 June, the bird was filmed in poor quality although its call was identified as a Spix's macaw. However, Birdlife noted it is possible the individual was a released captive bird.


title: Spix's macaw

text: A note on the references. There are only about a dozen original ornithological research papers devoted exclusively to the Spix written in the last 40 years. Most are collected at www.bluemacaws.org. A comprehensive natural and conservation history through late 2002 is available in Juniper's "Spix Macaw" book. More recent information is available in periodic reports about the parrots at Loro Parque and Al Wabra. Most other material is derived.


title: HPV vaccine

text: Human papillomavirus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus (HPV). Available HPV vaccines protect against either two, four, or nine types of HPV. All HPV vaccines protect against at least HPV types 16 and 18, which cause the greatest risk of cervical cancer. It is estimated that HPV vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and show more than 90% efficacy in preventing HPV-positive oropharyngeal cancers. They additionally prevent some genital warts, with the quadrivalent and nonavalent vaccines that protect against HPV types HPV-6 and HPV-11 providing greater protection.


title: HPV vaccine

text: The World Health Organization (WHO) recommends HPV vaccines as part of routine vaccinations in all countries, along with other prevention measures. The vaccines require two or three doses depending on a person's age and immune status. Vaccinating girls around the ages of nine to thirteen is typically recommended. The vaccines provide protection for at least 5 to 10 years. Cervical cancer screening is still required following vaccination. Vaccinating a large portion of the population may also benefit the unvaccinated.


title: HPV vaccine

text: HPV vaccines are very safe. Pain at the site of injection occurs in about 80% of people. Redness and swelling at the site and fever may also occur. No link to Guillain–Barré syndrome has been found.


title: HPV vaccine

text: The first HPV vaccine became available in 2006. As of 2017, 71 countries include it in their routine vaccinations, at least for girls. It is on the World Health Organization's List of Essential Medicines and prequalified vaccines. Vaccination may be cost effective in the low and middle-income countries. As of 2017, Gardasil 9 is the only version available in the United States as the older version, Gardasil has been discontinued as the Gardasil 9 offers protection against same four HPV types as Gardasil, as well as an additional five HPV types.


title: HPV vaccine

text: HPV vaccines are used to prevent HPV infection and therefore cervical cancer. Good evidence supports that vaccination of large percentage of people within a population decreases rates of HPV infections with part of the benefit from herd immunity. Some types are recommended in the United States for women and men who are 9–26 years of age, and are approved for those who are 27–45 years of age.


title: HPV vaccine

text: Since the vaccines only cover some high-risk types of HPV, cervical cancer screening is recommended even after vaccination. In the U.S., the recommendation is for women to receive routine Pap smears beginning at age 21. In Australia, the national screening program has changed from the two yearly cytology (pap smears) to being based on tests for HPV DNA, based on work by Karen Canfell and others.


title: HPV vaccine

text: The HPV vaccine has been shown to prevent cervical dysplasia from the high-risk HPV types 16 and 18 and provide some protection against a few closely related high-risk HPV types. However, there are other high-risk HPV types that are not affected by the vaccine. The protection against HPV 16 and 18 has lasted at least eight years after vaccination for Gardasil and more than nine years for Cervarix. It is thought that booster vaccines will not be necessary.


title: HPV vaccine

text: Cervarix is just as effective at protecting women against persistent HPV 16 and 18 infection in the anus as it is at protecting them from these infections in the cervix. Overall, about 30 percent of cervical cancers will not be prevented by these vaccines. Also, in the case of Gardasil, ten percent of genital warts will not be prevented by the vaccine. Neither vaccine prevents other sexually transmitted diseases, nor do they treat existing HPV infection or cervical cancer.


title: HPV vaccine

text: HPV types 16, 18 and 45 contribute to 94% of cervical adenocarcinoma (cancers originating in the glandular cells of the cervix). While most cervical cancer arises in the squamous cells, adenocarcinomas make up a sizable minority of cancers. Further, Pap smears are not as effective at detecting adenocarcinomas, so where Pap screening programs are in place, a larger proportion of the remaining cancers are adenocarcinomas. Trials suggest that HPV vaccines may also reduce the incidence of adenocarcinoma.


title: HPV vaccine

text: Two doses of the vaccine may work as well as three doses. The Centers for Disease Control and Prevention (CDC) recommends two doses in those less than 15 years and three doses in those over 15 years. A single dose might be effective.


title: HPV vaccine

text: A study with 9vHPV, a 9-valent HPV vaccine that protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, came to the result that the rate of high-grade cervical, vulvar, or vaginal disease was the same as when using a quadrivalent HPV vaccine. A lack of a difference may have been caused by the study design of including women 16 to 26 years of age, who may largely already have been infected with the five additional HPV types that are additionally covered by the 9-valent vaccine.


title: HPV vaccine

text: HPV vaccines are approved for males in several countries and regions, including Switzerland, Portugal, Canada, Australia, Ireland, South Korea, Hong Kong, the United Kingdom, New Zealand, and the United States.


title: HPV vaccine

text: In males, Gardasil may reduce their risk of genital warts and precancerous lesions caused by HPV. This reduction in precancerous lesions might be predicted to reduce the rates of penile and anal cancer in men. Gardasil has been shown to also be effective in preventing genital warts in males. While Gardasil and the Gardasil 9 vaccines have been approved for males, a third HPV vaccine, Cervarix, has not. Unlike the Gardasil-based vaccines, Cervarix does not protect against genital warts.


title: HPV vaccine

text: Since penile and anal cancers are much less common than cervical cancer, HPV vaccination of young men is likely to be much less cost-effective than for young women.


title: HPV vaccine

text: Gardasil is also used among men who have sex with men, who are at higher risk for genital warts, penile cancer, and anal cancer.


title: HPV vaccine

text: Australia introduced HPV vaccination for boys over 12 from 2013 onwards, while UK and Ireland introduced HPV vaccination for boys aged 12 and 13 as part of their National Immunization Plan in 2019. Portugal introduced universal HPV vaccination for boys aged 10 years and above as part of its National Immunization Plan in 2020.


title: HPV vaccine

text: On 9 September 2009, an advisory panel recommended that the Food and Drug Administration (FDA) of the USA license Gardasil in the United States for boys and men ages 9–26 for the prevention of genital warts. Soon after that, the vaccine was approved by the FDA for use in males aged 9 to 26 for prevention of genital warts and anal cancer.


title: HPV vaccine

text: In 2011, an advisory panel for the Centers for Disease Control and Prevention (CDC) recommended the vaccine for boys ages 11–12. This was intended to prevent genital warts and anal cancers in males, and possibly prevent head and neck cancer (though the vaccine's effectiveness against head and neck cancers has not yet been proven). The committee also made the vaccination recommendation for males 13 to 21 years who have not been vaccinated previously or who have not completed the three-dose series. For those under the age of 27 who have not been fully vaccinated the CDC recommends vaccination.


title: HPV vaccine

text: Harald zur Hausen's support for vaccinating boys (so that they will be protected, and thereby so will women) was joined by professors Harald Moi and Ole-Erik Iversen in 2011.


title: HPV vaccine

text: When Gardasil was first introduced, it was recommended as a prevention for cervical cancer for women that were 25 years old or younger. Evidence suggests that HPV vaccines are effective in preventing cervical cancer for women up to 45 years of age. In 2018, the Food and Drug Administration released a summary basis for regulatory action and approval for expansion of usage and indication for the 9-valent HPV vaccine to include men and women 27 to 45 years of age.


title: HPV vaccine

text: The National Cancer Institute states "Widespread vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds if all women were to take the vaccine and if protection turns out to be long-term. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up from abnormal Pap tests, thus helping to reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures."


title: HPV vaccine

text: Only 41% of women with cervical cancer in the developing world get medical treatment. Therefore, prevention of HPV by vaccination may be a more effective way of lowering the disease burden in developing countries than cervical screening. The European Society of Gynecological Oncology sees the developing world as most likely to benefit from HPV vaccination. However, individuals in many resource-limited nations, Kenya for example, are unable to afford the vaccine.


title: HPV vaccine

text: In more developed countries, populations that do not receive adequate medical care, such as poor or minorities in the United States or parts of Europe also have less access to cervical screening and appropriate treatment, and are similarly more likely to benefit. In 2009, Dr. Diane Harper, a researcher for the HPV vaccines, questioned whether the benefits of the vaccine outweigh its risks in countries where Pap smear screening is common. She has also encouraged women to continue pap screening after they are vaccinated and to be aware of potential adverse effects.


title: HPV vaccine

text: According to the CDC, in 2012, use of the HPV vaccine had cut rates of infection with HPV-6, -11, -16 and -18 in half in American teenagers (from 11.5% to 4.3%) and by one third in American women in their early twenties (from 18.5% to 12.1%).


title: HPV vaccine

text: The HPV vaccine is generally safe with no increased risk of serious adverse effects. HPV vaccines are approved for use in over 100 countries, with more than 100 million doses distributed worldwide. Extensive clinical trial and post-marketing safety surveillance data indicate that both Gardasil and Cervarix are well tolerated and safe. When comparing the HPV vaccine to a placebo (control) vaccine taken by women, there is no difference in the risk of severe adverse events.


title: HPV vaccine

text: Gardasil is a three-dose (injection) vaccine. , there were more than 57 million doses distributed in the United States, though it is unknown how many were administered. There have been 22,000 Vaccine Adverse Event Reporting System (VAERS) reports following the vaccination. 92% were reports of events considered to be non-serious (e.g., fainting, pain and swelling at the injection site (arm), headache, nausea and fever), and the rest were considered to be serious (death, permanent disability, life-threatening illness and hospitalization). However, VAERS reports include any reported effects whether coincidental or causal. In response to concerns regarding the rates of adverse events associated with the vaccine, the CDC stated: "When evaluating data from VAERS, it is important to note that for any reported event, no cause-and-effect relationship has been established. VAERS receives reports on all potential associations between vaccines and adverse events."


title: HPV vaccine

text: , in the US there were 44 reports of death in females after receiving the vaccine. None of the 27 confirmed deaths of women and girls who had taken the vaccine were linked to the vaccine. There is no evidence suggesting that Gardasil causes or raises the risk of Guillain–Barré syndrome. Additionally, there have been rare reports of blood clots forming in the heart, lungs, and legs. A 2015 review conducted by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee concluded that evidence does not support the idea that HPV vaccination causes complex regional pain syndrome or postural orthostatic tachycardia syndrome.


title: HPV vaccine

text: , the CDC continued to recommend Gardasil vaccination for the prevention of four types of HPV. The manufacturer of Gardasil has committed to ongoing research assessing the vaccine's safety.


title: HPV vaccine

text: According to the Centers for Disease Control and Prevention (CDC) and the FDA, the rate of adverse side effects related to Gardasil immunization in the safety review was consistent with what has been seen in the safety studies carried out before the vaccine was approved and were similar to those seen with other vaccines. However, a higher proportion of syncope (fainting) was seen with Gardasil than is usually seen with other vaccines. The FDA and CDC have reminded health care providers that, to prevent falls and injuries, all vaccine recipients should remain seated or lying down and be closely observed for 15 minutes after vaccination. The HPV vaccination does not appear to reduce the willingness of women to undergo pap tests.


title: HPV vaccine

text: While the use of HPV vaccines can help reduce cervical cancer deaths by two-thirds around the world, not everyone is eligible for vaccination. There are some factors that exclude people from receiving HPV vaccines. These factors include:


title: HPV vaccine

text: In the Gardasil clinical trials, 1,115 pregnant women received the HPV vaccine. Overall, the proportions of pregnancies with an adverse outcome were comparable in subjects who received Gardasil and subjects who received placebo. However, the clinical trials had a relatively small sample size. , the vaccine is not recommended for pregnant women.


title: HPV vaccine

text: The FDA has classified the HPV vaccine as a pregnancy Category B, meaning there is no apparent harm to the fetus in animal studies. HPV vaccines have not been causally related with adverse pregnancy outcomes or adverse effects on the fetus. However, data on vaccination during pregnancy is very limited and vaccination during the pregnancy term should be delayed until more information is available. If a woman is found to be pregnant during the three-dose series of vaccination, the series should be postponed until pregnancy has been completed. While there is no indication for intervention for vaccine dosages administered during pregnancy, patients and healthcare providers are encouraged to report exposure to vaccines to the appropriate HPV vaccine pregnancy registry.


title: HPV vaccine

text: The HPV vaccines are based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The natural virus capsid is composed of two proteins, L1 and L2, but vaccines only contain L1.


title: HPV vaccine

text: Gardasil contains inactive L1 proteins from four different HPV strains: 6, 11, 16, and 18, synthesized in the yeast "Saccharomyces cerevisiae". Each vaccine dose contains 225 µg of aluminum, 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 µg of polysorbate 80, 35 µg of sodium borate, and water. The combination of ingredients totals 0.5 mL.


title: HPV vaccine

text: HPV types 16 and 18 cause about 70% of all cervical cancer. Gardasil also targets HPV types 6 and 11, which together cause about 90 percent of all cases of genital warts.


title: HPV vaccine

text: Gardasil and Cervarix are designed to elicit virus-neutralizing antibody responses that prevent initial infection with the HPV types represented in the vaccine. The vaccines have been shown to offer 100 percent protection against the development of cervical pre-cancers and genital warts caused by the HPV types in the vaccine, with few or no side effects. The protective effects of the vaccine are expected to last a minimum of 4.5 years after the initial vaccination.


title: HPV vaccine

text: While the study period was not long enough for cervical cancer to develop, the prevention of these cervical precancerous lesions (or dysplasias) is believed highly likely to result in the prevention of those cancers.


title: HPV vaccine

text: The vaccine was first developed by the University of Queensland in Australia and the final form was made by researchers at the University of Queensland, Georgetown University Medical Center, University of Rochester, and the U.S. National Cancer Institute. Researchers Ian Frazer and Jian Zhou at the University of Queensland have been accorded priority under U.S. patent law for the invention of the HPV vaccine's basis, the VLPs. In 2006, the FDA approved the first preventive HPV vaccine, marketed by Merck & Co. under the trade name Gardasil. According to a Merck press release, by the second quarter of 2007 it had been approved in 80 countries, many under fast-track or expedited review. Early in 2007, GlaxoSmithKline filed for approval in the United States for a similar preventive HPV vaccine, known as Cervarix. In June 2007, this vaccine was licensed in Australia, and it was approved in the European Union in September 2007. Cervarix was approved for use in the U.S. in October 2009.


title: HPV vaccine

text: Harald zur Hausen, a German researcher who suspected, and later helped to prove that genital HPV infection can lead to cervical cancer, was awarded half of the $1.4 million Nobel Prize in Medicine in 2008 for his work. Verification that cervical cancer is caused by an infectious agent led several other groups to develop vaccines against HPV strains that cause most cases of cervical cancer. The other half of the award went to Françoise Barré-Sinoussi and Luc Montagnier, two French virologists, for their part in the discovery of HIV.


title: HPV vaccine

text: Harald zur Hausen was skeptical of the prevailing dogma and postulated that oncogenic human papilloma virus (HPV) caused cervical cancer. He realized that HPV-DNA could exist in an inactive state in the tumours, and should be detectable by specific searches for viral DNA. He and workers at the Pasteur Institute found HPV to be a heterogeneous family of viruses. Only some HPV types cause cancer.


title: HPV vaccine

text: Harald zur Hausen pursued his research for over ten years searching for different HPV types. This research was difficult because only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.


title: HPV vaccine

text: His observation of HPV oncogenic potential in human malignancy provided impetus within the research community to characterize the natural history of HPV infection, and to develop a better understanding of mechanisms of HPV-induced carcinogenesis.


title: HPV vaccine

text: In December 2014, the US Food and Drug Administration (FDA) approved a vaccine called Gardasil 9 to protect females between the ages of 9 and 26 and males between the ages of 9 and 15 against nine strains of HPV. Gardasil 9 protects against infection from the strains covered by the first generation of Gardasil (HPV-6, HPV-11, HPV-16, and HPV-18) and protects against five other HPV strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58).


title: HPV vaccine

text: , vaccinating girls and young women was estimated to be cost-effective in the low and middle-income countries, especially in places without organized programs for screening cervical cancer. When the cost of the vaccine itself, or the cost of administering it to individuals, were higher, or if cervical cancer screening were readily available, then vaccination was less likely to be cost-effective.


title: HPV vaccine

text: From a public health point of view, vaccinating men as well as women decreases the virus pool within the population, but is only cost-effective to vaccinate men when the uptake in the female population is extremely low. In the United States, the cost per quality-adjusted life year is greater than US$100,000 for vaccinating the male population, compared to the less than US$50,000 for vaccinating the female population. This assumes a 75% vaccination rate.


title: HPV vaccine

text: In 2013, the two companies who sell the most common vaccines announced a price cut to less than US$5 per dose to poor countries, as opposed to US$130 per dose in the U.S.


title: HPV vaccine

text: In developed countries, the widespread use of cervical "Pap smear" screening programs has reduced the incidence of invasive cervical cancer by 50% or more. Preventive vaccines reduce but do not eliminate the chance of getting cervical cancer. Therefore, experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination. School-entry vaccination requirements were found to increase the use of the HPV vaccine.


title: HPV vaccine

text: Due to the COVID-19 pandemic (2019–2021), HPV vaccination programs have been significantly affected in the United States, low-income and lower-middle income countries. On 30 August 2021, fifteen leading academic and freestanding cancer centers with membership in the Association of American Cancer Institutes (AACI), all National Cancer Institute (NCI)-designated cancer centers, the American Cancer Society, the American Society of Clinical Oncology, the American Association for Cancer Research, and the St. Jude Children's Research Hospital have issued a joint statement urging the U.S. health care systems, physicians, parents, children and young adults to get HPV vaccination and other recommended vaccinations back on track during the National Immunization Awareness Month.


title: HPV vaccine

text: With support from the GAVI Alliance, a number of low-income African countries have begun rollout of the HPV vaccine, with others to follow. In 2013 Ghana, Kenya, Madagascar, Malawi, Niger, Sierra Leone, and the United Republic of Tanzania begin implementation of the vaccine. In 2014, Rwanda will begin nationwide rollout, and demonstration programs will take place in Mozambique and Zimbabwe.


title: HPV vaccine

text: In April 2007, Australia became the second country—after Austria—to introduce a government-funded National Human Papillomavirus (HPV) Vaccination Program to protect young women against HPV infections that can lead to cancers and disease. The National HPV Vaccination Program is listed on the National Immunisation Program (NIP) Schedule and funded under the Immunise Australia Program. The Immunise Australia Program is a joint Federal, State, and Territory Government initiative to increase immunisation rates for vaccine-preventable diseases.


title: HPV vaccine

text: The National HPV Vaccination Program for females was made up of two components: an ongoing school-based program for 12- and 13-year-old girls; and a time-limited catch-up program (females aged 14–26 years) delivered through schools, general practices, and community immunization services, which ceased on 31 December 2009.


title: HPV vaccine

text: During 2007–2009, an estimated 83% of females aged 12–17 years received at least one dose of HPV vaccine and 70% completed the 3-dose HPV vaccination course. By 2017, HPV coverage data on the Immunise Australia website show that by 15 years of age, over 82% of Australian females had received all three doses.


title: HPV vaccine

text: Since the National HPV Vaccination Program commenced in 2007, there has been a reduction in HPV-related infections in young women. A study published in "The Journal of Infectious Diseases" in October 2012 found the prevalence of vaccine-preventable HPV types (6, 11, 16 and 18) in Papanicolaou test results of women aged 18–24 years has significantly decreased from 28.7% to 6.7% four years after the introduction of the National HPV Vaccination Program. A 2011 report published found the diagnosis of genital warts (caused by HPV types 6 and 11) had also decreased in young women and men.


title: HPV vaccine

text: In October 2010, the Australian regulatory agency, the Therapeutic Goods Administration, extended the registration of the quadrivalent vaccine (Gardasil) to include use in males aged 9 through 26 years of age, for the prevention of external genital lesions and infection with HPV types 6, 11, 16 and 18.


title: HPV vaccine

text: In November 2011, the Pharmaceutical Benefits Advisory Committee (PBAC) recommended the extension of the National HPV Vaccination Program to include males. The PBAC made its recommendation on the preventive health benefits that can be achieved, such as a reduction in the incidence of anal and penile cancers and other HPV-related diseases. In addition to the direct benefit to males, it was estimated that routine HPV vaccination of adolescent males would contribute to the reduction of vaccine HPV-type infection and associated disease in women through herd immunity.


title: HPV vaccine

text: In 2012, the Australian Government announced it would be extending the National HPV Vaccination Program to include males, through the National Immunisation Program Schedule.


title: HPV vaccine

text: In July 2006, human papillomavirus vaccine against four types of HPV was authorized in Canada for females 9 to 26 years. In February 2010, use in males 9 to 26 years of age for prevention of genital warts was authorized.


title: HPV vaccine

text: Canada has approved use of Gardasil. Initiating and funding free vaccination programs has been left to individual Province/Territory Governments. All Provincial/Territorial governments offer free vaccination for school-aged children, irrespective of gender, at grade 4 (Quebec), grade 6 (British Columbia, Alberta, Saskatchewan, Manitoba, Newfoundland and Labrador, Prince Edward Island, Yukon, Northwest Territories and Nunavut ) or grade 7 (Ontario, Nova Scotia and New Brunswick) level.


title: HPV vaccine

text: GlaxoSmithKline China announced in 2016, that Cervarix (HPV vaccine 16 and 18) had been approved by the China Food and Drug Administration (CFDA). Cervarix is registered in China for girls aged 9 to 45, adopting 3-dose program within 6 months. Cervarix was launched in China in 2017, and it was the first approved HPV vaccine in China.


title: HPV vaccine

text: The vaccine was introduced in 2012, approved for girls aged 9. The HPV vaccine was initially offered to girls aged 9 and older, and attending the fourth grade of school. Since 2013 the age of coverage was extended to girls in school from grade four (who have reached the age of 9) to grade eleven (independent of age); and no schooling from age 9–17 years 11 months and 29 days old.


title: HPV vaccine

text: Since June 2019, the vaccine is administered compulsorily by the state, free of charge to girls at ten years of age.


title: HPV vaccine

text: HPV vaccines are approved for use in Hong Kong. As part of the Hong Kong Childhood Immunisation Programme, HPV vaccines became mandatory for students in the 2019/2020 school year, exclusively for females at primary 5 and 6 levels.


title: HPV vaccine

text: HPV vaccination has been recommended by the National Technical Advisory Group on Immunization, but has not been implemented in India as of 2018.