title: Thom Yorke

text: Yorke composed music for a 2015 production of Harold Pinter's 1971 play "Old Times" by the Roundabout Theater Company in New York City. The director described the music as "primeval, unusual ... the sort of neurosis within [Yorke's] music certainly has elucidated elements of the compulsive repetition of the play." That year, Yorke performed with Godrich and the audiovisual artist Tarik Barri at the Latitude Festival in the UK and the Summer Sonic Festival in Japan. Radiohead released their ninth album, "A Moon Shaped Pool", on 8 May 2016. Yorke contributed vocals and appeared in the video for "Beautiful People" on Mark Pritchard's 2016 album "Under the Sun".


title: Thom Yorke

text: Yorke's first feature film soundtrack, "Suspiria," composed for the 2018 horror film, was released on 26 October 2018 by XL. It was produced by Yorke and Sam Petts-Davies and features the London Contemporary Orchestra and Choir and Yorke's son Noah on drums. Yorke cited inspiration from the 1982 "Blade Runner" soundtrack and music from "Surpiria"'s 1977 Berlin setting, such as krautrock. The lyrics do not follow the film narrative and were influenced by discourse surrounding President Donald Trump and Brexit. "Suspirium" was nominated for Best Song Written for Visual Media at the 2020 Grammy Awards.


title: Thom Yorke

text: Yorke performed two shows in 2017, and toured Europe and the US in 2018. That year, Yorke and the artist Tarik Barri created an audiovisual exhibition, "City Rats", commissioned by the Institute for Sound and Music in Berlin. "I See You", a limited-edition zine edited by Yorke with "Crack Magazine", was published in September 2018, with profits donated to Greenpeace. Yorke contributed music to the 2018 short films "Why Can't We Get Along?" and "Time of Day" for the fashion label Rag & Bone.


title: Thom Yorke

text: Radiohead were inducted into the Rock and Roll Hall of Fame on 29 March 2019. Yorke did not attend the induction ceremony, citing cultural differences between the UK and America and his negative experience of the Brit Awards, "which is like this sort of drunken car crash that you don't want to get involved with".


title: Thom Yorke

text: Yorke's third solo album, "Anima", was released on 27 June 2019, accompanied by a short film directed by Paul Thomas Anderson. "Anima" became Yorke's first number-one album on the "Billboard" Dance/Electronic Albums chart. At the 2020 Grammy Awards, it was nominated for Best Alternative Music Album and Best Boxed or Special Limited Edition Package; the "Anima" film was nominated for the Grammy for Best Music Film. The album was followed by "Not the News Rmx EP", comprising an extended version of the track "Not the News" plus remixes by various artists. A solo tour set to begin in March 2020 was canceled due to the COVID-19 pandemic.


title: Thom Yorke

text: For the 2019 film "Motherless Brooklyn", Yorke wrote "Daily Battles", with horns by his Atoms for Peace bandmate Flea. The director, Edward Norton, enlisted the jazz musician Wynton Marsalis to rearrange the song as a ballad reminiscent of 1950s Miles Davis. It was shortlisted for Best Original Song at the 92nd Academy Awards. Yorke's first classical composition, "Don't Fear the Light", written for the piano duo Katia and Marielle Labeque, debuted in April 2019. In April 2020, Yorke performed a new song from his home, "Plasticine Figures", for "The Tonight Show". In the same year, he collaborated with Four Tet and Burial again on "Her Revolution" and "His Rope".


title: Thom Yorke

text: In March 2021, Yorke contributed music to shows by the Japanese fashion designer Jun Takahashi, including a remixed version of "Creep". That August, he contributed two remixes of "Gazzillion Ear" by the rapper MF Doom.


title: Thom Yorke

text: In May, Yorke debuted a new band, the Smile, with Jonny Greenwood and the jazz drummer Tom Skinner, produced by Godrich. Greenwood said the project was a way for him and Yorke to work together during the COVID-19 lockdowns. The Smile made their surprise debut in a performance streamed by Glastonbury Festival on May 22, with Yorke singing and playing guitar, bass, Moog synthesiser and Rhodes piano. The "Guardian" critic Alexis Petridis said the Smile "sound like a simultaneously more skeletal and knottier version of Radiohead", exploring more progressive rock influences with unusual time signatures, complex riffs and "hard-driving" motorik psychedelia. That October, Yorke performed a Smile song, "Free in the Knowledge", at the Letters Live event at the Royal Albert Hall, London, and he and Stanley Donwood curated an exhibition of "Kid A" artwork and lyrics at Christie's headquarters in London.


title: Thom Yorke

text: On 9 April 2022, Yorke performed a solo concert at the Zeltbühne festival in Zermatt, Switzerland, playing songs from his work with Radiohead, the Smile and Unkle, and his solo records. In May 2022, the Smile released their debut album, "A Light for Attracting Attention", and began a European tour. Yorke contributed two songs, "5.17" and "That's How Horses Are", to the sixth series of the television drama "Peaky Blinders".


title: Thom Yorke

text: Yorke writes the first versions of most Radiohead songs, after which they are developed harmonically by Jonny Greenwood before the other band members develop their parts. He said the nature of being a creative person was "to retain a beginner's mind. The search is the point. The flailing around is the point. The process is the point."


title: Thom Yorke

text: Yorke's solo work comprises mainly electronic music. "Stereogum" characterised it as "largely interior", "frigid" and "beat-driven", unlike the "wide-open horizons" of Radiohead songs.


title: Thom Yorke

text: Yorke has worked with the producer Nigel Godrich on most of his projects, including Radiohead, the Smile and most of his solo work. Yorke credits Godrich with helping edit his work, identifying which parts need improvement and which have potential. He said they sometimes have arguments that last for days, but that they always resolve their differences, likening their relationship to brothers. Godrich said the pair were "very productive together and that's a really precious and important thing and it changes in within the context of whatever we're doing".


title: Thom Yorke

text: Yorke is a multi-instrumentalist, and plays instruments including guitar, piano, bass and drums. He played drums for performances of the 2007 Radiohead song "Bangers and Mash". With the Smile, Yorke has used a Fender Mustang bass with a fingerstyle technique.


title: Thom Yorke

text: Yorke uses electronic instruments such as synthesisers, drum machines and sequencers, and electronic techniques including programming, sampling and looping. In 2015, he said: "Really I just enjoy writing words sitting at a piano. I tend to lose interest in the drum machine." According to Godrich, "Thom will sit down and make some crazy, fractured cheese-grater-on-head mayhem on a computer, but at some point he always gets his guitar out to check he can actually play it."


title: Thom Yorke

text: Unlike Greenwood, Yorke does not read sheet music; he said: "You can't express the rhythms properly like that. It's a very ineffective way of doing it, so I've never really bothered picking it up." Explaining why he turned down a request to play piano on the song "Mr. Bellamy" on Paul McCartney's album "Memory Almost Full" (2007)"," Yorke said: "The piano playing involved two hands doing things separately. I don't have that skill available. I said to him, 'I strum piano, that's it.'"


title: Thom Yorke

text: Yorke has one of the widest vocal ranges in popular music. He is known for his falsetto", "which "Paste" described as "sweet", "cautious" and "haunting". "Rolling Stone "described his voice as a "broad, emotive sweep" with a "high, keening sound". The "Guardian" described it as "instrument-like" and "spectral", and wrote that it "transcends the egocentric posturing of the indie rock singer stereotype". The music journalist Robert Christgau wrote that Yorke's voice has "a pained, transported intensity, pure up top with hints of hysterical grit below ... Fraught and self-involved with no time for jokes, not asexual but otherwise occupied, and never ever common, this is the idealised voice of a pretentious college boy ... Like it or not the voice is remarkable."


title: Thom Yorke

text: Yorke often manipulates his voice with software and effects, transforming it into a "disembodied instrument". For example, on "Everything in Its Right Place" (2000), his vocals are treated to create a "glitching, stuttering collage". "Pitchfork" wrote in 2016 that, over the decades, Yorke's voice had evolved from "semi-interesting alt-rocker" to "left-field art-rock demigod" to "electronic grand wizard". In 2006, Yorke said: "It annoys me how pretty my voice is. That sounds incredibly immodest, but it annoys me how polite it can sound when perhaps what I'm singing is deeply acidic." He said he keeps vocals in mind whenever he builds music, no matter the genre: "It's almost impossible for me to listen to a dance tune from beginning to end without picturing a voice."


title: Thom Yorke

text: In 2005, readers of "Blender" and MTV2 voted Yorke the 18th greatest singer of all time. In 2008, "Rolling Stone" ranked him the 66th and wrote that he was one of the most influential singers of his generation, influencing bands including Muse, Coldplay, Travis and Elbow.


title: Thom Yorke

text: Though Yorke's early lyrics were personal, from "Kid A" he experimented with cutting up words and phrases and assembling them at random. He deliberately uses cliches, idioms and other common expressions, suggesting "a mind consumed by meaningless data". For example, according to the "Pitchfork" writer Rob Mitchum, the "Kid A" lyrics feature "hum-drum observations twisted into panic attacks". The "New Republic" writer Ryan Kearney speculated that Yorke's use of common expressions, which he described as "Radioheadisms", was an attempt "to sap our common tongue of meaning and expose the vapidity of everyday discourse". A 2021 study found that Yorke had among the largest vocabularies of pop singers, based on the number of different words used in each song.


title: Thom Yorke

text: Yorke's lyrics express paranoia; the "Guardian" critic Alexis Petridis described "what you might call the Yorke worldview: that life is a waking nightmare and everything is completely and perhaps irreparably screwed". According to Yorke, many of his lyrics are motivated by anger, expressing his political and environmental concerns and written as "a constant response to doublethink". The lyrics of the 2003 Radiohead album "Hail to the Thief "dealt with what Yorke called the "ignorance and intolerance and panic and stupidity" following the 2000 election of US President George W. Bush and the unfolding War on Terror. Yorke wrote his 2006 single "Harrowdown Hill" about David Kelly, the British weapons expert and whistleblower. In a 2008 television performance of "House of Cards", Yorke dedicated the "denial, denial" refrain to Bush for rejecting the Kyoto Protocol, an international treaty to reduce greenhouse gases. The 2011 single "The Daily Mail" attacks the right-wing "Daily Mail" newspaper.


title: Thom Yorke

text: In a 2015 interview with the activist and writer George Monbiot, Yorke said: "In the 60s, you could write songs that were like calls to arms, and it would work. It's much harder to do that now ... If I was going to write a protest song about climate change in 2015, it would be shit. It's not like one song or one piece of art or one book is going to change someone's mind." Working on Radiohead's ninth album, "A Moon Shaped Pool", Yorke worried that political songs alienated some listeners, but decided it was better than writing "another lovey-dovey song about nothing". "Pitchfork" wrote that Yorke's lyrics on "A Moon Shaped Pool" were less cynical, conveying wonder and amazement. Many critics felt the album's lyrics might address Yorke's separation from Rachel Owen, his partner of more than 20 years. However, in 2019, Yorke denied writing biographically, saying he instead writes "spasmodic" lyrics based on imagery.


title: Thom Yorke

text: Yorke often incorporates dance into his performances, described by the "Times" as his "on-stage signature". He began dancing on stage after Radiohead released "Kid A" in 2000, as "I suddenly didn't have a guitar around my neck". His dancing features in music videos for songs such as "Lotus Flower" and "Ingenue", and the short film "Anima". Critics have described it as "erratic", "flailing" and unconventional. In 2011, "Rolling Stone" readers voted Yorke their 10th-favourite dancing musician.


title: Thom Yorke

text: As a child, Yorke's favourite artists included Queen. He said the acts that "changed his life" as a teenager were R.E.M., Siouxsie and the Banshees, Joy Division and Bob Dylan. He also wrote that Mark Mulcahy of Miracle Legion had affected him "a great deal" at this time: "It was the voice of someone who was only truly happy when he was singing ... It changed the way I thought about songs and singing."


title: Thom Yorke

text: When he was 16, Yorke sent a demo to a music magazine, who wrote that he sounded like Neil Young. Unfamiliar with Young, Yorke purchased his 1970 album "After the Gold Rush" and "immediately fell in love with his music". Yorke said: "It was his attitude toward the way he laid songs down. It's always about laying down whatever is in your head at the time and staying completely true to that, no matter what it is." Yorke also credited Young as a major lyrical influence.


title: Thom Yorke

text: Yorke cited the Pixies, Björk and PJ Harvey as artists who "changed his life", and in 2006 he told "Pitchfork" that Radiohead had "ripped off R.E.M. blind for years". He said that Michael Stipe of R.E.M. is his favourite lyricist: "I loved the way he would take an emotion and then take a step back from it and in doing so make it so much more powerful." The chorus of "How to Disappear Completely" from "Kid A" was inspired by Stipe, who advised Yorke to relieve tour stress by repeating to himself: "I'm not here, this isn't happening." Yorke cited the Red Hot Chili Peppers guitarist John Frusciante as an influence on his guitar playing on "In Rainbows," and Scott Walker as an influence on his vocals and lyrics.


title: Thom Yorke

text: After "OK Computer", Yorke and Radiohead incorporated influences from electronic artists such as Aphex Twin and Autechre. In 2013, Yorke cited Aphex Twin as his biggest influence, saying: "He burns a heavy shadow ... Aphex opened up another world that didn't involve my fucking electric guitar ... I hated all the music that was around Radiohead at the time, it was completely fucking meaningless. I hated the Britpop thing and what was happening in America, but Aphex was totally beautiful."


title: Thom Yorke

text: Since "My Iron Lung" (1994), Yorke has created artwork for Radiohead and his other projects with Stanley Donwood. The pair met as art students at the University of Exeter; Donwood said his first impression of Yorke was that he was "mouthy. Pissed off. Someone I could work with." Yorke is credited for artwork alongside Donwood as the White Chocolate Farm, Tchock, Dr. Tchock and similar abbreviations.


title: Thom Yorke

text: Whereas Donwood described himself as having a "tendency towards Virgo-like detailing and perfectionism", he said Yorke is "completely opposed, fucking everything up ... I do something, then he fucks it up, then I fuck up what he's done … and we keep doing that until we're happy with the result. It's a competition to see who 'wins' the painting, which one of us takes possession of it in an artistic way." The artist Tarik Barri provides live visuals for Yorke's solo and multimedia projects and shows with Atoms for Peace.


title: Thom Yorke

text: Yorke has been critical of the music industry and has pioneered alternative release platforms with Radiohead and his solo work. Following Radiohead's tour of America in 1993, he became disenchanted with being "right at the sharp end of the sexy, sassy, MTV eye-candy lifestyle" he felt he was helping sell. After a 1995 "Melody Maker" article suggested that Yorke would kill himself like the Nirvana singer Kurt Cobain, Yorke developed an aversion to the British music press.


title: Thom Yorke

text: The 1998 documentary "Meeting People Is Easy" portrays Yorke's disaffection with the music industry and press during Radiohead's "OK Computer" tour. After Radiohead's fourth album, "Kid A" (2000), was leaked via the peer-to-peer filesharing software Napster weeks before release, Yorke told "Time" he felt Napster "encourages enthusiasm for music in a way that the music industry has long forgotten to do. I think anybody sticking two fingers up at the whole fucking thing is wonderful as far as I'm concerned."


title: Thom Yorke

text: After Radiohead's record contract with EMI ended with the release of "Hail to the Thief" (2003)," "Yorke told "Time": "I like the people at our record company, but the time is at hand when you have to ask why anyone needs one. And, yes, it probably would give us some perverse pleasure to say 'Fuck you' to this decaying business model." In 2006, he called major record labels "stupid little boys' games "–" especially really high up". Radiohead independently released their 2007 album "In Rainbows "as a download for which listeners could choose their price; Yorke said the "most exciting" part of the release was the removal of the barrier between artist and audience. However, in 2013, Yorke told the "Guardian" he feared the "In Rainbows" release had instead played into the hands of content providers such as Apple and Google: "They have to keep commodifying things to keep the share price up, but in doing so they have made all content, including music and newspapers, worthless, in order to make their billions. And this is what we want?" In 2015, he criticised YouTube for "seizing control" of contributor content, likening it to Nazis looting art during World War II.


title: Thom Yorke

text: In 2013, Yorke and Godrich made headlines for their criticism of the music streaming service Spotify, and removed Atoms for Peace and Yorke's solo music from the service. In a series of tweets, Yorke wrote: "Make no mistake, new artists you discover on Spotify will not get paid. Meanwhile, shareholders will shortly be rolling in it ... New artists get paid fuck-all with this model." Yorke called Spotify "the last gasp of the old industry", accusing it of only benefiting major labels with large back catalogues, and encouraged artists to build their own "direct connections" with audiences instead. His music was re-added to Spotify in December 2017.


title: Thom Yorke

text: For Yorke's second solo album, "Tomorrow's Modern Boxes" (2014)"," released via BitTorrent, he and Godrich expressed their hope to "hand some control of internet back to people who are creating the work ... bypassing the self-elected gatekeepers". Asked if the release had been a success, Yorke said: "No, not exactly ... I wanted to show that, in theory, today one could follow the entire chain of record production, from start to finish, on his own. But in practice it is very different. We cannot be burdened with all of the responsibilities of the record label."


title: Thom Yorke

text: In 2000, during the recording of "Kid A", Yorke became "obsessed" with the Worldwatch Institute website, "which was full of scary statistics about icecaps melting and weather patterns changing". He said he became involved in the movement to halt climate change after having children and "waking up every night just terrified".


title: Thom Yorke

text: Yorke has been a supporter of Friends of the Earth and their Big Ask Campaign since 2003. He and Jonny Greenwood headlined the Big Ask Live, a 2006 benefit concert to persuade the government to enact a new law on climate change. In a "Guardian" article, Yorke wrote:


title: Thom Yorke

text: In 2006, Yorke refused an invitation from Friends of the Earth to meet the British prime minister, Tony Blair, to discuss climate change. Yorke said that Blair had "no environmental credentials" and that his spin doctors would manipulate the meeting. He told the "Guardian" that Blair's advisers had wanted to vet Yorke beforehand, and that Friends of the Earth would lose access if Yorke said "the wrong thing" afterwards, which he equated to blackmail.


title: Thom Yorke

text: In 2008, Radiohead commissioned a study to reduce the carbon expended on tour. Based on the findings, they chose to play at venues supported by public transport, made deals with trucking companies to reduce emissions, used new low-energy LED lighting and encouraged festivals to offer reusable plastics. That year, Yorke guest-edited a special climate change edition of "Observer Magazine" and wrote: "Unlike pessimists such as James Lovelock, I don't believe we are all doomed ... You should never give up hope."


title: Thom Yorke

text: In 2009, Yorke performed via Skype at the premier of the environmentalist documentary "The Age of Stupid," and gained access to the COP 15 climate change talks in Copenhagen by posing as a journalist. In 2010, he performed a benefit concert at the Cambridge Corn Exchange for the British Green Party and supported the campaign for climate change mitigation. The following year, he joined the maiden voyage of "Rainbow Warrior III, "a yacht used by Greenpeace to monitor damage to the environment.


title: Thom Yorke

text: Yorke was one of several celebrities who endorsed the parliamentary candidacy of the Green candidate Caroline Lucas at the 2015 UK general election. In December 2015, he performed at the United Nations Climate Change Conference in Paris at a benefit concert in aid of 350.org, an environmental organisation raising awareness about climate change. His performance was included on the live album "Pathway to Paris", released in July 2016. Yorke contributed an electronic track, "Hands Off the Antarctic", to a 2018 Greenpeace campaign.


title: Thom Yorke

text: In April 2017, more than 50 prominent figures, including the musicians Roger Waters and Thurston Moore, the rights activist Desmond Tutu and the filmmaker Ken Loach, signed a petition urging Radiohead to cancel an Israel performance as part of Boycott, Divestment and Sanctions, a cultural boycott of Israel. In a "Rolling Stone" interview, Yorke said of the criticism: "I just can't understand why going to play a rock show or going to lecture at a university [is a problem to them] ... It's really upsetting that artists I respect think we are not capable of making a moral decision ourselves after all these years. They talk down to us and I just find it mind-boggling that they think they have the right to do that."


title: Thom Yorke

text: Yorke said that the petitioners had not contacted him. This was disputed by Waters, who wrote in an open letter in "Rolling Stone" that he had attempted to contact Yorke several times. In a statement, Yorke responded: "Playing in a country isn't the same as endorsing the government. Music, art and academia is about crossing borders not building them, about open minds not closed ones, about shared humanity, dialogue and freedom of expression."


title: Thom Yorke

text: Yorke is vegetarian and has criticised the meat industry. He stopped eating meat partially out of the desire to attract a girl he liked. In a 2005 film for the animal rights foundation Animal Aid, he said: "Society deems it necessary to create this level of suffering in order for [people] to eat food that they don't need ... you should at least be aware of what you're doing rather than assuming that that's your right as a human being to do it."


title: Thom Yorke

text: In 1999, Yorke travelled to the G8 summit to support the Jubilee 2000 movement calling for cancellation of third-world debt. In a 2003 "Guardian" article criticising the World Trade Organization, he wrote: "The west is creating an extremely dangerous economic, environmental and humanitarian time bomb. We are living beyond our means." In 2005, he performed at an all-night vigil for the Trade Justice Movement, calling for a better trade deal for poor countries.


title: Thom Yorke

text: In 2002, Yorke performed at the Bridge School Benefit, a charity concert organised by the American songwriter Neil Young, one of Yorke's influences. His set included a cover of Young's 1970 song "After the Gold Rush", performed on the piano Young wrote it on. In September 2004, Yorke was a key speaker at a Campaign for Nuclear Disarmament rally outside the Fylingdales air base in Yorkshire, protesting Tony Blair's support of the Bush administration's plans for the "Star Wars" missile defence system. In 2011, alongside Robert Del Naja of Massive Attack and Tim Goldsworthy of Unkle, Yorke played a secret DJ set for a group of Occupy activists in the abandoned offices of the investment bank UBS.


title: Thom Yorke

text: To celebrate the 2008 election of US president Barack Obama, Yorke released a remixed version of his single "Harrowdown Hill" as a free download. After the election of Donald Trump in 2016, he tweeted lyrics from Radiohead's single "Burn the Witch", interpreted as a criticism of Trump's policies. In June 2016, following the Orlando nightclub shooting in Florida, Yorke was one of nearly 200 music industry figures to sign an open letter published in "Billboard" urging the United States Congress to impose stricter gun control. He opposed Brexit, and in March 2019 joined the People's Vote march calling for a second referendum.


title: Thom Yorke

text: Yorke lives in Oxfordshire. He practises yoga and meditation. He has suffered from anxiety and depression, which he treats with exercise, yoga and reading. Yorke's only sibling, his younger brother Andy, was the singer of the band Unbelievable Truth from 1993 until 2000.


title: Thom Yorke

text: For 23 years, Yorke was in a relationship with the artist and lecturer Rachel Owen, whom he met while studying at the University of Exeter. In 2012, "Rolling Stone" reported that Owen and Yorke were not married. However, "The Times" later found that they had married in a secret ceremony in Oxfordshire in May 2003. Their son, Noah, was born in 2001, and their daughter, Agnes, in 2004. Agnes collaborated on the artwork and Noah played drums on two tracks on Yorke's 2018 soundtrack album "Suspiria". In September 2021, Noah released a song, "Trying Too Hard (Lullaby)"; "NME" likened its "ghostly" arrangement to Radiohead's album "In Rainbows".


title: Thom Yorke

text: In August 2015, Yorke and Owen announced that they had separated amicably. Owen died from cancer on 18 December 2016, aged 48. In September 2020, Yorke married the Italian actress Dajana Roncione in Bagheria, Sicily. Roncione appears in the video for the Radiohead song "Lift" and Yorke's short film "Anima."


title: David Boreanaz

text: David Boreanaz () is an American actor, television producer, and director known for playing the roles of vampire-turned-private investigator Angel on The WB/UPN "Buffy the Vampire Slayer" supernatural drama (1997–2003) and its spinoff "Angel" (1999–2004); FBI Special Agent Seeley Booth, a homicide investigator, on the Fox television crime procedural comedy-drama series "Bones" (2005–2017); and United States Navy SEAL Master Chief Special Warfare Operator Jason Hayes in the CBS/Paramount+ military drama series "SEAL Team" (2017–present).


title: David Boreanaz

text: Boreanaz was born in Buffalo, New York, where his father, Dave Roberts (born David Thomas Boreanaz), was working as a weather forecaster and children's show ("Rocketship 7") host as Dave Thomas, for ABC affiliate WKBW-TV. His mother, Patti Boreanaz, was a travel agent. He has two older siblings, Bo and Beth. He is of Italian and Slovenian descent on his father's side (the surname Boreanaz is of Slovenian origin). His mother is of half Slovak and part Irish, German, French, and Swiss descent.


title: David Boreanaz

text: When Boreanaz was seven years old, the family moved to the Philadelphia, Pennsylvania, area after his father took a job at WPVI-TV, the ABC affiliate in Philadelphia. Boreanaz was raised Catholic and attended Rosemont School of the Holy Child at Rosemont, Pennsylvania and then high school at Malvern Preparatory School in Malvern, Pennsylvania, where he was a keen athlete and played on the school football team. He graduated from Ithaca College in Ithaca, New York, in 1991 with a degree in cinema and photography.


title: David Boreanaz

text: Boreanaz moved to Los Angeles with a degree in filmmaking, but found it hard to gain work initially like many other struggling actors. Boreanaz slept on a couch at his sister's place, visiting film sets and doing production assistant work in order to learn more about the industry he hoped to be more involved with. He was a background extra in the 1993 movie "Aspen Extreme" as a fan waving at skiers. He also prepared props for "Best of the Best II" (also released in 1993), which stars Eric Roberts, where he also had a small uncredited role; Boreanaz is seen briefly standing to the left, as the characters Tommy Lee and Alex enter a nightclub (which is a front for an illegal fighting ring).


title: David Boreanaz

text: Boreanaz's first paid acting appearance was a 1993 guest spot on the American sitcom "Married... with Children", as Kelly's unfaithful biker boyfriend, who gets pummeled by her father, Al. He was cast in the television series "Buffy the Vampire Slayer", after being suggested for the role to Marti Noxon by one of Boreanaz's neighbors, after he was seen walking his dog past their house on a regular basis. In the cult series, he played the mysterious Angel, a vampire cursed by Romani people with a soul as punishment for his murdering a Romani girl, initially resulting in debilitating remorse and then a life of contrition. The show became enormously successful and Boreanaz starred in a spin-off series, "Angel", which gave the character a chance to evolve and concentrated on Angel's battle for redemption for the numerous murders he committed before he regained his soul. He appeared on "Buffy" from 1997 to 1999, at which point he began starring in "Angel", which ran until 2004, with a recurring role on "Buffy" after his departure. He also appeared in the film "Macabre Pair of Shorts" where he plays a vampire's victim (in the segment "MPS").


title: David Boreanaz

text: Boreanaz's only starring role in a major theatrical film was in 2001's slasher horror film "Valentine", alongside Denise Richards and Katherine Heigl. In 2002, he had a supporting role in a movie titled "I'm with Lucy". He was also to appear in the 2002 film "Resident Evil" as the main character, but turned down the role. In 2003, he appeared in the music video for singer Dido's hit single "White Flag", and was the voice of Leon (Squall Leonhart) in the video game "Kingdom Hearts", but he did not reprise his role in the sequel.


title: David Boreanaz

text: In 2005, Boreanaz began starring opposite Emily Deschanel on the prime time television series "Bones". He also appeared in "These Girls", a Canadian film in which he played a biker; the film received a limited theatrical release in Canada in March 2006, after premiering at the Toronto International Film Festival and the Vancouver International Film Festival. He has also starred in the independent films "Mr. Fix It" and "Suffering Man's Charity" (released on DVD as "Ghost Writer"), as well as the direct-to-DVD sequel "" in which he starred alongside Tara Reid. In 2006, he starred in another DVD release, "The Hard Easy", which also starred Steve Buscemi, Vera Farmiga and Nick Lachey.


title: David Boreanaz

text: In that same year, he also voiced Hal Jordan in the direct-to-video DC Comics animated feature "". In the season three finale of his TV series "Bones", Boreanaz's character Seeley Booth is seen in his bathtub reading an issue of Green Lantern, the character he voiced in that feature. As well as being a producer on "Bones" since its third season, Boreanaz also directed at least one episode every season since Season 4. BuddyTV ranked him No. 13 on its "TV's 100 Sexiest Men of 2010" list and No. 18 in 2011.


title: David Boreanaz

text: In the 2011 movie "The Mighty Macs", Boreanaz played the role of Ed T. Rush, NBA referee and husband of Immaculata basketball coach Cathy Rush. In 2013, Boreanaz starred in the miniseries "Full Circle" as Jace Cooper. The same year, Boreanaz starred in the independently made fantasy drama "Officer Down" as Detective Les Scanlon. Boreanaz has also appeared on "American Dad!" as Seeley Booth in the episode "Less Money, Mo' Problems", on "Family Guy" as himself in the episode "Road to the North Pole", and in the "Baby Blues" episode "Teddy-Cam" as the voice of Johnny.


title: David Boreanaz

text: On March 22, 2017, Boreanaz joined the cast of a CBS drama project based on the United States Navy SEALs. The project received a series order on May 12, 2017, and became known as "SEAL Team", which premiered on September 27, 2017.


title: David Boreanaz

text: Boreanaz was married to Ingrid Quinn from 1997 to 1999. He wed "Playboy" model Jaime Bergman on November 24, 2001. They have a son, born May 1, 2002, and a daughter, born August 31, 2009.


title: David Boreanaz

text: In 2004, Boreanaz underwent reconstructive surgery on the anterior cruciate ligament of his left knee, a result of a running injury he suffered in high school that was not fully corrected at that time. His recovery did not prevent "Angel" production from continuing, but did limit his mobility and physical activities in several episodes, including his directorial debut, "Soul Purpose".


title: David Boreanaz

text: In 2010, Boreanaz admitted to having an extramarital affair with Rachel Uchitel, the same woman with whom Tiger Woods was alleged to have cheated on his wife. Boreanaz has claimed that Uchitel tried to blackmail him. At the time of Boreanaz's affair, his wife was pregnant.


title: David Boreanaz

text: In 2013, Boreanaz, his wife and their friends Melissa and Aaron Ravo started the nail polish line Chrome Girl. The two wives run the day-to-day operations while their husbands help with the overall business. Boreanaz was involved with the creation of the NHL colors line and supports them publicly, while Aaron, who works in advertising, has helped out with PR work and marketing.


title: David Boreanaz

text: A female co-worker on the set of "Bones" sued him in 2010 for sexual harassment stating he repeatedly attempted to kiss and fondle her. In March 2011, the woman's attorney requested the lawsuit be dismissed stating the matter was resolved.


title: Desi Arnaz Jr.

text: Desiderio Alberto Arnaz IV (born January 19, 1953), known professionally as Desi Arnaz Jr., is an American actor and musician. He is the son of Lucille Ball and Desi Arnaz.


title: Desi Arnaz Jr.

text: Arnaz was born on January 19, 1953 at Cedars-Sinai Medical Center in Los Angeles, California. His older sister is actress Lucie Arnaz, who was born in 1951.


title: Desi Arnaz Jr.

text: His birth was one of the most publicized in television history. His parents were the stars of the television sitcom "I Love Lucy", and Ball's pregnancy was part of the story line, which was considered daring in 1952. The same day Ball gave birth to Desi Jr., the fictional Lucy Ricardo gave birth to "Little Ricky." As a testament to how interested the American public was in Lucy's TV baby, Arnaz appeared on the cover of the very first issue of "TV Guide" with the headline "Lucy's $50,000,000 baby," ($ in dollars) because revenue from advertising tie-ins was expected to top that mark. Actor Richard Keith (a.k.a. Keith Thibodeaux) later portrayed "Little Ricky" in the TV series; Keith spent much time with Lucie and Desi Jr. in childhood and became close friends with the family, teaching Desi Jr. how to play drums.


title: Desi Arnaz Jr.

text: At age 12, Arnaz was a drummer with Dino, Desi, & Billy. The others were Dean Paul Martin (son of Dean Martin) and Billy Hinsche. The band scored two hit singles with "I'm a Fool" and "Not the Lovin' Kind" in 1965.


title: Desi Arnaz Jr.

text: From 1968 to 1974, Desi Arnaz and his sister Lucie co-starred opposite their mother in "Here's Lucy" as her children. In 1968, he had a guest-starring role as Jerry and Suzie's drum-playing friend Tommy in the episode, "The Hombre Who Came to Dinner: Part 2," from the show "The Mothers-in-Law", executive-produced and directed by his father. In 1970, he appeared on "The Brady Bunch" episode "The Possible Dream." His best chance at enduring Hollywood fame came in 1973, when he played the title role in the film "Marco", a musical about the life of adventurer Marco Polo. However, like most Hollywood musicals of that period, it failed to register at the box office.


title: Desi Arnaz Jr.

text: In 1974, Arnaz played the title role in the Western movie "Billy Two Hats" with Gregory Peck. In 1976, he appeared on two episodes of the television series, "The Streets of San Francisco". Arnaz also appeared in a 1976 episode of "Saturday Night Live" (SNL) hosted by both Desi Arnaz and Desi Arnaz Jr.. The younger Arnaz played Ricky Ricardo while Gilda Radner played Lucy in spoofs of supposed ill-fated pilots for "I Love Lucy".


title: Desi Arnaz Jr.

text: In 1977, he was the lead in the film "Joyride" opposite fellow children of famous actors Melanie Griffith, Robert Carradine, and Anne Lockhart.


title: Desi Arnaz Jr.

text: Arnaz's acting extended into the late 1980s with various appearances on television, and a leading role in the series "Automan", which ran from 1983 to 1984.


title: Desi Arnaz Jr.

text: In 1992, he played his father in the movie "The Mambo Kings", based on a Pulitzer Prize-winning novel that he felt treated his father with respect. The film includes a scene in which Desi Jr., playing his father's character Ricky Ricardo, acts opposite his mother as Lucy Ricardo with film from the TV series intercut with the cast.


title: Desi Arnaz Jr.

text: Between 1998 and 2010, he was touring with a new configuration of Dino, Desi & Billy called Ricci, Desi & Billy, featuring Arnaz reunited with Billy Hinsche, and joined by Ricci Martin (youngest son of Dean Martin). The group performed original material as well as the songs the original band performed.


title: Desi Arnaz Jr.

text: From about 2002 to 2007, he was vice-president of the board of Directors of the Lucille Ball–Desi Arnaz Center in Jamestown, New York. He resigned over a dispute with the executive director over the center.


title: Desi Arnaz Jr.

text: In 2007, Arnaz appeared at the 5th Annual TV Land Awards with his sister Lucie to accept the "Legacy of Laughter" award posthumously given to their mother.


title: Desi Arnaz Jr.

text: Arnaz has also headlined "Babalu: A Celebration of the Music of Desi Arnaz and his Orchestra" with Lucie Arnaz, Raul Esparza, and Valarie Pettiford.


title: Desi Arnaz Jr.

text: On October 15, 2011, Arnaz performed in "Babalu" at the Coolidge Auditorium of the Library of Congress. The performance was in conjunction with the Library's Lucille Ball and Desi Arnaz Collection.


title: Desi Arnaz Jr.

text: Arnaz has a daughter, Julia Arnaz, from a relationship with model Susan Callahan-Howe in 1968 when they were both 15 years old; Julia's relationship to Desi Jr. was proven by a paternity test in 1991.


title: Desi Arnaz Jr.

text: Arnaz dated actress Patty Duke when he was 17 and she was 23. He accompanied Duke to the 1970 Emmy Awards ceremony where she won the Emmy for Outstanding Single Performance. The relationship became tabloid news and his mother did not approve of them together, and Duke became pregnant. After they broke up, writer and music producer Michael Tell offered to marry Duke as a way out of the scandal. Their marriage lasted only 13 days, and when Duke would later tell her son, Sean Astin, that Arnaz was his biological father, Arnaz and Astin developed a close relationship, although genetic tests later revealed that Tell was his father. Astin said, "I can call any of them on the phone any time I want to ... John, Desi, Mike or Papa Mike ... my four dads." (Michael Pearce, Duke's husband after John Astin, was his step-father.)


title: Desi Arnaz Jr.

text: Arnaz was subsequently involved with entertainer Liza Minnelli, another relationship of which his mother disapproved; Ball thought that the singer-actress was too old for her son and, because of Minnelli's perceived reckless lifestyle, not a good influence upon him. Arnaz accompanied Minnelli to the Academy Awards ceremony in March 1973 when she won the Academy Award for Best Actress.


title: Desi Arnaz Jr.

text: Arnaz married actress Linda Purl in 1979. On January 3, 1980, Purl filed for divorce, which was finalized later that year. On October 8, 1987, Arnaz married Amy Laura Bargiel. The couple lived in Boulder City, Nevada, with their daughter, Haley. In 1997, Arnaz purchased the Boulder Theatre in town and restored it, when it had been on the brink of ruin. After its conversion to a theatre, the cinema became the home of the Boulder City Ballet Company.


title: Desi Arnaz Jr.

text: Desi's wife Amy died of cancer in 2015, at the age of 63. Both Desi and Amy were followers of Vernon Howard and attended meetings of Howard's New Life Foundation in Boulder City. They also followed and have supported the spiritual writer Guy Finley (also one of Vernon Howard's students) and his Life of Learning Center for Spiritual Discovery.


title: Desi Arnaz Jr.

text: Arnaz's granddaughter (daughter of Julia) Desiree S. Anzalone, a photographer, died from breast cancer on September 27, 2020, at the age of 31. She was first diagnosed with cancer when she was 25.


title: Cystic fibrosis

text: Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.


title: Cystic fibrosis

text: Cystic fibrosis is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Those with a single working copy are carriers and otherwise mostly healthy. CFTR is involved in the production of sweat, digestive fluids, and mucus. When the CFTR is not functional, secretions which are usually thin instead become thick. The condition is diagnosed by a sweat test and genetic testing. Screening of infants at birth takes place in some areas of the world.


title: Cystic fibrosis

text: There is no known cure for cystic fibrosis. Lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. Sometimes, the antibiotic azithromycin is used long term. Inhaled hypertonic saline and salbutamol may also be useful. Lung transplantation may be an option if lung function continues to worsen. Pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. Airway clearance techniques such as chest physiotherapy have some short-term benefit, but long-term effects are unclear. The average life expectancy is between 42 and 50 years in the developed world. Lung problems are responsible for death in 80% of people with cystic fibrosis.


title: Cystic fibrosis

text: CF is most common among people of Northern European ancestry, for whom it affects about 1 out of 3,000 newborns, and among which around 1 out of 25 people is a carrier. It is least common in Africans and Asians though it does occur in all races. It was first recognized as a specific disease by Dorothy Andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595. The name "cystic fibrosis" refers to the characteristic fibrosis and cysts that form within the pancreas.


title: Cystic fibrosis

text: Cystic fibrosis typically manifests early in life. Newborns and infants with cystic fibrosis tend to have frequent, large, greasy stools (a result of malabsorption) and are underweight for their age. 15–20% of newborns have their small intestine blocked by meconium, often requiring surgery to correct. Newborns occasionally have neonatal jaundice due to blockage of the bile ducts. Children with cystic fibrosis lose excessive salt in their sweat, and parents often notice salt crystallizing on the skin, or a salty taste when they kiss their child.


title: Cystic fibrosis

text: The primary cause of morbidity and death in people with cystic fibrosis is progressive lung disease, which eventually leads to respiratory failure. This typically begins as a prolonged respiratory infection that continues until treated with antibiotics. Chronic infection of the respiratory tract is nearly universal in people with cystic fibrosis, with "Pseudomonas aeruginosa", fungi, and mycobacteria all increasingly common over time. Inflammation of the upper airway results in frequent runny nose and nasal obstruction. Nasal polyps are common, particularly in children and teenagers. As the disease progresses, people tend to have shortness of breath, and a chronic cough that produces sputum. Breathing problems make it increasingly challenging to exercise, and prolonged illness causes those affected to be underweight for their age. In late adolescence or adulthood, people begin to develop severe signs of lung disease: wheezing, digital clubbing, cyanosis, coughing up blood, pulmonary heart disease, and collapsed lung (atelectasis or pneumothorax).


title: Cystic fibrosis

text: In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some CF patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because clotting factors II, VII, IX, and X are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present.


title: Cystic fibrosis

text: Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing. Other signs include high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such as bilevel positive airway pressure machines or ventilators. "Staphylococcus aureus", "Haemophilus influenzae", and "Pseudomonas aeruginosa" are the three most common organisms causing lung infections in CF patients. In addition, opportunistic infection due to "Burkholderia cepacia" complex can occur, especially through transmission from patient to patient.


title: Cystic fibrosis

text: In addition to typical bacterial infections, people with CF more commonly develop other types of lung diseases. Among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus "Aspergillus fumigatus" causes worsening of breathing problems. Another is infection with "Mycobacterium avium" complex, a group of bacteria related to tuberculosis, which can cause lung damage and do not respond to common antibiotics.


title: Cystic fibrosis

text: Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. Recurrent sinonasal polyps can occur in 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties.


title: Cystic fibrosis

text: Cardiorespiratory complications are the most common causes of death (about 80%) in patients at most CF centers in the United States.


title: Cystic fibrosis

text: In addition, protrusion of internal rectal membranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF, and it is caused by increased fecal volume, malnutrition, and increased intra–abdominal pressure due to coughing.


title: Cystic fibrosis

text: The thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices that help break down food. These secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). The pancreatic ducts are totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive fibrosis.


title: Cystic fibrosis

text: In addition to the pancreas problems, people with CF experience more heartburn, intestinal blockage by intussusception, and constipation. Older individuals with CF may develop distal intestinal obstruction syndrome, which occurs when feces becomes thick with mucus (inspissated) and can cause bloating, pain, and incomplete or complete bowel obstruction.


title: Cystic fibrosis

text: Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF. It is mainly associated with "severe" CFTR mutations, where both alleles are completely nonfunctional (e.g. ΔF508/ΔF508). It occurs in 10% to 15% of patients with one "severe" and one "mild" CFTR mutation where little CFTR activity still occurs, or where two "mild" CFTR mutations exist. In these milder cases, sufficient pancreatic exocrine function is still present so that enzyme supplementation is not required. Usually, no other GI complications occur in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development. Despite this, idiopathic chronic pancreatitis can occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and life-threatening complications.


title: Cystic fibrosis

text: Thickened secretions also may cause liver problems in patients with CF. Bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. Impaired digestion or absorption of lipids can result in steatorrhea. Over time, this can lead to scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for blood clotting. Liver disease is the third-most common cause of death associated with CF.


title: Cystic fibrosis

text: Around 5–7% of people experience liver damage severe enough to cause symptoms: typically gallstones causing biliary colic.


title: Cystic fibrosis

text: The pancreas contains the islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. Damage to the pancreas can lead to loss of the islet cells, leading to a type of diabetes unique to those with the disease. This cystic fibrosis-related diabetes shares characteristics of type 1 and type 2 diabetes, and is one of the principal nonpulmonary complications of CF.


title: Cystic fibrosis

text: Vitamin D is involved in calcium and phosphate regulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone disease osteoporosis in which weakened bones are more susceptible to fractures.


title: Cystic fibrosis

text: Infertility affects both men and women. At least 97% of men with cystic fibrosis are infertile, but not sterile, and can have children with assisted reproductive techniques. The main cause of infertility in men with CF is congenital absence of the vas deferens (which normally connects the testes to the ejaculatory ducts of the penis), but potentially also by other mechanisms such as causing no sperm, abnormally shaped sperm, and few sperm with poor motility. Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Around 20% of women with CF have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes a lack of menstruation.


title: Cystic fibrosis

text: CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator ("CFTR"). The most common mutation, ΔF508, is a deletion (Δ signifying deletion) of three nucleotides that results in a loss of the amino acid phenylalanine (F) at the 508th position on the protein. This mutation accounts for two-thirds (66–70%) of CF cases worldwide and 90% of cases in the United States; however, over 1500 other mutations can produce CF. Although most people have two working copies (alleles) of the "CFTR" gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an autosomal recessive disease.


title: Cystic fibrosis

text: The "CFTR" gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long. More specifically, the location is between base pair 117,120,016 and 117,308,718 on the long arm of chromosome 7, region 3, band 1, subband 2, represented as 7q31.2. Structurally, the "CFTR" is a type of gene known as an ABC gene. The product of this gene (the CFTR protein) is a chloride ion channel important in creating sweat, digestive juices, and mucus. This protein possesses two ATP-hydrolyzing domains, which allows the protein to use energy in the form of ATP. It also contains two domains comprising six alpha helices apiece, which allow the protein to cross the cell membrane. A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase. The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction. The majority of CFTR in the lung's passages is produced by rare ion-transporting cells that regulate mucus properties.


title: Cystic fibrosis

text: In addition, the evidence is increasing that genetic modifiers besides "CFTR" modulate the frequency and severity of the disease. One example is mannan-binding lectin, which is involved in innate immunity by facilitating phagocytosis of microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections.


title: Cystic fibrosis

text: Up to one in 25 individuals of Northern European ancestry is considered a genetic carrier. The disease appears only when two of these carriers have children, as each pregnancy between them has a 25% chance of producing a child with the disease. Although only about one of every 3,000 newborns of the affected ancestry has CF, more than 900 mutations of the gene that causes CF are known. Current tests look for the most common mutations.


title: Cystic fibrosis

text: The mutations screened by the test vary according to a person's ethnic group or by the occurrence of CF already in the family. More than 10 million Americans, including one in 25 white Americans, are carriers of one mutation of the CF gene. CF is present in other races, though not as frequently as in white individuals. About one in 46 Hispanic Americans, one in 65 African Americans, and one in 90 Asian Americans carry a mutation of the CF gene.


title: Cystic fibrosis

text: Several mutations in the "CFTR" gene can occur, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function. ΔF508-CFTR gene mutation, which occurs in >90% of patients in the U.S., creates a protein that does not fold normally and is not appropriately transported to the cell membrane, resulting in its degradation.


title: Cystic fibrosis

text: Other mutations result in proteins that are too short (truncated) because production is ended prematurely. Other mutations produce proteins that do not use energy (in the form of ATP) normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately, and degrade at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.


title: Cystic fibrosis

text: The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body.


title: Cystic fibrosis

text: The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of halide anions from inside to outside of the cell; however, in the sweat ducts, it facilitates the movement of chloride from the sweat duct into the cytoplasm. When the CFTR protein does not resorb ions in sweat ducts, chloride and thiocyanate released from sweat glands are trapped inside the ducts and pumped to the skin.


title: Cystic fibrosis

text: Additionally hypothiocyanite, OSCN, cannot be produced by the immune defense system. Because chloride is negatively charged, this modifies the electrical potential inside and outside the cell that normally causes cations to cross into the cell. Sodium is the most common cation in the extracellular space. The excess chloride within sweat ducts prevents sodium resorption by epithelial sodium channels and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test.


title: Cystic fibrosis

text: Most of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions. These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick feces, etc. Several theories have been posited on how the defects in the protein and cellular function cause the clinical effects. The most current theory suggests that defective ion transport leads to dehydration in the airway epithelia, thickening mucus. In airway epithelial cells, the cilia exist in between the cell's apical surface and mucus in a layer known as airway surface liquid (ASL). The flow of ions from the cell and into this layer is determined by ion channels such as CFTR. CFTR not only allows chloride ions to be drawn from the cell and into the ASL, but it also regulates another channel called ENac, which allows sodium ions to leave the ASL and enter the respiratory epithelium. CFTR normally inhibits this channel, but if the CFTR is defective, then sodium flows freely from the ASL and into the cell.


title: Cystic fibrosis

text: As water follows sodium, the depth of ASL will be depleted and the cilia will be left in the mucous layer. As cilia cannot effectively move in a thick, viscous environment, mucociliary clearance is deficient and a buildup of mucus occurs, clogging small airways. The accumulation of more viscous, nutrient-rich mucus in the lungs allows bacteria to hide from the body's immune system, causing repeated respiratory infections. The presence of the same CFTR proteins in the pancreatic duct and sweat glands in the skin also cause symptoms in these systems.


title: Cystic fibrosis

text: The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread among individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs. This mucus leads to the formation of bacterial microenvironments known as biofilms that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lung by gradually remodeling the airways, which makes infection even more difficult to eradicate. The natural history of CF lung infections and airway remodeling is poorly understood, largely due to the immense spatial and temporal heterogeneity both within and between the microbiomes of CF patients.


title: Cystic fibrosis

text: Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such as "S. aureus" and "H. influenzae" colonize and infect the lungs. Eventually, "Pseudomonas aeruginosa" (and sometimes "Burkholderia cepacia") dominates. By 18 years of age, 80% of patients with classic CF harbor "P. aeruginosa", and 3.5% harbor "B. cepacia". Once within the lungs, these bacteria adapt to the environment and develop resistance to commonly used antibiotics. "Pseudomonas" can develop special characteristics that allow the formation of large colonies, known as "mucoid" "Pseudomonas", which are rarely seen in people who do not have CF. Scientific evidence suggests the interleukin 17 pathway plays a key role in resistance and modulation of the inflammatory response during "P. aeruginosa" infection in CF. In particular, interleukin 17-mediated immunity plays a double-edged activity during chronic airways infection; on one side, it contributes to the control of "P. aeruginosa" burden, while on the other, it propagates exacerbated pulmonary neutrophilia and tissue remodeling.


title: Cystic fibrosis

text: Infection can spread by passing between different individuals with CF. In the past, people with CF often participated in summer "CF camps" and other recreational gatherings. Hospitals grouped patients with CF into common areas and routine equipment (such as nebulizers) was not sterilized between individual patients. This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are now routinely isolated from one another in the healthcare setting, and healthcare providers are encouraged to wear gowns and gloves when examining patients with CF to limit the spread of virulent bacterial strains.


title: Cystic fibrosis

text: CF patients may also have their airways chronically colonized by filamentous fungi (such as "Aspergillus fumigatus", "Scedosporium apiospermum", "Aspergillus terreus") and/or yeasts (such as "Candida albicans"); other filamentous fungi less commonly isolated include "Aspergillus flavus" and "Aspergillus nidulans" (occur transiently in CF respiratory secretions) and "Exophiala dermatitidis" and "Scedosporium prolificans" (chronic airway-colonizers); some filamentous fungi such as "Penicillium emersonii" and "Acrophialophora fusispora" are encountered in patients almost exclusively in the context of CF. Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid treatments may also facilitate fungal growth. Although the clinical relevance of the fungal airway colonization is still a matter of debate, filamentous fungi may contribute to the local inflammatory response and therefore to the progressive deterioration of the lung function, as often happens with allergic bronchopulmonary aspergillosis – the most common fungal disease in the context of CF, involving a Th2-driven immune response to "Aspergillus" species.


title: Cystic fibrosis

text: In many localities all newborns are screened for cystic fibrosis within the first few days of life, typically by blood test for high levels of immunoreactive trypsinogen. Newborns with positive tests or those who are otherwise suspected of having cystic fibrosis based on symptoms or family history, then undergo a sweat test. An electric current is used to drive pilocarpine into the skin, stimulating sweating. The sweat is collected and analyzed for salt levels. Having unusually high levels of chloride in the sweat suggests CFTR is dysfunctional; the person is then diagnosed with cystic fibrosis. Genetic testing is also available to identify the CFTR mutations typically associated with cystic fibrosis. Many laboratories can test for the 30–96 most common CFTR mutations, which can identify over 90% of people with cystic fibrosis.


title: Cystic fibrosis

text: People with CF have less thiocyanate and hypothiocyanite in their saliva and mucus (Banfi et al.). In the case of milder forms of CF, transepithelial potential difference measurements can be helpful. CF can also be diagnosed by identification of mutations in the CFTR gene.


title: Cystic fibrosis

text: In many cases, a parent makes the diagnosis because the infant tastes salty. Immunoreactive trypsinogen levels can be increased in individuals who have a single mutated copy of the "CFTR" gene (carriers) or, in rare instances, in individuals with two normal copies of the "CFTR" gene. Due to these false positives, CF screening in newborns can be controversial.


title: Cystic fibrosis

text: By 2010 every US state had instituted newborn screening programs and , 21 European countries had programs in at least some regions.


title: Cystic fibrosis

text: Women who are pregnant or couples planning a pregnancy can have themselves tested for the "CFTR" gene mutations to determine the risk that their child will be born with CF. Testing is typically performed first on one or both parents and, if the risk of CF is high, testing on the fetus is performed. The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they are a carrier.


title: Cystic fibrosis

text: Because development of CF in the fetus requires each parent to pass on a mutated copy of the "CFTR" gene and because CF testing is expensive, testing is often performed initially on one parent. If testing shows that parent is a "CFTR" gene mutation carrier, the other parent is tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations. , typically only the most common mutations are tested for, such as ΔF508 Most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.


title: Cystic fibrosis

text: During pregnancy, testing can be performed on the placenta (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However, chorionic villus sampling has a risk of fetal death of one in 100 and amniocentesis of one in 200; a recent study has indicated this may be much lower, about one in 1,600.


title: Cystic fibrosis

text: Economically, for carrier couples of cystic fibrosis, when comparing preimplantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age around 40 years, after which NC, prenatal testing, and abortion have higher economic benefit.


title: Cystic fibrosis

text: While no cures for CF are known, several treatment methods are used. The management of CF has improved significantly over the past 70 years. While infants born with it 70 years ago would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Recent advances in the treatment of cystic fibrosis have meant that individuals with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are the proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. Pulmonary rehabilitation as a management of CF continues throughout a person's life, and is aimed at maximizing organ function, and therefore the quality of life. Occupational therapists use energy conservation techniques (ECT) in the rehabilitation process for patients with Cystic Fibrosis. Examples of energy conservation techniques are ergonomic principles, pursed lip breathing, and diaphragmatic breathing. Patients with CF tend to have fatigue and dyspnoea due to chronic pulmonary infections, so reducing the amount of energy spent during activities can help patients feel better and gain more independence. At best, current treatments delay the decline in organ function. Because of the wide variation in disease symptoms, treatment typically occurs at specialist multidisciplinary centers and is tailored to the individual. Targets for therapy are the lungs, gastrointestinal tract (including pancreatic enzyme supplements), the reproductive organs (including assisted reproductive technology), and psychological support.


title: Cystic fibrosis

text: The most consistent aspect of therapy in CF is limiting and treating the lung damage caused by thick mucus and infection, with the goal of maintaining quality of life. Intravenous, inhaled, and oral antibiotics are used to treat chronic and acute infections. Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time-consuming. Oxygen therapy at home is recommended in those with significant low oxygen levels. Many people with CF use probiotics, which are thought to be able to correct intestinal dysbiosis and inflammation, but the clinical trial evidence regarding the effectiveness of probiotics for reducing pulmonary exacerbations in people with CF is uncertain.


title: Cystic fibrosis

text: Many people with CF are on one or more antibiotics at all times, even when healthy, to prophylactically suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or a noticeable decline in lung function is seen, and are usually chosen based on the results of a sputum analysis and the person's past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a peripherally inserted central catheter or Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin, colistin, and aztreonam is often given for months at a time to improve lung function by impeding the growth of colonized bacteria. Inhaled antibiotic therapy helps lung function by fighting infection, but also has significant drawbacks such as development of antibiotic resistance, tinnitus, and changes in the voice. Inhaled levofloxacin may be used to treat "Pseudomonas aeruginosa" in people with cystic fibrosis who are infected. The early management of Pseudomonas aeruginosa infection is easier and better, using nebulised antibiotics with or without oral antibiotics may sustain its eradication up to two years. When choosing antibiotics to treat CF patients with lung infections caused by "Pseudomonas aeruginosa" in people with cystic fibrosis, it is still unclear whether the choice of antibiotics should be based on the results of testing antibiotics separately (one at a time) or in combination with each other.


title: Cystic fibrosis

text: Antibiotics by mouth such as ciprofloxacin or azithromycin are given to help prevent infection or to control ongoing infection. The aminoglycoside antibiotics (e.g. tobramycin) used can cause hearing loss, damage to the balance system in the inner ear or kidney failure with long-term use. To prevent these side-effects, the amount of antibiotics in the blood is routinely measured and adjusted accordingly.


title: Cystic fibrosis

text: All these factors related to the antibiotics use, the chronicity of the disease, and the emergence of resistant bacteria demand more exploration for different strategies such as antibiotic adjuvant therapy. Currently, no reliable clinical trial evidence shows the effectiveness of antibiotics for pulmonary exacerbations in people with cystic fibrosis and "Burkholderia cepacia" complex or for the use of antibiotics to treat nontuberculous mycobacteria in people with CF.


title: Cystic fibrosis

text: Aerosolized medications that help loosen secretions include dornase alfa and hypertonic saline. Dornase is a recombinant human deoxyribonuclease, which breaks down DNA in the sputum, thus decreasing its viscosity. Dornase alpha improves lung function and probably decreases the risk of exacerbations but there is insufficient evidence to know if it is more or less effective than other similar medications. Dornase alpha may improve lung function, however there is no strong evidence that it is better than other hyperosmolar therapies.


title: Cystic fibrosis

text: Denufosol, an investigational drug, opens an alternative chloride channel, helping to liquefy mucus. Whether inhaled corticosteroids are useful is unclear, but stopping inhaled corticosteroid therapy is safe. There is weak evidence that corticosteroid treatment may cause harm by interfering with growth. Pneumococcal vaccination has not been studied . , there is no clear evidence from randomized controlled trials that the influenza vaccine is beneficial for people with cystic fibrosis.


title: Cystic fibrosis

text: Ivacaftor is a medication taken by mouth for the treatment of CF due to a number of specific mutations responsive to ivacaftor-induced CFTR protein enhancement. It improves lung function by about 10%; however, it is expensive. The first year it was on the market, the list price was over $300,000 per year in the United States. In July 2015, the U.S. Food and Drug Administration approved lumacaftor/ivacaftor. In 2018, the FDA approved the combination ivacaftor/tezacaftor; the manufacturer announced a list price of $292,000 per year. Tezacaftor helps move the CFTR protein to the correct position on the cell surface, and is designed to treat people with the F508del mutation.


title: Cystic fibrosis

text: In 2019, the combination drug elexacaftor/ivacaftor/tezacaftor marketed as "Trikafta" in the United States, was approved for CF patients over the age of 12. In 2021, this was extended to include patients over the age of 6. In Europe this drug was approved in 2020 and marketed as "Kaftrio". It is used in those that have a f508del mutation, which occurs in about 90% of patients with cystic fibrosis. According to the Cystic Fibrosis Foundation, "this medicine represents the single greatest therapeutic advancement in the history of CF, offering a treatment for the underlying cause of the disease that could eventually bring modulator therapy to 90 percent of people with CF." In a clinical trial, participants who were administered the combination drug experienced a subsequent 63% decrease in pulmonary exacerbations and a 41.8 mmol/L decrease in sweat chloride concentration. By mitigating a repertoire of symptoms associated with cystic fibrosis, the combination drug significantly improved quality-of-life metrics among patients with the disease as well. The combination drug is also known to interact with CYP3A inducers, such as carbamazepine used in the treatment of bipolar disorder, causing elexafaftor/ivacaftor/tezacaftor to circulate in the body at decreased concentrations. As such, concomitant use is not recommended. The list price in the US is going to be $311,000 per year; however, insurance may cover much of the cost of the drug.


title: Cystic fibrosis

text: Ursodeoxycholic acid, a bile salt, has been used, however there is insufficient data to show if it is effective.


title: Cystic fibrosis

text: It is uncertain whether vitamin A or beta-carotene supplementation have any effect on eye and skin problems caused by vitamin A deficiency.


title: Cystic fibrosis

text: There is no strong evidence that people with cystic fibrosis can prevent osteoporosis by increasing their intake of vitamin D.


title: Cystic fibrosis

text: For people with vitamin E deficiency and cystic fibrosis, there is evidence that vitamin E supplementation may improve vitamin E levels, although it is still uncertain what effect supplementation has on vitamin E‐specific deficiency disorders or on lung function.


title: Cystic fibrosis

text: Robust evidence regarding the effects of vitamin K supplementation in people with cystic fibrosis is lacking as of 2020.


title: Cystic fibrosis

text: Various studies have examined the effects of omega-3 fatty acid supplementation for people with cystic fibrosis but the evidence is uncertain whether it has any benefits or adverse effects.


title: Cystic fibrosis

text: Several mechanical techniques are used to dislodge sputum and encourage its expectoration. One technique good for short-term airway clearance is chest physiotherapy where a respiratory therapist percusses an individual's chest by hand several times a day, to loosen up secretions. This "percussive effect" can be administered also through specific devices that use chest wall oscillation or intrapulmonary percussive ventilator. Other methods such as biphasic cuirass ventilation, and associated clearance mode available in such devices, integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use.


title: Cystic fibrosis

text: Another technique is positive expiratory pressure physiotherapy that consists of providing a back pressure to the airways during expiration. This effect is provided by devices that consists of a mask or a mouthpiece in which a resistance is applied only on the expiration phase. Operating principles of this technique seems to be the increase of gas pressure behind mucus through collateral ventilation along with a temporary increase in functional residual capacity preventing the early collapse of small airways during exhalation.


title: Cystic fibrosis

text: As lung disease worsens, mechanical breathing support may become necessary. Individuals with CF may need to wear special masks at night to help push air into their lungs. These machines, known as bilevel positive airway pressure (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. Non-invasive ventilators may be used during physical therapy to improve sputum clearance. It is not known if this type of therapy has an impact on pulmonary exacerbations or disease progression. It is not known what role non-invasive ventilation therapy has for improving exercise capacity in people with cystic fibrosis. However, the authors noted that "non‐invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum." During severe illness, a tube may be placed in the throat (a procedure known as a tracheostomy) to enable breathing supported by a ventilator.


title: Cystic fibrosis

text: For children, preliminary studies show massage therapy may help people and their families' quality of life.


title: Cystic fibrosis

text: Some lung infections require surgical removal of the infected part of the lung. If this is necessary many times, lung function is severely reduced. The most effective treatment options for people with CF who have spontaneous or recurrent pneumothoraces is not clear.


title: Cystic fibrosis

text: Lung transplantation may become necessary for individuals with CF as lung function and exercise tolerance decline. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung might contain bacteria that could infect the transplanted lung. A pancreatic or liver transplant may be performed at the same time to alleviate liver disease and/or diabetes. Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or someone's survival is threatened. According to Merck Manual, "bilateral lung transplantation for severe lung disease is becoming more routine and more successful with experience and improved techniques. Among adults with CF, median survival posttransplant is about 9 years."


title: Cystic fibrosis

text: Newborns with intestinal obstruction typically require surgery, whereas adults with distal intestinal obstruction syndrome typically do not. Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the feces. However, the best dosage and form of pancreatic enzyme replacement is unclear, as are the risks and long-term effectiveness of this treatment.


title: Cystic fibrosis

text: So far, no large-scale research involving the incidence of atherosclerosis and coronary heart disease in adults with cystic fibrosis has been conducted. This is likely because the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.


title: Cystic fibrosis

text: Diabetes is the most common nonpulmonary complication of CF. It mixes features of type 1 and type 2 diabetes, and is recognized as a distinct entity, cystic fibrosis-related diabetes. While oral antidiabetic drugs are sometimes used, the recommended treatment is the use of insulin injections or an insulin pump, and, unlike in type 1 and 2 diabetes, dietary restrictions are not recommended. While Stenotrophomonas maltophilia is relatively common in people with cystic fibrosis, the evidence about the effectiveness of antibiotics for "S. maltophilia" is uncertain.


title: Cystic fibrosis

text: Bisphosphonates taken by mouth or intravenously can be used to improve the bone mineral density in people with cystic fibrosis. When taking bisphosphates intravenously, adverse effects such as pain and flu-like symptoms can be an issue. The adverse effects of bisphosphates taken by mouth on the gastrointestinal tract are not known.


title: Cystic fibrosis

text: Poor growth may be avoided by insertion of a feeding tube for increasing food energy through supplemental feeds or by administration of injected growth hormone.


title: Cystic fibrosis

text: Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose, and over time reduce the person's sense of smell. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as fluticasone propionate are used to decrease nasal inflammation.


title: Cystic fibrosis

text: Female infertility may be overcome by assisted reproduction technology, particularly embryo transfer techniques. Male infertility caused by absence of the vas deferens may be overcome with testicular sperm extraction, collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneous fertilization, intracytoplasmic sperm injection can be performed. Third party reproduction is also a possibility for women with CF. Whether taking antioxidants affects outcomes is unclear.


title: Cystic fibrosis

text: Physical exercise is usually part of outpatient care for people with cystic fibrosis. Aerobic exercise seems to be beneficial for aerobic exercise capacity, lung function and health-related quality of life; however, the quality of the evidence was poor.


title: Cystic fibrosis

text: Due to the use of aminoglycoside antibiotics, ototoxicity is common. Symptoms may include "tinnitus, hearing loss, hyperacusis, aural fullness, dizziness, and vertigo".


title: Cystic fibrosis

text: Problems with the gastrointestinal system including constipation and obstruction of the gastrointestinal tract including distal intestinal obstruction syndrome are frequent complications for people with cystic fibrosis. Treatment of gastrointestinal problems is required in order to prevent a complete obstruction, reduce other CF symptoms, and improve the quality of life. While stool softeners, laxatives, and prokinetics (GI-focused treatments) are often suggested, there is no clear consensus from experts at to which approach is the best and comes with the least risks. Mucolytics or systemic treatments aimed at dysfunctional CFTR are also sometimes suggested to improve symptoms.


title: Cystic fibrosis

text: The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening and better treatment and access to health care. In 1959, the median age of survival of children with CF in the United States was six months.


title: Cystic fibrosis

text: In 2010, survival is estimated to be 37 years for women and 40 for men. In Canada, median survival increased from 24 years in 1982 to 47.7 in 2007. In the United States those born with CF in 2016 have an predicted life expectancy of 47.7 when cared for in specialty clinics.


title: Cystic fibrosis

text: In the US, of those with CF who are more than 18 years old as of 2009, 92% had graduated from high school, 67% had at least some college education, 15% were disabled, 9% were unemployed, 56% were single, and 39% were married or living with a partner.


title: Cystic fibrosis

text: Chronic illnesses can be difficult to manage. CF is a chronic illness that affects the "digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections". The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections. If it is compromised, it affects the quality of life of someone with CF and their ability to complete such tasks as everyday chores.


title: Cystic fibrosis

text: According to Schmitz and Goldbeck (2006), CF significantly increases emotional stress on both the individual and the family, "and the necessary time-consuming daily treatment routine may have further negative effects on quality of life". However, Havermans and colleagues (2006) have established that young outpatients with CF who have participated in the Cystic Fibrosis Questionnaire-Revised "rated some quality of life domains higher than did their parents". Consequently, outpatients with CF have a more positive outlook for themselves. As Merck Manual notes, "with appropriate support, most patients can make an age-appropriate adjustment at home and school. Despite myriad problems, the educational, occupational, and marital successes of patients are impressive."


title: Cystic fibrosis

text: Furthermore, there are many ways to enhance the quality of life in CF patients. Exercise is promoted to increase lung function. Integrating an exercise regimen into the CF patient's daily routine can significantly improve quality of life. No definitive cure for CF is known, but diverse medications are used, such as mucolytics, bronchodilators, steroids, and antibiotics, that have the purpose of loosening mucus, expanding airways, decreasing inflammation, and fighting lung infections, respectively.


title: Cystic fibrosis

text: Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. In the United States, about 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, about 4,000 people have CF. Around 1 in 25 people of European descent, and one in 30 of white Americans, is a carrier of a CF mutation. Although CF is less common in these groups, roughly one in 46 Hispanics, one in 65 Africans, and one in 90 Asians carry at least one abnormal "CFTR" gene. Ireland has the world's highest prevalence of CF, at one in 1353.


title: Cystic fibrosis

text: Although technically a rare disease, CF is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is Finland, where only one in 80 people carries a CF mutation. The World Health Organization states, "In the European Union, one in 2000–3000 newborns is found to be affected by CF". In the United States, one in 3,500 children is born with CF. In 1997, about one in 3,300 white children in the United States was born with CF. In contrast, only one in 15,000 African American children have it, and in Asian Americans, the rate was even lower at one in 32,000.


title: Cystic fibrosis

text: Cystic fibrosis is diagnosed equally in males and females. For reasons that remain unclear, data have shown that males tend to have a longer life expectancy than females, though recent studies suggest this gender gap may no longer exist, perhaps due to improvements in health care facilities. A recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF.


title: Cystic fibrosis

text: The distribution of CF alleles varies among populations. The frequency of ΔF508 carriers has been estimated at one in 200 in northern Sweden, one in 143 in Lithuanians, and one in 38 in Denmark. No ΔF508 carriers were found among 171 Finns and 151 Saami people. ΔF508 does occur in Finland, but it is a minority allele there. CF is known to occur in only 20 families (pedigrees) in Finland.


title: Cystic fibrosis

text: The ΔF508 mutation is estimated to be up to 52,000 years old. Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population. Other common autosomal recessive diseases such as sickle-cell anemia have been found to protect carriers from other diseases, an evolutionary trade-off known as heterozygote advantage. Resistance to the following have all been proposed as possible sources of heterozygote advantage:


title: Cystic fibrosis

text: CF is supposed to have appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned ("Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die"), recognizing the association between the salt loss in CF and illness.


title: Cystic fibrosis

text: In the 19th century, Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with CF. Meconium ileus was first described in 1905 by Karl Landsteiner. In 1936, Guido Fanconi described a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.


title: Cystic fibrosis

text: In 1938, Dorothy Hansine Andersen published an article, "Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study", in the "American Journal of Diseases of Children". She was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF. She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952, Paul di Sant'Agnese discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.


title: Cystic fibrosis

text: The first linkage between CF and another marker (Paroxonase) was found in 1985 by Hans Eiberg, indicating that only one locus exists for CF. In 1988, the first mutation for CF, ΔF508 was discovered by Francis Collins, Lap-Chee Tsui, and John R. Riordan on the seventh chromosome. Subsequent research has found over 1,000 different mutations that cause CF.


title: Cystic fibrosis

text: Because mutations in the "CFTR" gene are typically small, classical genetics techniques had been unable to accurately pinpoint the mutated gene. Using protein markers, gene-linkage studies were able to map the mutation to chromosome 7. Chromosome walking and chromosome jumping techniques were then used to identify and sequence the gene. In 1989, Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF. CF represents a classic example of how a human genetic disorder was elucidated strictly by the process of forward genetics.


title: Cystic fibrosis

text: People with CF may be listed in a disease registry that allows researchers and doctors to track health results and identify candidates for clinical trials.


title: Cystic fibrosis

text: Gene therapy has been explored as a potential cure for CF. Results from clinical trials have shown limited success , and using gene therapy as routine therapy is not suggested. A small study published in 2015 found a small benefit.


title: Cystic fibrosis

text: The focus of much CF gene therapy research is aimed at trying to place a normal copy of the "CFTR" gene into affected cells. Transferring the normal "CFTR" gene into the affected epithelium cells would result in the production of functional CFTR protein in all target cells, without adverse reactions or an inflammation response. To prevent the lung manifestations of CF, only 5–10% the normal amount of CFTR gene expression is needed. Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options, mainly because very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable. There has been a functional repair in culture of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients.


title: Cystic fibrosis

text: A number of small molecules that aim at compensating various mutations of the "CFTR" gene are under development. CFTR modulator therapies have been used in place of other types of genetic therapies. These therapies focus on the expression of a genetic mutation instead of the mutated gene itself. Modulators are split into two classes: potentiators and correctors. Potentiators act on the CFTR ion channels that are embedded in the cell membrane, and these types of drugs help open up the channel to allow transmembrane flow. Correctors are meant to assist in the transportation of nascent proteins, a protein that is formed by ribosomes before it is morphed into a specific shape, to the cell surface to be implemented into the cell membrane.


title: Cystic fibrosis

text: Most target the transcription stage of genetic expression. One approach has been to try and develop medication that get the ribosome to overcome the stop codon and produce a full-length CFTR protein. About 10% of CF results from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target nonsense mutations such as G542X, which consists of the amino acid glycine in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with protein synthesis and error-correction. In some cases, they can cause the cell to overcome a premature stop codon by inserting a random amino acid, thereby allowing expression of a full-length protein. Future research for these modulators is focused on the cellular targets that can be effected by a change in a gene's expression. Otherwise, genetic therapy will be used as a treatment when modulator therapies do not work given that 10% of people with cystic fibrosis are not affected by these drugs.


title: Cystic fibrosis

text: Elexacaftor/ivacaftor/tezacaftor was approved in the United States in 2019 for cystic fibrosis. This combination of previously developed medicines is able to treat up to 90% of people with cystic fibrosis. This medications restores some effectiveness of the CFTR protein so that it can work as an ion channel on the cell's surface.


title: Cystic fibrosis

text: It has previously been shown that inter-species interactions are an important contributor to the pathology of CF lung infections. Examples include the production of antibiotic degrading enzymes such as β-lactamases and the production of metabolic by-products such as short-chain fatty acids (SCFAs) by anaerobic species, which can enhance the pathogenicity of traditional pathogens such as Pseudomonas aeruginosa. Due to this, it has been suggested that the direct alteration of CF microbial community composition and metabolic function would provide an alternative to traditional antibiotic therapies.


title: Japanese battleship Yamato

text: Named after the ancient Japanese Yamato Province, "Yamato" was designed to counter the numerically superior battleship fleet of the United States, Japan's main rival in the Pacific. She was laid down in 1937 and formally commissioned a week after the Pearl Harbor attack in late 1941. Throughout 1942, she served as the flagship of the Combined Fleet, and in June 1942 Admiral Isoroku Yamamoto directed the fleet from her bridge during the Battle of Midway, a disastrous defeat for Japan. "Musashi" took over as the Combined Fleet flagship in early 1943, and "Yamato" spent the rest of the year moving between the major Japanese naval bases of Truk and Kure in response to American threats. In December 1943, "Yamato" was torpedoed by an American submarine which necessitated repairs at Kure, where she would also be refitted with additional anti-aircraft guns and radar in early 1944. Although present at the Battle of the Philippine Sea in June 1944, she played no part in the battle.


title: Japanese battleship Yamato

text: The only time "Yamato" fired her main guns at enemy surface targets was in October 1944, when she was sent to engage American forces invading the Philippines during the Battle of Leyte Gulf. While threatening to sink American troop transports, they encountered a light escort carrier group of the U.S. Navy's Task Force 77, "Taffy 3", in the Battle off Samar. The Japanese turned back after American air attacks convinced them they were engaging a powerful US carrier fleet.