title: Milk chocolate

text: In 2018, the global market for milk chocolate was worth $63.2 billion, and is expected to approach $73 billion by 2024. Consumption is dominated by the United States and Europe, which between them consumed over 80 percent of global production. However, the new century saw expansion in different markets. For example, between 2000 and 2013, the areas that saw the highest growth included the Middle East and Africa (where retail value rose 239 percent), Latin America (up 228 percent). Even in China and Japan, which traditionally are places of very low milk consumption, milk chocolate sales increased at the start of the 21st Century. Between 1999 and 2003, Chinese chocolate imports rose from $17.7 million to $50 million. By 2007, over 38 percent of chocolate sales in China were milk chocolate. By 2018, the value of sales by Japanese chocolatier Meiji was approaching that of the top producers in Europe, and the total sales by the group had surpassed the total for all confectionery sales by Hershey, putting the American company outside a top five ranking.


title: Milk chocolate

text: While all milk chocolate contains cocoa, milk and sugar, the proportion of these ingredients varies between countries and brands, which in turn affects its nutritional value. The driving force for these differences is taste. For example, Belgian chocolate is known for its mild milky flavour, while some Russian brands have a strong cocoa taste. The taste drives the ingredients, although these are also affected by other factors, particularly economics. For example, cost is the main reason for the introduction of cocoa butter replacements like coconut and palm oil. However, there are also regulatory reasons. In 1973, for example, the European Union decreed that chocolate must have a minimum of 35 percent dry cocoa solids. More recently, China has also introduced legislation to require locally produced milk chocolate to contain 25 percent cocoa butter.


title: Milk chocolate

text: All these have effects on human health and in the 21st Century, milk chocolate lost market to dark chocolate which is considered healthier. However, this has not always been the case. Milk chocolate has been presented as a health food since Cadburys first advertised Sloane's Milk Chocolate for its medicinal properties in the 19th Century. The health benefits to children were particularly highlighted. For example, in the 1920s, the Baby Ruth bar was touted as a health food for children by Allan Roy Dafoe, who had gained fame for delivering the Dionne quintuplets. At the same time, advertisements pronounced that chocolate bars combined both a source of essential energy and the "perfectly balanced food" of milk.


title: Milk chocolate

text: The benefits claimed were broad. Cocoa butter, for example, as it coated the teeth, was claimed to reduce tooth decay. Chocolate was claimed to produce calming effects, reducing stress, and even producing a similar feeling to falling in love. Scientific evidence increasingly backed up claims for the health benefits of chocolate. For example, magnetic resonance imaging (MRI) scans have demonstrated that chocolate consumption can reduce the risk of heart disease. A typical milk chocolate bar also contains about caffeine per , which can stimulate the nervous system and help the body balance its internal water balance. At the same time, the amount of caffeine is a concern to some healthy living advocates. Chocolate is also a source of polyphenols that have antioxidant properties, which may also have health benefits.


title: Milk chocolate

text: Milk chocolate is manufactured from cocoa, milk and sugar. The ingredient which defines the product as chocolate, cocoa bean, is mainly grown in Southeast Asia, South America, and West Africa, particularly the Ivory Coast, which supplies 40 percent of the total global cocoa market. Once the cocoa pods are harvested, the seeds, known as "beans", are removed and fermented, then dried. They are then taken to a processing plant where they are cleaned and roasted. The beans are then ground, usually in a two-stage process, first with an impact mill to liquify the cocoa, and then a ball mill. The liquified cocoa liquor is then separated into cocoa mass and cocoa butter.


title: Milk chocolate

text: At this stage, the two other key ingredients come into the process. Milk is often added in powdered form as excess water would damage the flowing properties of the liquid chocolate. Spray dried full fat milk powder is normally used, but alternatives include anhydrous full fat or skimmed milk powders. Condensed milk is preferred by some manufacturers, particularly where milk production is seasonal. Milk ingredients are complex and critical in delivering the properties and taste to milk chocolate. Milk-origin (terroir) and associated farming have become an important marketing topic. Milk substitutes like rice milk are also used to create lactose-free milk-like chocolate. Sugar, the last major ingredient, is added at the same time as the milk powder, either in a roll refiner or conche. Sugar is an international commodity, with production of sugar cane led by Brazil, India, Thailand, China and Australia. Sugar beet is also used. Sometimes the milk and sugar are mixed separately before being added to the liquid cocoa mass and cocoa butter. The liquid chocolate is then poured into moulds and formed into bars or any other shape.


title: Milk chocolate

text: At the beginning of the 20th century, bars which combined milk chocolate with other sweet ingredients appeared on both sides of the Atlantic. In 1904, Cailler launched its Branche, a praline-filled and branch-looking bar. Other Swiss chocolatiers, Theodor Tobler and Emil Baumann, invented Toblerone in 1908 which contained almonds, honey and nougat. In the United States, the Goo Goo Cluster was first introduced in 1912 which added caramel, marshmallow and peanuts to the list of ingredients. These were soon followed, in 1914, by Fry's Turkish Delight in the UK. Shortly afterwards, Clark introduced the Clark Bar, which has been called the first combination bar, in 1917. In 1920, Otto Schnering of the Curtiss Candy Company created the Baby Ruth bar. By 1925, it was the most popular bar in the US. Soon afterwards, two other brands that would become global giants followed, the Mars Bar in 1932 and, three years later, Rowntree's introduced the Kit Kat. By 2014, 650 Kit Kat bars were being consumed each second. Combination bars came to dominate the confectionery market with sales surpassing $140 billion in 2018.


title: Milk chocolate

text: Ethical issues have been intrinsically linked to chocolate in general since the early days. Many of the early chocolatiers, including Cadbury, Fry's, Rowntree's and Terry's, were founded by Quakers who saw the wellbeing of their workers part of their business ethic. The companies were pioneers in social welfare, providing a safe working environment, high quality housing and other benefits to employees that were ahead of many of the industrial norms. Cadbury, for example, provided paid holidays, insurance and night schools for workers, as well as constructing Bournville in Birmingham, UK. However, the working conditions of many in the wider chocolate supply chain remained poor. Slavery, and later bonded labour, was often employed on the plantations that provided the sugar used to make chocolate. Even after the abolition of slavery, the working conditions in many plantations was still poor, with reports of child labour being frequent and unreported. In 1975, the first in a series of International Cocoa Agreements tried to set what were termed "fair labour conditions" and eliminate child labour.


title: Milk chocolate

text: Rising consumer awareness, as well as greater corporate and employee interest, led to increasing voluntary action to address human rights issues. Fundamental to this has been the rise of Fair Trade and UTZ Certified chocolate. Initially launched by Stichting Max Havelaar in the Netherlands in 1988, the Fair Trade movement expanded into the mainstream in the following decades, with cocoa second to coffee in terms of sales and volume by 2011. Much of this is driven by the use of Fair Trade ingredients by major brands. For example, in Germany, major supermarket Lidl commenced promoting their own brand milk chocolate with their own Fair Trade label in 2006. Similarly, in the UK, two of the best selling milk chocolate bars, Cadburys Dairy Milk and Nestlé's Kit Kat were marketed with a Fair Trade label starting in 2009 and 2010 respectively.


title: Marie Byrd Land

text: Marie Byrd Land (MBL) is an unclaimed region of Antarctica. With an area of , it is the largest unclaimed territory on Earth. It was named after the wife of American naval officer Richard E. Byrd, who explored the region in the early 20th century.


title: Marie Byrd Land

text: The territory lies in West Antarctica, east of the Ross Ice Shelf and the Ross Sea and south of the Pacific Ocean portion of the Southern Ocean, extending eastward approximately to a line between the head of the Ross Ice Shelf and Eights Coast. It stretches between 158°W and 103°24'W. The inclusion of the area between the Rockefeller Plateau and Eights Coast is based upon Byrd's exploration.


title: Marie Byrd Land

text: Because of its remoteness, even by Antarctic standards, most of Marie Byrd Land (the portion east of 150°W) has not been claimed by any sovereign state. It is by far the largest single unclaimed territory on Earth, with an area of (including Eights Coast, immediately east of Marie Byrd Land). In 1939, United States President Franklin D. Roosevelt instructed members of the United States Antarctic Service Expedition to take steps to claim some of Antarctica as United States territory. Although this appears to have been done by members of this and subsequent expeditions, these do not appear to have been formalized prior to 1959, when the Antarctic Treaty System was set up. Some publications in the United States have shown this as a United States territory in the intervening period, and the United States Department of Defense has stated that the United States has a solid basis for a claim in Antarctica resulting from its activities prior to 1959. The portion west of 150°W is part of Ross Dependency claimed by New Zealand.


title: Marie Byrd Land

text: Marie Byrd Land was first explored from the west where it could be accessed from the Ross Sea. The far western coast of Marie Byrd Land was seen from the decks of Robert Falcon Scott's ship "Discovery" in 1902. He named the peninsula adjacent to the Ross Sea King Edward VII Land and the scattered outcrops that were within sight, the Alexandra Mountains. In 1911, during Roald Amundsen's South Pole expedition, Kristian Prestrud led a sledge party that visited these isolated outcrops (nunataks) in the region bordering the eastern Ross Sea and Ross Ice Shelf. At the same time the first Japanese Antarctic Expedition led by Nobu Shirase landed a shore party on the peninsula.


title: Marie Byrd Land

text: Dean Smith was the pilot during aerial overflights in 1929 with Richard E. Byrd's first Antarctic expedition (1928–1930). It originated from Little America near Amundsen's original base camp "Framheim" in the Bay of Whales, led to the discovery of the Rockefeller Mountains and the Edsel Ford Ranges farther to the east. Byrd named the region after his wife Marie. A geological party led by L. Gould briefly explored parts of the Rockefeller Mountains.


title: Marie Byrd Land

text: The first deep overland exploration occurred during the second Byrd expedition (1933–1935) when a sledge party led by Paul Siple and Franklin Alton Wade reached as far east as the Fosdick Mountains in 1934. Aerial exploration discovered lands farther east along the Ruppert Coast.


title: Marie Byrd Land

text: The Third Byrd Antarctic Expedition, also called the United States Antarctic Service Expedition, took place from 1939 to 1941. This expedition established two base camps apart. West Base was near the former Little America base (68° 29' S, 163° 57' W) and East Base was near the Antarctic Peninsula on Stonington Island (68° 12' S, 67° 03' W). Exploration flights out of these two bases led to the discovery of most of the Marie Byrd Land Volcanic Province (e.g. Executive Committee Range) and much of the coastal region including the Walgreen, Hobbs, and Ruppert Coasts. During the expedition trail parties from West Base visited the northern Ford Ranges and south slopes of the Fosdick Mountains.


title: Marie Byrd Land

text: The United States Navy (USN) mounted several expeditions to Antarctica in the period 1946 to 1959. These expeditions (Operation Highjump led by R. E. Byrd, Windmill, and Deep Freeze I–IV) included aerial photography using the Trimetrogon system of aerial photographs (TMA; vertical, left, and right oblique images over the same point) over portions of coastal Marie Byrd Land.


title: Marie Byrd Land

text: The USN began construction of Byrd Station at 80°S, 120°W with traverses out of Little America V in 1956–57 during Deep Freeze II. These efforts were in advance of the International Geophysical Year (IGY; from July 1957 to end of 1958) that saw several exploratory overland traverses with tractor trains (Sno-cats and modified bulldozers). Starting in January 1957 (pre-IGY) Charles R. Bentley led a traverse from Little America V to the new Byrd station along the route blazed by United States Army engineers a few months before (the Army-Navy Drive). His team conducted measurements of ice thickness and of the Earth's magnetic and gravity field. The following summer season (1957–58) he led a second traverse out of Byrd Station that visited volcanoes of the Marie Byrd Land Volcanic Province for the first time. The traverse reached the Sentinel Mountains beyond eastern Marie Byrd Land before returning to Byrd Station. Bentley led a third traverse out of Byrd Station to the Horlick Mountains in 1958–59. These three traverses led to the discovery of the Bentley Subglacial Trench or Trough, a deep bedrock chasm between MBL and the Transantarctic Mountains of East Antarctica.


title: Marie Byrd Land

text: During 1958–1960 TMA flights and a traverse out of Byrd Station visited and mapped the Executive Committee Range. TMA were flown in western Marie Byrd Land in 1964 and 1965. Following these efforts the United States Geological Survey (USGS) mounted land surveys to establish a series of reference points and benchmarks throughout much of Marie Byrd Land during 1966–1968.


title: Marie Byrd Land

text: The United States Byrd Coastal Survey during 1966–1969, led by F. A. Wade, conducted geologic mapping of the Alexandra and Rockefeller Mountains and the Ford Ranges and produced a series of 1:250,000 geologic maps of the region. This was a complex expedition involving remote helicopter camps and airborne geophysics.


title: Marie Byrd Land

text: Several geological expeditions explored Marie Byrd Land during the period 1978–1993. New Zealand geologists surveyed the Ford Ranges and Edward VII Peninsula in two expeditions, 1978–79 and 1987–88. Exploration of the Marie Byrd Land Volcanic Province began in earnest by U.S. geologists in 1984–85. The WAVE project (West Antarctic Volcano Exploration) focused on the volcanic province during the period 1989–1991. The SPRITE project (South Pacific Rim International Tectonic Expedition) explored regions and surroundings of the Hobbs Coast in 1990–1993. Members of both projects were from the U.S., Britain, and New Zealand. During the Austral summers of 1989–1990 and 1990–1991, a geological party from the University of California, Santa Barbara (UCSB) explored several of the mountain ranges within the northern Ford Ranges of Marie Byrd Land (FORCE expedition; Ford Ranges Crustal Exploration). GANOVEX VII a multinational expedition led by Germany visited Edward VII Peninsula in 1992–93.


title: Marie Byrd Land

text: Colorado College geologists led expeditions to the Ford Ranges in 1998–2001 (Ford Ranges), 2005–2007 and 2011–2013 (Fosdick Mountains).


title: Marie Byrd Land

text: Marie Byrd Land hosted the Operation Deep Freeze base Byrd Station (NBY; originally at 80°S, 120°W, rebuilt at 80°S, 119°W), beginning in 1957, in the hinterland of Bakutis Coast. Byrd Station was the only major base in the interior of West Antarctica for many years. In 1968, the first ice core to fully penetrate the Antarctic Ice Sheet was drilled here. The year-round station was abandoned in 1972, and after operating for years as a temporary summer encampment, Byrd Surface Camp, Byrd Station was reopened by the United States Antarctic Program (USAP) in 2009–2010 to support operations in northern West Antarctica.


title: Marie Byrd Land

text: On Ruppert Coast of Marie Byrd Land is the Russian station Russkaya, which was occupied 1980–1990 and is now closed.


title: Marie Byrd Land

text: East of the Siple Coast off the Ross Ice Shelf, Siple Dome was established as a summer science camp in 1996. Ice cores have been drilled here to retrieve the climate history of the last 100,000 years. This camp also served as a base for airborne geophysical surveys supported by the University of Texas Institute for Geophysics (UTIG).


title: Marie Byrd Land

text: In 1998–1999, a camp was operated at the Ford Ranges (FRD) in western Marie Byrd Land, supporting a part of a United States Antarctic Program (USAP) airborne survey initiated by UCSB and supported by the UTIG flying out of Siple Dome.


title: Marie Byrd Land

text: In 2004–05, a large camp, Thwaites (THW) was established by the USAP north of NBY, in order to support a large airborne geophysical survey of eastern Marie Byrd Land by the UTIG.


title: Marie Byrd Land

text: In 2006, a major encampment, WAIS Divide (WSD) was established on the divide between the Ross Sea Embayment and the Amundsen Sea Embayment, in easternmost Marie Byrd Land, in order to drill a high resolution ice core. Drilling and coring ended in 2014.


title: Marie Byrd Land

text: In 2018, the International Thwaites Glacier Collaboration commenced with a large and ongoing physical presence onshore of the Amundsen Sea. It entails marine, airborne, and on-ice geophysical exploration that will illuminate the character of Marie Byrd Land bedrock geology and the nature of the eastern boundary of the province. The goal is determining the stability of the glacier and prediction of global sea level rise from shrinking of the WAIS.


title: Marie Byrd Land

text: Adjacent to the continent, Marie Byrd Land is bordered by the Amundsen Sea in the east and the Ross Sea and Ross Ice Shelf in the west. Mountain ranges are prominent along and near the coastline with a few exceptions. Marie Byrd Land is covered by the vast West Antarctic Ice Sheet (WAIS). The WAIS in Marie Byrd Land drains off the continent to the east into the Ross Ice Shelf via seven ice streams. Along the coast of the Southern Ocean and the Amundsen Sea, ice drains via glaciers, the major one being the Thwaites. West Antarctica and Marie Byrd Land have elevations of up to 1500 to 2000 meters on the surface of the WAIS. In contrast, East Antarctica has interior elevations on its ice sheet of over 4000 meters.


title: Marie Byrd Land

text: The West Antarctic Rift System (WARS) that evolved over the last hundred million years, includes all or part of Marie Byrd Land. The WARS extends from the Ross Sea continental shelf east into Marie Byrd Land. The ice streams and glaciers that drain the WAIS have been proposed to follow rift valleys, now buried by ice, which formed in the WARS. The WARS contains a volcanic province with volcanoes active from the Eocene epoch to a few thousand years ago.


title: Marie Byrd Land

text: A mantle plume was discovered deep below Marie Byrd Land. Heat from the plume has been proposed responsible for uplift of a significant portion of West Antarctica to form the Marie Byrd Land Dome.


title: Marie Byrd Land

text: A digital map of Antarctica includes the geology of Marie Byrd Land. The geologic history of Marie Byrd Land in West Antarctica was summarized in a 2020 publication.


title: Marie Byrd Land

text: Prominent glaciers that drain the WAIS in MBL include the Thwaites, and also the Pine Island Glacier, both of which empty into the Amundsen Sea. Of the seven ice streams that drain into the Ross Ice Shelf, the Bindschadler and Whillans ice streams are the most extensive. The seven ice streams discharge 40 percent of the WAIS. Besides the Ross Ice Shelf, significant ice shelves on the coast of the Southern Ocean include the Sulzberger, and Nickerson.


title: Marie Byrd Land

text: Due to the burial of the continental basement of MBL by the WAIS, mountain ranges are exposed towards the coast of MBL where ice thickness is smaller. Prominent ranges include the Ford Ranges in western MBL, The Flood Range, the Executive Committee Range, and the Kohler Range. The Ford Ranges are the most extensive and include more than six individual named mountains groups. The Executive Committee Range includes five volcanoes, some proposed to be dormant or active. The Flood Range comprises a linear chain of Neogene and Quaternary age volcanoes. The Fosdick mountains in the northern Ford Ranges are a thirty-kilometer-long span of Cretaceous metamorphic rocks. Most other exposed rock in MBL is Paleozoic metamorphosed sedimentary rock and granitiods, and Mesozoic granitiod.


title: Marie Byrd Land

text: Away from the coasts, the WAIS buries individual mountains and ranges that are not named, the exception being major features such as the Bentley Subglacial Trench.


title: Marie Byrd Land

text: Marie Byrd Seamount () is a seamount named in association with Marie Byrd Land; name approved June, 1988 (Advisory Committee on Undersea Features, 228).


title: Eric Fisher (American football)

text: Eric William Fisher (born January 5, 1991) is an American football offensive tackle for the Miami Dolphins of the National Football League (NFL). He played college football at Central Michigan University, and was selected first overall by the Kansas City Chiefs in the 2013 NFL Draft. He played for the Chiefs for eight seasons from 2013 to 2020, making two Pro Bowls and winning Super Bowl LIV over the San Francisco 49ers.


title: Eric Fisher (American football)

text: Fisher and his sister were raised in Rochester, Michigan by his mother. During that time, she also overcame thyroid cancer while raising them on her own. He attended Stoney Creek High School, where he was an All-State honorable mention lineman for the football team. Regarded as a two-star recruit by Rivals.com, he was not ranked among the best offensive tackle prospects in his class. According to Fisher, this was due to him being undersized for an offensive tackle, weighing only 225 pounds as a high school senior.


title: Eric Fisher (American football)

text: Fisher played at Central Michigan University from 2009 to 2012 where he was recognized as a first-team All-American by "Pro Football Weekly", a second-team selection by "Sports Illustrated", and received third-team honors from the Associated Press. He was also a first-team All-Mid-American Conference (MAC) selection. Fisher was a part of two bowl wins while at Central Michigan; the 2010 GMAC Bowl and the 2012 Little Caesars Pizza Bowl.


title: Eric Fisher (American football)

text: Fisher was considered one of the top offensive tackles (and overall players) available in the 2013 NFL Draft. He was selected by the Kansas City Chiefs with the first overall pick, becoming the first MAC player to be drafted No. 1 overall. Fisher is one of two Central Michigan players to be selected in the first round of an NFL Draft; the other is Joe Staley.


title: Eric Fisher (American football)

text: On July 26, 2013, Fisher signed a guaranteed contract with the Chiefs worth $22.1 million with a $14.5 million signing bonus. Despite playing left tackle during college, Fisher transitioned to right tackle for the 2013 season. He allowed 7 sacks and 35 hurries. According to Pro Football Focus, his run-blocking grade of −6.5 ranked 55th out of 76 NFL tackles who played at least 25 percent of their team's snaps. His overall grade as a tackle ranked 70th. Despite Fisher's struggles during his rookie season, Chiefs general manager John Dorsey noted Fisher's potential and expressed confidence that he would develop into a good player. Fisher played in 14 games, of which he started 13, during his rookie year of 2013.


title: Eric Fisher (American football)

text: In March 2014, head coach Andy Reid announced that he was moving Fisher to the left tackle position for the upcoming 2014 season, following the loss of Branden Albert in free agency. During the 2015 season, Fisher played in 16 games, starting in 14.


title: Eric Fisher (American football)

text: On May 2, 2016, the Chiefs picked up the fifth-year option Fisher's contract. On July 30, 2016, Fisher signed a four-year contract extension with the Chiefs worth $48 million, including $40 million guaranteed. In Week 1, after a strong performance, Pro Football Focus ranked Fisher as the number one left tackle of the week. In the divisional round of the 2016 playoffs against the Pittsburgh Steelers, the Chiefs were down 18–10 in the 4th quarter. Following a successful two-point conversion, Fisher was called on a holding penalty that resulted in a loss of 10 yards. On the second attempt from the Steelers' 12-yard line, the Chiefs failed the two-point conversion, resulting in their elimination from the playoffs as they lost to the Steelers by a score of 18–16.


title: Eric Fisher (American football)

text: In 2019, Fisher was limited to eight games due to injuries. Fisher and the Chiefs went on to win Super Bowl LIV, their first championship in 50 years.


title: Eric Fisher (American football)

text: Following the release of long-time Chiefs punter Dustin Colquitt in the 2020 offseason, Fisher became tied with Anthony Sherman and fellow 2013 draftee Travis Kelce as the longest tenured members of the Chiefs. In the Week 3 game of the Chiefs' 2020 season against the Baltimore Ravens, Fisher lined up as an eligible receiver and caught a two-yard pass for a touchdown, the first of his career. The touchdown was the first receiving touchdown scored by a number one overall selection since Keyshawn Johnson in 2006. Fisher was placed on the reserve/COVID-19 list by the Chiefs on November 16, 2020, and activated three days later.


title: Eric Fisher (American football)

text: On January 24, 2021, against the Buffalo Bills in the AFC Championship Game, Fisher suffered a torn Achilles, forcing him to miss Super Bowl LV. He was placed on injured reserve on February 6. The Chiefs would go on to lose 31–9 to the Tampa Bay Buccaneers.


title: Paul Kalanithi

text: Paul Sudhir Arul Kalanithi (April 1, 1977 – March 9, 2015) was an American neurosurgeon and writer. His book "When Breath Becomes Air" is a memoir about his life and illness with stage IV metastatic lung cancer. It was posthumously published by Random House in January 2016. It was on "The New York Times" Non-Fiction Best Seller list for multiple weeks.


title: Paul Kalanithi

text: Paul Kalanithi was born on April 1, 1977, and lived in Westchester, New York. He was born to a Christian family hailing from Tamil Nadu and Andhra Pradesh, India. Kalanithi had two brothers, Jeevan and Suman; Jeevan is a computer/robotics engineer and Suman is a neurologist. The family moved from Bronxville, New York, to Kingman, Arizona, when Kalanithi was 10. Kalanithi attended Kingman High School, where he graduated as valedictorian.


title: Paul Kalanithi

text: Kalanithi attended Stanford University, where he graduated with a Bachelor of Arts and a Master of Arts in English literature and a Bachelor of Science in human biology in 2000. After Stanford, he attended the University of Cambridge, where he studied at Darwin College and graduated with a Master of Philosophy in the History and Philosophy of Science and Medicine. Although he initially considered pursuing a Ph.D. in English Literature, Kalanithi then attended the Yale School of Medicine, where he graduated in 2007 "cum laude", winning the Dr. Louis H. Nahum Prize for his research on Tourette’s syndrome. He was inducted into the Alpha Omega Alpha national medical honor society.


title: Paul Kalanithi

text: After graduating from medical school, Kalanithi returned to Stanford to complete his residency training in neurosurgery and a postdoctoral fellowship in neuroscience at Stanford University School of Medicine.


title: Paul Kalanithi

text: In May 2013, Kalanithi was diagnosed with metastatic stage IV non-small-cell EGFR-positive lung cancer. He died on March 9, 2015, aged 37.


title: Paul Kalanithi

text: Kalanithi was married to Lucy (née Goddard), with whom he had a daughter in 2014, Elizabeth Acadia ("Cady"). Lucy is an associate professor at Stanford University School of Medicine and wrote the epilogue to "When Breath Becomes Air". She is the twin sister of Joanna Goddard of the blog A Cup of Jo.


title: Paul Kalanithi

text: Although Kalanithi was raised in a devout Christian family, he turned away from the faith in his teens and twenties in favor of other ideas. However, he retained "the central values of Christianity — sacrifice, redemption, forgiveness" and returned to Christianity later in his life. In his book, he writes that if he had been more religious in his youth, he would have become a pastor.


title: Skardu

text: Skardu (, ; , ) is a city located in Gilgit−Baltistan, a part of Pakistan-administered Kashmir. Skardu serves as the capital of Skardu District and the Baltistan Division. Skardu is situated at an elevation of nearly in the Skardu Valley, at the confluence of the Indus and Shigar Rivers. The city is an important gateway to the eight-thousanders of the nearby Karakoram mountain range. The Indus River running through the region separates the Karakoram from the Himalayas.


title: Skardu

text: The name "Skardu" is believed to be derived from the Balti word meaning "a low land between two high places." The two referenced "high places" are Shigar city, and the high-altitude Satpara Lake


title: Skardu

text: The first mention of Skardu dates to the first half of the 16th century. Mirza Haidar (1499–1551) described "Askardu" in the 16th-century text "Tarikh-i-Rashidi Baltistan" as one of the districts of the area. The first mention of Skardu in European literature was made by Frenchman François Bernier (1625–1688), who mentions the city by the name of "Eskerdou." After his mention, Skardu was quickly drawn into Asian maps produced in Europe, and was first mentioned as "Eskerdow" the map "Indiae orientalis nec non insularum adiacentium nova descriptio" by Dutch engraver Nicolaes Visscher II, published between 1680 and 1700.


title: Skardu

text: The Skardu Valley, at the confluence of the Indus and Shigar Rivers, is wide by long. Active erosion in the nearby Karakoram Mountains has resulted in enormous deposits of sediment throughout the Skardu valley. Glaciers from the Indus and Shigar valleys broadened the Skardu valley between 3.2 million years ago up to the Holocene approximately 11,700 years ago.


title: Skardu

text: The Skardu region was part of the cultural sphere of Buddhist Tibet since the founding of the Tibetan Empire under Songsten Gampo in the mid 7th-century CE. Tibetan tantric scriptures were found all over Baltistan until about the 9th century. Given the region's close proximity to Central Asia, Skardu remained in contact with tribes near Kashgar, in what is now China's westernmost province of Xinjiang.


title: Skardu

text: Following the dissolution of Tibetan suzerainty over Baltistan around the 9th-10th century CE, Baltistan came under control of the local Maqpon Dynasty, a dynasty of Turkic extraction, which according to local tradition, is said to have been founded after a migrant from Kashmir named Ibrahim Shah married a local princess.


title: Skardu

text: Around the year 1500, "Maqpon Bokha" was crowned ruler, and founded the city of Skardu as his capital. The Skardu Fort was established around this time. During his reign, King "Makpon Bokha" imported craftsmen to Skardu from Kashmir and Chilas to help develop the area's economy. While nearby Gilgit fell out of the orbit of Tibetan influence, Skardu's Baltistan region remained connected due to its close proximity to Ladakh, the region which Skardu and neighbouring Khaplu routinely fought against. Sikhs traditionally believe that Guru Nanak, the founder of Sikhism, visited Skardu during his second "udasi" journey between 1510 and 1515. Gurudwara Chota Nanakiana, locally known as Asthan Nanak Peer, is believed to be the place where the Guru stayed in Skardu.


title: Skardu

text: In the early 1500s, Sultan Said Khan of the Timurid "Yarkent" Khanate, based in what is now Xinjiang province of China, raided Skardu and Baltistan. Given the threat illustrated by the Sultan Said's invasion, Mughal attention was roused, prompting the 1586 conquest of Baltistan by the Mughal Emperor Akbar. The local Maqpon rulers pledged allegiance, and from that point onwards beginning with Ali Sher Khan Anchan, the kings of Skardu were mentioned as rulers of Little Tibet in the historiography of the Mughal Empire.


title: Skardu

text: Mughal forces again incurred into the region during the reign of Shah Jahan in 1634-6 under the forces of Zafar Khan, in order to settle a dispute to Skardu's throne between Adam Khan, and his elder brother Abdul Khan. It was only after this point, during the rule of Shah Jahan and Aurangzeb, that Skardu's ruling family was firmly under Mughal control. The ability of the Mughal crown to fund expeditions to territories of marginal value, such as Baltistan, emphasises the wealth of the Mughal coffers.


title: Skardu

text: In 1839, Dogra commander Zorawar Singh Kahluria defeated Balti forces in battles at Wanko Pass and Thano Kun plains, clearing his path for invasion of the Skardu valley. He seized Skardu Fort on behalf of the Dogra Kingdom based in Jammu. Singh's forces massacred a large number of the garrison's defenders, and publicly tortured Kahlon Rahim Khan of Chigtan in front of a crowd of local Baltis and their chiefs.


title: Skardu

text: Dogra forces failed in their 1841 attempt to conquer Tibet. Following their defeat, Ladakhis rose in rebellion against Dogra rule. Baltis under the leadership of Raja Ahmed Shah soon also rose in rebellion against the Dogras, and so Maharaja Gulab Singh dispatched his commander Wazir Lakhpat to recapture Skardu. His forces were able to convince a guard to betray the garrison by leaving a gate unlocked, thereby allowing Dogra forces to recapture the fort and massacre its Balti defenders. The Raja of the Baltis was forced to pay an annual tribute to the Dogra Maharaja in Jammu, while the fort's provisions were provided for by the Balti Raja.


title: Skardu

text: Following the Dogra victory, Muhammad Shah was crowned Raja of Skardu in return for his loyalty to the Jammu crown during the rebellion, and was able to exercise some power under Dogra administration. Military commanders held real governing power in the area until 1851 when Kedaru Thanedar was installed as a civilian administrator of Baltistan. During this time, Skardu and Kargil were governed as a single district. Ladakh would later be joined to the district, while Skardu would serve as the district's winter capital, with Leh as the summer capital, up until 1947.


title: Skardu

text: Under the administration of Mehta Mangal between 1875 and 1885, Skardu's "Ranbirgarh" was built as his headquarters and residence. A cantonment, and various other government buildings were built in Skardu during this period. Sikhs from Punjab were also encouraged to migrate to Skardu in order to set up commercial enterprises during this period. The Sikh population prospered, and continued to grow - eventually also settling in nearby Shigar and Khaplu.


title: Skardu

text: After the Partition of British India, on 22 October 1947, Pakistan launched a tribal invasion of Kashmir by Pashtuns leading to the Maharaja Hari Singh acceding to India. The Gilgit Scouts, under the leadership of Major William Brown, mutinied on 1 November 1948, bringing the Gilgit Agency under the control of Pakistan. Major Aslam Khan took over the command of the Gilgit Scouts, organised a force of some 600 men from the rebels and local recruits, and launched attacks on the remaining parts of the State under Indian control. Skardu was an important target because Aslam Khan felt that Gilgit could be threatened from there. The Skardu garrison defended by a contingent of 6th Jammu and Kashmir Infantry under the command of Col. Sher Jung Thapa. The initial attack was repulsed, but the city fell into the rebel hands. After holding the garrison for 6 months and 3 days, Thapa and his forces surrendered on 14 August 1948, Pakistan's independence day.


title: Skardu

text: Skardu's Airport is situated at an elevation of above sea level, though the mountain peaks surrounding Skardu reach elevations of . Upstream from Skardu are some of the largest glaciers in the world, including the Baltoro Glacier, Biafo Glacier, and Chogo Lungma Glacier. Some of the surrounding glaciers are surrounded by some of the world's tallest mountains, including K2, the world's second tallest mountain at , Gasherbrum at , and Masherbrum at . The Deosai National Park, the world's second highest alpine plain, is located upstream of Skardu as well. Downstream from Skardu is located the Nanga Parbat mountain at .


title: Skardu

text: Skardu is located along the Kohistan-Ladakh terrane, formed as a magmatic arch over a Tethyan subduction zone that was later accreted onto the Eurasian Plate. The region has low seismic activity compared to surrounding regions, suggesting that Skardu is located in a passive structural element of the Himalayan thrust. The stone in the Skardu region is Katzara schist, with a radiometric age of 37 to 105 million years.


title: Skardu

text: Numerous complex granitic pegmatites and a few alpine-cleft metamorphic deposits are found in the Shigar Valley and its tributaries. Shigar Valley contains the Main Karokoram Thrust separating the metasediments (chlorite to amphibolite grade) on the Asian plate from the southern volcanoclastic rocks of the Kohistan-Ladakh island arc.


title: Skardu

text: Skardu features a cold semi-arid climate (Köppen climate classification "BSk"). The climate of Skardu during the summer is moderated by its mountain setting; the intense heat of lowland Pakistan does not reach it. The mountains block out the summer monsoon, and summer rainfall is thus quite low. However, these mountains result in very severe winter weather. During the April-to-October tourist season, temperatures vary between a maximum of and a minimum (in October) .


title: Skardu

text: Temperatures can drop to below in the December-to-January midwinter period. The lowest recorded temperature was on 7 January 1995.


title: Skardu

text: Skardu, along with Gilgit, is a major tourism, trekking and expedition hub in Gilgit–Baltistan. The mountainous terrain of the region, which includes four of the world's 14 Eight-thousander peaks, attracts tourists, trekkers and mountaineers from around the world. The main tourist season is from April to October; at other times of the year, the area can be cut off for extended periods by the snowy, freezing winter weather.


title: Skardu

text: Accessible from Skardu by road, the nearby Askole and Hushe are the main gateways to the snow-covered peaks including K2, the Gasherbrums, Broad Peak, and the Trango Towers, and to the huge glaciers of Baltoro, Biafo and Trango. This makes Skardu the main tourist and mountaineering base in the area, which has led to the development of a reasonably extensive tourist infrastructure including shops and hotels. The popularity of the region results in high prices, especially during the main trekking season.


title: Skardu

text: Treks to the Deosai Plains, the second highest in the world at above sea level, after the Chang Tang in Tibet, either start from or end at Skardu. In the local Balti language, Deosai is called Byarsa "བྱིར་ས", meaning 'summer place'. With an area of approximately , the plains extend all the way to Ladakh and provides a habitat for snow leopards, ibex, Tibetan blue bears and wild horses.


title: Skardu

text: Skardu Fort or Kharphocho Fort lies on the eastern face of the Khardrong or Mindoq-Khar ("Castle of Queen Mindoq") hill above Skardu town. The fort dates from the 8th century CE and contains an old mosque probably dating back to the arrival of Islam in the 16th century CE. The fort provides a panoramic view of Skardu town, the Skardu valley and the Indus River. It was built by Maqpon dynasty rulers of Baltistan. It was a seven-storey building. Mostly local people say that Kharpoocho is made by a ghost as they were servants of the ruler of that time.


title: Skardu

text: Kharphocho (Skardu) fort was built on a design similar to that of Leh Palace and the Potala Palace in Lhasa, Tibet. The name Kharpochhe means the great fort — "Khar" in Tibetan means castle or fort and "Chhe" means great.


title: Skardu

text: Located on the route to the world's second highest mountain, K-2 is Shigar Fort. It is also known as Fong-Khar, which in the local language means the "Palace on the Rock". The complex at Shigar comprises the 400-year-old fort/palace and two more recent buildings: the "Old House" and the "Garden House". The former palace of the Raja of Shigar has been transformed into a 20-room heritage guesthouse, with the grand audience hall serving as a museum of Balti culture and featuring select examples of fine wood-carvings, as well as other heritage objects.


title: Skardu

text: There are two Kachura lakes in Kachura Valley — the less well-known (Upper) Kachura Lake and the more famous Shangrila Lake ("Lower Kachura Lake"). Shangrila Lake is home to the Shangrila Resort hotel complex (possibly the reason for the lake's alternative name), built in a Chinese style and another popular destination for tourists in Pakistan-administered Kashmir. The resort has a unique restaurant, set up inside the fuselage of an aircraft that crashed On 3 October 1953, a DC-3 Aircraft belonging to Orient Airways crashed landed after three minutes of taking off. Although all people on the aircraft survived the crash, the plane never saw another day in the sky.


title: Skardu

text: Satpara Lake is Skardu Valley's main lake. In 2002, the Federal Government decided to build a dam on the Satpara Lake allocating $10 million to the project, in 2004. Progress has, however, been slow. Satpara Lake is from Skardu. Satpara Lake is one of the largest fresh water lakes in the countryside offering trout fishing and row boating. This lake is the source of Skardu's drinking water. The dam was mostly completed in 2011 and four powerhouse units are operational; the latest started operation in June 2013.


title: Skardu

text: The normal road route into Skardu is via the Karakorum Highway and a Skardu Road (S1) into the Skardu Valley from it. Roads once linked Skardu to Srinagar and Leh, though none are open for cross-LoC travel.


title: Skardu

text: Skardu's weather can have adverse effects on transport in and out of the region, as Skardu is often snowbound during the winter months. Roads in and out of Skardu can be blocked for extended periods of time, sometimes leaving air travel as the only feasible alternative.


title: Skardu

text: On 2 December 2021, the Skardu International Airport was designated and re-inaugurated as an international airport after providing upgrades to the airport to become a tourism hub for Gilgit-Baltistan.


title: Skardu

text: Flydubai has submitted a request to start international operations to and from Skardu airport, which would potentially become the first airline to start international routes from Skardu.


title: Skardu

text: The Satpara Dam development project on the Satpara Lake was inaugurated in 2003. It was completed in 2011. It is south of Skardu city and is at an elevation of from mean sea level. The main source of water is melting ice of the Deosai plains during the summer season. Now Satpara Dam provides drinking water to the whole city of Skardu and agricultural water to major areas of Skardu, for example, Gayoul, Newrangha, Khlangranga, Shigari Khurd, etc.


title: Skardu

text: It is a multipurpose project, which will produce 17.36 megawatts hydro generation, irrigate of land and provide 13 cusecs drinking water daily to Skardu city.


title: Hemophagocytic lymphohistiocytosis

text: Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages, characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes. There are inherited and non-inherited (acquired) causes of hemophagocytic lymphohistiocytosis (HLH).


title: Hemophagocytic lymphohistiocytosis

text: The onset of HLH occurs before the age of one year in approximately 70 percent of cases. Familial HLH should be suspected if siblings are diagnosed with HLH or if symptoms recur when therapy has been stopped. Familial HLH is an autosomal recessive disease, hence each sibling of a child with familial HLH has a twenty-five–percent chance of developing the disease, a fifty-percent chance of carrying the defective gene (which is very rarely associated with any risk of disease), and a twenty-five–percent chance of not being affected and not carrying the gene defect.


title: Hemophagocytic lymphohistiocytosis

text: Patients with HLH, especially when untreated, may need intensive therapy. Therefore, HLH should be included in the differential diagnosis of intensive care unit patients with cytopenia and hyperferritinemia. Patients in the earlier stages of HLH are frequently hospitalized at internal medicine wards.


title: Hemophagocytic lymphohistiocytosis

text: HLH clinically manifests with fever, enlargement of the liver and spleen, enlarged lymph nodes, yellow discoloration of the skin and eyes, and a rash. Laboratory findings may include elevated triglyceride levels, low fibrinogen levels, transaminitis, and elevated ferritin levels (among others).


title: Hemophagocytic lymphohistiocytosis

text: Primary HLH is caused by loss of function, (i.e. inactivating) mutations in genes that code for proteins cytotoxic T cells and NK cells use to kill targeted cells, such as those infected with pathogens like the Epstein-Barr virus (EBV) or the Dengue virus. These mutations include those in the following genes: "UNC13D, STX11, RAB27A, STXBP2, LYST, PRF1 1, SH2D1A, BIRC4, ITK, CD27," and "MAGT1".


title: Hemophagocytic lymphohistiocytosis

text: Secondary HLH (sHLH) is associated with, and thought to be promoted by, malignant and non-malignant diseases that likewise weaken the ability of the immune system to attack EBV-infected cells. Malignant disorders associated with secondary HLH include T-cell lymphoma, B-cell lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome. Non-malignant disorders associated with secondary HLH include: autoimmune disorders such as juvenile idiopathic arthritis, juvenile Kawasaki disease, systemic lupus erythematosus, the juvenile onset and adult onset forms of Still's disease, and rheumatoid arthritis; immunodeficiency disorders such as severe combined immunodeficiency, DiGeorge syndrome, Wiskott–Aldrich syndrome, ataxia–telangiectasia, and dyskeratosis congenita); and infections caused by EBV, cytomegalovirus, HIV/AIDS, bacteria, protozoa, fungi and SARS-CoV-2. Secondary HLH may also result from iatrogenic causes such as bone marrow or other organ transplantations; chemotherapy; or therapy with immunosuppressing agents;


title: Hemophagocytic lymphohistiocytosis

text: About 33% of all HLH cases, ~75% of Asian HLH cases, and nearly 100% of HLH cases caused by mutations in "SH2D1A" (see X-linked lymphoproliferative disease type 1) are associated with, and thought triggered or promoted by, EBV infection. These cases of HLH are classified as belonging to the class of Epstein–Barr_virus–associated_lymphoproliferative_diseases and termed EBV+ HLH.


title: Hemophagocytic lymphohistiocytosis

text: Five genetic subtypes (FHL1, FHL2, FHL3, FHL4, and FHL5) are described, with an estimated overall prevalence of one in 50,000 and equal gender distribution. Molecular genetic testing for four of the causative genes, PRF1 (FHL2), UNC13D (FHL3), STX11 (FHL4), and STXBP2 (FHL5), is available on a clinical basis. Symptoms of FHL are usually evident within the first few months of life and may even develop "in utero". However, symptomatic presentation throughout childhood and even into young adulthood has been observed in some cases.


title: Hemophagocytic lymphohistiocytosis

text: Nearly half of the cases of type 2 familial hemophagocytic lymphohistiocytosis are due to bi-allelic PRF1 mutations.


title: Hemophagocytic lymphohistiocytosis

text: The underlying causes, either inherited or acquired, lead to an unchecked immune response when exposed to triggers. Impaired NK-cell cytotoxicity is the hallmark of HLH. All genetic defects for familial HLH are related to granule-dependent cytotoxicity. This inability to remove infected and antigen-presenting cells and terminate the immune response leads to uncontrolled proliferation and activation of the immune system with release of excessive cytokines. These cells then infiltrate organs, releasing more cytokines, which gives the clinical picture. The fever is caused by IL-1, IL-6 and TNF-alpha; the cytopenia is due to the suppressive effect on hematopoiesis by TNF-alpha and TNF-gamma. TNF-alpha and TNF-gamma may also lead to inhibition of lipoprotein lipase or stimulate triglyceride synthesis. Activated macrophages secrete ferritin and plasminogen activator leading to hyperfibrinolysis.


title: Hemophagocytic lymphohistiocytosis

text: The blood count typically shows decreased numbers of blood cells—including a decreased number of circulating red blood cells, white blood cells, and platelets. The bone marrow may show hemophagocytosis. The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.


title: Hemophagocytic lymphohistiocytosis

text: The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.


title: Hemophagocytic lymphohistiocytosis

text: Primary HLH, also known as familial haemophagocytic lymphohistiocytosis (FHL) or familial erythrophagocytic lymphohistiocytosis, is a heterogeneous autosomal recessive disorder found to be more prevalent with parental consanguinity.


title: Hemophagocytic lymphohistiocytosis

text: Secondary haemophagocytic lymphohistiocytosis (acquired haemophagocytic lymphohistiocytosis) occurs after strong immunologic activation, such as that which can occur with systemic infection, immunodeficiency, or underlying malignancy.


title: Hemophagocytic lymphohistiocytosis

text: Both forms are characterized by the overwhelming activation of normal T lymphocytes and macrophages, invariably leading to clinical and haematologic alterations and death in the absence of treatment.


title: Hemophagocytic lymphohistiocytosis

text: A subtype of primary HLH where the inflammation is limited to the central nervous system has been described.


title: Hemophagocytic lymphohistiocytosis

text: 1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11.


title: Hemophagocytic lymphohistiocytosis

text: Not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis as delay results in increased mortality. The diagnostic criteria were developed in pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individual's risk of HLH. In adults, soluble IL-2 receptor has been found to be a very sensitive marker for HLH, demonstrating 100% sensitivity for ruling out HLH below a cutoff of 2400 U/mL and optimal cutoff for ruling in at 2515 U/mL (sensitivity, 100%; specificity, 72.5%), with 93% specificity at >10 000 U/mL.


title: Hemophagocytic lymphohistiocytosis

text: The differential diagnosis of HLH includes secondary HLH and macrophage-activation syndrome or other primary immunodeficiencies that present with hemophagocytic lymphohistiocytosis, such as X-linked lymphoproliferative disease.


title: Hemophagocytic lymphohistiocytosis

text: Other conditions that may be confused with this condition include autoimmune lymphoproliferative syndrome. As a syndrome of intense inflammation it needs to be differentiated from sepsis, which may be extremely challenging.


title: Hemophagocytic lymphohistiocytosis

text: The diagnosis of acquired, or secondary, HLH is usually made in association with infection by viruses, bacteria, fungi, or parasites or in association with lymphoma, autoimmune disease, or metabolic disease. Acquired HLH may have decreased, normal, or increased NK cell activity.


title: Hemophagocytic lymphohistiocytosis

text: A major differential diagnosis of HLH is Griscelli syndrome (type 2). This is a rare autosomal recessive disorder characterized by partial albinism, hepatosplenomegaly, pancytopenia, hepatitis, immunologic abnormalities, and lymphohistiocytosis. Most cases have been diagnosed between 4 months and 7 years of age, with a mean age of about 17 months.


title: Hemophagocytic lymphohistiocytosis

text: Three types of Griscelli syndrome are recognised: type 1 has neurologic symptoms and mutations in MYO5A. Prognosis depends on the severity of neurologic manifestations. Type 2 has mutations in RAB27A and haemophagocytic syndrome, with abnormal T-cell and macrophage activation. This type has a grave prognosis if untreated. Type 3 has mutations in melanophilin and is characterized by partial albinism. This type does not pose a threat to those so affected.


title: Hemophagocytic lymphohistiocytosis

text: In secondary cases, treatment of the cause, where possible, is indicated. Additionally, treatment for HLH itself is usually required.


title: Hemophagocytic lymphohistiocytosis

text: While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.


title: Hemophagocytic lymphohistiocytosis

text: On 20 November 2018, the FDA approved the anti-IFN-gamma monoclonal antibody emapalumab (proprietary name Gamifant) for the treatment of pediatric and adult primary HLH.


title: Hemophagocytic lymphohistiocytosis

text: In October 2021 NHS England published "Clinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages", allowing Anakinra (a modified recombinant interleukin 1 receptor antagonist) to be used in the treatment of HLH.


title: Hemophagocytic lymphohistiocytosis

text: The prognosis is guarded with an overall mortality of 50%. Poor prognostic factors included HLH associated with malignancy, with half the patients dying by 1.4 months compared to 22.8 months for non-tumour associated HLH patients.


title: Hemophagocytic lymphohistiocytosis

text: Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with involvement of the central nervous system (brain and/or spinal cord).


title: Hemophagocytic lymphohistiocytosis

text: The first case report of HLH was published in 1939 under the term HISTIOCYTIC MEDULLARY RETICULOSIS. A second report would come out in 1952 that would rename the disorder that same year.


title: Hemophagocytic lymphohistiocytosis

text: A systematic review recently reported the pooled proportion are fever 97.2%, hepatomegaly 70.2%, splenomegaly 78.4%, thrombocytopenia 90.1%, anemia 76.0%, and serum ferritin ≥500 μg/L 97.1%. The case fatality rate is 14.6% among dengue hemophagocytic lymphohistiocytosis patients.


title: Akira (2016 Hindi film)

text: Akira is a 2016 Indian Hindi-language action crime thriller film co-written, produced and directed by A. R. Murugadoss. It is a remake of the 2011 Tamil-language film "Mouna Guru", and features Sonakshi Sinha, Konkana Sen Sharma and Anurag Kashyap in the lead roles.


title: Akira (2016 Hindi film)

text: Principal photography began in March 2015, and the film released worldwide on 2 September 2016. The soundtrack composed by Vishal–Shekhar, was released on 16 August 2016. The film received mixed reviews from critics with praise for the performances of the cast but criticism for writing of the film.


title: Akira (2016 Hindi film)

text: Akira Sharma, a young girl, witnesses a group of men throwing acid on a woman's face. She helps the police catch one of the criminals. and is therefore harassed by the accused who slash her face out of revenge, giving her a scar. Subsequently, her father enrolls her in a self-defense class. A couple of days later, she comes across the same men who had escaped earlier and tries to catch them. One of them tries to throw acid on her, but it ends up on his own face in the brawl. Akira is arrested, convicted and sent to a remand home for the attack.


title: Akira (2016 Hindi film)

text: 3 years later, Akira is released and later grows into a rebellious tough woman. When she starts going to college, her brother comes to pick her mother and her. And hence she moves from Jodhpur to Mumbai. She joins a college and begins living in a hostel, where she finds it difficult to adjust to normal life. The college is also dealing with a thieving student, as more and more electronics keep getting stolen. When a corrupt and drunk-on-power police officer, ACP Rane hits an elderly college professor with his car and then beats him up, the college students take out a massive protest. The protests turn violent, however Akira patiently waits to hand over their petition to the Commissioner.


title: Akira (2016 Hindi film)

text: A couple of days later, Rane goes to help a car crash victim but robs and kills him, when he finds loot in his trunk. His girlfriend, Maya, who is in the same college as Akira, secretly records his conversation about evidence disposal. Her bag with the camera is, however, stolen, and someone starts blackmailing Rane. Suspecting Maya, he brutally kills her. Despite his insistence, the case is handled by SP Rabiya, who suspects Maya's murder.


title: Akira (2016 Hindi film)

text: Meanwhile, the college announces that they will pardon the electronic thief if they return all the stolen items anonymously. Akira finds a bag full of stolen items, including the camera, in front of her dorm. Rane's associates catch her with the camera and decide to kill her and two other witnesses. She, however, escapes when the men reload their gun after killing the other two.


title: Akira (2016 Hindi film)

text: Rane and his men, declare Akira to be mentally unstable. Given her violent past and her rebellious behaviour, her family members as well as her friends are easily convinced. She is taken away to a mental asylum, and, with the help of a corrupt doctor, they give her electric shocks to drive her insane. With the help of another mentally ill patient, she brutally murders the doctors and the guards and escapes. She abducts one of Rane's associates and blackmails him to prove her innocence. Rane, however, traces her hideout and attacks it. Rabiya, with an arrest-warrant for Rane, arrives and seizes all the arms but is stopped by the Commissioner, as the car-crash victim was the brother of a major politician – something which will lead to riots if the news of his murder breaks out. Rane gets back the charge, and the commissioner orders him to take Akira to a mental asylum. Helpless, Rabiya leaves but quietly carries along the seized arms, leaving those inside unarmed. Akira easily kills Rane and his associates in hand-to-hand combat and then goes back to the mental asylum. Completely sane, she is released three months later. In the end, she starts living her late father's life in Jodhpur and is living peacefully there teaching deaf children.


title: Akira (2016 Hindi film)

text: The songs featured in the film were composed by the duo Vishal–Shekhar. The background score of the film was composed by John Stewart Eduri.


title: Akira (2016 Hindi film)

text: The song "Kehkasha Tu Meri" is a remake of the duo's Marathi song "Harvali Pakhare" from the 2012 film "Balak-Palak", sung by Shekhar Ravjiani.


title: Akira (2016 Hindi film)

text: On review aggregator website Rotten Tomatoes, the film holds an approval rating of 33% based on 9 reviews, with an average rating of 5.60/10.


title: Akira (2016 Hindi film)

text: Anupama Chopra giving the film 2.5/5, praised the performances of Sinha, Kashyap and Sharma, but criticised the second half. She wrote that "Anurag [Kashyap] gives Rane just the right touches of menace and sleaze." The second half, however, "strikes so badly in this film that it almost completely negates the first half, which is effective."


title: Akira (2016 Hindi film)

text: Anna M.M. Vetticad, praised the acting but criticised the character development. For Sinha's character, she wrote, "Akira is the most poorly fleshed out character in the entire story...a woman who can fight as skillfully and strongly as any man. That is it. The workings of her mind, her motivations and her feelings, remain a mystery." She, however, praised Kashyap's portrayal of Rane, calling it the "best-written character" whose "drug-addled brain is never so clouded as to make him lose sight of his self-interest."


title: Akira (2016 Hindi film)

text: Writing for "Reuters", Shilpa Jamkhandikar praised the acting but criticised the writing calling it a mashup of "many half-baked sub-plots" and very similar in style to cop movies from the 80s. She believes that "[Akira] is a great example of a movie with a timely topic that suffers from outdated treatment." She, however, praised Kahyap's character, Rane, writing "[he] channels every 80s bad cop character we’ve seen. If it wasn’t for him, “Akira” would have been a complete loss as a film."


title: Akira (2016 Hindi film)

text: The film collected on its opening day in India. By the end of its first weekend, "Akira" had grossed and its first week collection was approximately domestically.


title: Akira (2016 Hindi film)

text: "Akira" collected from North America (America and Canada), from UAE, from UK. The film collected from Pakistan.


title: Orders of precedence in the United Kingdom

text: The order of precedence in the United Kingdom is the sequential hierarchy for Peers of the Realm, officers of state, senior members of the clergy, holders of the various Orders of Chivalry and other persons in the three legal jurisdictions within the United Kingdom:


text: The order of precedence is determined by various methods. The Precedence Act (which technically applies only to determine seating in the House of Lords Chamber) and the Acts of Union with Scotland and Ireland generally set precedence for members of the nobility. The statutes of the various Orders of Chivalry set precedence for their members. In other cases, precedence may be decided by the sovereign's order, by a Royal Warrant of Precedence, by letters patent, by Acts of Parliament, or by custom.


text: One may acquire precedence for various reasons. Firstly, one may be an office-holder. Secondly, one may be of a particular degree such as duke. Thirdly, in the case of women, one may be the wife of a title-holder (note that wives acquire precedence due to their husbands, but husbands do not gain any special precedence due to their wives). Finally, one may be the son or daughter of a title-holder.


text: One does not gain precedence as a child of a lady, unless that lady is a peeress in her own right. Furthermore, if a daughter of a peer marries a commoner, then she retains her precedence as a daughter of a peer. However, if she marries a peer, then her precedence is based on her husband's status, and not on her father's.


text: The King or Queen of the United Kingdom, as the sovereign, is always first in the order of precedence. A king is followed by his queen consort, the first in the order of precedence for women. The reverse, however, is not always true for queens regnant. There is no established law of precedence for a prince consort, so he is usually specially granted precedence above all other males by letters patent or, on the other hand, may rank lower than the heir apparent or the heir presumptive, even if the heir is his own son, such as with Prince Albert and Edward VII, who outranked his father as Prince of Wales.


text: In England and Wales, the Archbishop of Canterbury is the highest in precedence following the royal family. Then come, assuming the post of Lord High Steward is vacant (as it usually has been since 1421), the Lord Chancellor, and the Archbishop of York. Next come the Prime Minister, the Lord President of the Privy Council, the Speaker of the House of Commons, the Lord Speaker of the House of Lords (since July 2006), the President of the Supreme Court of the United Kingdom (since October 2009), the Lord Chief Justice of England and Wales (since November 2007) and the Lord Privy Seal.


text: The precedence of the Lord Great Chamberlain, the Earl Marshal, the Lord Steward and the Lord Chamberlain are determined by the rank and class of the peerage of the holders of such offices.


text: In Scotland, the Keeper of the Great Seal of Scotland and the Keeper of the Privy Seal of Scotland, if Peers, rank after the Lord Speaker of the House of Lords. If not so, then they rank after the younger sons of dukes. The Hereditary High Constable of Scotland and the Master of the Household in Scotland rank above dukes. If the Keepers of the Seals are Peers, then the Keepers precede the High Constable and Master.


text: The ranks of Peers are as follows: Duke (and Duchess), Marquess (and Marchioness), Earl (and Countess), Viscount (and Viscountess), and Baron (and Baroness) together with Scottish Lord (and Lady) of Parliament.


text: Within their own respective ranks, the rank of Peers correspond to the age ("venerability") of the creation of their peerages; that is, the older the title, the more senior the title's holder is. However, seniority rules also depend on the country within the current UK where the title originated, so that English peers hold the highest ranks, followed by Scottish peers. After English and Scottish peers, peers created in Great Britain as whole in (1707–1801) follow. Together over the Pre-Union Peerage of Ireland (pre-1801), and together they all take precedence over either the senior Peerage of the United Kingdom (post-1801), or the junior Post-Union Peerage of Ireland (1801–1922).


text: Subject to the same governing rules as detailed in the paragraphs above, the rank of the wives of Peers is also governed by the venerability (age) of the peerage. A dowager Peeress (widow of a deceased Peer) would however always precede the wife of the present Peer.


text: Barons and Baronesses of the life peerage rank immediately below Barons and Baronesses of the hereditary peerage and Scottish Lords and Ladies in Parliament.


text: In England and Wales, the Archbishop of Canterbury, Primate of All England, is the most senior person outside of Royalty, and after the Lord Chancellor, immediately followed by the Archbishop of York, Primate of England. Primates (i.e. archbishops) and bishops of the Church of England rank immediately above Peers. First come the Bishops of London and Durham, followed by the Bishop of Winchester, followed by the other diocesan bishops in order of seniority, and then the suffragan bishops in order of seniority.


text: The Bishop of Sodor and Man and the Anglican Bishop of Gibraltar in Europe, whose "Sees" are full and integral parts of the Ecclesiastical Provinces of York and Canterbury, respectively, are also usually included as suffragan bishops of the Church of England for the purpose of precedence.


text: In Scotland, the Lord High Commissioner to the General Assembly of the Church of Scotland ranks immediately below the sovereign or consort (depending on their respective sex), but only when the General Assembly is in session, and immediately followed by the Moderator of the General Assembly of the Church of Scotland.


text: According to the "unofficial" order of precedence for Northern Ireland published by the publishers of "Burke's Peerage", 106th Edition, , the precedence of "all" of the primates and archbishops of the Roman Catholic Church in Ireland and the Church of Ireland, together with the Moderator of the Presbyterian Church in Ireland, are to be determined solely by seniority, according to the dates of consecration or translation, or the date of election, in the case of the Presbyterian Moderator, without any presumption of automatic Roman Catholic or Protestant seniority, Anglican or Presbyterian.


text: The two highest orders of chivalry in England and Wales, and in Scotland, are the Orders of the Garter, and the Thistle, respectively. Knights of the Order of the Garter and Order of the Thistle precede baronets. After the baronets come the members of all the other orders of chivalry in the following order of their ranks: Knight or Dame Grand Cross, Knight or Dame Commander, Commander or Companion, Lieutenant or Officer, and Member.


text: For individual members with equivalent ranks but of different orders, precedence is accorded based on the seniority of the orders of chivalry: the Order of the Bath, the Order of St Michael and St George, the Royal Victorian Order, and the Order of the British Empire. For equivalent ranks and orders, those appointed earlier precede those appointed later. Knights Bachelor come after Knights Commander of the Order of the British Empire.


text: Wives of Knights of the Garter, Knights of the Thistle, Knights Grand Cross, Knights Commanders, and Commanders or Companions receive precedence based on their husbands' positions. Wives of individuals of a certain rank follow in precedence after female holders of the same rank. Thus, wives of Knights Grand Cross follow Dames Grand Cross.


text: Wives of baronets go immediately above all Dames Grand Cross, but are below (though not immediately below) Ladies and Wives of Knights of the Garter, the Thistle, and St Patrick. Baronets' widows follow rules similar to dowager peeresses; a widow of a previous baronet comes immediately before the wife of the present baronet.


title: Tau Ceti

text: Tau Ceti, Latinized from τ Ceti, is a single star in the constellation Cetus that is spectrally similar to the Sun, although it has only about 78% of the Sun's mass. At a distance of just under from the Solar System, it is a relatively nearby star and the closest solitary G-class star. The star appears stable, with little stellar variation, and is metal-deficient relative to the Sun.


title: Tau Ceti

text: It can be seen with the unaided eye with an apparent magnitude of 3.5. As seen from Tau Ceti, the Sun would be in the northern hemisphere constellation Boötes with an apparent magnitude of about 2.6.


title: Tau Ceti

text: Observations have detected more than ten times as much dust surrounding Tau Ceti as is present in the Solar System. Since December 2012, there has been evidence of at least four planets—all confirmed as super-Earths—orbiting Tau Ceti, with two of these being potentially in the habitable zone. There are an additional four unconfirmed planets, one of which is a Jovian planet between 3 and 20 AU from the star. Because of its debris disk, any planet orbiting Tau Ceti would face far more impact events than Earth. Despite this hurdle to habitability, its solar analog (Sun-like) characteristics have led to widespread interest in the star. Given its stability, similarity and relative proximity to the Sun, Tau Ceti is consistently listed as a target for the Search for Extra-Terrestrial Intelligence (SETI) and appears in some science fiction literature.


title: Tau Ceti

text: The name "Tau Ceti" is the Bayer designation for this star, established in 1603 as part of German celestial cartographer Johann Bayer's "Uranometria" star catalogue: it is "number T" in Bayer's sequence of constellation Cetus. In the catalogue of stars in the "Calendarium" of Al Achsasi al Mouakket, written at Cairo about 1650, this star was designated "Thālith al Naʽāmāt" (ثالث النعامات - "thālith al-naʽāmāt"), which was translated into Latin as "Tertia Struthionum", meaning "the third of the ostriches". This star, along with η Cet (Deneb Algenubi), θ Cet (Thanih Al Naamat), ζ Cet (Baten Kaitos), and υ Cet, were "Al Naʽāmāt" (النعامات), the Hen Ostriches.


title: Tau Ceti

text: In Chinese astronomy, the "Square Celestial Granary" () refers to an asterism consisting of τ Ceti, ι Ceti, η Ceti, ζ Ceti, θ Ceti and 57 Ceti. Consequently, the Chinese name for τ Ceti itself is "the Fifth Star of Square Celestial Granary" ().


title: Tau Ceti

text: The proper motion of a star is its rate of movement across the celestial sphere, determined by comparing its position relative to more distant background objects. Tau Ceti is considered to be a high-proper-motion star, although it only has an annual traverse of just under 2 arc seconds. Thus it will require about 2000 years before the location of this star shifts by more than a degree. A high proper motion is an indicator of closeness to the Sun. Nearby stars can traverse an angle of arc across the sky more rapidly than the distant background stars and are good candidates for parallax studies. In the case of Tau Ceti, the parallax measurements indicate a distance of . This makes it one of the closest star systems to the Sun and the next-closest spectral class-G star after Alpha Centauri A.


title: Tau Ceti

text: The radial velocity of a star is the component of its motion that is toward or away from the Sun. Unlike proper motion, a star's radial velocity cannot be directly observed, but can be determined by measuring its spectrum. Due to the Doppler shift, the absorption lines in the spectrum of a star will be shifted slightly toward the red (or longer wavelengths) if the star is moving away from the observer, or toward blue (or shorter wavelengths) when it moves toward the observer. In the case of Tau Ceti, the radial velocity is about −17 km/s, with the negative value indicating that it is moving toward the Sun. The star will make its closest approach to the Sun in about 43,000 years, when it comes to within .


title: Tau Ceti

text: The distance to Tau Ceti, along with its proper motion and radial velocity, together give the motion of the star through space. The space velocity relative to the Sun is . This result can then be used to compute an orbital path of Tau Ceti through the Milky Way. It has a mean galacto-centric distance of () and an orbital eccentricity of 0.22.


title: Tau Ceti

text: The Tau Ceti system is believed to have only one stellar component. A dim optical companion has been observed with magnitude 13.1. As of 2000, it was distant from the primary. It may be gravitationally bound, but it is considered more likely to be a line-of-sight coincidence.


title: Tau Ceti

text: Most of what is known about the physical properties of Tau Ceti and its system has been determined through spectroscopic measurements. By comparing the spectrum to computed models of stellar evolution, the age, mass, radius and luminosity of Tau Ceti can be estimated. However, using an astronomical interferometer, measurements of the radius of the star can be made directly to an accuracy of 0.5%. Through such means, the radius of Tau Ceti has been measured to be of the solar radius. This is about the size that is expected for a star with somewhat lower mass than the Sun.


title: Tau Ceti

text: The rotation period for Tau Ceti was measured by periodic variations in the classic H and K absorption lines of singly ionized calcium (Ca II). These lines are closely associated with surface magnetic activity, so the period of variation measures the time required for the activity sites to complete a full rotation about the star. By this means the rotation period for Tau Ceti is estimated to be . Due to the Doppler effect, the rotation rate of a star affects the width of the absorption lines in the spectrum (light from the side of the star moving away from the observer will be shifted to a longer wavelength; light from the side moving towards the observer will be shifted toward a shorter wavelength). By analyzing the width of these lines, the rotational velocity of a star can be estimated. The projected rotation velocity for Tau Ceti is


title: Tau Ceti

text: where "v" is the velocity at the equator, and "i" is the inclination angle of the rotation axis to the line of sight. For a typical G8 star, the rotation velocity is about . The relatively low rotational velocity measurements may indicate that Tau Ceti is being viewed from nearly the direction of its pole.


title: Tau Ceti

text: The chemical composition of a star provides important clues to its evolutionary history, including the age at which it formed. The interstellar medium of dust and gas from which stars form is primarily composed of hydrogen and helium with trace amounts of heavier elements. As nearby stars continually evolve and die, they seed the interstellar medium with an increasing portion of heavier elements. Thus younger stars tend to have a higher portion of heavy elements in their atmospheres than do the older stars. These heavy elements are termed "metals" by astronomers, and the portion of heavy elements is the metallicity. The amount of metallicity in a star is given in terms of the ratio of iron (Fe), an easily observed heavy element, to hydrogen. A logarithm of the relative iron abundance is compared to the Sun. In the case of Tau Ceti, the atmospheric metallicity is


title: Tau Ceti

text: This lower abundance of iron indicates that Tau Ceti is almost certainly older than the Sun. Its age had previously been estimated to be about , but is now thought to be around half that, at . This compares with for the Sun. However, computed age estimates for Tau Ceti can range from 4.4 to , depending on the model adopted.


title: Tau Ceti

text: Besides rotation, another factor that can widen the absorption features in the spectrum of a star is pressure broadening. The presence of nearby particles affects the radiation emitted by an individual particle. So the line width is dependent on the surface pressure of the star, which in turn is determined by the temperature and surface gravity. This technique was used to determine the surface gravity of Tau Ceti. The , or logarithm of the star's surface gravity, is about 4.4, very close to the for the Sun.


title: Tau Ceti

text: The luminosity of Tau Ceti is equal to only 55% of the Sun's luminosity. A terrestrial planet would need to orbit this star at a distance of about to match the solar insolation level of Earth. This is approximately the same as the average distance between Venus and the Sun.


title: Tau Ceti

text: The chromosphere of Tau Ceti—the portion of a star's atmosphere just above the light-emitting photosphere—currently displays little or no magnetic activity, indicating a stable star. One 9-year study of temperature, granulation, and the chromosphere showed no systematic variations; Ca II emissions around the H and K infrared bands show a possible 11-year cycle, but this is weak relative to the Sun. Alternatively it has been suggested that the star could be in a low-activity state analogous to a Maunder minimum—a historical period, associated with the Little Ice Age in Europe, when sunspots became exceedingly rare on the Sun's surface. Spectral line profiles of Tau Ceti are extremely narrow, indicating low turbulence and observed rotation. The star's asteroseismological oscillations have an amplitude about half that of the Sun and a lower mode lifetime.


title: Tau Ceti

text: Principal factors driving research interest in Tau Ceti are its proximity, its Sun-like characteristics, and the implications for possible life on its planets. For categorization purposes, Hall and Lockwood report that "the terms 'solarlike star', 'solar analog', and 'solar twin' [are] progressively restrictive descriptions". Tau Ceti fits the second category, given its similar mass and low variability, but relative lack of metals. The similarities have inspired popular culture references for decades, as well as scientific examination.


title: Tau Ceti

text: In 1988, radial-velocity observations ruled out any periodical variations attributable to massive planets around Tau Ceti inside of Jupiter-like distances. Ever more precise measurements continue to rule out such planets, at least until December 2012. The velocity precision reached is about 11 m/s measured over a 5-year time span. This result excludes hot Jupiters and probably excludes any planets with minimal mass greater than or equal to Jupiter's mass and with orbital periods less than 15 years. In addition, a survey of nearby stars by the Hubble Space Telescope's Wide Field and Planetary Camera was completed in 1999, including a search for faint companions to Tau Ceti; none were discovered to limits of the telescope's resolving power.


title: Tau Ceti

text: However, these searches only excluded larger brown dwarf bodies and closer orbiting giant planets, so smaller, Earth-like planets in orbit around the star, like those discovered in 2012, were not precluded. If hot Jupiters were to exist in close orbit, they would likely disrupt the star's habitable zone; their exclusion was thus considered positive for the possibility of Earth-like planets. General research has shown a positive correlation between the presence of planets and a relatively high-metallicity parent star, suggesting that stars with lower metallicity such as Tau Ceti have a lower chance of having planets.


title: Tau Ceti

text: On December 19, 2012, evidence was presented that suggested a system of five planets orbiting Tau Ceti. The planets' estimated minimal masses were between 2 and 6 Earth masses, with orbital periods ranging from 14 to 640 days. One of them, Tau Ceti e, appears to orbit about half as far from Tau Ceti as Earth does from the Sun. With Tau Ceti's luminosity of 52% that of the Sun and a distance from the star of 0.552 AU, the planet would receive 1.71 times as much stellar radiation as Earth does, slightly less than Venus with 1.91 times Earth's. Nevertheless, some research places it within the star's habitable zone. The Planetary Habitability Laboratory has estimated that Tau Ceti f, which receives 28.5% as much starlight as Earth, would be within the star's habitable zone, albeit narrowly.


title: Tau Ceti

text: The discovery team refined their methodology, improved their radial-velocity measurements, and published their new results in August 2017. They confirmed Tau Ceti e and f as candidates but failed to consistently detect planets b (which may be a false negative), c (whose weakly defined apparent signal was correlated to stellar rotation), and d (which did not show up in all data sets). Instead, they found two new planetary candidates, g and h, with orbits of 20 and 49 days. The signals detected from the candidate planets have radial velocities as low as 30 cm/s, and the experimental method used in their detection, as it was applied to HARPS, could in theory have detected down to around 20 cm/s. The updated 4-planet model is dynamically packed and potentially stable for billions of years.


title: Tau Ceti

text: However, with further refinements, even more candidate planets have been detected. In 2019, a paper published in "Astronomy & Astrophysics" suggested that Tau Ceti could have a Jupiter or super-Jupiter based on a tangential astrometric velocity of around 11.3 m/s. The exact size and position of this conjectured object have not been determined, though it is at most 5 Jupiter masses if it orbits between 3 and 20 AU. A 2020 "Astronomical Journal" study by astronomers Jeremy Dietrich and Daniel Apai analyzed the orbital stability of the known planets and, considering statistical patterns identified from hundreds of other planetary systems, explored the orbits in which the presence of additional, yet-undetected planets are most likely. This analysis predicted three planet candidates at orbits coinciding with planet candidates b, c, and d. The close match between the independently predicted planet periods and the periods of the three planet candidates previously identified in radial velocity data strongly supports the genuine planet nature of candidates b, c, and d. Furthermore, the study also predicts at least one yet-undetected planet between planets e and f, i.e., within the habitable zone. This predicted exoplanet is identified as PxP-4.


title: Tau Ceti

text: If Tau Ceti is aligned in such a way that it is nearly pole-on to Earth (as its rotation could indicate), its planets would be less similar to Earth's mass and more to Neptune, Saturn, or Jupiter. For example, were Tau Ceti f's orbit inclined 70 degrees from being face-on to Earth, its mass would be Earth masses, making it a middle-to-low end super-Earth. However, these scenarios aren't necessarily true; since Tau Ceti's debris disk has an inclination of , the planets' orbits could be similarly inclined. If the debris disk and f's orbits were assumed to be equal, f would be between and Earth masses, making it slightly more likely to be a mini-Neptune.


title: Tau Ceti

text: Tau Ceti e is a confirmed planet orbiting Tau Ceti that was detected by statistical analyses of the data of the star's variations in radial velocity that were obtained using HIRES, AAPS, and HARPS. Its possible properties were refined in 2017: it orbits at a distance of 0.552 AU (between the orbits of Venus and Mercury in the Solar System) with an orbital period of 168 days and has a minimum mass of 3.93 Earth masses. If Tau Ceti e possessed an Earth-like atmosphere, the surface temperature would be around . Based upon the incident flux upon the planet, a study by Güdel et al. (2014) speculated that the planet may lie outside the habitable zone and closer to a Venus-like world.


title: Tau Ceti

text: Tau Ceti f is a confirmed super-Earth orbiting Tau Ceti that was discovered in 2012 by statistical analyses of the star's variations in radial velocity, based on data obtained using HIRES, AAPS, and HARPS. It is of interest because its orbit places it in Tau Ceti's extended habitable zone. However, a 2015 study implies that it has been in the temperate zone for less than one billion years, so there may not be a detectable biosignature.


title: Tau Ceti

text: Few properties of the planet are known other than its orbit and mass. It orbits Tau Ceti at a distance of 1.35 AU (near Mars's orbit in the Solar System) with an orbital period of 642 days and has a minimum mass of 3.93 Earth masses.


title: Tau Ceti

text: In 2004, a team of UK astronomers led by Jane Greaves discovered that Tau Ceti has more than ten times the amount of cometary and asteroidal material orbiting it than does the Sun. This was determined by measuring the disk of cold dust orbiting the star produced by collisions between such small bodies. This result puts a damper on the possibility of complex life in the system, because any planets would suffer from large impact events roughly ten times more frequently than Earth. Greaves noted at the time of her research that "it is likely that [any planets] will experience constant bombardment from asteroids of the kind believed to have wiped out the dinosaurs". Such bombardments would inhibit the development of biodiversity between impacts. However, it is possible that a large Jupiter-sized gas giant (such as the proposed planet "i") could deflect comets and asteroids.


title: Tau Ceti

text: The debris disk was discovered by measuring the amount of radiation emitted by the system in the far infrared portion of the spectrum. The disk forms a symmetric feature that is centered on the star, and its outer radius averages . The lack of infrared radiation from the warmer parts of the disk near Tau Ceti implies an inner cut-off at a radius of . By comparison, the Solar System's Kuiper belt extends from 30 to . To be maintained over a long period of time, this ring of dust must be constantly replenished through collisions by larger bodies. The bulk of the disk appears to be orbiting Tau Ceti at a distance of 35–, well outside the orbit of the habitable zone. At this distance, the dust belt may be analogous to the Kuiper belt that lies outside the orbit of Neptune in the Solar System.


title: Tau Ceti

text: Tau Ceti shows that stars need not lose large disks as they age, and such a thick belt may not be uncommon among Sun-like stars. Tau Ceti's belt is only 1/20 as dense as the belt around its young neighbor, Epsilon Eridani. The relative lack of debris around the Sun may be the unusual case: one research-team member suggests the Sun may have passed close to another star early in its history and had most of its comets and asteroids stripped away. Stars with large debris disks have changed the way astronomers think about planet formation because debris disk stars, where dust is continually generated by collisions, appear to form planets readily.


title: Tau Ceti

text: Tau Ceti's habitable zone—the locations where liquid water could be present on an Earth-sized planet—spans a radius of 0.55–1.16 AU, where 1 AU is the average distance from the Earth to the Sun. Primitive life on Tau Ceti's planets may reveal itself through an analysis of atmospheric composition via spectroscopy, if the composition is unlikely to be abiotic, just as oxygen on Earth is indicative of life.


title: Tau Ceti

text: The most optimistic search project to date was Project Ozma, which was intended to "search for extraterrestrial intelligence" (SETI) by examining selected stars for indications of artificial radio signals. It was run by the astronomer Frank Drake, who selected Tau Ceti and Epsilon Eridani as the initial targets. Both are located near the Solar System and are physically similar to the Sun. No artificial signals were found despite 200 hours of observations. Subsequent radio searches of this star system have turned up negative.


title: Tau Ceti

text: This lack of results has not dampened interest in observing the Tau Ceti system for biosignatures. In 2002, astronomers Margaret Turnbull and Jill Tarter developed the Catalog of Nearby Habitable Systems (HabCat) under the auspices of Project Phoenix, another SETI endeavour. The list contained more than theoretically habitable systems, approximately 10% of the original sample. The next year, Turnbull would further refine the list to the 30 most promising systems out of within 100 light-years from the Sun, including Tau Ceti; this will form part of the basis of radio searches with the Allen Telescope Array. She chose Tau Ceti for a final shortlist of just five stars suitable for searches by the (now cancelled) Terrestrial Planet Finder telescope system, commenting that "these are places I'd want to live if God were to put our planet around another star".


title: Tamar (Genesis)

text: In the Book of Genesis, Tamar (; ) was the daughter-in-law of Judah (twice), as well as the mother of two of his children: the twins Perez and Zerah.


title: Tamar (Genesis)

text: In , Tamar is first described as marrying Judah's eldest son, Er. Because of his wickedness, Er was killed by God. By way of a levirate union, Judah asked his second son, Onan, to provide offspring for Tamar so that the family line might continue. This could have substantial economic repercussions, with any son born deemed the heir of the deceased Er, and able to claim the firstborn's double share of inheritance. However, if Er was childless, Onan would inherit as the oldest surviving son.


title: Tamar (Genesis)

text: Onan performed "coitus interruptus". His action displeased God and so, like his older brother, God killed him. At this point, Judah is portrayed as viewing Tamar to be cursed and therefore as being reluctant to give her his remaining and youngest son Shelah. Rather, he tells Tamar to wait for Shelah. However, even after Shelah has grown up, Judah still does not give Tamar to him in marriage. ()


title: Tamar (Genesis)

text: After Shelah had grown up, Judah became a widower. After Judah mourned the death of his wife, he planned on going to Timnath to shear his sheep. Upon hearing this news, Tamar disguised herself as a prostitute and immediately went to Timnath which was en route to Judah's destination. Upon arriving at a place near Timnath, where two roads met, Judah saw the woman but did not recognize her as Tamar because of the veil she wore over her face. Thinking she was a prostitute, he requested her services. Tamar's plan was to become pregnant by this ruse so that she might bear a child in Judah's line, since Judah had not given her to his son Shelah. So she played the part of a prostitute and struck a bargain with Judah for a goat, secured by his staff, seal, and cord. When Judah was able to have a goat sent to Timnath, in order to collect his staff and seal, the woman was nowhere to be found and no one knew of any prostitute in Timnath. ()


title: Tamar (Genesis)

text: Three months later, Tamar was accused of prostitution on account of her pregnancy. Upon hearing this news, Judah ordered that she be burned to death. Tamar sent the staff, seal, and cord to Judah with a message declaring that the owner of these items was the man who had made her pregnant. Upon recognizing these items as his security, Judah released Tamar from her sentence. Tamar, having thus secured her place in the family as well as Judah's posterity, gave birth to twins, Perez and Zerah. Their birth is reminiscent of the birth of Rebekah's twin sons. The midwife marks Zerah's hand with a scarlet cord when he emerges first from the womb, though Perez is born first. Perez is identified in the Book of Ruth as the ancestor of King David. () The Genesis narrative also makes a note that Judah did not have further sexual relations with Tamar. ()


title: Tamar (Genesis)

text: Literary critics have focused on the relationship between the Judah story in chapter 38 and the Joseph story in chapters 37 and 39. Victor P. Hamilton notes some "intentional literary parallels" between the chapters, such as the exhortation to "identify" (38:25–26 and 37:32–33). John Emerton regards the connections as evidence for including chapter 38 in the J corpus, and suggests that the J writer dovetailed the Joseph and Judah traditions. Derek Kidner points out that the insertion of chapter 38 "creates suspense for the reader", but Robert Alter goes further and suggests it is a result of the "brilliant splicing of sources by a literary artist." He notes that the same verb "identify” will play "a crucial thematic role in the dénouement of the Joseph story when he confronts his brothers in Egypt, he recognizing them, they failing to recognize him."


title: Tamar (Genesis)

text: J. A. Emerton also suggests that the "Judah and Tamar narrative" contains "aetiological motifs concerned with the eponymous ancestors of the clans of Judah.' Emerton notes that Dillman and Noth considered the account of the deaths of Er and Onan to "reflect the dying out of two clans of Judah bearing their names, or at least of their failure to maintain a separate existence." However, this view was "trenchantly criticized" by Thomas L. Thompson.


title: Tamar (Genesis)

text: According to the Talmud, Judah's confession of guilt itself atoned for some of his prior faults, and resulted in his being divinely rewarded by a share in the future world. The Talmud also suggests that Tamar's actions were for the purpose of avoiding Judah's humiliation, although the Genesis Rabbah portrays her as boastful and unashamed in regard to the pregnancy itself.


title: Tamar (Genesis)

text: Both the Genesis Rabbah and Talmud state that Tamar was an Israelite, and that Judah ended up marrying her and had further sexual liaisons with her as a result.


title: Tamar (Genesis)

text: Frymer-Kensky finds Tamar's traits of assertiveness in action, willingness to be unconventional, and deep loyalty to family to be qualities that distinguish her descendant, King David.


title: Tamar (Genesis)

text: According to "Legends of the Jews", Tamar was endowed with a prophetic gift which allowed her to know the future of her descendants. From this gift, she knew that she would be the ancestress of royal line of David and mighty prophets. While she was standing in gate of Timnah and wearing a veil; Judah, who was intoxicated from wine that twisted his understanding away, came to her. After that, he left her with three symbolical pledges; his staff, the stay of Tribe of Judah; his mantle, representation of his strength; and his signet-diadem, the glory of kingdom of Judah. When her state became known, Tamar was dragged before the court, in which Isaac, Jacob, and Judah as the judges.


title: Tamar (Genesis)

text: As a judge, Judah gave a decision that Tamar was liable to the death penalty by burning according to the law, for she was the daughter of the high priest (Shem) who was accused of leading an unchaste demeanor. After Tamar showed the three pledges from the man who came to her, Judah's countenance grew pale to green color when he publicly confessed his relationship with her.


title: Tamar (Genesis)

text: According to the Gospel of Matthew, Judah and Tamar are ancestors of Jesus through their son Perez. ()