title: Walking catfish

text: This fish needs to be handled carefully when fishing it due to its embedded sting or thorn-like defensive mechanism hidden behind its fins (including the middle ones before the tail fin, similar to the majority of all catfishes).


title: Walking catfish

text: The walking catfish is a tropical species native to Southeast Asia. The native range of true "Clarias batrachus" is confirmed from the Indonesian island of Java only, but three closely related and more widespread species frequently have been confused with this species. These are "C. magur" of northeast India and Bangladesh, a likely undescribed species from Indochina, and another likely undescribed species from the Thai-Malay Peninsula, Sumatra, and Borneo. Both of these undescribed species have been referred to as, "Clarias "aff." batrachus". At present, the taxonomic position of the Philippines population (called "hito" or simply "catfish" by the locals) is unclear, and it also is unclear whether South Indian populations are "C. magur" or another species. As a consequence, much information (behavioral, ecological, related to introduced populations, etc.) listed for "C. batrachus", may be for the closely related species that have been confused with true "C. batrachus". True "C. batrachus", "C. magur" and the two likely undescribed species are all kept in aquaculture.


title: Walking catfish

text: Walking catfish thrive in stagnant, frequently hypoxic waters, and often are found in muddy ponds, canals, ditches, and similar habitats. The species spends most of its time on, or right above, the bottom, with occasional trips to the surface to gulp air.


title: Walking catfish

text: In the wild, this creature is omnivorous; it feeds on smaller fish, molluscs, and other invertebrates, as well as detritus and aquatic weeds. It is a voracious eater that consumes food supplies rapidly, so it is considered harmful when invasive.


title: Walking catfish

text: Within Asia, this species has been introduced widely. It has also been introduced outside its native range where it is considered an invasive species. It consumes the food supplies of native fish and preys on their young. It also is regarded as an invasive species because they can destroy fish farms.


title: Walking catfish

text: In the United States, it is established in Florida. It is reported in California, Connecticut, Georgia, Massachusetts, and Nevada.


title: Walking catfish

text: The walking catfish was imported to Florida, reportedly from Thailand, in the early 1960s for the aquaculture trade. The first introductions apparently occurred in the mid-1960s when adult fish imported as brood stock escaped, either from a fish farm in northeastern Broward County or from a truck transporting brood fish between Dade and Broward Counties. Additional introductions in Florida, supposedly purposeful releases, were made by fish farmers in the Tampa Bay area, Hillsborough County in late 1967 or early 1968, after the state banned the importation and possession of walking catfish.


title: Walking catfish

text: Aquarium releases likely are responsible for introductions in other states. Dill and Cordone (1997) reported this species has been sold by tropical fish dealers in California for some time. They also have been spotted occasionally in the Midwest.


title: Walking catfish

text: In Florida, walking catfish are known to have invaded aquaculture farms, entering ponds where they prey on agricultural fish stocks. In response, fish farmers have had to erect fences to protect ponds. Authorities have also created laws that ban possession of walking catfish.


title: Walking catfish

text: In Thailand, this fish is known as, "pla duk dan" (). It is a common, inexpensive food item, prepared in a variety of ways. It often is offered by street vendors, especially grilled or fried.


title: Walking catfish

text: This fish is one of the most common freshwater catfish in the Philippines where it is known as "hito" in the local language.


title: Walking catfish

text: In Indonesia, it is called "lele", and it is the main ingredient in several native dishes, such as "pecel lele".


title: Walking catfish

text: Not true "C. batrachus", but "C. magur" is eaten in West Bengal as magur curry (), and is considered good during illness, particularly for body weakness. It is prepared in a light curry sauce with coriander powder and cinnamon powder. It reportedly is fed to children to develop body strength.


title: Walking catfish

text: In Karnataka, "C. magur" is called "murgodu" (ಮುರ‍್ಗೋಡು). In coastal Karnataka, it is called "mugudu" (), and is considered a delicacy. Neither the Thai nor the Indian populations are likely to be "C. batrachus", however.


title: Walking catfish

text: A white variation with black patterns is commonly seen in the aquarium fish trade. However, this color variation also is prohibited where walking catfish are banned. Very well-rooted plants and large structures that provide some shade should be included in an aquarium with these fish. Any small tankmates will be eaten by this fish.


title: The Ms. Pat Show

text: The Ms. Pat Show is an American television sitcom created by Jordan E. Cooper and Patricia "Ms. Pat" Williams that premiered on the streaming service BET+ on August 12, 2021. The show is based on the comedy and life story of comedian Ms. Pat as a convicted felon from the streets of Atlanta turned reluctant suburban mother. On September 2, 2021, BET+ renewed the series for a second season which premiered on August 11, 2022. On July 6, 2022, BET+ renewed the series for a third season. The show was nominated for Outstanding Directing for a Comedy Series at the 74th Primetime Emmy Awards in 2022.


title: The Ms. Pat Show

text: The show is set in Ms. Pat's real-life hometown of Plainfield, Indiana. It follows Ms. Pat's fictional family, the Carsons: Pat (Ms. Pat); her husband (J. Bernard Calloway); her sister (Tami Roman); and Pat's children (Brittany Inge, Vince Swann, Briyana Guadalupe, and Theodore Barnes).


title: The Ms. Pat Show

text: A modern day "Archie Bunker", Pat sometimes struggles to adjust with the changing times and ways of her conservative hometown in Indiana. Although blunt and sometimes hardheaded, Pat loves her family and has an open-minded side that helps her to succeed as a black woman in a suburban white neighborhood.


title: Nathan (prophet)

text: Nathan ( "Nāṯān", "Given"; fl. BC) is a prophet in the Hebrew Bible. His actions are described in the Books of Samuel, Kings, and Chronicles (especially , ).


title: Nathan (prophet)

text: Nathan was a court prophet in the time of King David. He is introduced in and as an advisor to David, with whom David reflects on the contrast between his own comfortable home and the tent in which the Ark of the Covenant is accommodated. Nathan then announces to David the covenant God was making with him (, a passage known as "Nathan's Oracle"), contrasting David's proposal to build a house (i.e. a building) for the Ark with God's plan to build a house (i.e. a dynasty) for David. Later, he comes to David to reprimand him for committing adultery with Bathsheba while she was the wife of Uriah the Hittite, whose death the King had also arranged to hide his previous transgression ().


title: Nathan (prophet)

text: According to Chronicles, Nathan wrote histories of the reigns of both David () and Solomon (), and was involved in the music of the temple (see ).


title: Nathan (prophet)

text: In it is Nathan who tells the dying David of the plot of Adonijah to become king, resulting in Solomon being proclaimed king instead. Nathan presides at the anointing of King Solomon. The Midrash teaches that two honorary seats flanked the throne of King Solomon, one for Nathan and the other for Gad the Seer.


title: Nathan (prophet)

text: A lost Book of Nathan the Prophet is mentioned in 1 and 2 Chronicles. Although the work appears to have been lost, some speculate that some of its content have been incorporated into the books of Samuel or Kings.


title: Nathan (prophet)

text: In the Eastern Orthodox Church, and those Eastern Catholic Churches which follow the Byzantine Rite, he is commemorated as a saint on the Sunday of the Holy Fathers (i.e., the Sunday before the Great Feast of the Nativity of the Lord). According to the Orthodox Church in America website, the Prophet Nathan is commemorated on December 14.


title: Ola Solbakken

text: Ola Selvaag Solbakken (born 7 September 1998) is a Norwegian professional footballer who plays as a winger for Bodø/Glimt and the Norway national team. He will join Serie A club Roma in January 2023.


title: Ola Solbakken

text: After starting his career at Ranheim, Solbakken signed a two-year contract with Bodø/Glimt on 18 December 2019, joining the club on 1 January 2020.


title: Ola Solbakken

text: On 23 November 2022, Serie A club Roma announced to have signed Solbakken as a free agent, agreeing a contract until 30 June 2027. As being under contract with Bodø/Glimt until the end of the year, he will officially join Roma on 2 January 2023.


title: Ola Solbakken

text: Solbakken made his debut for Norway national team on 13 November 2021 in a World Cup qualifier against Latvia.


title: Wan'Dale Robinson

text: Wan'Dale Robinson (born January 5, 2001) is an American football wide receiver for the New York Giants of the National Football League (NFL). He played college football at Nebraska before transferring to Kentucky.


title: Wan'Dale Robinson

text: Robinson was born on January 5, 2001, in Frankfort, Kentucky. He attended Western Hills High School. Throughout his career, he was versatile on both offense and defense. In total, he played as a safety, linebacker, receiver, quarterback, running back, punt returner, and kickoff returner according to his high school coach. Rated as the No. 87 player in the country by 247Sports.com, he originally committed to Kentucky before committing to Nebraska.


title: Wan'Dale Robinson

text: As a freshman at Nebraska, Robinson was used as both a rusher and receiver, rushing for 340 yards on 88 rushes and recording 40 receptions for 453 yards. After the season, he was named a Freshman AllAmerican by "The Athletic".


title: Wan'Dale Robinson

text: Robinson's role increased in 2020, as he had almost the same amount of scrimmage yards he had in 2019 in two fewer games. He recorded 46 rushes for 240 yards, along with 51 receptions for 461 yards. He was voted honorable mention AllBig Ten by the conference coaches after the season.


title: Wan'Dale Robinson

text: On January 11, 2021, Robinson announced that he was entering the transfer portal and leaving Nebraska. Four days later, he committed to Kentucky, where he was once committed to in high school. Robinson was the No. 1 receiver for the team, accumulating 104 receptions, 1,334 yards and 7 touchdown receptions in 13 games. His season total receptions and yards broke single-season school records. Later that year he helped the Wildcats win the Citrus Bowl.


title: Wan'Dale Robinson

text: Robinson was selected by the New York Giants in the second round (43rd overall) of the 2022 NFL Draft. Robinson made his NFL debut in the Giants' 2022 season opener against the Tennessee Titans and opened the season as the team's starting slot receiver, recording one reception for 5 yards, but suffered a knee injury and was out for the rest of the game. He returned from his injury in Week 6 against the Baltimore Ravens and recorded 3 receptions for 37 yards and a touchdown as the Giants beat the Ravens 24-20. In Week 7 win against the Jacksonville Jaguars, Robinson recorded 6 catches for 50 yards. In Week 11 lost against the Detroit Lions, Robinson had 9 catches for 100 yards but suffered an ACL tear and was placed on injured reserve.


title: Henri Young

text: Henri Theodore Young (born June 20, 1911 – disappeared 1972) was an American convicted bank robber and murderer who, while serving one of a series of prison terms, attempted a 1939 escape from Alcatraz Federal Penitentiary with four other inmates. During the escape attempt two inmates were shot, and one died of his wounds. All survivors were quickly recaptured. Two of the men, Young and Rufus McCain, were sentenced to solitary confinement and served the terms at Alcatraz for a period of three years (until autumn of 1942). Eleven days after re-entering the Alcatraz general prison population in 1942, Young murdered fellow escapee McCain.


title: Henri Young

text: No apparent motive was ever disclosed for this crime. Young's defense put Alcatraz and the penal system on trial, leading to questions about how the prison was run. In 1948, Young was transferred from Alcatraz to the Medical Center for Federal Prisoners, Springfield, Missouri. Upon completion of his federal sentence, he was later transferred to Washington State Penitentiary at Walla Walla to begin a life sentence for a 1933 murder conviction.


title: Henri Young

text: After release from Walla Walla, Young "jumped parole" in 1972 and his whereabouts were reported as "unknown". Young was portrayed as a fictional character of the same name in the film "Murder in the First" (1995), in which he was played by actor Kevin Bacon. Henri Young is the subject of the song "Behind the Eyes of Henri Young", featured on the album "Dragonfly" (2017), by Australian singer Kasey Chambers.


title: Henri Young

text: Young was born in Kansas City, Missouri on June 20, 1911. Beginning a life of crime, he became a bank robber and was known for aggressively taking hostages.


title: Henri Young

text: In 1933, Young was convicted of murder in Washington state. After serving time in prisons in Washington and Montana for other crimes, he was sent to the federal prison on Alcatraz Island. On the night of January 13, 1939, Young, with prisoners Rufus McCain, Arthur Barker, Dale Stamphill, and William Martin, attempted to escape. Martin, Young, and McCain surrendered, while Barker and Stamphill refused to surrender and were subsequently shot. Barker eventually died from his injuries.


title: Henri Young

text: At his trial for McCain's murder in 1942, Young and his attorney argued that the harsh system at Alcatraz had brutalized and dehumanized him. According to the "San Francisco Examiner",


title: Henri Young

text: "Emphasis which [the defense] repeatedly laid on the fact that Young was in isolation or solitary confinement for more than three years—and that he drove his knife into McCain's abdomen just eleven days after release from such confinement, made it clear that the defense hopes to show not only that Young was 'punch drunk' but that the punches were administered by the Alcatraz 'system'."


title: Henri Young

text: In 1954, Young was transferred to the Washington State Penitentiary at Walla Walla to begin a life sentence for the 1933 murder conviction. He was released from Washington State Penitentiary in 1972, at age 61. He "jumped parole and, according to Washington State authorities, his whereabouts are unknown." No further records exist on Young.


title: Henri Young

text: The film "Murder in the First" (1995) has a number of inaccuracies compared to the facts of Young's life. It mistakenly presents Young as being arrested for stealing $5 in order to feed himself and his younger sister. It shows that he was tortured by officials after his escape attempt. It shows him killing McCain in the cafeteria immediately after his return to the general population, rather than later. It also showed that he was found dead in his prison cell in 1942, just before his appeal, with the word "victory" on the wall.


title: Henri Young

text: As noted above, Young had a prior murder conviction before arriving at Alcatraz. He was transferred from Alcatraz to serve the remainder of that murder sentence later in life at a Washington state prison. He disappeared after jumping parole after being released in 1972 from Walla Walla.


title: Dalton Schultz

text: Dalton Chase Schultz (born July 11, 1996) is an American football tight end for the Dallas Cowboys of the National Football League (NFL). He played college football at Stanford.


title: Dalton Schultz

text: Schultz attended Bingham High School in South Jordan, Utah. Along with football, he played basketball for the Miners athletic teams. As a senior, he caught 31 passes for 512 yards and nine touchdowns.


title: Dalton Schultz

text: For his high school career, he had 76 receptions for 1,120 yards and 12 touchdowns. He committed to play college football for the Stanford Cardinal in January 2014.


title: Dalton Schultz

text: Schultz accepted a football scholarship from Stanford University. He did not see any action as a true freshman in 2014 and was redshirted.


title: Dalton Schultz

text: In 2015 as a redshirt freshman, he played in all 14 games as a backup to Austin Hooper, catching 10 passes for 121 yards and one touchdown.


title: Dalton Schultz

text: As a sophomore in 2016, he was named the starter after Hooper declared for the NFL Draft. He played in all 13 games, having 23 receptions for 222 yards (fourth on the team) and one touchdown. He helped block for running backs Christian McCaffrey and Bryce Love, while receiving honorable-mention All-Pac-12 honors.


title: Dalton Schultz

text: Prior to the 2017 season, Schultz was named to the John Mackey Award watch list. In 13 games he was used mostly as a blocker, catching 22 passes for 212 yards (fifth on the team) and three touchdowns, while helping running back Love rush for 2,118 yards. He was named to the All-Pac-12 First-team, declaring for the 2018 NFL Draft after the season.


title: Dalton Schultz

text: Schultz was selected by the Dallas Cowboys in the fourth round (137th overall) of the 2018 NFL Draft, to improve the depth at tight end after the surprising retirements of Jason Witten and James Hanna. He was the third-string tight end behind Geoff Swaim and Blake Jarwin.


title: Dalton Schultz

text: After Swaim was lost to an injury in Week 11, Schultz passed Jarwin on the depth chart as the starter and was used mostly for blocking purposes. He started seven of the eleven games he played and both playoff contests. He tallied 12 receptions for 116 yards, while contributing to running back Ezekiel Elliott being the NFL rushing champion.


title: Dalton Schultz

text: In 2019, although Geoff Swaim left via free agency, Jason Witten returned to play professional football after spending one season as a "Monday Night Football" commentator, keeping Schultz as the team's third-string tight end. He appeared in 16 games, registering one reception for six yards and one kickoff return for five yards in limited play during the season.


title: Dalton Schultz

text: On March 17, 2020, it was announced in the media that Jason Witten would be leaving the Cowboys to sign with the Las Vegas Raiders, opening the door for Schultz to compete for the backup position behind Blake Jarwin. After Jarwin was lost for the year with an ACL injury suffered in the season opener against the Los Angeles Rams, Schultz took over the starting tight end position. In Week 2 against the Atlanta Falcons, Schultz caught nine passes for 88 yards and his first career touchdown reception during the 40–39 comeback victory. Schultz exceeded expectations, becoming the fourth tight end in franchise history to have at least 60 receptions in a regular season (63), while collecting 615 receiving yards and four touchdowns, even though the Cowboys lost their starting quarterback Dak Prescott in Week 5 against the New York Giants.


title: Dalton Schultz

text: The 2021 season would see Schultz have career highs in every statistical category, accumulating 78 receptions, 808 yards and 8 touchdowns (tied for team lead).


title: Miguel Tejada

text: Miguel Odalis Tejada ( Tejeda; born May 25, 1974) is a Dominican former professional baseball shortstop who played 16 seasons in Major League Baseball (MLB). He played for six teams, most notably the Oakland Athletics and Baltimore Orioles, before short stints with the Houston Astros, San Diego Padres, San Francisco Giants, and Kansas City Royals.


title: Miguel Tejada

text: Tejada spent his first six seasons in MLB with the Athletics, where he began a streak of 1,152 consecutive games that ended with the Orioles on June 22, 2007. He is a six-time All-Star and a two-time Silver Slugger Award winner. In 2002, he won the American League Most Valuable Player (MVP) Award, and was the 2005 All-Star Game MVP. Tejada's nickname is "La Guagua", which means "the bus" in certain Spanish dialects, after his ability to drive in runs.


title: Miguel Tejada

text: On February 11, 2009, he pleaded guilty to one count of perjury for lying to Congress in his testimony on whether Rafael Palmeiro lied about his steroid use. On August 17, 2013, MLB suspended Tejada for 105 games for violating MLB drug policy. It was the third-longest non-lifetime suspension ever issued by MLB for a drug-related violation.


title: Miguel Tejada

text: Tejada grew up in extreme poverty in Baní, a city about 40 miles (65 km) southwest of Santo Domingo, capital of the Dominican Republic. He grew up idolizing the Baltimore Orioles shortstop Cal Ripken Jr.


title: Miguel Tejada

text: Tejada's rise from the slums of Baní through the minors and into the Major Leagues is chronicled in the book "Away Games: The Life and Times of a Latin Ballplayer" by Marcos Breton and Jose Luis Villegas. "Away Games" describes the struggles of Dominican players in general and Tejada in particular as they arrive in the U.S. speaking very little English, often in small towns playing for minor league teams, with dreams of making it big.


title: Miguel Tejada

text: Tejada developed quickly into a top-notch prospect, showing early signs of power. He reached the Majors towards the end of the 1997 season, joining a struggling Oakland Athletics club. Though he only hit .202 in 26 games that year, the A's saw potential in the 23-year-old Tejada. This was bolstered by his performance with the Edmonton Trappers (AAA) in the Pacific Coast League during the season, and returning to the minors to lead the Trappers to a PCL championship that year. He was rewarded with the starting shortstop job beginning in 1998.


title: Miguel Tejada

text: The A's, and Tejada, steadily improved over the next two years. His hitting improved as he gained more discipline at the plate. In 1998, he hit .233 with 11 home runs and in 1999 his average jumped to .251 with 21 home runs.


title: Miguel Tejada

text: After a solid 87-win campaign in 1999, Tejada and a core of young players led their A's to their first American League Western Division title in eight years in 2000. Bolstered by an American League MVP-winning performance by first baseman Jason Giambi, and aided by Tejada's .275 average and 30 home runs, the A's won 91 games. The A's faced the New York Yankees in the first round of the postseason, which was won by the Yankees 3–2.


title: Miguel Tejada

text: In 2001, Tejada had a comparable offensive year, hitting .267 with 31 homers. The A's captured the American League wild card with a 102–60 record. In the postseason, however, the A's fell to the Yankees in five games, blowing an initial 2–0 series lead.


title: Miguel Tejada

text: Tejada's breakout year came in 2002. With the departure of Jason Giambi to the New York Yankees during the offseason, and a leg injury to slugger Jermaine Dye, the A's lost two of their key offensive players. Tejada hit .308 with 34 homers and led the A's to their second Western Division title in three years. Their campaign included an American League record 20 game winning-streak. Tejada contributed one-out, game-winning hits in the 18th and 19th games of that run: a three-run homer off Minnesota Twins closer Eddie Guardado for a 7–5 victory and a bases-loaded single against Kansas City Royals reliever Jason Grimsley to break a 6–6 tie. Tejada also showed modest speed on the basepaths with 18 steals over a two-year stretch. His performance was rewarded with the 2002 American League MVP award. For the third straight year, though, the A's fell in the fifth game of the ALDS, this time to the Minnesota Twins.


title: Miguel Tejada

text: The next year, both the A's and Tejada got off to a slow start, with the shortstop hitting under .200 for the first month of the season. Improved play in the second half of the season led the A's to their second straight Western Division title and their third in four years. Tejada hit .278 with 27 homers for the year, a decrease from his numbers in 2002, but still leading many offensive categories for shortstops.


title: Miguel Tejada

text: In a tension-filled series, the powerful offense of the Boston Red Sox narrowly edged out the A's in the first round, once again in five games. Tejada was known for his public display of anger toward Boston starting pitcher Derek Lowe at the series' conclusion for what he perceived as obscene gestures. Lowe denied the accusation, claiming his fist pump was in celebration only.


title: Miguel Tejada

text: By the end of the 2003 season, Tejada had established himself as one of baseball's premier shortstops. The A's elected not to re-sign the free agent, citing budget concerns and a young Bobby Crosby coming through the system, so Tejada signed a six-year, $72 million deal with the Baltimore Orioles during the offseason.


title: Miguel Tejada

text: On arrival in Baltimore, Tejada was given uniform number 10, since 4, his number in Oakland, had been retired for former manager Earl Weaver. As an Oriole, Tejada followed in the footsteps of legendary Baltimore shortstop Cal Ripken Jr. Like Ripken, Tejada was a strong and durable shortstop with unusual power numbers for a middle infielder.


title: Miguel Tejada

text: On July 12, 2004, Tejada won the Century 21 Home Run Derby in Houston. Tejada hit a (then) record 27 home runs in the contest, including a record 15 homers in the second round. He defeated Houston Astros outfielder Lance Berkman (who would later become his teammate) 5–4 in the final round of the contest. Both records were broken the following year in Detroit by Bobby Abreu. Tejada finished the 2004 season with 34 home runs and an MLB-leading 150 RBIs, and won his first career Silver Slugger Award.


title: Miguel Tejada

text: While Tejada did not participate in the Home Run Derby in 2005, he was an All-Star and starter for the AL. In his first All-Star start, Tejada hit a solo home run against John Smoltz of the Atlanta Braves, had a sacrifice RBI and was part of an all-Oriole double play with teammate Brian Roberts. His efforts earned him the All-Star MVP, winning a Chevrolet Corvette.


title: Miguel Tejada

text: In the winter of 2005, Tejada asked the Orioles for a trade, citing unhappiness with the team's direction, while commenting briefly on his alleged non-involvement in Palmeiro's steroid scandal. Weeks would go by before Tejada relented on the idea of being traded away, although the Orioles would later try to offload him during the 2006 All-Star break (with the Los Angeles Angels being one of the teams that failed to meet the asking price).


title: Miguel Tejada

text: Tejada's streak was at 1,151 games when he was hit on his left wrist by a pitch on June 20, 2007. The next day, he went up to bunt in the top of the first inning, bunted into a force play, and was replaced by a pinch runner. Following that game, it was announced that he had a broken wrist. On June 22 he was placed on the disabled list, ending his streak at 1,152 consecutive games, the fifth longest in Major League history, behind Cal Ripken Jr. (2,632), Lou Gehrig (2,130), Everett Scott (1,307), and Steve Garvey (1,217).


title: Miguel Tejada

text: On December 12, 2007, Tejada was dealt to the Houston Astros for five players, including SP Troy Patton, OF Luke Scott, RP Dennis Sarfate and RP/SP Matt Albers.


title: Miguel Tejada

text: Tejada scored his 1,000th career run on July 7, 2008, at PNC Park. In the 2008 All-Star Game Tejada singled leading off the top of the eighth stole second with one out and advanced to third on a throwing error and scored on Padres' first baseman Adrián González's sacrifice fly.


title: Miguel Tejada

text: In the 2008 season he grounded into 32 double plays, the most in the major leagues. In 2009, he again led the majors in grounding into double plays, this time with 29. He became the first player in major league history to lead the league in double plays grounded into five times.


title: Miguel Tejada

text: On July 29, the Orioles traded Tejada to the San Diego Padres for minor league pitcher Wynn Pelzer. On September 22, Tejada hit his 300th career home run off Ted Lilly of the Los Angeles Dodgers.


title: Miguel Tejada

text: Tejada signed a one-year, $6.5 million, contract with the San Francisco Giants. He was designated for assignment on August 31, 2011 after batting .239 with four home runs and 26 RBIs in 91 games. He was released on September 8, 2011.


title: Miguel Tejada

text: On May 6, 2012, Tejada reached an agreement on a contract with the Orioles. He failed to make the Major League club's roster however, and played for their Triple-A affiliate Norfolk team until requesting his outright release, which was granted on June 25, 2012.


title: Miguel Tejada

text: On December 31, 2012, Tejada signed a minor league contract with the Kansas City Royals. According to the Associated Press, he was to earn $1.1 million plus performance incentives worth an additional $400,000 if he made the Royals Major League 40-man roster for 2013.


title: Miguel Tejada

text: On August 17, 2013, Tejada received a 105-game suspension from Major League Baseball following two positive drug tests for amphetamines. Tejada claimed to have been in the process of re-applying for a therapeutic use exemption as he used the drug to treat a medical condition, but he chose not to appeal the decision. Due to a calf injury suffered prior to the ban, Tejada was not likely to play in the remaining 41 games of the 2013 season anyway, though they counted toward his suspension. He also was not allowed to play in the first 64 games of the 2014 season.


title: Miguel Tejada

text: On May 16, 2014, Tejada signed a minor league contract with the Miami Marlins. Tejada was required to serve the remaining 64 games left on his suspension before being available to be called up by the Marlins. On August 2, Tejada was released by the Marlins.


title: Miguel Tejada

text: Tejada was eligible to be elected into the Hall of Fame in 2019, but received less than 5% of the vote and became ineligible for the 2020 ballot.


title: Miguel Tejada

text: In 2171 games over 16 seasons, Tejada posted a career .285 batting average (2407-for-8434) which includes 1230 runs, 468 doubles, 23 triples, 307 home runs, 1302 RBI, 85 stolen bases, 553 walks, .336 on-base percentage, and .456 slugging percentage. Defensively, he recorded an overall .971 fielding percentage primarily as a shortstop.


title: Miguel Tejada

text: On September 22, 2005, ESPN reported that Rafael Palmeiro, who had tested positive for steroids and was suspended for 10 games under Major League Baseball's steroid policy, implicated Tejada to baseball's arbitration panel, suggesting that a supplement given to him by Tejada was responsible for the steroid entering his system. Tejada denied the allegations, saying that the only thing he gave Palmeiro was vitamin B-12, a legal substance under MLB policy.


title: Miguel Tejada

text: On September 24, 2005, the "Baltimore Sun" reported that "The Health Policy Advisory Committee, which oversees baseball's testing policy, issued a statement that exonerated Tejada and chastised the media for reporting that he might have distributed steroids to another player."


title: Miguel Tejada

text: In José Canseco's 2005 book, "", he mentioned that he believed Tejada might have taken steroids. He claims to have spoken to him about them and the next season seeing him at spring training looking more defined. He never claims to have injected him with them, like he did with Palmeiro, McGwire, and other ballplayers.


title: Miguel Tejada

text: On September 30, 2006, the "Los Angeles Times" reported that former relief pitcher Jason Grimsley, during a June 6, 2006, federal raid, told federal agents investigating steroids in baseball named Tejada as a user of "anabolic steroids." The "Times" reported that Tejada was one of five names blacked out in an affidavit filed in federal court. However, on October 3, 2006, the "Washington Post" reported that San Francisco United States attorney Kevin Ryan said that the "Los Angeles Times" report contained "significant inaccuracies." Tejada, along with the other four players named, denounced the story.


title: Miguel Tejada

text: On December 13, 2007, Tejada was mentioned in the Mitchell Report in connection to steroids. In the report, Tejada is said to have received $1,500 worth of steroids.


title: Miguel Tejada

text: A report surfaced on January 15, 2008, stating that Rep. Henry Waxman had asked the Justice Department to investigate whether Tejada was truthful when speaking to the House committee when being interviewed in 2005 regarding possible connections to Rafael Palmeiro.


title: Miguel Tejada

text: On February 10, 2009, Tejada was charged with lying to Congress about performance-enhancing drug usage in Major League Baseball. On February 11, Tejada pleaded guilty to charges that he lied to Congress in 2005. He faced up to one year in federal prison and deportation. On March 26, 2009, he received one-year probation.


title: Miguel Tejada

text: On August 17, 2013, Tejada was suspended 105 games for testing positive twice for amphetamines, specifically the prescription medication adderall. Tejada claimed he had medical permission from MLB to use the drug to treat ADD, but it expired on April 15, 2013, and he continued to use it without gaining a new permission from MLB. The suspension was the third-longest non-lifetime ban issued by MLB for a drug violation.


title: Miguel Tejada

text: On April 17, 2008, Tejada was confronted by an ESPN reporter during a sit-down interview with documentation revealing that Tejada had been lying about his age ever since he first signed a Major League Baseball contract in 1993. Tejada had claimed to have been born in 1976 when a Dominican birth certificate showed that he was born in 1974 as "Miguel Tejeda." He struggled to take off his microphone and kept questioning who the interviewer was referring to. Tejada stormed off the set, ending the interview. Before the interview was aired on April 22, 2008, he acknowledged having been born in 1974.


title: Miguel Tejada

text: Tejada has a chicken farm in Florida where he lives with his wife, Alejandra, and his daughter, Alexa. His son, Miguel Jr., was a shortstop in the Philadelphia Phillies organization.


title: Prima materia

text: In alchemy and philosophy, prima materia, materia prima or first matter (for a philosophical exposition refer to: Prime Matter), is the ubiquitous starting material required for the alchemical magnum opus and the creation of the philosopher's stone. It is the primitive formless base of all matter similar to chaos, the quintessence or aether. Esoteric alchemists describe the prima materia using simile, and compare it to concepts like the anima mundi.


title: Prima materia

text: The concept of prima materia is sometimes attributed to Aristotle. The earliest roots of the idea can be found in the philosophy of Anaxagoras, who described the nous in relation to chaos. Empedocles' cosmogony is also relevant.


title: Prima materia

text: When alchemy developed in Greco-Roman Egypt on the foundations of Greek philosophy, it included the concept of prima materia as a central tenet. Mary Anne Atwood uses words attributed to Arnaldus de Villa Nova to describe the role of prima materia in the fundamental theory of alchemy: "That there abides in nature a certain pure matter, which, being discovered and brought by art to perfection, converts to itself proportionally all imperfect bodies that it touches." Although descriptions of the prima materia have changed throughout history, the concept has remained central to alchemical thought.


title: Prima materia

text: Alchemical authors used similes to describe the universal nature of the prima materia. Arthur Edward Waite states that all alchemical writers concealed its "true name". Since the prima materia has all the qualities and properties of elementary things, the names of all kinds of things were assigned to it. A similar account can be found in the "Theatrum Chemicum":


title: Prima materia

text: Comparisons have been made to Hyle, the primal fire, Proteus, Light, and Mercury. Martin Ruland the Younger lists more than fifty synonyms for the prima materia in his 1612 alchemical dictionary. His text includes justifications for the names and comparisons. He repeats that, "the philosophers have so greatly admired the Creature of God which is called the Primal Matter, especially concerning its efficacy and mystery, that they have given to it many names, and almost every possible description, for they have not known how to sufficiently praise it." Waite lists an additional eighty four names.


title: Josh Cullen

text: Joshua Jon Cullen (born 7 April 1996) is a professional footballer who plays as a midfielder for Burnley and the Republic of Ireland national team.


title: Josh Cullen

text: Cullen was born in Westcliff-on-Sea, Essex. His grandparents on his father's side were from County Leitrim, Ireland. He played junior football for Rayleigh Boys before joining West Ham United at the age of nine. He attended St Thomas More High School.


title: Josh Cullen

text: Cullen was first included in a West Ham matchday squad for their Premier League fixture against Arsenal at the Emirates Stadium on 14 March 2015, remaining an unused substitute as they lost 3–0. He was also called up and unused on 9 May, as West Ham lost 1–0 at Aston Villa.


title: Josh Cullen

text: On 2 July 2015, he made his first-team debut for the club in a 3–0 home victory over Lusitanos of Andorra in the UEFA Europa League first qualifying round first leg, replacing Joey O'Brien after 60 minutes; he started in their 1–0 victory in the second leg a week later, making way for Amos Nasha after 63 minutes. With manager Slaven Bilić putting priority on the team's Premier League performance, he made an array of changes for their third qualifying round second leg away to Astra Giurgiu on 6 August, including starting Cullen in his first competitive match against a professional opponent. Twenty-three days later he made his Premier League debut, replacing Diafra Sakho at the end of a 3–0 win over Liverpool at Anfield.


title: Josh Cullen

text: Cullen returned from loan at Bolton Wanderers in January 2018 making an appearance in the FA Cup away at Shrewsbury Town. He was praised for his performance by West Ham manager, David Moyes, in a poor performance by West Ham which ended 0–0. Cullen also had two front teeth kicked-out accidentally by Shrewsbury player Abu Ogogo.


title: Josh Cullen

text: In the summer of 2020, Cullen returned to his parent club at the end of his loan spell at Charlton Athletic, where he immediately impressed in West Ham's EFL Cup tie with Charlton. He received significant praise from manager David Moyes after the game. Before West Ham's EFL Cup fixture with Hull City on 23 September 2020, Cullen returned a positive test for COVID-19 along with manager David Moyes and teammate Issa Diop.


title: Josh Cullen

text: Cullen signed on loan for Bradford City in February 2016. In March 2016 his loan was extended until the end of the 2015–16 season.


title: Josh Cullen

text: On 8 August 2016, Cullen re-signed for Bradford City on a five-month loan deal. He scored his first league goal for the club in the 2–1 victory at MK Dons on 16 August 2016. His loan at the club was extended on 3 January 2017 until the end of the season.


title: Josh Cullen

text: On 1 August 2017, Cullen, along with West Ham teammate Reece Burke, joined Bolton Wanderers on loan until the following January.


title: Josh Cullen

text: On 30 August 2018, Cullen joined Charlton Athletic on loan until the end of the 2018–19 season. He dislocated his shoulder on 6 November 2018 playing against Walsall, leaving the pitch in the 80th minute. He returned to the first team in January 2019 against Accrington Stanley. On 26 May 2019, Cullen played the full 90 minutes of the League One play-off final as Charlton won 2–1 to return to the Championship. Having spent the season on-loan, he returned to West Ham and played in several pre 2019–20 season friendlies. In August 2019, he returned to Charlton on-loan for the 2019–20 season.


title: Josh Cullen

text: On 5 October 2020, Cullen joined Belgian First Division A side Anderlecht on a permanent deal until 30 June 2023, after fifteen years at West Ham. He sent an emotional farewell message to West Ham fans on 12 October 2020 thanking them for their support and citing Mark Noble as one of his heroes. Upon joining Anderlecht, Sporting director Peter Verbeken described Cullen as "a true team player known for his winning mentality." On 22 January 2021, Cullen captained Anderlecht for the first time in a 0–0 draw against Waasland-Beveren, in just his 13th appearance for the club.


title: Josh Cullen

text: On 12 July 2022, Burnley signed Cullen on a three-year contract, for an undisclosed fee. He made his Burnley debut on 29 July 2022 in a 1-0


title: Josh Cullen

text: Having already played for England U16 in 2011, He made his debut for Republic of Ireland U19 in September 2014, in a 1–0 victory against Netherlands U19. On 4 September 2015, he made his debut for Republic of Ireland U21 in a 4–1 victory against Qatar U23 in a friendly at Gigg Lane. On 25 March 2017, Cullen captained the Republic of Ireland U21s to a win 1–0 win over Kosovo U21 in a UEFA Under-21 has Championship Qualifier.


title: Josh Cullen

text: On 15 March 2019, Cullen received his first international call-up to the senior Republic of Ireland national team. He made his full debut on 10 September 2019, playing the full 90 minutes in a 3–1 win against Bulgaria.


title: Gladys West

text: Gladys Mae West (née Brown; born October 27, 1930) is an American mathematician known for her contributions to the mathematical modeling of the shape of the Earth, and her work on the development of the satellite geodesy models that were eventually incorporated into the Global Positioning System (GPS). West was inducted into the United States Air Force Hall of Fame in 2018. West was awarded the Webby Lifetime Achievement Award at 25th Annual Webby Awards for the development of the satellite geodesy models.


title: Gladys West

text: West was born as Gladys Mae Brown in Sutherland, Virginia, in Dinwiddie County, a rural county south of Richmond. Her family was an African-American farming family in a community of sharecroppers. She spent much of her childhood working on her family's small farm. Her mother worked at a tobacco factory. Her father was a farmer who also worked for the railroad. West realized early on that she did not want to work in the tobacco fields or factories like the rest of her family, and decided that education would be her way out.


title: Gladys West

text: When West was on her way to graduate high school, the only obstacle keeping her from higher education was financial. Her parents tried to save but supporting an entire family on a sharecropper's wage did not leave much left for West's education. West began babysitting to help save but, ultimately, her superior academic performance resulted in her securing two scholarships. At West's high school, the top two students of each graduating class received full scholarships to Virginia State College (now formally University), a historically black public university. West graduated as valedictorian in 1948, and received the much needed scholarship. She was initially unsure what college major to pursue at VSU, as she had excelled in all her subjects in high school. She was encouraged to major in science or mathematics because of their difficulty, and West ultimately chose to study mathematics, a subject mostly studied at her college by men. She also became a member of the Alpha Kappa Alpha sorority. West graduated in 1952 with a Bachelor of Science in mathematics. After graduating, she taught math and science for two years in Waverly, Virginia. West then returned to VSU to complete her Master of Mathematics degree, graduating in 1955. Afterward, she briefly took another teaching position in Martinsville, Virginia.


title: Gladys West

text: In 1956, West was hired to work at the Naval Proving Ground in Dahlgren, Virginia, (now called the Naval Surface Warfare Center), where she was the second black woman ever hired and one of only four black employees. West was a programmer in the Naval Surface Warfare Center Dahlgren Division for large-scale computers and a project manager for data-processing systems used in the analysis of satellite data. Concurrently, West earned a second master's degree in public administration from the University of Oklahoma.


title: Gladys West

text: In the early 1960s, she participated in an award-winning astronomical study that proved the regularity of Pluto’s motion relative to Neptune. Subsequently, West began to analyze data from satellites, especially satellite altimeters such as GEOS 3, putting together models of the Earth's shape. She became project manager for the Seasat radar altimetry project, the first satellite that could remotely sense oceans.


title: Gladys West

text: West consistently put in extra hours, cutting her team's processing time in half. She was recommended for a commendation in 1979.


title: Gladys West

text: From the mid-1970s through the 1980s, West programmed an IBM 7030 Stretch computer to deliver increasingly precise calculations to model the shape of the Earth; an ellipsoid with additional undulations, known as the "geoid". Generating an extremely accurate geopotential model required her to employ complex algorithms to account for variations in gravitational, tidal, and other forces that distort Earth's shape. In her autobiography, West spoke of some of the complex problems she solved, which had proven too difficult for other members of the team. West's model ultimately became the basis for the Global Positioning System (GPS).


title: Gladys West

text: In 1986, West published "Data Processing System Specifications for the Geosat Satellite Radar Altimeter", a 51-page technical report from The Naval Surface Weapons Center (NSWC). The guide was published to explain how to increase the accuracy of the estimation of geoid heights and vertical deflection, important components of satellite geodesy. This was achieved by processing the data created from the radio altimeter on the Geosat satellite, which went into orbit on March 12, 1984.


title: Gladys West

text: West worked at Dahlgren for 42 years, retiring in 1998. After retiring, she completed a PhD in Public Administration from Virginia Tech.


title: Gladys West

text: West's vital contributions to GPS technology were rediscovered when a member of West's sorority Alpha Kappa Alpha read a short biography Gladys had submitted for an alumni function.


title: Gladys West

text: West was inducted into the United States Air Force Hall of Fame in 2018, one of the highest honors bestowed by Air Force Space Command (AFSPC). The AFSPC press release at the time called her one of "the so-called 'Hidden Figures' part of the team who did computing for the US military in the era before electronic systems", a reference to the by Margot Lee Shetterly, which was adapted into the film "Hidden Figures". Capt. Godfrey Weekes, commanding officer at the Naval Surface Warfare Center Dahlgren Division in 2018, described the role played by West in the development of Global Positioning System: "She rose through the ranks, worked on the satellite geodesy, and contributed to the accuracy of GPS and the measurement of satellite data. As Gladys West started her career as a mathematician at Dahlgren in 1956, she likely had no idea that her work would impact the world for decades to come." West agreed, saying that she had no idea at the time that her work would affect so many: “When you’re working every day, you’re not thinking, 'What impact is this going to have on the world?' You're thinking, 'I've got to get this right.'"


title: Gladys West

text: As an alumna of Virginia State University Dr. Gladys West was nominated and won the award for "Female Alumna of the Year" at the Historically Black Colleges and Universities Awards sponsored by "HBCU Digest" in 2018.


title: Gladys West

text: West was selected by the BBC as part of their 100 Women of 2018. In 2021, she was awarded the Prince Philip Medal by the UK's Royal Academy of Engineering, their highest individual honour.


title: Gladys West

text: She met her husband Ira West at the Naval Surface Warfare Center Dahlgren Division, where he also worked as a mathematician. They were two of only four black employees at the time. They were married in 1957. They have three children: Carolyn, David and Michael and seven grandchildren. The West family went to Chapel on the Proving Ground every Sunday. , West lives in King George County, Virginia.


title: Gladys West

text: Before being hired by the base, West initially turned down the job due to its location and the requirement to interview. West didn't have a car and couldn't find Dahlgren on a map, along with her fear that they would reject her after the interview because of her race, she decided she'd wait to hear back from other applications. Much time went by, and no other applications were accepted elsewhere. Luckily, Dahlgren reached out to her again, offering her the job without the need to interview. The job was offering double than her current teaching position and no other job opportunities were coming in. Being hired solely on her qualifications, with a salary that would eventually help her support her family, was a rare find for a black woman at that time.


title: Gladys West

text: At this time, The Supreme Court had made a landmark decision on "Brown vs. Board of Education" that ruled that American state laws establishing racial segregation in public schools were unconstitutional. However, Virginia was still segregated since the Supreme Court had not specified which states were required to reestablish in accordance to the new ruling. This contributed to West's nervousness about taking the job in a rural part of a Southern state. Different groups like the Ku Klux Klan were still at large and the prospect of moving to a rural neighborhood in a southern state was daunting for an unmarried black woman. However, West wouldn't let the ignorance of others derail her on the path she felt God had destined her to go on.


title: Gladys West

text: The Civil Rights movement was in full swing during her time at the base. Though she supported the movement, she could not participate in protests because she was a government employee. In Boomtown, where married people lived on base, she was part of a club of black women who discussed civil rights topics.


title: Gladys West

text: During her career, she encountered many hardships because of racism against African Americans, primary of which was the lack of recognition she received while working, while her white coworkers received praise and added privileges. Within her biography, her disappointment at not being granted the projects that included travel and exposure is clear.


title: Gladys West

text: In 2018, West completed a PhD via a distance-learning program with the School of Public and International Affairs at Virginia Tech.


title: Gladys West

text: West continues to prefer using a paper map over a tracking system, saying she still trusts her brain above all. She stated, "I'm a doer, hands-on kind of person. If I can see the road and see where it turns and see where it went, I am more sure."


title: United States men's national under-20 soccer team

text: The United States U-20 men's national soccer team is controlled by the United States Soccer Federation. The highest level of competition in which the team competes is the FIFA U-20 World Cup, which is held every two years.


text: The United States' best finish came in the 1989 FIFA World Youth Championship, when the U.S. beat Iraq in the quarterfinal before losing to Nigeria in overtime in the semifinal and Brazil in the third-place match. Steve Snow tied for second in the tournament with three goals.


text: The U.S. reached the quarterfinals in 1993 but lost to Brazil. After missing out in 1995, the U.S. began a run of six consecutive qualifications in 1997, reaching the second round in five consecutive tournaments. Of those tournaments, the best U.S. performance came in 2003, when the U.S. reached the quarterfinal and led Argentina 1–0 in the final minutes before falling 2–1 in extra time. The U.S. also reached the quarterfinal of the 2007 Cup before losing 2–1 in extra time to Austria.


title: FedEx Express Flight 80

text: FedEx Express Flight 80 was a scheduled cargo flight from Guangzhou Baiyun International Airport in the People's Republic of China, to Narita International Airport in Narita, Chiba Prefecture (near Tokyo), Japan. On March 23, 2009, the McDonnell Douglas MD-11F (N526FE) operating the flight crashed at 6:48 am JST (21:48 UTC, March 22), while attempting a landing on Runway 34L in gusty wind conditions. The aircraft became destabilized at flare and touchdown resulting in an unrecovered "bounced" landing with structural failure of the landing gear and airframe, and came to rest off the runway, inverted, and burning fiercely. The captain and first officer, the jet's only occupants, were both killed.


title: FedEx Express Flight 80

text: After making an approximately overnight flight from Guangzhou, China, the aircrew made an early morning approach to Narita Airport outside Tokyo. Other traffic landing just ahead of the accident aircraft reported "wind shear at an altitude of under ," and this information was relayed to the FedEx aircrew. Surface winds at the time of the accident were reported from 320° at gusting to . After making a hard landing on runway 34L, the plane bounced three times, coming back down on its nose gear first (a condition called "porpoising") resulting in the loss of directional and altitudinal control. The left wing struck the ground as the gear failed, causing the aircraft to veer to the left, burst into flames and invert as the airframe broke up, and came to rest upside down in the grass to the left of the runway. It took firefighters about two hours to extinguish the blaze, which completely destroyed the aircraft and its contents.


title: FedEx Express Flight 80

text: The only people on board the aircraft were the Captain, Kevin Kyle Mosley, 54, of Hillsboro, Oregon, and First Officer Anthony Stephen Pino, 49, of San Antonio, Texas. Both pilots were removed to the Japanese Red Cross Narita Hospital (成田赤十字病院 "Narita Seki Jūji Byōin") where they were pronounced dead. Captain Mosley, a former United States Marine Corps fighter pilot, had been with FedEx Express since July 1, 1996 and had accumulated more than 12,800 total career flight hours, including 3,648 hours on the MD-11. First Officer Pino, a former C-5 Galaxy pilot in the United States Air Force, joined FedEx Express in 2006 and had accumulated more than 6,300 total career flight hours, 879 of them on the MD-11. Nobody on the ground was injured.


title: FedEx Express Flight 80

text: Runway 16R/34L (length ) was closed for many hours after the accident (with passenger flight cancellations or delays), leaving the shorter 16L/34R as the only available active runway. As a result, many flights operated by larger aircraft had to be canceled or diverted to other airports such as nearby Haneda Airport, as 16L/34R is too short (length ) for some types to operate safely, and some large aircraft types such as Boeing 777-300ER and Airbus A340-600 are restricted from using taxiway "B" (Bravo) which services that runway because of inadequate horizontal clearances.


title: FedEx Express Flight 80

text: The aircraft was built in 1994 as an MD-11 passenger airliner. It was acquired temporarily by NASA to use as the test bed for their Propulsion-Controlled Aircraft system (PCA) in 1995. Later it was owned and operated by Delta Air Lines from 1996 to 2004 under the FAA registration N813DE in such configuration. The trijet was sold to FedEx in October 2004 when Delta retired its MD-11 fleet in favor of switching to more-efficient twin-engine Boeing 767s and Boeing 777s on its long-haul routes. Following its acquisition by FedEx, the plane was stored at Phoenix Goodyear Airport in Goodyear, Arizona pending its conversion there to an MD-11F by Dimension Aviation, Inc., Boeing's Douglas Products Division airframe conversion contractor located at that field. The aircraft entered service with FedEx in its all-cargo configuration in late 2006 as N526FE. It was powered by three Pratt & Whitney PW4462 engines.


title: FedEx Express Flight 80

text: The Japan Transport Safety Board (JTSB) dispatched six investigators to the airport. The United States's National Transportation Safety Board (NTSB) sent a team to Japan to assist with the investigation. The crash was FedEx's second fatal accident involving a jet aircraft, following the loss of a FedEx owned B747-249F that crashed February 18, 1989, near Kuala Lumpur, while still painted in the Flying Tigers livery after the acquisition of the Flying Tigers Line by FedEx in December 1988. This was the first fatal accident at Narita Airport.


title: FedEx Express Flight 80

text: The accident was attributed by the JTSB to a series of "porpoising oscillations" that developed during touchdown, following a high sink rate during the final approach. The first officer executed a late flare, in which sink rate was not suppressed until the plane was nearly on the runway, but which also would minimize "float" that might carry the plane further down the runway and reduce its safe stopping distance, or carry it off the centerline in the existing crosswinds. This high touchdown sink rate, coupled with large nose-up inputs, caused the first bounce. A large nose-down input was applied, causing a touchdown on the nose gear. This deviates from approved procedures for the MD-11 during a bounce, which specifies the pilot is to hold a pitch angle of 7.5 deg and use thrust to adjust the descent rate. The plane bounced off this second touchdown, pitching upward. The large control inputs by the first officer resulted in a hard touchdown on the main landing gear. This final touchdown was hard enough () to cause the left wing to fail as the left main landing gear transferred force up into the wing, exceeding its design limit. The JTSB report suggested the fire might have been averted if the landing gear fuse pin had failed as designed, but that much of the touchdown force was horizontal to the pin rather than vertical, keeping it intact. The report also cited the crew's use of autothrottle during landing despite gusty wind conditions.


title: FedEx Express Flight 80

text: As a result of this accident the Japan Transport Safety Board published its final report on April 26, 2013, in which it made a number of new safety recommendations including that "in order to reduce the occurrence of MD-11 series airplanes' severe hard landing and bounce in which an overload is transferred to the MLGs and their supporting structure, the Boeing Company should improve the controllability and maneuver characteristics by improving the LSAS (Longitudinal Stability Augmentation System) functions, reducing the AGS (Auto Ground Spoilers) deployment delay time and other possible means. Possible improvement on LSAS functions may include: a function to limit large nose-down elevator input during touchdown phase, which is a common phenomenon in severe hard landing cases accompanied by structural destruction for MD-11; and a function to assist bounce recovery and go-around in case of bounce. In order to help pilots to conduct recovery operation from large bounces and judge the necessity of go-around, studies should be made to install a visual display and an aural warning system which show gear touchdown status on MD-11 series airplanes."


title: FedEx Express Flight 80

text: On July 31, 1997, another FedEx MD-11F (N611FE), operating as FedEx Express Flight 14, was written off after a similar destabilized landing accident at Newark Liberty International Airport. After a flight from Anchorage, Alaska, that aircraft crashed at the airport just before midnight when it bounced twice after a hard touchdown on Runway 22R, resulting in the failure of the right main landing gear. As in the Narita accident, the plane also caught fire as the airframe broke up, flipped over, and came to rest inverted off the runway. The captain, first officer, and three passengers on board all survived the 1997 Newark crash and were able to escape from the burning aircraft with only minor injuries.


title: FedEx Express Flight 80

text: The crashes of both FedEx Express Flights 80 and 14 were covered on Season 14 of "Mayday" ("Air Crash Investigation"), episode 5 (episode 114 overall), titled "The Final Push".


title: Assassin's Creed (book series)

text: The Assassin's Creed series, by Anton Gill, Andrew Holmes (both under the pen name Oliver Bowden), Christie Golden, Matthew J. Kirby and Gordon Doherty is a collection of novels set within the "Assassin's Creed" video game universe. The books are set across various time periods and, like the games, revolve around the secret war fought for centuries between the Assassin Brotherhood and the Templar Order. Most of the novels are direct adaptations of one of the games, with several added or slightly modified elements.


title: Assassin's Creed (book series)

text: The first official "Assassin's Creed" novel, "Assassin's Creed: Renaissance", was written by Anton Gill (under the pen name Oliver Bowden) and is a novelization of "Assassin's Creed II". It was released on 20 November 2009 in the United Kingdom, and on 23 February 2010 in the United States. While the novel follows the game's events involving Ezio Auditore da Firenze (with the modern-day aspect entirely excluded), it changes most of the dialogue, the appearances of certain characters, and how some events occurred. It also omits certain events, while adding in others not featured in the game (some of these, such as Ezio's relationship with his first girlfriend, Cristina Vespucci, would later be adapted in "").


title: Assassin's Creed (book series)

text: "Assassin's Creed: Brotherhood", the second novel in the series, was also written by Gill and is based on the . It was released on 25 November 2010 in the United Kingdom, and on 30 November in the United States. Like "Renaissance", the novel changes some elements of the game, including omitting or adding in certain events, to better fit its narrative, but is overall a much more faithful adaptation.


title: Assassin's Creed (book series)

text: "Assassin's Creed:" "The Secret Crusade" is the first novel in the series written by Andrew Holmes (using the same name pen name of Oliver Bowden), and depicts the story of Altaïr Ibn-LaʼAhad, as told by Niccolò Polo, adapting the events of "Assassin's Creed", "", and the Altaïr sequences from "". It also features many events not depicted in any of the games, including Altaïr's childhood and his life in exile after being deposed as Mentor of the Assassin Order by his former friend, Abbas Sofian. The novel is presented as Niccolò's journal, which is recovered by Ezio at the beginning of "Revelations". The epilogue reveals that Ezio is the actual narrator, as he is reading through the journal on his way to Constantinople during the events of the game. "The Secret Crusade" was released on 23 June 2011 in the United Kingdom, and on 28 June in the United States.


title: Assassin's Creed (book series)

text: "Assassin's Creed:" "Revelations" is the final novel in the series written by Gill and is an adaptation of the , focusing on Ezio's side of the story. The novel also describes the final years of Ezio's life, after the events of the game. It was released on 24 November 2011 in the United Kingdom and on 29 November 2011 in the United States.


title: Assassin's Creed (book series)

text: "Assassin's Creed:" "Forsaken", again written by Holmes, is based on "Assassin's Creed III", but is not a direct adaptation. Instead, it tells the story of Haytham Kenway, the game's main antagonist, from his childhood until his death, showing a mirrored perspective to what the game portrays. Similarly to "The Secret Crusade", the novel is presented as Haytham's journal, which is recovered by his son Connor (the game's main protagonist), who proceeds to read through it to better understand his father, and later completes it with events that occurred after Haytham's death. "Forsaken" was released on 4 December 2012 (the in-universe birth date of Haytham).


title: Assassin's Creed (book series)

text: "Assassin's Creed:" "Black Flag", again written by Holmes, is based on "". The novel is presented as the journal of protagonist Edward Kenway, and explores his early life and his thoughts on the events that occur in the game. It was released on 26 November 2013.


title: Assassin's Creed (book series)

text: "Assassin's Creed:" "Unity", again written by Holmes, is based on the video game of the same name. Similarly to "Forsaken", it presents the events of the game from the perspective of a different character (in this case, Élise de la Serre), as well as the experiences of protagonist Arno Dorian after the game. It was released on 20 November 2014 in the United Kingdom, and on 2 December in the United States.


title: Assassin's Creed (book series)

text: "Assassin's Creed:" "Underworld" was again written by Holmes and is based on "Assassin's Creed Syndicate". The first two thirds of the book follow Henry Green, a major supporting character from the game, and Detective Frederick Abberline in 1862, with the final third covering the events of the game itself six years later. It was released on 5 November 2015 in the United Kingdom, and on 1 December in the United States.


title: Assassin's Creed (book series)

text: "Assassin's Creed: The Official Movie Novelization", written by Christie Golden, is an adaptation of the live-action "Assassin's Creed" film released in 2016. In addition to retelling the film's events, it also includes an anthology of short stories from Nathan, Emir, Moussa, Lin, and their respective ancestors, and an excerpt from "Assassin's Creed: Heresy". The novelization was released on 21 December 2016, the same day as the film.


title: Assassin's Creed (book series)

text: "Assassin's Creed Origins: Desert Oath", again written by Andrew Holmes 31, is a prequel novel to "Assassin's Creed Origins", telling the story of a young Bayek of Siwa and his father Sabu in Ptolemaic Egypt. It was published on 10 October 2017.


title: Assassin's Creed (book series)

text: "Assassin’s Creed Odyssey (The Official Novelization)", written by Gordon Doherty, tells one of the possible story paths of "Assassin's Creed Odyssey" featuring Kassandra, one of the two protagonists of the game. It was published on 30 October 2018 by Ace Books.


title: Assassin's Creed (book series)

text: "Assassin's Creed: Valhalla – Geirmund's Saga", written by Matthew J. Kirby, is a tie-in novel to "Asssassin's Creed Valhalla". It does not follow the events of the game, instead telling the story of the Viking Geirmund Hel-hide within roughly the same time frame as "Valhalla". It was published on 10 November 2020.


title: Phage therapy

text: Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections. This therapeutic approach emerged at the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the second world war. Bacteriophages, known as phages, are a form of virus that attach to bacterial cells and inject their genome into the cell. The bacteria's production of the viral genome interferes with its ability to function, halting the bacterial infection. The bacterial cell causing the infection is unable to reproduce, and instead produces additional phages. Phages are very selective in the strains of bacteria they are effective against.


title: Phage therapy

text: Advantages include reduced side-effects and reduced risk of the bacterium developing resistance since bacteriophages are much more specific than antibiotics. They are typically harmless not only to the host organism but also to other beneficial bacteria, such as the gut microbiota, reducing the chances of opportunistic infections. They have a high therapeutic index, that is, phage therapy would be expected to give rise to few side effects, even at higher-than-therapeutic levels. Because phages replicate "in vivo" (in cells of living organism), a smaller effective dose can be used.


title: Phage therapy

text: Disadvantages include the difficulty of finding an effective phage for a particular infection: a phage will kill a bacterium only if it matches the specific strain. However, virulent phages can be isolated much more easily than other compounds and natural products. Consequently, phage mixtures ("cocktails") are sometimes used to improve the chances of success. Alternatively, samples taken from recovering patients sometimes contain appropriate phages that can be grown to cure other patients infected with the same strain. Ongoing challenges include the need to increase phage collections from reference phage banks, the development of efficient phage screening methods for the fast identification of the therapeutic phage(s), the establishment of efficient phage therapy strategies to tackle infectious biofilms, the validation of feasible phage production protocols that assure quality and safety of phage preparations, and the guarantee of stability of phage preparations during manufacturing, storage and transport.


title: Phage therapy

text: Phages tend to be more successful than antibiotics where there is a biofilm covered by a polysaccharide layer, which antibiotics typically cannot penetrate. However, the interactions between phages and biofilms can be complex, with phages developing symbiotic as well as predatory relationships with biofilms.


title: Phage therapy

text: Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics, particularly in Russia and Georgia. There is also a phage therapy unit in Wrocław, Poland, established in 2005, which continues several decades long research of the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences, the only such centre in a European Union country. Phages are the subject of renewed clinical attention in western countries, such as the United States. In 2019, the United States Food and Drug Administration approved the first US clinical trial for intravenous phage therapy.


title: Phage therapy

text: Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture. If the target host of a phage therapy treatment is not an animal, the term "biocontrol" (as in phage-mediated biocontrol of bacteria) is usually employed, rather than "phage therapy".


title: Phage therapy

text: The discovery of bacteriophages was reported by British bacteriologist Frederick Twort in 1915, and by French-Canadian microbiologist Felix d'Hérelle in 1917. D'Hérelle said that the phages always appeared in the stools of "Shigella" dysentery patients shortly before they began to recover. He "quickly learned that bacteriophages are found wherever bacteria thrive: in sewers, in rivers that catch waste runoff from pipes, and in the stools of convalescent patients". Phage therapy was immediately recognized by many to be a key way forward for the eradication of pathogenic bacterial infections. A Georgian, George Eliava, was making similar discoveries. He travelled to the Pasteur Institute in Paris where he met d'Hérelle, and in 1923 he founded the Eliava Institute in Tbilisi, Georgia, devoted to the development of phage therapy. Phage therapy is used in Russia, Georgia and Poland, and was used prophylactically for a time in the Soviet army.


title: Phage therapy

text: In Russia, extensive research and development soon began in this field. In the United States during the 1940s commercialization of phage therapy was undertaken by Eli Lilly and Company.


title: Phage therapy

text: While knowledge was being accumulated regarding the biology of phages and how to use phage cocktails correctly, early uses of phage therapy were often unreliable. Since the early 20th century, research into the development of viable therapeutic antibiotics had also been underway, and by 1942 the antibiotic penicillin G had been successfully purified and saw use during the Second World War. The drug proved to be extraordinarily effective in the treatment of injured Allied soldiers whose wounds had become infected. By 1944, large-scale production of Penicillin had been made possible, and in 1945 it became publicly available in pharmacies. Due to the drug's success, it was marketed widely in the U.S. and Europe, leading Western scientists to mostly lose interest in further use and study of phage therapy for some time.


title: Phage therapy

text: Isolated from Western advances in antibiotic production in the 1940s, Russian scientists continued to develop already successful phage therapy to treat the wounds of soldiers in field hospitals. During World War II, the Soviet Union used bacteriophages to treat many soldiers infected with various bacterial diseases e.g. dysentery and gangrene. Russian researchers continued to develop and to refine their treatments and to publish their research and results. However, due to the scientific barriers of the Cold War, this knowledge was not translated and did not proliferate across the world. A summary of these publications was published in English in 2009 in "A Literature Review of the Practical Application of Bacteriophage Research".


title: Phage therapy

text: There is an extensive library and research center at the George Eliava Institute in Tbilisi, Georgia. Phage therapy is today a widespread form of treatment in that region.


title: Phage therapy

text: As a result of the development of antibiotic resistance since the 1950s and an advancement of scientific knowledge, there has been renewed interest worldwide in the ability of phage therapy to eradicate bacterial infections and chronic polymicrobial biofilm (including in industrial situations).


title: Phage therapy

text: Phages have been investigated as a potential means to eliminate pathogens like "Campylobacter" in raw food and "Listeria" in fresh food or to reduce food spoilage bacteria. In agricultural practice phages were used to fight pathogens like "Campylobacter", "Escherichia" and "Salmonella" in farm animals, "Lactococcus" and "Vibrio" pathogens in fish from aquaculture and "Erwinia", "Xanthomonas", and others in plants of agricultural importance. The oldest use was, however, in human medicine. Phages have been used against diarrheal diseases caused by "E. coli", "Shigella" or "Vibrio" and against wound infections caused by facultative pathogens of the skin like staphylococci and streptococci. Recently the phage therapy approach has been applied to systemic and even intracellular infections and the addition of non-replicating phage and isolated phage enzymes like lysins to the antimicrobial arsenal. However, actual proof for the efficacy of these phage approaches in the field or the hospital is not available.


title: Phage therapy

text: Some of the interest in the West can be traced back to 1994, when Soothill demonstrated (in an animal model) that the use of phages could improve the success of skin grafts by reducing the underlying "Pseudomonas aeruginosa" infection. Recent studies have provided additional support for these findings in the model system.


title: Phage therapy

text: Although not "phage therapy" in the original sense, the use of phages as delivery mechanisms for traditional antibiotics constitutes another possible therapeutic use. The use of phages to deliver antitumor agents has also been described in preliminary "in vitro" experiments for cells in tissue culture.


title: Phage therapy

text: In June 2015 the European Medicines Agency hosted a one-day workshop on the therapeutic use of bacteriophages and in July 2015 the National Institutes of Health (US) hosted a two-day workshop "Bacteriophage Therapy: An Alternative Strategy to Combat Drug Resistance".


title: Phage therapy

text: In January 2016, Phages were used successfully at Yale University by Benjamin Chan to treat a chronic "Pseudomonas aeruginosa" infection in ophthalmologist Ali Asghar Khodadoust. This successful treatment of a life-threatening infection sparked a resurgence of interest in phage therapy in the United States.


title: Phage therapy

text: In 2017, a pair of genetically engineered phages along with one naturally occurring (so-called "phage Muddy") each from among those catalogued by Science Education Alliance-Phages Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) at the Howard Hughes Medical Institute by Graham Hatfull and colleagues, was used by microbiologist James Soothill at Great Ormond Street Hospital for Children in London to treat an antibiotic-resistant bacterial ("Mycobacterium abscessus") infection in a young woman with cystic fibrosis.


title: Phage therapy

text: In 2022 two mycobacteriophages were administered intravenously twice daily to a young man with treatment-refractory "Mycobacterium abscessus"  pulmonary infection and severe cystic fibrosis lung disease. Airway cultures for "M. abscessus" became negative after approximately 100 days of combined phage and antibiotic treatment, and a variety of biomarkers confirmed the therapeutic response. The individual received a bilateral lung transplant after 379 days of treatment, and cultures from the explanted lung tissue confirmed eradication of the bacteria. In a second case, successful treatment of disseminated cutaneous "Mycobacterium chelonae" was reported with a single phage administered intravenously twice daily in conjunction with antibiotic and surgical management.


title: Phage therapy

text: Bacteriophage treatment offers a possible alternative to conventional antibiotic treatments for bacterial infection. It is conceivable that, although bacteria can develop resistance to phages, the resistance might be easier to overcome than resistance to antibiotics. Just as bacteria can evolve resistance, viruses can evolve to overcome resistance.


title: Phage therapy

text: Bacteriophages are very specific, targeting only one or a few strains of bacteria. Traditional antibiotics have a more wide-ranging effect, killing both harmful bacteria and useful bacteria such as those facilitating food digestion. The species and strain specificity of bacteriophages makes it unlikely that harmless or useful bacteria will be killed when fighting an infection.


title: Phage therapy

text: A few research groups in the West are engineering a broader spectrum phage, and also a variety of forms of MRSA treatments, including impregnated wound dressings, preventative treatment for burn victims, phage-impregnated sutures. Enzybiotics are a new development at Rockefeller University that create enzymes from phage. Purified recombinant phage enzymes can be used as separate antibacterial agents in their own right.


title: Phage therapy

text: Phage therapy also has the potential of preventing or treating infectious diseases of corals. This could assist with decline of coral around the world.


title: Phage therapy

text: Phage for therapeutic use can be collected from environmental sources that likely contain high quantities of bacteria and bacteriophages, such as effluent outlets, sewage or even soil. The samples are taken and applied to bacterial cultures that are to be targeted. If the bacteria die, as seen by plaques formed on a bacterial lawn, the phages can be grown in liquid cultures, which is then centrifuged to pellet the bacteria, and collected from the supernatant, which is then passed through a filter to remove all but the phages. The phage lysate can then be further tested to see which ones show growth suppression effects (lysogeny) or destruction (lysis) of the target bacteria.


title: Phage therapy

text: Phages are "bacterium-specific" and it is, therefore, necessary in many cases to take a swab from the patient and culture it prior to treatment. Occasionally, isolation of therapeutic phages can require a few months to complete, but clinics generally keep supplies of phage cocktails for the most common bacterial strains in a geographical area.


title: Phage therapy

text: Phage cocktails are sold in pharmacies in eastern countries. The composition of bacteriophagic cocktails has been periodically modified to add phages effective against emerging pathogenic strains.


title: Phage therapy

text: Phages in practice are applied orally, topically on infected wounds or spread onto surfaces, or used during surgical procedures. Injection is rarely used, avoiding any risks of trace chemical contaminants that may be present from the bacteria amplification stage, and recognizing that the immune system naturally fights against viruses introduced into the bloodstream or lymphatic system.


title: Phage therapy

text: Reviews of phage therapy indicate that more clinical and microbiological research is needed to meet current standards.


title: Phage therapy

text: Funding for phage therapy research and clinical trials is generally insufficient and difficult to obtain, since it is a lengthy and complex process to patent bacteriophage products. An official view is that the effectiveness of each individual phage would need to be demonstrated separately, because administering them in combinations would be too complicated. Due to the specificity of phages, phage therapy would be most effective as a cocktail injection, a modality generally rejected by the U.S. Food and Drug Administration (FDA). Therefore, researchers and observers have predicted that if phage therapy is to gain traction, the FDA must change its regulatory stance on combination drug cocktails. Public awareness and education about phage therapy are generally limited to scientific or independent research rather than mainstream media.


title: Phage therapy

text: In 2007 Phase 1 and 2 clinical trials were completed at the Royal National Throat, Nose and Ear Hospital, London, for "Pseudomonas aeruginosa" infections (otitis).


title: Phage therapy

text: Phase 1 clinical trials were conducted at the Southwest Regional Wound Care Center of Lubbock, Texas, for a cocktail of phages against "P. aeruginosa", "Staphylococcus aureus" and "Escherichia coli" developed by Intralytix. PhagoBurn, a Phase 1 and 2 trial of phage therapy against "P. aeruginosa" wound infection in France and Belgium in 2015–17, was terminated early due to lack of effectiveness.


title: Phage therapy

text: Locus Biosciences created a cocktail of three CRISPR-modified phages. A 2019 study examined its effectiveness against "E. coli" in the urinary tract, a Phase I trial the completed shortly before March 2021. In February 2019, the FDA approved the first clinical trial of intravenously administered phage therapy in the United States.


title: Phage therapy

text: In July 2020, the FDA approved the first clinical trial of nebulized phage therapy in the United States. This double-blind, placebo-controlled study at Yale University will be focused on treating "P. aeruginosa" infections in patients with cystic fibrosis.


title: Phage therapy

text: In February 2020, the FDA approved a clinical trial to evaluate bacteriophage therapy in patients with urinary tract infections. The study started in December 2020 and aim to identify ideal bacteriophage treatment regimens based on improvements in disease control rates.


title: Phage therapy

text: In February 2021, the FDA approved a clinical trial to evaluate bacteriophage therapy in patients with chronic prosthetic joint infections (PJI). This study will start in October 2022 and be conducted by Adaptive Phage Therapeutics in collaboration with Mayo Clinic.


title: Phage therapy

text: Phages can usually be freeze-dried and turned into pills without materially reducing efficiency. Temperature stability up to 55 °C and shelf lives of 14 months have been shown for some types of phages in pill form. Application in liquid form is possible, stored preferably in refrigerated vials. Oral administration works better when an antacid is included, as this increases the number of phages surviving passage through the stomach. Topical administration often involves application to gauzes that are laid on the area to be treated.


title: Phage therapy

text: Phages were used successfully at Yale University by Benjamin Chan to treat a "Pseudomonas" infection in 2016. Intravenous phage drip therapy was successfully used to treat a patient with multidrug-resistant "Acinetobacter baumannii" in Thornton Hospital at UC San Diego in 2017. Nebulized phage therapy has been used successfully to treat numerous patients with cystic fibrosis and multidrug-resistant bacteria at Yale University as part of their compassionate use program. In 2019, a Brownsville, Minnesota, resident with a longstanding bacterial infection in his knee received a phage treatment at the Mayo Clinic that eliminated the need for amputation of his lower leg. Individualised phage therapy was also successfully used by Robert T. Schooley and others to treat a case of multi-drug-resistant "Acinetobacter baumannii" in 2015. In 2022, an individually adjusted phage-antibiotic combination as an antimicrobial resistance treatment was demonstrated and described in detail. The scientists called for scaling up the research and for further development of this approach.


title: Phage therapy

text: Phage therapy is being used to great effect in the treatment of biofilm infections, especially Pseudomonas aeruginosa and Staphylococcus aureus. From 78 recent cases of treatment of biofilm infections, 96% of patients saw clinical improvement when phage therapy, and 52% of patients saw complete symptom relief or a full expunge of the effecting bacteria. Biofilm infections are very challenging to treat with antibiotics. The biofilm matrix and surrounding bacterial membranes can bind to the antibiotics, preventing them from penetrating the biofilm. The matrix contains enzymes with enzymes that deactivate the antibiotics. Biofilm infection cells also have low metabolic activity which means antibiotics that target growing processes have much lower efficacy. These factors make phage therapy an enticing option for the treatment of such infections, and there are currently two ways to go about such treatment. The first way is to isolate the initial bacteria and make a specific treatment phage to target it, while the second way is to use a combination of more general phages to treat it. The advantage of the second method is that it can easily be made commercially available for easy treatment, although there are some concerns that it may be substantially less effective.


title: Phage therapy

text: The high bacterial strain specificity of phage therapy may make it necessary for clinics to make different cocktails for treatment of the same infection or disease because the bacterial components of such diseases may differ from region to region or even person to person. In addition, this means that "banks" containing many different phages must be kept and regularly updated with new phages.


title: Phage therapy

text: Further, bacteria can evolve different receptors either before or during treatment. This can prevent phages from completely eradicating bacteria.


title: Phage therapy

text: The need for banks of phages makes regulatory testing for safety harder and more expensive under current rules in most countries. Such a process would make the large-scale use of phage therapy difficult. Additionally, patent issues (specifically on living organisms) may complicate distribution for pharmaceutical companies wishing to have exclusive rights over their "invention", which would discourage a commercial corporation from investing capital in this.


title: Phage therapy

text: As has been known for at least thirty years, mycobacteria such as "Mycobacterium tuberculosis" have specific bacteriophages. No lytic phage has yet been discovered for "Clostridium difficile", which is responsible for many nosocomial diseases, but some "temperate phages" (integrated in the genome, also called lysogenic) are known for this species; this opens encouraging avenues but with additional risks as discussed below.


title: Phage therapy

text: The negative public perception of viruses may also play a role in the reluctance to embrace phage therapy.


title: Phage therapy

text: One of the major concerns usually associated with phage therapy is the emergence of phage-insensitive mutants (BIMs) that could hinder the success of this therapy. In fact, several "in vitro" studies have reported a fast emergence of BIMs within a short period of time after phage treatment. The emergence of BIMs has also been observed "in vivo" using different animal models, although usually occurs later than "in vitro" (reviewed in ). This fast adaptation of bacteria to phage attack is usually caused by mutations on genes encoding phage receptors, which include lipopolysaccharides (LPS), outer membrane proteins, capsules, flagella, pili, among others. However, some studies suggested that when phage resistance is caused by mutations in phage receptors, this might result in fitness costs to the resistance bacterium, which will ultimately become less virulent. Moreover, it has been shown that the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Therefore, it is conceivable to think that phage therapy that uses phages that exert selection for MDR (multidrug-resistant) bacteria to become antibiotic sensitive could potentially reduce the incidence of antibiotic-resistant infections.


title: Phage therapy

text: Besides the prevention of phage adsorption by loss or modification of bacterial receptors, phage-insensitivity can be caused by: (i) prevention of phage DNA entry by superinfection exclusion systems; (ii) degradation of phage DNA by restriction-modification systems or by CRISPR-Cas systems; and (iii) use of abortive infection systems that block phage replication, transcription or translation, usually in conjugation with suicide of the host cell. Altogether, these mechanisms promote a quick adaptation of bacteria to phage attack and therefore, the emergence of phage-resistance mutants is frequent and unavoidable.


title: Phage therapy

text: It is still unclear whether the wide use of phages would cause resistance similar to what has been observed for antibiotics. In theory this is not very likely to occur, since phages are very specific and therefore their selective pressure would affect a very narrow group of bacteria. However, we should also consider the fact that many phage resistance systems are mounted on mobile genetic elements, including prophages and plasmids, and thus may spread quite rapidly even without direct selection. Nevertheless, in contrast to antibiotics, phage preparations for therapeutic applications are expected to be developed in a personalized way because of the high specificity of phages. In addition, strategies have been proposed to counter the problem of phage resistance. One of the strategies is use of phage cocktails with complementary host ranges (different host ranges, which - when combined - result in an overall broader host range) and targeting different bacterial receptors. Another strategy is the combination of phages with other antimicrobials such as antibiotics, disinfectants or enzymes that could enhance their antibacterial activity. The genetic manipulation of phage genomes can also be a strategy to circumvent phage resistance.


title: Phage therapy

text: Bacteriophages are bacterial viruses, evolved to infect bacterial cells; to do that, phages must use characteristic structures at cell surfaces (receptors), and to propagate they need appropriate molecular tools inside the cells. Bacteria are Prokaryotes and their cells differ substantially from Eukaryotes including humans or animals. For this reason phages meet the major safety requirement: they do not infect treated individuals. Even engineered phages and induced artificial internalization of phage into mammalian cells did not result in phage propagation. Internalization can be induced e.g. by adding adenovirus penton base protein on the phage surface, it allows for the attachment of engineered phages to integrin receptors and for endocytosis. These mimic adenoviral infection, but no resulting propagation of phage nor any cell damage were observed. Natural transcytosis of unmodified phages, that is: uptake and internal transport to the other side of a cell, which was observed in human epithelial cells, did not result in phage propagation or cell damage. Recently, however, it was reported that filamentous temperate phages of "P. aeruginosa" can be endocytosed into human and murine leukocytes, resulting in transcription of the phage DNA. In turn, the product RNA triggers maladaptive innate viral pattern-recognition responses and thus inhibits the immune clearance of the bacteria. Whether this also applies to dsDNA phages like the Caudovirales has not yet been established; this is obviously an important question to be addressed as it may affect the overall safety of phage therapy.


title: Phage therapy

text: Due to many experimental treatments in human patients conducted in past decades, and to already existing RCTs (see section: Clinical experience and randomized controlled trials), phage safety can be assessed directly. The first safety trial in healthy human volunteers for a phage was conducted by Bruttin and Brüssow in 2005; they investigated the oral administration of "Escherichia coli" phage T4 and they found no adverse effects of the treatment. Historical record shows that phages are safe, with mild side effects if any. The most frequent (though still rare) adverse reactions to phage preparations found in patients were symptoms from the digestive tract, local reactions at the site of administration of a phage preparation, superinfections, and a rise in body temperature. Notably, these reactions may have been (i) due to the liberation of endotoxins from bacteria lysed in vivo by the phages, since such effects also can be observed when antibiotics are used, or (ii) caused by bacterial debris that accompanied phage in cases where unpurified lysates were used.


title: Phage therapy

text: Bacteriophages must be produced in bacteria that are lysed (i.e. fragmented) during phage propagation. As such, phage lysates contain bacterial debris that may affect the human organism even when the phage itself is unharmful. For these and other reasons, purification of bacteriophages is considered important and phage preparations need to be assessed for their safety as the whole, particularly when phages are to be administered intravenously. This is consistent with general procedures for other drug candidates. In 2015, a group of phage therapy experts summarized Quality and Safety Requirements for Sustainable Phage Therapy.


title: Phage therapy

text: Phage effects on human microbiome also contribute to the safety issues in phage therapy. It is important to note that many phages, especially temperate phages, carry genes that can affect the pathogenicity of the host. Even the famous lambda, a temperate phage of the "E. coli" K-12 laboratory strain, carries two genes that provide potential virulence benefits to the lysogenic host, one that increases intestinal adherence and the other that confers resistance to complement killing in the blood. For this reason, temperate phages are generally to be avoided as candidates for phage therapy, although in some cases, the lack of lytic phage candidates and emergency conditions may make such considerations moot. Another potential problem is generalized transduction, a term for the ability of some phages to transfer bacterial DNA from one host to another. This occurs because the systems for packaging of the phage DNA into capsids can mistakenly package host DNA instead. Indeed, with some well-characterized phages, up to 5% of the virus particles contain only bacterial DNA; thus in a typical lysate, the entire genome of the propagating host is present in more than a million copies in every milliliter. For these reasons, it is imperative that any phage to be considered for therapeutic usage should be subjected to thorough genomic analysis and tested for the capacity for generalized transduction.


title: Phage therapy

text: As antibacterials, phages may also affect the composition of microbiomes, by infecting and killing phage-sensitive strains of bacteria. However, a major advantage of bacteriophages over antibiotics is the high specificity of bacteriophages; this specificity limits antibacterial activity to a sub-species level, typically a phage kills only selected bacterial strains. For this reason phages are much less likely (than antibiotics) to disturb the composition of natural microbiome or to induce dysbiosis. This was demonstrated in experimental studies where microbiome composition was assessed by next-generation sequencing (NGS) that revealed no important changes correlated with phage treatment in phage human treatments.


title: Phage therapy

text: Much of the difficulty in obtaining regulatory approval is proving to be the risks of using a self-replicating entity which has the capability to evolve.