title: Derry

text: However, concerted efforts have been made by local community, church and political leaders from both traditions to redress the problem. A conference to bring together key actors and promote tolerance was held in October 2006. Ken Good, the Church of Ireland Bishop of Derry and Raphoe, said he was happy living on the cityside. "I feel part of it. It is my city and I want to encourage other Protestants to feel exactly the same", he said.


title: Derry

text: Support for Protestants in the district has been strong from the SDLP politician Helen Quigley, who formerly served as the Mayor of Derry. She made inclusion and tolerance key themes of her mayoralty. Cllr. Quigley said it was time for "everyone to take a stand to stop the scourge of sectarian and other assaults in the city."


title: Derry

text: The economy of the district was based significantly on the textile industry until relatively recently. For many years women were commonly the sole wage earners working in the shirt factories while the men in comparison had high levels of unemployment. This led to significant male emigration. The history of shirt making in the city dates to 1831, said to have been started by William Scott and his family who first exported shirts to Glasgow. Within 50 years, shirt making in the city was the most prolific in the UK with garments being exported all over the world. It was known so well that the industry received a mention in "Das Kapital" by Karl Marx, when discussing the factory system:


title: Derry

text: The industry reached its peak in the 1920s employing around 18,000 people. In modern times, however, the textile industry declined due largely to lower Asian wages.


title: Derry

text: A long-term foreign employer in the area is Du Pont, which has been based at Maydown since 1958, its first European production facility. Originally Neoprene was manufactured at Maydown and subsequently followed by Hypalon. More recently Lycra and Kevlar production units were active. Thanks to a worldwide demand for Kevlar, which is made at the plant, the facility undertook a £40 million upgrade to expand its global Kevlar production.


title: Derry

text: As of 2002, the three largest private-sector employers were American firms. Economic successes have included call centres and a large investment by Seagate, which has operated a factory in the Springtown Industrial Estate since 1993. As of 2019, Seagate was employing approximately 1,400 people in Derry.


title: Derry

text: A controversial new employer in the area was Raytheon Systems Limited, a software division of the American defence contractor, which was set up in Derry in 1999. Although some of the local people welcomed the jobs boost, others in the area objected to the jobs being provided by a firm involved heavily in the arms trade. Following four years of protest by the Foyle Ethical Investment Campaign, in 2004 Derry City Council passed a motion declaring the district a "A 'No – Go' Area for the Arms Trade", and in 2006 its offices were briefly occupied by anti-war protestors who became known as the Raytheon 9. In 2009, the company announced that it was not renewing its lease when it expired in 2010 and was looking for a new location for its operations.


title: Derry

text: Other significant multinational employers in the region include Firstsource of India, INVISTA, Stream International, Perfecseal, NTL, Northbrook Technology of the United States, Arntz Belting and Invision Software of Germany, and Homeloan Management of the UK. Major local business employers include Desmonds, Northern Ireland's largest privately owned company, manufacturing and sourcing garments, E&I Engineering, St. Brendan's Irish Cream Liqueur and McCambridge Duffy, one of the largest insolvency practices in the UK.


title: Derry

text: Even though the city provides cheap labour by standards in Western Europe, critics have noted that the grants offered by the Northern Ireland Industrial Development Board have helped land jobs for the area that only last as long as the funding lasts. This was reflected in questions to the Parliamentary Under-Secretary of State for Northern Ireland, Richard Needham, in 1990. It was noted that it cost £30,000 to create one job in an American firm in Northern Ireland.


title: Derry

text: Critics of investment decisions affecting the district often point to the decision to build a new university building in nearby (predominantly Protestant) Coleraine rather than developing the Ulster University Magee Campus. Another major government decision affecting the city was the decision to create the new town of Craigavon outside Belfast, which again was detrimental to the development of the city. Even in October 2005, there was perceived bias against the comparatively impoverished North West of the province, with a major civil service job contract going to Belfast. Mark Durkan, the Social Democratic and Labour Party (SDLP) leader and Member of Parliament (MP) for Foyle was quoted in the "Belfast Telegraph" as saying:


title: Derry

text: In July 2005, the Irish Minister for Finance, Brian Cowen, called for a joint task force to drive economic growth in the cross border region. This would have implications for Counties Londonderry, Tyrone, and Donegal across the border.


title: Derry

text: The city is the north west's foremost shopping district, housing two large shopping centres along with numerous shop packed streets serving much of the greater county, as well as Tyrone and Donegal.


title: Derry

text: The city centre has two main shopping centres; the Foyleside Shopping Centre which has 45 stores and 1,430 parking spaces, and the Richmond Centre, which has 39 retail units. The Quayside Shopping Centre also serves the city-side and there is also Lisnagelvin Shopping Centre in the Waterside. These centres, as well as local-run businesses, feature numerous national and international stores. Crescent Link Retail Park, located in the Waterside, has several chain stores and has become the second largest retail park in Northern Ireland (second only to Sprucefield in Lisburn). Plans have also been approved for Derry's first Asda store, which will be located at the retail park sharing a unit with Homebase. Sainsbury's also applied for planning permission for a store at Crescent Link, but Environment Minister Alex Attwood turned it down.


title: Derry

text: Until the store's closure in March 2016, the city was also home to the world's oldest independent department store, Austins. Established in 1830, Austins predates Jenners of Edinburgh by 5 years, Harrods of London by 15 years and Macy's of New York by 25 years. The store's five-story Edwardian building is located within the walled city in the area known as The Diamond.


title: Derry

text: Derry is renowned for its architecture. This can be primarily ascribed to the formal planning of the historic walled city of Derry at the core of the modern city. This is centred on the Diamond with a collection of late Georgian, Victorian and Edwardian buildings maintaining the gridlines of the main thoroughfares (Shipquay Street, Ferryquay Street, Butcher Street and Bishop Street) to the City Gates. St Columb's Cathedral does not follow the grid pattern reinforcing its civic status. This Church of Ireland Cathedral was the first post-Reformation Cathedral built for an Anglican church. The construction of the Roman Catholic St Eugene's Cathedral in the Bogside in the 19th-century was another major architectural addition to the city. The Townscape Heritage Initiative has funded restoration works to key listed buildings and other older structures.


title: Derry

text: In the three centuries since their construction, the city walls have been adapted to meet the needs of a changing city. The best example of this adaptation is the insertion of three additional gates – Castle Gate, New Gate and Magazine Gate – into the walls in the course of the 19th century. Today, the fortifications form a continuous promenade around the city centre, complete with cannon, avenues of mature trees and views across Derry. Historic buildings within the city walls include St Augustine's Church, which sits on the city walls close to the site of the original monastic settlement; the copper-domed Austin's department store, which claims to the oldest such store in the world; and the imposing Greek Revival Courthouse on Bishop Street. The red-brick late-Victorian Guildhall, also crowned by a copper dome, stands just beyond Shipquay Gate and close to the river front.


title: Derry

text: There are many museums and sites of interest in and around the city, including the Foyle Valley Railway Centre, the Amelia Earhart Centre And Wildlife Sanctuary, the Apprentice Boys Memorial Hall, Ballyoan Cemetery, The Bogside, numerous murals by the Bogside Artists, Derry Craft Village, Free Derry Corner, O'Doherty Tower (now home to part of the Tower Museum), the Harbour Museum, the Museum of Free Derry, Chapter House Museum, the Workhouse Museum, the Nerve Centre, St. Columb's Park and Leisure Centre, Creggan Country Park, Brooke Park, The Millennium Forum and the Foyle and Craigavon bridges.


title: Derry

text: Attractions include museums, a vibrant shopping centre and trips to the Giant's Causeway, which is approximately away, though poorly connected by public transport. Lonely Planet called Derry the fourth best city in the world to see in 2013.


title: Derry

text: On 25 June 2011, the Peace Bridge opened. It is a cycle and foot bridge that begins from the Guild Hall in the city centre of Derry City to Ebrington Square and St Columb's Park on the far side of the River Foyle. It was funded jointly by the Department for Social Development (NI), the Department of the Environment, Community and Local Government along with matching funding, totalling £14 million, from the SEUPB Peace III programme.


title: Derry

text: Future projects include the Walled City Signature Project, which intends to ensure that the city's walls become a world class tourist experience.


title: Derry

text: The transport network is built out of a complex array of old and modern roads and railways throughout the city and county. The city's road network also makes use of two bridges to cross the River Foyle, the Craigavon Bridge and the Foyle Bridge, the longest bridge in Ireland. Derry also serves as a major transport hub for travel throughout nearby County Donegal.


title: Derry

text: In spite of it being the second city of Northern Ireland (and it being the second-largest city in all of Ulster), road and rail links to other cities are below par for its standing. Many business leaders claim that government investment in the city and infrastructure has been badly lacking. Some have stated that this is due to its outlying border location whilst others have cited a sectarian bias against the region west of the River Bann due to its high proportion of Catholics. There is no direct motorway link with Dublin or Belfast. The rail link to Belfast has been downgraded over the years so that, presently, it is not a viable alternative to the roads for industry to rely on. As of 2008, there were plans for £1 billion worth of transport infrastructure investment in and around the district. Planned upgrades to the A5 Dublin road agreed as part of the Good Friday Agreement and St. Andrews Talks fell through when the government of the Republic of Ireland reneged on its funding citing the post-2008 economic downturn.


title: Derry

text: Most public transport in Northern Ireland is operated by the subsidiaries of Translink. Originally the city's internal bus network was run by Ulsterbus, which still provides the city's connections with other towns in Northern Ireland. The city's buses are now run by Ulsterbus Foyle, just as Translink Metro now provides the bus service in Belfast. The Ulsterbus Foyle network offers 13 routes across the city into the suburban areas, excluding an Easibus link which connects to the Waterside and Drumahoe, and a free Rail Link Bus runs from the Waterside Railway Station to the city centre. All buses leave from the Foyle Street Bus Station in the city centre.


title: Derry

text: Long-distance buses depart from Foyle Street Bus Station to destinations throughout Ireland. Buses are operated by both Ulsterbus and Bus Éireann on cross-border routes. Lough Swilly formerly operated buses to Co. Donegal, but the company entered liquidation and is no longer in operation. There is a half-hourly service to Belfast every day, called the Maiden City Flyer, which is the Goldline Express flagship route. There are hourly services to Strabane, Omagh, Coleraine, Letterkenny and Buncrana, and up to twelve services a day to bring people to Dublin. There is a daily service to Sligo, Galway, Shannon Airport and Limerick.


title: Derry

text: City of Derry Airport, the council-owned airport near Eglinton, has grown during the early 21st century, with new investment in extending the runway and plans to redevelop the terminal.


title: Derry

text: The A2 (a dual carriageway) from Maydown to Eglinton, serves the airport. City of Derry airport is the main regional airport for County Donegal, County Londonderry and west County Tyrone as well as Derry City itself.


title: Derry

text: The airport is served by Loganair and Ryanair with scheduled flights to Glasgow Airport, Edinburgh Airport, Manchester Airport, Liverpool John Lennon Airport and London Stansted all year round with a summer schedule to Mallorca with TUI Airways


title: Derry

text: The city is served by a single rail link that is subsidised, alongside much of Northern Ireland's railways, by Northern Ireland Railways (N.I.R.). The link primarily provides passenger services from the city to Belfast, via several stops that include , , and , and connections to links with other parts of Northern Ireland. The route itself is the only remaining rail link used by trains; most of the lines developed in the mid 19th century fell into decline towards the mid 20th century from competition by new road networks. The original rail network that served the city included four different railways that, between them, linked the city with much of the province of Ulster, plus a harbour railway network that linked the other four lines, and a tramway on the City side of the Foyle. Usage of the rail link between Derry and Belfast remains questionable for commuters, due to the journey time of over two hours making it slower centre-to-centre than the 100-minute Ulsterbus Goldline Express service.


title: Derry

text: Several railways began operation around the city of Derry within the middle of the 19th century. The companies that set up links helped to provide key links for the city towards other towns and cities across Ireland, for the transportation of passengers and freight. The lines that were constructed featured a mixture of Irish gauge and narrow gauge railways, and companies that operated them included:


title: Derry

text: In 1900, the gauge Donegal Railway was extended to the city from Strabane, with construction establishing the Londonderry Victoria Road railway terminus and creating a junction with the LPHC railway. The LPHC line was altered to dual gauge which allowed gauge traffic between the Donegal Railway and L&LSR as well as Irish gauge traffic between the GNR and B&NCR. By 1905, the government of the United Kingdom offered subsidies to both the L&LSR and the Donegal Railway to build extensions to their railway networks into remote parts of County Donegal, which soon developed Derry (alongside Strabane) into becoming a key rail hub by 1905 for the county and surrounding regions. In 1906 the Northern Counties Committee (NCC, successor to the B&NCR) and the GNR jointly took over the Donegal Railway, making it the County Donegal Railways Joint Committee (CDRJC).


title: Derry

text: Alongside the railways, the city was served by a standard gauge () tramway, the City of Derry Tramways. The tramway was opened in 1897 and consisted of horse trams that operated along a single line, long, which ran along the City side of the Foyle parallel to the LPHC's line on that side of the river. The line never converted to electrically operated trams, and was closed in 1919.


title: Derry

text: In 1922, the partition of Ireland dramatically caused disruptions to the city's rail links, except for the NNC route to . The creation of an international frontier with County Donegal changed trade patterns to the detriment of the railways affected by the partition, placing border posts on every line to and from Derry, causing great delays to trains and disrupting timekeeping from custom inspections - the L&LSR faced inspections between Pennyburn and Bridge End; the CDRJC faced inspections beyond Strabane; and the GNR line faced inspections between Derry and Strabane. Custom agreements negotiated over the next few years between Britain and Ireland enabled GNR trains to travel to and from Derry - such trains would be allowed to pass without inspection through the Free State, unless they served local stations on the west bank of the Foyle - while goods transported by all railways between different parts of the Free State would be allowed to pass through Northern Ireland under customs bond. Despite these agreements, local passenger and goods traffic continued to be delayed by customs examinations.


title: Derry

text: The decline of most of Derry's rail links took place after the Second World War, due to increasing competition by road links. The L&LSR closed its line in 1953, followed by the CDRJC in 1954. The Ulster Transport Authority, who took over the NCC in 1949 and the GNR's lines in Northern Ireland in 1958, took control of the LPHC railway before closing it in 1962, before eventually shutting down the former GNR line to Derry in 1965, after the submission of The Benson Report to the Northern Ireland Government two years prior to the closure. This left the former L&CR line to Coleraine as the sole railway link for the city, providing a passenger service to Belfast, alongside CIÉ freight services to Donegal. By the 1990s, the service began to deteriorate.


title: Derry

text: In 2008, the Department for Regional Development announced plans to relay the track between Derry and Coleraine - the plan, aimed at being completed by 2013, included adding a passing loop to increase traffic capacity, and increasing the number of trains with two additional diesel multiple units. Additional phases of the plan also included improvements to existing stations along the line, and the restoration of the former Victoria Road terminus building to prepare for the relocation of the city's current terminus station to the site, all for completion by late 2019. Costing around £86 million, the improvements were aimed at reducing the journey time to Belfast by 30 minutes and allowing commuter trains to arrive before 9 a.m. for the first time.


title: Derry

text: The largest road investment in the north west's history took place during 2010, with the building of the 'A2 Broadbridge Maydown to City of Derry Airport dualling' project and announcement of the 'A6 Londonderry to Dungiven Dualling Scheme' with the intention to reduce the travel time to Belfast. The latter project brings a dual-carriageway link between Northern Ireland's two largest cities one step closer. The project is costing £320 million and is expected to be completed in 2016.


title: Derry

text: In October 2006 the Government of Ireland announced that it was to invest €1 billion in Northern Ireland; with the planned projects including 'the A5 Western Transport Corridor', the complete upgrade of the A5 Derry – Omagh – Aughnacloy (– Dublin) road, around long, to dual carriageway standard.


title: Derry

text: In June 2008 Conor Murphy, Minister for Regional Development, announced that there will be a study into the feasibility of connecting the A5 and A6. Should it proceed, the scheme would most likely run from Drumahoe to south of Prehen along the south east of the city.


title: Derry

text: Londonderry Port at Lisahally is the United Kingdom's most westerly port and has capacity for 30,000-ton vessels. The Londonderry Port and Harbour Commissioners (LPHC) announced record turnover, record profits and record tonnage figures for the year ended March 2008. The figures are the result of a significant capital expenditure programme for the period 2000 to 2007 of about £22 million. Tonnage handled by LPHC increased almost 65% between 2000 and 2007.


title: Derry

text: The port gave vital Allied service in the longest running campaign of the Second World War, the Battle of the Atlantic, and saw the surrender of the German U-boat fleet at Lisahally on 8 May 1945.


title: Derry

text: The tidal River Foyle is navigable from the coast at Derry to approximately inland. In 1796, the Strabane Canal was opened, continuing the navigation a further southwards to Strabane. The canal was closed in 1962.


title: Derry

text: Derry is home to the Magee Campus of Ulster University, formerly Magee College. However, Lockwood's 1960s decision to locate Northern Ireland's second university in Coleraine rather than Derry helped contribute to the formation of the civil rights movement that ultimately led to The Troubles. Derry was the town more closely associated with higher learning, with Magee College already more than a century old by that time. In the mid-1980s an attempt was made at address this by forming Magee College as a campus of the Ulster University, but this failed to stifle calls for the establishment of an independent University in Derry. As of 2021, the Magee campus reportedly accommodated approximately 4,400 students, out of a total Ulster University student population of approximately 24,000, of which 15,000 are in the Belfast campus.


title: Derry

text: The North West Regional College is also based in the city, and accommodates over 10,000 student enrolments annually.


title: Derry

text: One of the two oldest secondary schools in Northern Ireland, Foyle College, is located in Derry. It was founded in 1616 by the Merchant Taylors. Other secondary schools include St. Columb's College, Oakgrove Integrated College, St Cecilia's College, St Mary's College, St. Joseph's Boys' School, Lisneal College, Thornhill College, Lumen Christi College and St. Brigid's College. There are also numerous primary schools.


title: Derry

text: The city is home to sports clubs and teams. Both association football and Gaelic football are popular in the area.


title: Derry

text: In association football, the city's most prominent clubs include Derry City who play in the national league of the Republic of Ireland; Institute of the NIFL Championship as well as Maiden City and Trojans, both of the Northern Ireland Intermediate League.


title: Derry

text: In addition to these clubs, who all play in national leagues, other clubs are based in the city. The local football league governed by the IFA is the North-West Junior League, which contains many clubs from the city, such as BBOB (Boys Brigade Old Boys) and Lincoln Courts. The city's other junior league is the Derry and District League and teams from the city and surrounding areas participate, including Don Boscos and Creggan Swifts. The Foyle Cup youth soccer tournament is held annually in the city. It has attracted many notable teams in the past, including Werder Bremen, IFK Göteborg and Ferencváros.


title: Derry

text: In Gaelic football Derry GAA are the county team and play in the Gaelic Athletic Association's National Football League, Ulster Senior Football Championship and All-Ireland Senior Football Championship. They also field hurling teams in the equivalent tournaments. There are many Gaelic games clubs in and around the city, for example Na Magha CLG, Steelstown GAC, Doire Colmcille CLG, Seán Dolans GAC, Na Piarsaigh CLG Doire Trasna and Slaughtmanus GAC.


title: Derry

text: There are many boxing clubs, the most well-known being "The Ring Boxing Club", which is based on the City side, and associated with boxers Charlie Nash and John Duddy. Rochester's Amateur Boxing club is a club in the city's Waterside area.


title: Derry

text: Rugby union is also quite popular in the city, with the City of Derry Rugby Club situated not far from the city centre. City of Derry won both the Ulster Towns Cup and the Ulster Junior Cup in 2009.


title: Derry

text: Londonderry YMCA RFC is another rugby club and is based in the village of Drumahoe which is in the outskirts of the city.


title: Derry

text: The city's only basketball club is North Star Basketball Club which has teams in the Basketball Northern Ireland senior and junior Leagues.


title: Derry

text: Cricket is also played in the city, particularly in the Waterside. The city is home to two cricket clubs, Brigade Cricket Club and Glendermott Cricket Club, both of whom play in the North West Senior League.


title: Derry

text: There are two golf clubs situated in the city, City of Derry Golf Club and Foyle International Golf Centre.


title: Derry

text: Artists and writers associated with the city and surrounding countryside include the Nobel Prize-winning poet Seamus Heaney, poet Seamus Deane, playwright Brian Friel, writer and music critic Nik Cohn, artist Willie Doherty, socio-political commentator and activist Eamonn McCann and bands such as The Undertones. The large political gable-wall murals of Bogside Artists, Free Derry Corner, the Foyle Film Festival, the Derry Walls, St Eugene's and St Columb's Cathedrals and the annual Halloween street carnival are popular tourist attractions. In 2010, Derry was named the UK's tenth 'most musical' city by PRS for Music.


title: Derry

text: In May 2013 a perpetual Peace Flame Monument was unveiled by Martin Luther King III and Presbyterian minister Rev. David Latimer. The flame was lit by children from both traditions in the city and is one of only 15 such flames across the world.


title: Derry

text: The local newspapers, the "Derry Journal" (known as the "Londonderry Journal" until 1880) and the "Londonderry Sentinel", reflect the divided history of the city: the "Journal" was founded in 1772 and is Ireland's second oldest newspaper; the "Sentinel" newspaper was formed in 1829 when new owners of the "Journal" embraced Catholic Emancipation, and the editor left the paper to set up the "Sentinel".


title: Derry

text: There are numerous radio stations receivable: the largest stations based in the city are BBC Radio Foyle and the commercial station Q102.9.


title: Derry

text: There was a locally based television station, C9TV, one of only two local or 'restricted' television services in Northern Ireland, which ceased broadcasts in 2007.


title: Derry

text: The city's night-life is mainly focused on the weekends, with several bars and clubs providing "student nights" during the weekdays. Waterloo Street and Strand Road provide the main venues. Waterloo Street, a steep street lined with both Irish traditional and modern pubs, frequently has live rock and traditional music at night.


title: Ravana

text: Ravana (; , , ) is a rakshasa king of the island of Lanka, and the chief antagonist of the Hindu epic "Ramayana" and its adaptations.


title: Ravana

text: In the "Ramayana", Ravana is described to be the eldest son of sage Vishrava and rakshasi Kaikesi. He abducted Prince Rama's wife Sita and took her to his kingdom of Lanka, where he held her in the Ashoka Vatika. Later, Rama, with the support of vanara King Sugriva and his army of vanaras, launched an invasion against Ravana in Lanka. Ravana was subsequently slain and Rama rescued his beloved wife Sita.


title: Ravana

text: Ravana is widely portrayed to be an evil character, though he also has many qualities that make him a learned scholar. He was well-versed in the six shastras and the four Vedas. Ravana is also considered to be the most revered devotee of Shiva. Images of Ravana are seen associated with Shiva at some temples. He also appears in the Buddhist Mahayana text "Laṅkāvatāra Sūtra", in Buddhist Ramayanas and Jatakas, as well as in Jain Ramayanas. In some scriptures, he is depicted as one of Vishnu's cursed doorkeepers.


title: Ravana

text: The word "Rāvaṇa" (Sanskrit: रावण) means ""roaring"" (active), the opposite of Vaiśravaṇa, meaning ""hear distinctly"" (passive). Both "Ravana" and "Vaiśravaṇa", who is popularly known as Kubera, are considered to be patronymics derived as "sons of Vishrava".


title: Ravana

text: "Rāvana" was a title taken on later by Dashānana, and it means "the one with ten(dasha) faces(anana)". Further, "roravana" is Sanskrit for "loud roaring." In Abhinava Gupta's Krama Shaiva scripture, "yāsām rāvanam" is used as an expression to mean people who are truly aware in terms of the materialism of their environment.


title: Ravana

text: Ravana has many other popular names, such as Dasis Ravana, Dasis Sakvithi Maha Ravana, Dashaanan, Ravula, Lankapati, Lankeshwar, Lankeshwaran, Ravanasura, Ravanaeshwaran, and Eela Vendhar.


title: Ravana

text: Ravana is depicted and described as having ten heads, although sometimes he is shown with only nine heads, as he cut one off to convince Shiva. He is described as a devout follower of Shiva, a great scholar, a capable ruler and a maestro of the Veena (pronounced veh-nah; a chordophone instrument). Ravana is also depicted as the author of the "Ravana Samhita", a book on Hindu astrology, and the "Arka Prakasham", a book on Siddha medicine and treatment. Ravana possessed a thorough knowledge of Siddha and political science. He is said to have possessed the nectar of immortality, which was stored inside his belly, thanks to a celestial boon by Brahma.


title: Ravana

text: Ravana was born to the great sage Vishrava, and his wife, the Rakshasa princess Kaikesi in the Treta Yuga. People of Bisrakh village in Uttar Pradesh claim that Bisrakh was named after Vishrava, and that Ravana was born there. But according to Hela historical sources and folklore, Ravana was born in Lanka, where he later became king.


title: Ravana

text: Ravana's grandfather on his father's side, the sage Pulastya, was one of the ten Prajapatis or mind-born sons of Brahma and one of the Saptarishi (Seven Great Sages Rishi) in the first Manvantara (age of Manu). His maternal grandfather was Sumali (or Sumalaya); the king of the Rakshasas and the son of Sukesha. Sumali had ten sons and four daughters. Sumali wished Kaikeshi to marry the most powerful being in the mortal world, so as to produce an exceptional heir. He rejected the kings of the world, as they were less powerful than he. Kaikesi searched among the sages and finally chose Vishrava, the father of Kubera. Ravana and his siblings were born to the couple. They completed their education from their father, with Ravana being a great scholar of the Vedas.


title: Ravana

text: Ravana and his two brothers "Kumbhakarna" and "Vibhishana" performed penances on Mt Gokarna for 11,000 years and won boons from Brahma. Ravana was blessed with a boon that would make him invincible to all the creations of Brahma, except for humans. He also received weapons, a chariot as well as the ability to shapeshift from Brahma. Ravana later usurped Lanka from his half-brother Kubera and became the King of Lanka. He appointed Shukracharya as his priest and learned the Arthashastra (Science of Politics) from him.


title: Ravana

text: One of the most popular images of Shiva is called "Ravananugraha", which was popular in the Gupta era and depicts Ravana beneath Mount Kailash playing the veena made out of his head and hand with strings made out of his tendons while Shiva and Parvati sit on top of the mountain. According to scriptures, Ravana once tried to lift Mount Kailash, but Shiva pushed the mountain into place and trapped Ravana beneath it. For a thousand years, the imprisoned Ravana sang hymns (Shiva Tandava Stotra) in praise of Shiva, who finally blessed him and granted him an invincible sword and a powerful linga (Shiva's iconic symbol, Atmalinga) to worship.


title: Ravana

text: Ravana's family are hardly mentioned outside the "Ramayana", which is viewed by some as being only the point of view of Rama devotees. According to that:


title: Ravana

text: Ravana is said in some version to have had Shukracharya, the priest of the Asuras, as his minister, and in some versions Brihaspati, the priest of the Devas.


title: Ravana

text: One of the most original, which is not found in earlier manuscripts, tells how Ravana orders his court priest Brhaspati (all the gods being his slaves) to read the Chandi stava (mantras of Chandi), that is, the "Devi Mahatmya", in order to stave off defeat if he can recite it. According to the "Krttivasa" text, Ravana arranged for a peaceful yajna (sacrifice) and to start the recitation of Chandi, Brihaspati was invited. Accordingly, Brihaspati recited the same correctly.


title: Ravana

text: In the Bhagavata Purana, Ravana and his brother, Kumbhakarna, were said to be reincarnations of Jaya and Vijaya, gatekeepers at Vaikuntha (the abode of Vishnu) and were cursed to be born on Earth for their insolence.


title: Ravana

text: These gatekeepers refused entry to the Sanatha Kumara monks — who, because of their powers and austerity, appeared as young children. For their insolence, the monks cursed them to be expelled from Vaikuntha and to be born on Earth.


title: Ravana

text: Vishnu agreed that they should be punished. They were given two choices, that they could be born seven times as normal mortals and devotees of Vishnu, or three times as powerful and strong people, but as enemies of Vishnu. Eager to be back with the Lord, they choose the latter one. Ravana and his brother Kumbhakarna were born to fulfill the curse on the second birth as enemies of Vishnu in the Treta Yuga. The curse of first birth was fulfilled by Hiranyakashipu and his brother Hiranyaksha in Satya Yuga when they were both vanquished by earlier avatars of Vishnu (Hiranyaksha by Varaha and Hiranyakashipu by Narasimha) and the curse of third birth was fulfilled by Dantavakra and Shishupala in the Dvapara Yuga when they both were slain by Krishna, the eighth avatar.


title: Ravana

text: As he is considered one of the most revered devotees of Shiva, Ravana is worshiped in several places. There are some Shiva temples where Ravana is worshiped.


title: Ravana

text: The Kanyakubja Brahmins of the Vidisha district worship Ravana; they personify him as a symbol of prosperity and regard him as a saviour, claiming that Ravana was also a Kanyakubja Brahmin. Thousands of Kanyakubja Brahmins of the village Ravangram of Netaran, in the Vidisha District of Madhya Pradesh, perform daily puja (worship) in the Ravana temple and offer naivedyam / bhog (a ritual of sacrifice to the Gods). Centuries ago King Shiv Shankar built a Ravana temple at Kanpur, Uttar Pradesh. The Ravana temple is opened once a year, on Dashehra Day, to perform puja for the welfare of Ravana.


title: Ravana

text: The Sachora Brahmins of Gujarat also claim to be descendants of Ravana, and sometimes have "Ravan" as their surnames.


title: Ravana

text: There is also reference to "Ravani", the lineage of Upadhyaya Yasastrata II, who was of the Gautama gotra and was a son of Acharya Vasudatta, and described as "born of Ravani".


title: Ravana

text: The Gondi people of central India claim to be descendants of Ravana, and they have temples set up for him, his wife Mandodari, and their son Meghnad. They also state that Ravana was an ancient Gond king, the tenth "dharmaguru" of their tribe, and the eighteenth lingo (divine teacher). Every year on Dussehra, the Gondis of the village of Paraswadi carry an image of Ravana riding on an elephant in a procession


title: Ravana

text: A Ramleela actor wears the traditional attire of Ravana. One of the most important literary works of ancient India, the "Ramayana" has had a profound impact on art and culture in the Indian subcontinent and Southeast Asia.


title: Ravana

text: Effigies of Ravana are burned on Vijayadashami in many places throughout India. It is said that this symbolizes Rama's triumph over evil (i.e., Ravana).


title: Ravana

text: The "ravanahatha", an ancient bowed-string instrument, continues to be used as a Rajasthani folk instrument. Mythology credits this instrument as a creation of Ravana.


title: Ravana

text: In Rin-spuns-pa Tibetan Ramayana, it is prophesied that "Ravana" will return as the Buddha incarnation of Vishnu in the Kali Yuga.


title: Ravana

text: The Tai Khamti Ramayana (Phra Chow Lamang) of Arunachal Pradesh as well describes Rama as a Bodhisattva incarnated to get tortured by Ravana.


title: Ravana

text: In the Laotian Buddhist text "Phra Lak Phra Lam", Rama is a Bodhisattva and the embodiment of virtues, while Ravana is a Brahmin (""mahabrahma"") son of Virulaha who is highly materialistic.


title: Ravana

text: In the Cambodian Buddhist text "Preah Ream", Buddha is an incarnation of Rama and Ravana. He is a rakshasa.


title: Ravana

text: In the Thai Buddhist text "Ramakien", Rāvana is a rakshasa. There, he is instead known as "Thotsakan" (ทศกัณฐ์, from Sanskrit दशकण्ठ, Daśakaṇṭha, "ten necks"), and he is depicted with green skin.


title: Ravana

text: In the "Lankavatara Sutra", Gautama Buddha pays a visit to Lanka, and in the scripture he is addressed as a "Rakshasa". He is normally identified as a demon.


title: Ravana

text: In the "Karandavyuha Sutra", the god Yama asks if the visitor in hell (Avalokitesvara) whom he hasn't seen yet is a god or a demon, and asks whether he is Vishnu, Mahesvara, or the "rakshasa" ("demon") Ravana.


title: Ravana

text: Jain accounts vary from the traditional Hindu accounts of "Ramayana". The incidents are placed at the time of the 20th Tirthankara, Munisuvrata. According to Jain version, both Rama as well as Ravana were devout Jains. Ravana was a Vidyadhara King who had magical powers. Also, as per the Jain accounts, Ravana was killed by Lakshmana and not Rama in the end.


title: Ravana

text: Pulavar Kuzhanthai's Ravana Kaaviyam, is a panegyric on Ravana. The book is made of 3100 poetic stanzas in which Ravana is the hero. The book was released in 1946. The book was banned by the then Congress state government. The ban was lifted only in 1971.


title: We Own This City

text: We Own This City is an American miniseries based on the nonfiction book of the same name by "Baltimore Sun" reporter Justin Fenton. The miniseries was developed and written by George Pelecanos and David Simon, and directed by Reinaldo Marcus Green. The six-episode series premiered on HBO on April 25, 2022.


title: We Own This City

text: The miniseries details the rise and fall of the Baltimore Police Department's Gun Trace Task Force and the corruption surrounding it. The story centers on Sergeant Wayne Jenkins, one of eight officers who were convicted on various corruption charges in 2018 and 2019. It follows a non-linear narrative with frequent flashbacks.


title: We Own This City

text: In March 2021, HBO ordered a six-episode series based on the book "We Own This City: A True Story of Crime, Cops and Corruption" by "Baltimore Sun" investigative journalist Justin Fenton, to be written by David Simon and George Pelecanos.


title: We Own This City

text: In May 2021, it was confirmed that Reinaldo Marcus Green would direct the series. Production was reported to begin in July 2021 with filming occurring in Baltimore. Production was temporarily halted for a week in September 2021 due to a "COVID-19 event".


title: We Own This City

text: In May 2021, Jon Bernthal, Josh Charles and Jamie Hector were announced to have been cast in leading roles. Darrell Britt-Gibson, Rob Brown, McKinley Belcher III, Larry Mitchell and Wunmi Mosaku were cast in June. In August, several castings were announced, including Dagmara Domińczyk, Don Harvey, Delaney Williams, David Corenswet, Ian Duff, Lucas Van Engen, Gabrielle Carteris, Treat Williams and Domenick Lombardozzi. In September, several recurring and guest roles were announced, including Thaddeus Street, Tray Chaney, Chris Clanton, Jermaine Crawford and Nathan E. Corbett.


title: We Own This City

text: The review aggregator website Rotten Tomatoes reported a 93% approval rating with an average rating of 8.3/10, based on 54 critic reviews. The website's critics consensus reads, "A spiritual successor to "The Wire" with an even more pessimistic outlook on law enforcement, "We Own This City" deftly explores compromised individuals to paint an overall picture of systemic corruption." Metacritic, which uses a weighted average, assigned a score of 83 out of 100 based on 27 critics, indicating "universal acclaim".


title: We Own This City

text: Andy Greenwald of "The Ringer" said Jon Bernthal gave "one of the great TV performances of this century."


title: Taxonomic rank

text: In biological classification, taxonomic rank is the relative level of a group of organisms (a taxon) in an ancestral or hereditary hierarchy. A common system consists of species, genus, family, order, class, phylum, kingdom, domain. While older approaches to taxonomic classification were phenomenological, forming groups on the basis of similarities in appearance, organic structure and behaviour, methods based on genetic analysis have opened the road to cladistics.


title: Taxonomic rank

text: A given rank subsumes under it less general categories, that is, more specific descriptions of life forms. Above it, each rank is classified within more general categories of organisms and groups of organisms related to each other through inheritance of traits or features from common ancestors. The rank of any "species" and the description of its "genus" is "basic"; which means that to identify a particular organism, it is usually not necessary to specify ranks other than these first two.


title: Taxonomic rank

text: Consider a particular species, the red fox, "Vulpes vulpes": the specific name or specific epithet "vulpes" (small "v") identifies a particular species in the genus "Vulpes" (capital "V") which comprises all the "true" foxes. Their close relatives are all in the family Canidae, which includes dogs, wolves, jackals, and all foxes; the next higher major rank, the order Carnivora, includes caniforms (bears, seals, weasels, skunks, raccoons and all those mentioned above), and feliforms (cats, civets, hyenas, mongooses). Carnivorans are one group of the hairy, warm-blooded, nursing members of the class Mammalia, which are classified among animals with backbones in the phylum Chordata, and with them among all animals in the kingdom Animalia. Finally, at the highest rank all of these are grouped together with all other organisms possessing cell nuclei in the domain Eukarya.


title: Taxonomic rank

text: The "International Code of Zoological Nomenclature" defines "rank" as: "The level, for nomenclatural purposes, of a taxon in a taxonomic hierarchy (e.g. all families are for nomenclatural purposes at the same rank, which lies between superfamily and subfamily)."


title: Taxonomic rank

text: In his landmark publications, such as the "Systema Naturae", Carl Linnaeus used a ranking scale limited to kingdom, class, order, genus, species, and one rank below species. Today, the nomenclature is regulated by the nomenclature codes. There are seven main taxonomic ranks: kingdom, phylum or division, class, order, family, genus, and species. In addition, "domain" (proposed by Carl Woese) is now widely used as a fundamental rank, although it is not mentioned in any of the nomenclature codes, and is a synonym for dominion (lat. dominium), introduced by Moore in 1974.


title: Taxonomic rank

text: A taxon is usually assigned a rank when it is given its formal name. The basic ranks are species and genus. When an organism is given a species name it is assigned to a genus, and the genus name is part of the species name.


title: Taxonomic rank

text: The species name is also called a binomial, that is, a two-term name. For example, the zoological name for the human species is "Homo sapiens". This is usually italicized in print or underlined when italics are not available. In this case, "Homo" is the generic name and it is capitalized; "sapiens" indicates the species and it is not capitalized.


title: Taxonomic rank

text: There are definitions of the following taxonomic ranks in the International Code of Zoological Nomenclature: superfamily, family, subfamily, tribe, subtribe, genus, subgenus, species, subspecies.


title: Taxonomic rank

text: The International Code of Zoological Nomenclature divides names into "family-group names", "genus-group names" and "species-group names". The Code explicitly mentions the following ranks for these categories:


title: Taxonomic rank

text: The rules in the Code apply to the ranks of superfamily to subspecies, and only to some extent to those above the rank of superfamily. Among "genus-group names" and "species-group names" no further ranks are officially allowed. Zoologists sometimes use additional terms such as "species group", "species subgroup", "species complex" and "superspecies" for convenience as extra, but unofficial, ranks between the subgenus and species levels in taxa with many species, e.g. the genus "Drosophila". (Note the potentially confusing use of "species group" as both a category of ranks as well as an unofficial rank itself.)


title: Taxonomic rank

text: At higher ranks (family and above) a lower level may be denoted by adding the prefix ""infra"", meaning "lower", to the rank. For example, "infra"order (below suborder) or "infra"family (below subfamily).


title: Taxonomic rank

text: According to Art 3.1 of the International Code of Nomenclature for algae, fungi, and plants (ICN) the most important ranks of taxa are: kingdom, division or phylum, class, order, family, genus, and species. According to Art 4.1 the secondary ranks of taxa are tribe, section, series, variety and form. There is an indeterminate number of ranks. The ICN explicitly mentions:


title: Taxonomic rank

text: There are definitions of the following taxonomic categories in the International Code of Nomenclature for Cultivated Plants: cultivar group, cultivar, grex.


title: Taxonomic rank

text: The rules in the ICN apply primarily to the ranks of family and below, and only to some extent to those above the rank of family. Also see descriptive botanical name.


title: Taxonomic rank

text: Taxa at the rank of genus and above have a botanical name in one part (unitary name); those at the rank of species and above (but below genus) have a botanical name in two parts (binary name); all taxa below the rank of species have a botanical name in three parts (an infraspecific name). To indicate the rank of the infraspecific name, a "connecting term" is needed. Thus "Poa secunda" subsp. "juncifolia", where "subsp." is an abbreviation for "subspecies", is the name of a subspecies of "Poa secunda".


title: Taxonomic rank

text: Hybrids can be specified either by a "hybrid formula" that specifies the parentage, or may be given a name. For hybrids receiving a hybrid name, the same ranks apply, prefixed with "notho" (Greek: 'bastard'), with nothogenus as the highest permitted rank.


title: Taxonomic rank

text: If a different term for the rank was used in an old publication, but the intention is clear, botanical nomenclature specifies certain substitutions:


title: Taxonomic rank

text: Classifications of five species follow: the fruit fly familiar in genetics laboratories ("Drosophila melanogaster"), humans ("Homo sapiens"), the peas used by Gregor Mendel in his discovery of genetics ("Pisum sativum"), the "fly agaric" mushroom "Amanita muscaria", and the bacterium "Escherichia coli". The eight major ranks are given in bold; a selection of minor ranks are given as well.


title: Taxonomic rank

text: Taxa above the genus level are often given names based on the type genus, with a standard termination. The terminations used in forming these names depend on the kingdom (and sometimes the phylum and class) as set out in the table below.


title: Taxonomic rank

text: Pronunciations given are the most Anglicized. More Latinate pronunciations are also common, particularly rather than for stressed "a".


title: Taxonomic rank

text: There is an indeterminate number of ranks, as a taxonomist may invent a new rank at will, at any time, if they feel this is necessary. In doing so, there are some restrictions, which will vary with the nomenclature code which applies.


title: Taxonomic rank

text: The following is an artificial synthesis, solely for purposes of demonstration of relative rank (but see notes), from most general to most specific:


title: Taxonomic rank

text: Ranks are assigned based on subjective dissimilarity, and do not fully reflect the gradational nature of variation within nature. In most cases, higher taxonomic groupings arise further back in time: not because the rate of diversification was higher in the past, but because each subsequent diversification event results in an increase of diversity and thus increases the taxonomic rank assigned by present-day taxonomists. Furthermore, some groups have many described species not because they are more diverse than other species, but because they are more easily sampled and studied than other groups.


title: Taxonomic rank

text: Of these many ranks, the most basic is species. However, this is not to say that a taxon at any other rank may not be sharply defined, or that any species is guaranteed to be sharply defined. It varies from case to case. Ideally, a taxon is intended to represent a clade, that is, the phylogeny of the organisms under discussion, but this is not a requirement.


title: Taxonomic rank

text: A classification in which all taxa have formal ranks cannot adequately reflect knowledge about phylogeny. Since taxon names are dependent on ranks in traditional Linnaean systems of classification, taxa without ranks cannot be given names. Alternative approaches, such as using circumscriptional names, avoid this problem. The theoretical difficulty with superimposing taxonomic ranks over evolutionary trees is manifested as the boundary paradox which may be illustrated by Darwinian evolutionary models.


title: Taxonomic rank

text: There are no rules for how many species should make a genus, a family, or any other higher taxon (that is, a taxon in a category above the species level). It should be a natural group (that is, non-artificial, non-polyphyletic), as judged by a biologist, using all the information available to them. Equally ranked higher taxa in different phyla are not necessarily equivalent (e.g., it is incorrect to assume that families of insects are in some way evolutionarily comparable to families of mollusks). For animals, at least the phylum rank is usually associated with a certain body plan, which is also, however, an arbitrary criterion.


title: Taxonomic rank

text: There are several acronyms intended to help memorise the taxonomic hierarchy, such as "King Phillip came over for great spaghetti". See taxonomy mnemonic. In Season 3, episode 16 ("Virtual Systems Analysis" ) of the NBC comedy Community the character Hawthorne Pierce (Chevy Chase) refers to the mnemonic variant "Kevin, Please Come Over for Gay Sex."


title: Respiratory syncytial virus

text: Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. Its name is derived from the large cells known as "syncytia" that form when infected cells fuse.


title: Respiratory syncytial virus

text: RSV is the single most common cause of respiratory hospitalization in infants, and reinfection remains common in later life: it is an important pathogen in all age groups. Infection rates are typically higher during the cold winter months, causing bronchiolitis in infants, common colds in adults, and more serious respiratory illnesses such as pneumonia in the elderly and immunocompromised.


title: Respiratory syncytial virus

text: RSV can cause outbreaks both in the community and in hospital settings. Following initial infection via the eyes or nose, the virus infects the epithelial cells of the upper and lower airway, causing inflammation, cell damage, and airway obstruction. A variety of methods are available for viral detection and diagnosis of RSV including antigen testing, molecular testing, and viral culture. The main prevention measures include hand-washing and avoiding close contact with infected individuals; prophylactic use of palivizumab is also available to prevent RSV infection in high-risk infants. Currently, there is no vaccine against RSV, although many are under development.


title: Respiratory syncytial virus

text: Treatment for severe illness is primarily supportive, including oxygen therapy and more advanced breathing support with CPAP or nasal high flow oxygen, as required. In cases of severe respiratory failure, intubation and mechanical ventilation may be required. Ribavirin is the only antiviral medication currently licensed for the treatment of RSV in children, although its use remains controversial.


title: Respiratory syncytial virus

text: RSV infection can present with a wide variety of signs and symptoms that range from mild upper respiratory tract infections (URTI) to severe and potentially life-threatening lower respiratory tract infections (LRTI) requiring hospitalization and mechanical ventilation. While RSV can cause respiratory tract infections in people of all ages and is among the most common childhood infections, its presentation often varies between age groups and immune status. Reinfection is common throughout life, but infants and the elderly remain at highest risk for symptomatic infection.


title: Respiratory syncytial virus

text: Most children will experience at least one RSV infection by age 2. Most childhood RSV infections are fairly self-limited with typical upper respiratory tract signs and symptoms, such as nasal congestion, runny nose, cough, and low-grade fever. Inflammation of the nasal mucosa (rhinitis) and throat (pharyngitis), as well as redness of the eyes (conjunctival infection), may be seen on exam. Approximately 15–50% of children will go on to develop more serious lower respiratory tracts infections, such as bronchiolitis, viral pneumonia, or croup. Infants are at the highest risk of disease progression.


title: Respiratory syncytial virus

text: Bronchiolitis is a common lower respiratory tract infection characterized by inflammation and obstruction of the small airways in the lungs. While several viruses can cause bronchiolitis, RSV is responsible for about 70% of cases. It usually presents with 2 to 4 days of runny nose and congestion followed by worsening cough, noisy breathing, tachypnea (fast breathing), and wheezing. As infants work harder to breathe, they can also show signs of respiratory distress, such as subcostal retractions (when the belly pulls under the ribcage), intercostal retractions (when the muscles between the ribs pull inward), grunting, and nasal flaring. If the child has not been able to feed adequately, signs of dehydration may also be present. Fever may be present, but high-grade fever is uncommon. Crackles and wheezing can often be heard on auscultation, and oxygen saturation levels may be decreased.


title: Respiratory syncytial virus

text: In very young infants under 6 weeks of age, and particularly in premature infants, signs of infection may be less specific. They may have minimal respiratory involvement. Instead, they may exhibit decreased activity, irritability, poor feeding, or breathing with difficulties. This can also be accompanied by apneic spells, or brief pauses in breathing.


title: Respiratory syncytial virus

text: Reinfection with RSV remains common throughout life. Reinfection in adulthood often produces only mild to moderate symptoms indistinguishable from the common cold or sinus infection. Infection may also be asymptomatic. If present, symptoms are generally isolated to the upper respiratory tract: runny nose, sore throat, fever, and malaise. In the vast majority of cases, nasal congestion precedes the development of cough. In contrast to other upper respiratory infections, RSV is also more likely to cause new onset wheeze in adults. Only about 25% of infected adults will progress to significant lower respiratory tract infection, such as bronchitis or tracheobronchitis.


title: Respiratory syncytial virus

text: While RSV very rarely causes severe disease in healthy adults, it can cause significant morbidity and mortality in the elderly and in those with underlying immune compromise or cardiopulmonary disease. Older adults have a similar presentation to younger adults but tend to have greater symptom severity with increased risk of lower respiratory tract involvement. In particular, the elderly are more likely to experience pneumonia, respiratory distress, and death.


title: Respiratory syncytial virus

text: In both adults and children, those who are immunocompromised are at an increased risk of severe infection with RSV. Infected individuals in this group are more likely to progress from upper to lower respiratory tract involvement and have prolonged viral shedding. Symptom severity seems to be closely related to the extent of immune suppression. Those who have undergone hematopoietic stem cell transplant (HSCT), intensive chemotherapy, and lung transplant are particularly susceptible. Bone marrow transplant patients appear to be at highest risk, especially prior to marrow engraftment. In this group, RSV infection carries a nearly 80% risk of both pneumonia and death.


title: Respiratory syncytial virus

text: Risk factors for development of severe lower respiratory tract infection with RSV vary by population.


title: Respiratory syncytial virus

text: RSV is a negative-sense, single-stranded RNA virus. The scientific name for this viral species is "Human orthopneumovirus." This is synonymous with "Human respiratory syncytial virus" (hRSV), which is often shortened to just RSV. It belongs to the genus "Orthopneumovirus," family "Pneumoviridae", order "Mononegavirales". Its name comes from the fact that F proteins on the surface of the virus cause neighboring cell membranes to merge, creating large multinucleated syncytia.


title: Respiratory syncytial virus

text: RSV is divided into two antigenic subtypes, A and B, based on the reactivity of the F and G surface proteins to monoclonal antibodies. The subtypes tend to circulate simultaneously within local epidemics, although subtype A tends to be more prevalent. Generally, RSV subtype A (RSVA) is thought to be more virulent than RSV subtype B (RSVB), with higher viral loads and faster transmission time. To date, 16 RSVA and 22 RSVB clades have been identified. Among RSVA, the GA1, GA2, GA5, and GA7 clades predominate; GA7 is found only in the United States. Among RSVB, the BA clade predominates worldwide.


title: Respiratory syncytial virus

text: RSV has a negative-sense, single-stranded RNA genome. The genome is linear and approximately 15,000 nucleotides in length. It is non-segmented which means that, unlike influenza, RSV cannot participate in the type of genetic reassortment and antigenic shifts responsible for large pandemics. It has 10 genes encoding for 11 proteins. The gene order is NS1-NS2-N-P-M-SH-G-F-M2-L, with the NS1 and NS2 gene serving as nonstructural promoter genes.


title: Respiratory syncytial virus

text: RSV is a medium-sized (~150 nm) enveloped virus. While most particles are spherical, filamentous species have also been identified. The genome rests within a helical nucleocapsid and is surrounded by matrix protein and an envelope containing viral glycoproteins. There are 11 proteins, described further in the table below.


title: Respiratory syncytial virus

text: Surface protein G (glycoprotein) is primarily responsible for viral attachment to host cells. This protein is highly variable between strains. G protein exists in both membrane-bound and secreted forms. The membrane-found form is responsible for attachment by binding to glycosaminoglycans (GAGs), such as heparan sulfate, on the surface of host cells. The secreted form acts as a decoy, interacting with antigen presenting cells to inhibit antibody-mediated neutralization. G protein also contains a CX3C fractalkine-like motif that binds to the CX3C chemokine receptor 1 (CX3CR1) on the surface of ciliated bronchial host cells. This binding may alter cellular chemotaxis and reduce the migration of immune cells into the lungs of infected individuals. G protein also alters host immune response by inhibiting signaling from several toll-like receptors, including TLR4.


title: Respiratory syncytial virus

text: Surface protein F (fusion protein) is responsible for fusion of viral and host cell membranes, as well as syncytium formation between viral particles. Its sequence is highly conserved between strains. While viral attachment appears to involve both F and G proteins, F fusion occurs independently of G. F protein exists in multiple conformational forms. In the prefusion state (PreF), the protein exists in a trimeric form and contains the major antigenic site Ø. Ø serves as a primary target of neutralizing antibodies in the body. After binding to its target on the host cell surface (its exact ligand remains unclear), PreF undergoes a conformational change during which Ø is lost. This change enables the protein to insert itself into the host cell membrane and leads to fusion of the viral and host cell membranes. A final conformational shift results in a more stable and elongated form of the protein (postfusion, PostF). Opposite of the RSV G protein, the RSV F protein also binds to and activates toll-like receptor 4 (TLR4), initiating the innate immune response and signal transduction.


title: Respiratory syncytial virus

text: Following fusion of the viral and host cell membranes, the viral nucleocapsid (containing the viral genome) and the associated viral polymerase are delivered into the host cell cytoplasm. Transcription and translation both occur within the cytoplasm. RNA-dependent RNA polymerase transcribes the genome into 10 segments of messenger RNA (mRNA) which is translated into structural proteins by host cell machinery. During replication of the negative-sense viral genome, RNA-dependent RNA polymerase synthesizes a positive-sense complement called the antigenome. This complementary strand is used as a template to construct genomic negative-sense RNA, which is packaged into nucleocapsids and transported to the plasma membrane for assembly and particle budding.


title: Respiratory syncytial virus

text: RSV is highly contagious and can cause outbreaks from both community and hospital transmission. For each person infected with RSV, it is estimated that an average of 5 to 25 uninfected people will become infected. RSV can spread when an infected person coughs or sneezes, releasing contaminated droplets into the air. Transmission usually occurs when these droplets come into contact with another person's eyes, nose, or mouth. RSV can also live for up to 25 minutes on contaminated skin (i.e. hands) and several hours on other surfaces like countertops and doorknobs. It has an incubation period of 2 to 8 days. Once infected, people are usually contagious for 3 to 8 days. In infants and in people with weakened immune systems, however, the virus may continue to spread for up to 4 weeks (even after they are no longer showing symptoms).


title: Respiratory syncytial virus

text: Following transmission through the nose or eyes, RSV infects ciliated columnar epithelial cells of the upper and lower airway. RSV continues to replicate within these bronchial cells for about 8 days. After the first several days, RSV-infected cells will become more rounded and ultimately slough into the smaller bronchioles of the lower airway. This sloughing mechanism is also thought to be responsible for the spread of virus from the upper to lower respiratory tract. Infection causes generalized inflammation within the lungs, including the migration and infiltration of inflammatory cells (such as monocytes and T-cells), necrosis of the epithelial cell wall, edema, and increased mucous production. Inflammation and cell damage tends to be patchy rather than diffuse. Together, the sloughed epithelial cells, mucous plugs, and accumulated immune cells cause obstruction of the lower airway.


title: Respiratory syncytial virus

text: A variety of laboratory tests are available for the diagnosis of RSV infection. While the American Academy of Pediatrics (AAP) does not routinely recommend the use of lab testing to diagnosis RSV bronchiolitis (for which the treatment is largely supportive), confirmation of RSV infection may be warranted in high-risk groups if the result will guide clinical decisions. Common identification techniques include antigen testing, molecular testing, and viral culture.


title: Respiratory syncytial virus

text: Antigen testing involves detection of RSV antigen fragments (or pieces of molecular viral structures), usually from an nasopharyngeal swab or aspirate. This can be accomplished either by viewing fluorescently labeled antigens under a microscope (direct fluorescence assay, or DFA) or using a commercially available rapid antigen detection test (RADT). Overall, antigen testing is highly sensitive in young children (80–90%) but substantially less reliable in older children and adults, who have less viral shedding. Antigen tests are also subject to higher false positive rates outside of the peak RSV season, such as in the summer months. In these scenarios, the use of either viral culture or nucleic acid amplification testing (NAAT) may aid in an accurate RSV diagnosis.


title: Respiratory syncytial virus

text: Molecular assays, such as nucleic acid amplification tests (NAATs), enable sensitive detection of very small amounts of virus in nasopharyngeal swabs and aspirates. NAAT assays such as polymerase chain reaction (PCR) detect virus-specific genetic material, rather than viral antigens. They have a sensitivity and specificity approaching 100%. However, they tend to be more expensive and require more complex equipment than other testing methods, making them less practical in resource limited areas.


title: Respiratory syncytial virus

text: In traditional viral culture, a sample of the virus is introduced to different cell lines and allowed to replicate so it can be studied. Benefits of this technique include the ability to perform genetic characterization, strain typing, and antiviral susceptibility testing. However, it is limited by its prolonged turnaround time of 3–7 days, making it less common in patient care and more common in research settings.


title: Respiratory syncytial virus

text: Serology (the measurement of virus-specific antibodies in the serum) is not frequently used in RSV diagnosis. The time required for the body to mount a significant serologic response (and demonstrate a significant rise in antibodies that can be detected in serum) is usually not useful in guiding patient care. Up to 30% of patients with documented RSV infection will have negative serology results. As such, this method is generally reserved for research and surveillance studies.


title: Respiratory syncytial virus

text: Chest X-rays findings in children with RSV bronchiolitis are generally nonspecific and include perihilar markings, patchy hyperinflation, and atelectasis. However, the American Academy of Pediatrics (AAP) does not recommend routine imaging for children with presumed RSV bronchiolitis because it does not change clinical outcomes and is associated with increased antibiotic use. Chest X-ray is sometimes considered when the diagnosis of bronchiolitis is unclear or when there is an unexpected worsening. In adults with RSV infection, chest films are often normal or demonstrate nonspecific changes consistent with viral pneumonia, such as patchy bilateral infiltrates.


title: Respiratory syncytial virus

text: The differential diagnosis for individuals presenting with signs and symptoms of upper and lower respiratory tract infection includes other viral infections (such as rhinovirus, metapneumovirus, and influenza) and primary bacterial pneumonia. In children, inhaled foreign bodies and congenital conditions such as cystic fibrosis or asthma should also be considered.


title: Respiratory syncytial virus

text: The main prevention measure is to avoid close contact with infected individuals. In community and daycare settings, careful hand washing can help reduce transmission. In hospital settings, strict adherence to infection control measures can help prevent the spread of RSV to high-risk individuals. Alcohol-based disinfectants are recommended for hand decontamination.


title: Respiratory syncytial virus

text: Although there is no vaccine against RSV, passive immunization is available to prevent RSV infection and hospitalization in the highest risk infants. Historically, RSV-specific intravenous immunoglobin (IVIG) was used to provide passive immunity. This involved monthly administration of RSV-neutralizing antibodies (or immunoglobins) from human donors recovering from the disease. While this transfer of antibodies was reasonably effective in providing short-term immunization to at-risk infants, it was limited by both its intravenous administration and cost.


title: Respiratory syncytial virus

text: RSV-IVIG has since been replaced with the use of a monoclonal antibody (MAb) that can be delivered through muscular injection. While several monoclonal antibodies have been developed for RSV prophylaxis, the most successful of these has been palivizumab (brand name Synagis). Palivizumab is a monoclonal antibody directed against the surface fusion (F) protein of the RSV virus. It was licensed in 1998 and is effective in providing temporary prophylaxis against both RSV A and B. It is given by monthly injections, which are begun just prior to the RSV season and are usually continued for five months. Palivizumab has been shown to reduce both hospitalization rates and all-cause mortality in certain groups of high-risk children (such as those with chronic lung disease, congenital heart disease, and those born preterm). However, its cost limits its use in many parts of the world. More potent derivatives of this antibody have since been developed (including motavizumab) but were associated with considerable adverse events.


title: Respiratory syncytial virus

text: The American Academy of Pediatrics (AAP 2014) recommends RSV prophylaxis with palivizumab during RSV season for:


title: Respiratory syncytial virus

text: , there is no licensed vaccine to prevent infection by RSV. There has been tremendous interest and research in RSV vaccine discovery, given the virus's significant disease burden and the relative lack of disease-specific therapies. However, vaccine development has faced significant obstacles that have blocked its progress. Among these are infant-specific factors, such as the immature infant immune system and the presence of maternal antibodies, which make infantile immunization difficult.


title: Respiratory syncytial virus

text: Attempts to develop an RSV vaccine began in the 1960s with a formalin-inactivated vaccine that was developed for use in infants and children. While a similar method was used to create a safe and effective poliovirus vaccine, this vaccine resulted in a dangerous phenomenon that came to be known as vaccine-associated enhanced respiratory disease (VAERD). In VAERD, the vaccinated infants went on to develop significantly worse respiratory disease than non-vaccinated infants during subsequent natural infection. Some 80% of such children (vs. 5% of virus-exposed controls) were hospitalized, with two cases leading to death. This disaster led to extreme caution and hindered vaccine development for many years.


title: Respiratory syncytial virus

text: A 2019 paper claimed that research toward vaccine development had greatly advanced over the preceding 5–10 years, with more than 30 candidates in some stage of development. The same study predicted that a vaccine would be available within 10 years. The types of vaccines currently in research fall into five broad categories: live-attenuated, protein subunit, vector-based, particle-based, and messenger RNA. Each targets different immune responses, and thus may be better suited to prevent disease in different at-risk groups. Live-attenuated vaccines have shown some success in RSV-naive infants. Other vaccine candidates hope to target vulnerable populations across the lifespan, including pregnant women and the elderly.


title: Respiratory syncytial virus

text: Treatment for RSV infection is focused primarily on supportive care. This may include monitoring a patient's breathing or using suction to remove secretions from the upper airway. Supplemental oxygen may also be delivered though a nasal cannula or face mask in order to improve airflow. In severe cases of respiratory failure, intubation and mechanical ventilation may be required to support breathing. If signs of dehydration are present, fluids may also be given orally or through an IV.


title: Respiratory syncytial virus

text: Additional supportive treatments have been investigated specifically in infants hospitalized with RSV bronchiolitis. These include the following:


title: Respiratory syncytial virus

text: Bronchodilators, medications commonly used to treat asthma, are sometimes used to treat the wheezing associated with RSV infection. These medications (such as albuterol or salbutamol) are beta-agonists that relax the muscles of the airways to allow for improved airflow. However, bronchodilators have not been found to improve clinical severity of infection or rate of hospitalization among those with RSV infection. Given their limited benefit, plus their adverse event profile, they are not routinely recommended for use in RSV bronchiolitis.


title: Respiratory syncytial virus

text: Antibiotic therapy is not appropriate for treatment of RSV-related bronchiolitis or viral pneumonia. Antibiotics target bacterial pathogens, not viral pathogens such as RSV. However, antibiotics may be considered if there is clear evidence that a secondary bacterial infection has developed. Ear infections may also develop in a small number of infants with RSV bronchiolitis, in which case oral antibiotics may sometimes be used.


title: Respiratory syncytial virus

text: Worldwide, RSV is the leading cause of bronchiolitis and pneumonia in infants and children under the age of 5. The risk of serious infection is highest during the first 6 months of life. Of those infected with RSV, 2–3% will develop bronchiolitis, necessitating hospitalization. Each year, approximately 30 million acute respiratory illnesses and over 60,000 childhood deaths are caused by RSV worldwide. An estimated 87% of infants will have experienced an RSV infection by the age of 18 months, and nearly all children will have been infected by 3 years. In the United States, RSV is responsible for up to 20% of acute respiratory infection hospitalizations in children under the age of 5. However, the vast majority of RSV-related deaths occur in low-income countries that lack access to basic supportive care.


title: Respiratory syncytial virus

text: It is rare for healthy young adults to develop severe illness requiring hospitalization from RSV. However, it is now recognized as a significant cause of morbidity and mortality in certain adult populations, including the elderly and those with underlying heart or lung diseases. Its clinical impact among elderly adults is estimated to be similar to that of influenza. Each year, approximately 5–10% of nursing home residents will experience RSV infection, with significant rates of pneumonia and death. RSV is also responsible for 2–5% of adult community-acquired pneumonias.


title: Respiratory syncytial virus

text: In both adults and children, immunosuppression increases susceptibility to RSV infection. Children living with HIV are more likely to develop acute illness, and are 3.5 times more likely to require hospitalization than children without HIV. Bone marrow transplant patients prior to marrow engraftment are at particularly high risk, with RSV accounting for nearly half of the viral infections in this population. This group has also demonstrated mortality rates of up to 80% among those with RSV pneumonia. While infection may occur within the community, hospital-acquired infection is thought to account for 30–50% of cases among immunocompromised individuals.


title: Respiratory syncytial virus

text: RSV seasonality varies around the world. In temperate climates, infection rates tend to be highest during the cold winter months. This is often attributed to increased indoor crowding and increased viral stability in the lower temperatures. In tropical and arctic climates, however, the annual variation is less well defined and seems to be more prevalent during the rainy season. Annual epidemics are generally caused by the presence of several different viral strains. Subtype A and B viruses will often circulate simultaneously within a specific geographic region, although group A viruses are more prevalent.


title: Respiratory syncytial virus

text: Public health measures taken in response to the COVID-19 pandemic resulted in a significant decline in the prevalence of RSV. There was then a significant unseasonal rebound when lockdowns and other restrictive measures were relaxed. In November 2022, the RSV hospitalization rate for newborns was seven times the rate in 2018. This, combined with increasing influenza circulation caused Oregon to declare a state of emergency. The Children's Hospital Association and the American Academy of Pediatrics asked Biden to declare a state of emergency.


title: Respiratory syncytial virus

text: RSV was first discovered in 1956 when researchers isolated a virus from a population of chimpanzees with respiratory illness. They named the virus CCA ("Chimpanzee Coryza Agent"). In 1957, this same virus was identified by Robert M. Chanock in children with respiratory illness. Studies of human antibodies in infants and children revealed that the infection was common in early life. The virus was later renamed human orthopneumovirus, or human respiratory syncytial virus (hRSV).


title: Respiratory syncytial virus

text: Several other pneumoviruses exist that show great similarity to hRSV. Most notable of these is bovine RSV (bRSV), which shares approximately 80% of its genome with hRSV. It also shares hRSV's predilection for the young, causing more severe disease in calves less than 6 months old. Because bRSV-infected calves have an almost identical presentation to hRSV-infected children, this has proven to be an important animal model in RSV research.


title: Amyloidosis

text: Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing. In AL amyloidosis, specific indicators can include enlargement of the tongue and periorbital purpura. In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.


title: Amyloidosis

text: There are about 36 different types of amyloidosis, each due to a specific protein misfolding. Within these 36 proteins, 19 are grouped into localized forms, 14 are grouped as systemic forms, and 3 proteins can identify as either. These proteins can become irregular due to genetic effects, as well as through acquired environmental factors. The four most common types of systemic amyloidosis are light chain (AL), inflammation (AA), dialysis-related (AβM), and hereditary and old age (ATTR and Wild-type transthyretin amyloid).


title: Amyloidosis

text: Diagnosis may be suspected when protein is found in the urine, organ enlargement is present, or problems are found with multiple peripheral nerves and it is unclear why. Diagnosis is confirmed by tissue biopsy. Due to the variable presentation, a diagnosis can often take some time to reach.


title: Amyloidosis

text: Treatment is geared towards decreasing the amount of the involved protein. This may sometimes be achieved by determining and treating the underlying cause. AL amyloidosis occurs in about 3–13 per million people per year and AA amyloidosis in about 2 per million people per year. The usual age of onset of these two types is 55 to 60 years old. Without treatment, life expectancy is between six months and four years. In the developed world about 1 per 1,000 people die annually from systemic amyloidosis. Amyloidosis has been described since at least 1639.


title: Amyloidosis

text: The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. The kidney and heart are the most common organs involved.


title: Amyloidosis

text: Amyloid deposition in the kidney often involve the glomerular capillaries and mesangial regions, affecting the organ's ability to filter and excrete waste and retain plasma protein. This can lead to high levels of protein in the urine (proteinuria) and nephrotic syndrome. Several types of amyloidosis, including the AL and AA types, are associated with nephrotic syndrome. Approximately 20% and 40-60% of people with AL and AA amyloidosis respectively progress to end-stage kidney disease requiring dialysis.


title: Amyloidosis

text: Amyloid deposition in the heart can cause both diastolic and systolic heart failure. EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction. On echocardiography, the heart shows a restrictive filling pattern, with normal to mildly reduced systolic function. AA amyloidosis usually spares the heart. Cardiac amyloidosis can present with symptoms of heart failure including shortness of breath, fatigue, and edema. As cardiac amyloidosis progresses, the amyloid deposition can affect the heart's ability to pump and fill blood as well as its ability to maintain normal rhythm, which leads to worsening heart function and decline in people's quality of life.


title: Amyloidosis

text: People with amyloidosis do not get central nervous system involvement but can develop sensory and autonomic neuropathies. Sensory neuropathy develops in a symmetrical pattern and progresses in a distal to proximal manner. Autonomic neuropathy can present as orthostatic hypotension but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety.


title: Amyloidosis

text: Neuropathic presentation can depend on the etiology of amyloidosis. People with amyloidosis may experience dysfunction in various organ systems depending on the location and extent of nervous system involvement. For example, peripheral neuropathy can cause erectile dysfunction, incontinence and constipation, pupillary dysfunction, and sensory loss depending on the distribution of amyloidosis along different peripheral nerves. Amyloidosis of the central nervous system can have more severe and systemic presentations that may include life-threatening arrhythmias, cardiac failure, malnutrition, infection, or death.


title: Amyloidosis

text: Accumulation of amyloid proteins in the gastrointestinal system may be caused by a wide range of amyloid disorders and have different presentations depending on the degree of organ involvement. Potential symptoms include weight loss, diarrhea, abdominal pain, heartburn (gastrointestinal reflux), and GI bleeding. Amyloidosis may also affect accessory digestive organs including the liver, and may present with jaundice, fatty stool, anorexia, fluid buildup in the abdomen, and spleen enlargement.


title: Amyloidosis

text: Accumulation of amyloid proteins in the liver can lead to elevations in serum aminotransferases and alkaline phosphatase, two biomarkers of liver injury, which is seen in about one third of people. Liver enlargement is common. In contrast, spleen enlargement is rare, occurring in 5% of people. Splenic dysfunction, leading to the presence of Howell-Jolly bodies on blood smear, occurs in 24% of people with amyloidosis. Malabsorption is seen in 8.5% of AL amyloidosis and 2.4% of AA amyloidosis. One suggested mechanism for the observed malabsorption is that amyloid deposits in the tips of intestinal villi (fingerlike projections that increase the intestinal area available for absorption of food), begin to erode the functionality of the villi, presenting a sprue-like picture.


title: Amyloidosis

text: Both the thyroid and adrenal glands can be infiltrated. It is estimated that 10–20% of people with amyloidosis have hypothyroidism. Adrenal infiltration may be harder to appreciate given that its symptoms of orthostatic hypotension and low blood sodium concentration may be attributed to autonomic neuropathy and heart failure.


title: Amyloidosis

text: "Amyloid deposits occur in the pancreas of people who also have diabetes mellitus, although it is not known if this is functionally important. The major component of pancreatic amyloid is a 37-amino acid residue peptide known as islet amyloid polypeptide or 'amylin.' This is stored with insulin in secretory granules in [beta] cells and is co secreted with insulin." (Rang and Dale's Pharmacology, 2015.)


title: Amyloidosis

text: Amyloid proteins deposit most commonly inside the knee, followed by hands, wrists, elbow, hip, and ankle, causing joint pain. In males with advanced age (>80 years), there is significant risk of wild-type transthyretin amyloid deposition in synovial tissue of knee joint, but predominantly in old age deposition of wild type transthyretin is seen in cardiac ventricles. ATTR deposits have been found in ligamentum flavum of patients that underwent surgery for lumbar spinal stenosis.


title: Amyloidosis

text: In beta 2-microglobulin amyloidosis, males have high risk of getting carpal tunnel syndrome. Aβ2MG amyloidosis (Hemodialysis associated amyloidosis) tends to deposit in synovial tissue, causing chronic inflammation of the synovial tissue in knee, hip, shoulder and interphalangeal joints. Amyloid light chains deposition in shoulder joint causes enlarged shoulders, also known as "shoulder pad sign". Amyloid light chain depositions can also cause bilateral symmetric polyarthritis.


title: Amyloidosis

text: The deposition of amyloid proteins in the bone marrow without causing plasma cell dyscrasias is called amyloidoma. It is commonly found in cervical, lumbar, and sacral vertebrae. Those affected may be presented with bone pain due to bone lysis, lumbar paraparesis, and a variety of neurological symptoms. Vertebral fractures are also common.


title: Amyloidosis

text: A rare development is amyloid purpura, a susceptibility to bleeding with bruising around the eyes, termed "raccoon-eyes". Amyloid purpura is caused by amyloid deposition in the blood vessels and reduced activity of thrombin and factor X, two clotting proteins that lose their function after binding with amyloid.


title: Amyloidosis

text: Amyloid deposits in tissue can cause enlargement of structures. Twenty percent of people with AL amyloidosis have an enlarged tongue, that can lead to obstructive sleep apnea, difficulty swallowing, and altered taste. Tongue enlargement does not occur in ATTR or AA amyloidosis. Deposition of amyloid in the throat can cause hoarseness.


title: Amyloidosis

text: Amyloidoses can be considered protein misfolding diseases. The vast majority of proteins that have been found to form amyloid deposits are secreted proteins, so the misfolding and formation of amyloid occurs outside cells, in the extracellular space. Of the 37 proteins so far identified as being vulnerable to amyloid formation, only four are cytosolic. Most amyloid-forming proteins are relatively small, but otherwise there is currently no evidence of structural or functional similarities among proteins known to form disease-associated amyloids. One third of amyloid disease is hereditary, in which case there is normally an early age of onset. Half of amyloid-related diseases are sporadic and have a late age of onset – in these cases, the protein aggregation may be associated with aging-related decline in protein regulation. Rarely, some medical treatments are associated with amyloid disease.


title: Amyloidosis

text: Amyloid-forming proteins aggregate into distinctive fibrillar forms with a beta-sheet structure. The beta-sheet form of amyloid is proteolysis-resistant, meaning it can not be degraded or broken down. As a result, amyloid deposits into the body's extracellular space. The process of forming amyloid fibrils is thought to have intermediate oligomeric forms. Both the oligomers and amyloid fibrils can be toxic to cells and can interfere with proper organ function. The relative significance of different aggregation species may depend on the protein involved and the organ system affected.


title: Amyloidosis

text: Diagnosis of amyloidosis generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy. Also, thioflavin T stain may be used. A number of imaging techniques such as a DPD scan or SAP scan are also in use.


title: Amyloidosis

text: A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is subcutaneous abdominal fat, known as a "fat pad biopsy", due to its ease of acquisition. An abdominal fat biopsy is not completely sensitive and may result in false negatives, which means a negative result does not exclude the diagnosis of amyloidosis. However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can also be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people.


title: Amyloidosis

text: In the amyloid deposition of the joints, there will be a decreased signal in both T1 and T2 weighted MRI images. In amyloidoma, there will be low T1 signal with gadolinium injection and low T2 signal.


title: Amyloidosis

text: The type of the amyloid protein can be determined in various ways: the detection of abnormal proteins in the bloodstream (on protein electrophoresis or light chain determination); binding of particular antibodies to the amyloid found in the tissue (immunohistochemistry); or extraction of the protein and identification of its individual amino acids. Immunohistochemistry can identify AA amyloidosis the majority of the time, but can miss many cases of AL amyloidosis. Laser microdissection with mass spectrometry is the most reliable method of identifying the different forms of amyloidosis.


title: Amyloidosis

text: AL was previously considered the most common form of amyloidosis, and a diagnosis often begins with a search for plasma cell dyscrasia, memory B cells producing aberrant immunoglobulins or portions of immunoglobulins. Immunofixation electrophoresis of urine or serum is positive in 90% of people with AL amyloidosis. Immunofixation electrophoresis is more sensitive than regular electrophoresis but may not be available in all centers. Alternatively immunohistochemical staining of a bone marrow biopsy looking for dominant plasma cells can be sought in people with a high clinical suspicion for AL amyloidosis but negative electrophoresis.


title: Amyloidosis

text: ATTR is now considered to be the most common form of amyloidosis, and no longer considered as a rare disease. It may be either age related in wild-type ATTR (ATTRv) or familial transthyretin-associated amyloidosis, is suspected in people with family history of idiopathic neuropathies or heart failure who lack evidence of plasma cell dyscrasias. ATTR can be identified using isoelectric focusing which separates mutated forms of transthyretin. Findings can be corroborated by genetic testing to look for specific known mutations in transthyretin that predispose to amyloidosis.


title: Amyloidosis

text: AA is suspected on clinical grounds in individuals with longstanding infections or inflammatory diseases. AA can be identified by immunohistochemistry staining.


title: Amyloidosis

text: Historical classification systems were based on clinical factors. Until the early 1970s, the idea of a single amyloid substance predominated. Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. Most classification systems included primary (i.e., idiopathic) amyloidosis, in which no associated clinical condition was identified, and secondary amyloidosis (i.e., secondary to chronic inflammatory conditions). Some classification systems included myeloma-associated, familial, and localized amyloidosis.


title: Amyloidosis

text: The modern era of amyloidosis classification began in the late 1960s with the development of methods to make amyloid fibrils soluble. These methods permitted scientists to study the chemical properties of amyloids. Descriptive terms such as primary amyloidosis, secondary amyloidosis, and others (e.g., senile amyloidosis), which are not based on cause, provide little useful information and are no longer recommended.


title: Amyloidosis

text: The modern classification of amyloid disease tends to use an abbreviation of the protein that makes the majority of deposits, prefixed with the letter A. For example, amyloidosis caused by transthyretin is termed "ATTR". Deposition patterns vary between people but are almost always composed of just one amyloidogenic protein. Deposition can be systemic (affecting many different organ systems) or organ-specific. Many amyloidoses are inherited, due to mutations in the precursor protein.


title: Amyloidosis

text: Other forms are due to different diseases causing overabundant or abnormal protein production – such as with overproduction of immunoglobulin light chains (termed AL amyloidosis), or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA amyloidosis).


title: Amyloidosis

text: About 60 amyloid proteins have been identified so far. Of those, at least 36 have been associated with a human disease.


title: Amyloidosis

text: All amyloid fibril proteins start with the letter "A" followed by the protein suffix (and any applicable specification). See below for a list of amyloid fibril proteins which have been found in humans:


title: Amyloidosis

text: Additionally, based on the tissues in which it is deposited, it is divided into mesenchymal (organs derived from mesoderm) or parenchymal (organs derived from ectoderm or endoderm).


title: Amyloidosis

text: Treatment depends on the type of amyloidosis that is present. Treatment with high dose melphalan, a chemotherapy agent, followed by stem cell transplantation has shown promise in early studies and is recommended for stage I and II AL amyloidosis. However, only 20–25% of people are eligible for stem cell transplant. Chemotherapy treatment including cyclophosphamide-bortezomib-dexamethasone is currently the recommended treatment option for people with AL Amyloidosis not eligible for transplant.


title: Amyloidosis

text: In AA, symptoms may improve if the underlying condition is treated. In people who have inflammation caused by AA amyloidosis, tumour necrosis factor (TNF)-alpha inhibitors such as infliximab and etanercept are used for an average duration of 20 months. If TNF-alpha inhibitors are not effective, Interleukin-1 inhibitors (e.g. anakinra, canakinumab, rilonacept) and interleukin-6 inhibitors (e.g. tocilizumab) may be considered.


title: Amyloidosis

text: Management of ATTR amyloidosis will depend on its classification as wild type or variant. Both may be treated with tafamidis, a low toxicity oral agent that prevents destabilization of correctly folded protein. Studies showed tafamidis reduced mortality and hospitalization due to heart failure. Previously, for variant ATTR amyloidosis, liver transplant was the only effective treatment. New therapies include diflunisal, inotersen, and patisiran.


title: Amyloidosis

text: Diflunisal binds to misfolded mutant TTR protein to prevent its buildup, like how tafamidis works. Low-certainty evidence indicates that it mitigates worsening of peripheral neuropathy and disability from disease progression.


title: Amyloidosis

text: Inotersen blocks gene expression of both wild-type and mutant TTR, reducing amyloid precursor. Moderate-certainty evidence suggests that it mitigates worsening of peripheral neuropathy. Long-term efficacy and safety of inotersen use in people with mutant TTR-related amyloidosis is still be evaluated in a phase-III clinical trial as of 2021. Both diflunisal and inotersen may also mitigate declines in quality-of-life, though the evidence for this effect is unclear. For people with cardiac ATTR the effect of inotersen use is inconclusive and requires further investigation. In 2018, inotersen was approved by the European Medicines Agency to treat polyneuropathy in adults with hereditary transthyretin amyloidosis. It has since been approved for use in Canada, the European Union and in the USA.


title: Amyloidosis

text: Patisiran functions similarly to inotersen. Moderate-certainty evidence suggests that patisiran mitigates worsening of peripheral neuropathy and disability from disease progression. Additionally, low-certainty evidence suggests that patisiran mitigates decreases in quality-of-life and slightly reduces the rate of adverse events versus placebo. There is no evidence of an effect on mortality rate. A review of early data from use of patisiran in people with variant cardiac ATTR suggests that it may reduce mortality and hospitalization, however this is still being investigated and requires further investigation. In 2018, patisiran was not recommended by NICE in the UK for hereditary transthyretin-related amyloidosis. As of July 2019 further review however is occurring. It was approved for this use in the United States, however.


title: Amyloidosis

text: In 2021, in a clinical trial using the CRISPR gene-editing technique, several participants had an "80% to 96% drop in TTR levels, on par or better than the average of 81%" who were given patisiran.


title: Amyloidosis

text: Vutrisiran was approved by the U.S. Food and Drug Administration (FDA) in June 2022, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.