title: Estimator

text: Among unbiased estimators, there often exists one with the lowest variance, called the minimum variance unbiased estimator (MVUE). In some cases an unbiased efficient estimator exists, which, in addition to having the lowest variance among unbiased estimators, satisfies the Cramér–Rao bound, which is an absolute lower bound on variance for statistics of a variable.


title: Estimator

text: Concerning such "best unbiased estimators", see also Cramér–Rao bound, Gauss–Markov theorem, Lehmann–Scheffé theorem, Rao–Blackwell theorem.


title: Aperture Desk Job

text: Aperture Desk Job is an action game developed and published by Valve for Windows and Linux. A spin-off of the "Portal" series, it was released concurrently with the Steam Deck as a tech demo showcasing the Steam Deck's controller functions.


title: Aperture Desk Job

text: The gameplay consists of product inspection aided by Grady, an artificial intelligence "core" much like many others seen in the "Portal" franchise. The game serves as a tech demo for the Steam Deck, with most of the game taking place in front of a desk that acts as an in-world representation of the console. A few different scenarios are used to test different functions of the controls, such as a shooting segment making use of gyroscopic control, or a situation where the player must write their name making use of the Steam Deck's touchscreen. The game could also be played on standard computer hardware with the use of a game controller.


title: Aperture Desk Job

text: The player, whose name is up to them to decide, starts work at Aperture as a product tester at a desk that from that point on they seem incapable of leaving. A core named Grady (Nate Bargatze) arrives and tasks the player with testing toilets. A defective toilet destroys a transport pipe filled with ammunition, filling the cistern with bullets which the toilet the fires off. Inspired, Grady decides to try and pitch a new idea to the heads of Aperture.


title: Aperture Desk Job

text: Six months later, Grady introduces a turret cobbled together from weapon parts and the shell of a toilet. He urges the player to test it out and the player ends up destroying the warehouse. Grady leaves the player to take the fall while he attempts to improve the design of the turret. Eighteen months later the player is released from Aperture prison, and Grady has become a parole officer in order to monitor them. Grady enthusiastically urges them back to work to test his new and improved turret on appliances stolen from the Housewares Department. He claims that he has organised a meeting with CEO Cave Johnson (J. K. Simmons), and as they journey to Johnson's office on the 80th floor Grady fantasizes about spending the money they are going to make on paying back the loan sharks he used to fund the turret's development. They are suddenly attacked by appliances modelled into (far superior) turrets by Housewares engineers. The player battles through an onslaught of appliance turrets, before using the desk's inbuilt rocket propulsion system to speed them to the top floor.


title: Aperture Desk Job

text: Upon reaching Johnson's office, Grady reveals that he lied about organising the meeting and that he suspects Johnson is a recluse, given that no-one has seen him in years. Upon entering his office, it's revealed that Johnson no longer exists as a physical being—he was stricken with a terrible disease years prior and had his consciousness uploaded into a supercomputer designed to look like a giant statue of his head. Having lived this way for years, he begs the player to kill him; the player and Grady oblige by using the turret to at first try to destroy the head's clay shell before eventually shutting off the power supply. At first this seems to work, only for the backup power to turn Johnson back on, prompting him to fire the two. However, the weight of his head and damage caused by the player causes him to fall through the floor all the way to the bottom of the building.


title: Aperture Desk Job

text: Months later, Grady and the player have entered into a witness protection program having informed on Grady's loan sharks, and now go by "Gary" and "Charlie". The two of them still 'work' in the damaged Aperture building, with the player 'testing' toilets that simply fall off the conveyor belt into a hole in the floor caused by Johnson's falling head. The head, along with several other toilet turrets, are briefly given power by an advanced device created by a colony of praying mantises that infest the building, and they perform a choir song over the credits together.


title: Aperture Desk Job

text: "Aperture Desk Job" was developed by Valve on the Source 2 engine as a tech demo for the Steam Deck. It was released for free on March 1, 2022. Mike Morasky composed the soundtrack for the game.


title: Hiranyagarbha

text: Hiraṇyagarbha (Sanskrit: हिरण्यगर्भः ; literally the 'golden womb', poetically translated as 'universal womb') is the source of the creation of universe or the manifested cosmos in Vedic philosophy. It finds mention in one hymn of the Rigveda (RV 10.121), known as the Hiraṇyagarbha Sūkta, suggesting a single creator deity (verse 8: "", Griffith: "He is the God of gods, and none beside him."), identified in the hymn as Prajāpati. The concept of the "golden womb" is first mentioned in the Vishvakarma Sūkta (RV 10.82.5,6) which picturized the "primeval womb" as being rested set upon the navel of Vishvakarman. This imagery was later transferred to Vishnu and Surya.


title: Hiranyagarbha

text: The Upanishad calls it the Soul of the Universe or Brahman, and elaborates that Hiraṇyagarbha floated around in emptiness and the darkness of the non-existence for about a year, and then broke into two halves which formed the "Svarga" and the "Pṛthvi".


title: Hiranyagarbha

text: In Modern science its often compared with principle of big bang theory, where its considered that world is emerged from a single point.


title: Hiranyagarbha

text: In classical Purāṇic Hinduism, Hiraṇyagarbha is the term used in the Vedanta for the "creator". Hiraṇyagarbha is also Brahmā, so called because it is said he was born in a golden egg ("Manu Smṛti" 1.9), while the "Mahābhārata" calls it the Manifest.


title: Hiranyagarbha

text: Some classical yoga traditions consider a person named Hiraṇyagarbha as the originator of yoga, though this may also be a name for Rishi Kapila.


title: Hiranyagarbha

text: The Matsya Purāṇa (2.25–30) gives an account of initial creation. After Mahāprālaya, the great dissolution of the Universe, there was darkness everywhere. Everything was in a state of sleep. There was nothing, either moving or static. Then Svayambhu, self-manifested being arose, which is a form beyond senses. It created the primordial waters first and established the seed of creation into it. The seed turned into a golden womb, Hiraṇyagarbha. Then Svayambhu entered into that egg.


title: Hiranyagarbha

text: The Nārāyaṇa Sūkta exclaims that everything that is, visible or invisible, all this is pervaded by Nārāyaṇa within and without.


title: Hiranyagarbha

text: The Īśvara Upaniṣad says that the universe is pervaded by Īśvara (God), who is both within and without it. He is the moving and the unmoving, He is far and near, He is within all these and without all these.


title: Hiranyagarbha

text: The Vedānta Sūtra further states that Brahman is That from Whom this Universe proceeds, in Whom it subsists, and to Whom, in the end, it returns.


title: Hiranyagarbha

text: The Saṃkhya school holds that there are only two primary principles, Puruṣa and Prākṛti, and creation is only a manifestation or evolution of the constituents of Prākṛti due to the action of Puruṣa's Consciousness.


title: Hiranyagarbha

text: The Bhagavata states that Nārāyaṇa alone was in the beginning, who was the pious of principles of creation, sustenance, and dissolution (also known as the Hindu Trinity of Brahmā, Viṣṇu and Shiva) - the Supreme Hari, multi-headed, multi-eyed, multi-footed, multi-armed, multi-limbed. This was the Supreme Seed of all creation, subtler than the subtlest, greater than the greatest, larger than the largest, and more magnificent than even the best of all things, more powerful, than even the wind and all the gods, more resplendent than the Sun and the Moon, and more internal than even the mind and the intellect. He is the Creator, the Supreme. The term can also mean as He who, having become first the Creator, has come to be considered as the womb of all objects.


title: Hiranyagarbha

text: The Hiraṇyagarbha Sūkta of the Rigveda declares that God manifested Himself in the beginning as the Creator of the Universe, encompassing all things, including everything within Himself, the collective totality, as it were, of the whole of creation, animating it as the Supreme Intelligence.


title: Shannen Doherty filmography

text: American actress Shannen Doherty has appeared in numerous television programs and motion pictures. After her television debut in "Father Murphy" in 1981, she landed her first major role in the dramatic western television series "Little House on the Prairie" (1982–1983), and reprised her role in its three television specials. Doherty received two Young Artist Award nominations for playing the oldest Witherspoon sibling Kris in the family drama "Our House" (1986–1988). She appeared in four films during the 1980s, including the positively-received, animated film "The Secret of NIMH" (1982) and the cult classic "Heathers" (1988). Her breakthrough role was as Brenda Walsh in the teen drama "Beverly Hills, 90210" (1990–1994), but she was later dropped from the series because of backstage issues and her negative image as a "bad girl". She starred in television films in the early and mid-1990s, and played Rene Mosier in the romantic comedy "Mallrats" (1995) in an attempt to rebuild her career.


title: Shannen Doherty filmography

text: Doherty enjoyed a resurgence in popularity after being cast by producer Aaron Spelling to play Prue Halliwell on the supernatural drama "Charmed" (1998–2001). The series was their second collaboration following "Beverly Hills, 90210". The character was praised by critics and fans, earning a spot as one of the best witches in television history according to a "TVLine" article, and Doherty took an active role in the show's production, directing three of its episodes. Following disagreements with Spelling and co-star Alyssa Milano, Doherty left the series in its third season. Doherty starred in a string of television films and had a recurring role on the prime-time soap opera "North Shore" (2004–2005). The following year, she was cast as Denise Johnson in the unaired pilot of the sitcom "Love, Inc.", but was dropped from the show by producers from United Paramount Network (UPN). She reprised her role as Brenda Walsh in the reboot of "90210" (2008–2009), appearing as a special guest star in seven episodes in its first season.


title: Shannen Doherty filmography

text: While acting in scripted material, Doherty also participated in five reality television shows, none of which had much success, except "Shannen Says" (2012), in which she received positive reviews. In 2010, Doherty competed in the tenth season of "Dancing with the Stars" to honor her father who had a stroke in December 2009. Later that year, she also voiced the identical twins Mari and Kari on the animated web series "Mari-Kari", and starred in the independent satirical thriller "Burning Palms" after a nine-year absence from film. In 2012 and 2014, she directed two music videos for the band Radical Something. She starred alongside Alec Baldwin, Danny Glover, and Michael Madsen in the 2016 sports drama film "Back in the Day". In 2018, she appeared in a television series based on "Heathers" and the television movie "No One Would Tell", a remake of the 1996 film of the same name. The following year, she portrayed a heightened version of herself for "BH90210", and guest-starred on "Riverdale" as part of a Luke Perry tribute. Doherty appeared in two action films "Fortress" (2021) and "Hot Seat" (2022), as well as two television films, "Dying to Belong" and "List of a Lifetime", in 2021


title: Bonner Fellers

text: Brigadier General Bonner Frank Fellers (February 7, 1896 – October 7, 1973) was a United States Army officer who served during World War II as a military attaché and director of psychological warfare. He is notable as the military attaché in Egypt whose extensive transmissions of detailed British tactical information were unknowingly intercepted by Axis agents and passed to Nazi German "Generalfeldmarschall" Erwin Rommel for over six months, which contributed to disastrous British defeats at Gazala and Tobruk in June 1942.


title: Bonner Fellers

text: Fellers entered the United States Military Academy at West Point, New York in June 1916, ten months before the American entry into World War I. The increased need for junior officers during World War I caused Fellers's class to be accelerated and to graduate on November 1, 1918, ten days before the armistice with the German "Reich" which ended the war. Upon his graduation, Fellers was commissioned as a second lieutenant in the United States Army Coast Artillery Corps.


title: Bonner Fellers

text: Fellers was promoted to first lieutenant in October 1919 and graduated from the Coast Artillery School Basic Course in 1920. The drastic reduction in the size of the army after the war created limited opportunities for promotion and so Fellers was not promoted to captain until December 3, 1934. In 1935, he graduated from the Command and General Staff School and the Chemical Warfare Service Field Officers Course, when he completed his soon-to-be-influential thesis "The Psychology of the Japanese Soldier."


title: Bonner Fellers

text: Fellers served three tours of duty in the Philippines in the 1920s and the 1930s, including assignment to the Office of the Military Advisor to the Commonwealth Government of the Philippines, under General Douglas MacArthur; while there, Captain Fellers interacted with Major (later Lieutenant Colonel) Dwight D. Eisenhower, a senior member of MacArthur's staff. His assignments included helping to open the Philippine Military Academy, the Philippines' "West Point," and liaisoning with Philippine President Manuel Quezon. The Philippines awarded him its Distinguished Service Star for his contributions to its defenses.


title: Bonner Fellers

text: Fellers graduated from the Army War College in 1939 and was promoted to major on July 1, 1940. He was promoted to lieutenant colonel in the war-footing Army of the United States (as compared to his rank of major in the Regular Army) on September 15, 1941, and to colonel the following month.


title: Bonner Fellers

text: In October 1940, Major Fellers was assigned as military attaché to the US embassy in Egypt. He was assigned the duty of monitoring and reporting on British military operations in the Mediterranean and Middle East Theatre. The British granted Fellers access to their activities and information. He dutifully reported everything he learned to his superiors in the United States. His reports were read by President Franklin Roosevelt, the head of American intelligence, and the Joint Chiefs of Staff.


title: Bonner Fellers

text: Fellers was concerned about the security of the "Black Code" of the US State Department, used when he sent his reports by radiogram. His concerns were overridden. Fellers was right to be concerned, as the details of the code had been stolen from the US embassy in Italy in September 1941 in a covert night raid into the embassy by Italian spies from the Servizio Informazioni Militare (SIM), the Italian military intelligence service. This enabled the Italians to read the reports, and within eight hours, the most secret data on British "strengths, positions, losses, reinforcements, supply, situation, plans, morale etc" would be in the hands of the German and the Italian militaries.


title: Bonner Fellers

text: Around the same time, the Black Code was also broken by Nazi Germany's cryptanalysts. The Germans could identify Fellers's report, starting just before the US entered into WWII through to June 29, 1942, when Fellers switched to a newly adopted US code system.


title: Bonner Fellers

text: Fellers's deciphered radiograms provided the Axis with detailed, extensive, and timely information about troop movements and equipment. Information from his messages alerted the Axis to British convoy operations in the Battle of the Mediterranean, including efforts to resupply the garrison of Malta. In January 1942 information about numbers and the condition of British forces was provided to "Generalleutnant" Erwin Rommel ("Generalfeldmarschall" from May onwards), the German commander in Africa, who could thus plan his operations with reliable knowledge of what the opposing forces were. The Germans referred to Fellers as "die gute Quelle" ("the good source"). Rommel referred to him as "the little fellow."


title: Bonner Fellers

text: The deciphered code cost the Allies many lives. For example, in June 1942, the British attempted to resupply Malta, which was under constant air attack and was being starved. The British determined to sail two supply convoys simultaneously in the hopes that if one were to become discovered, attacks upon it would distract the Axis from the other. Codenamed Operation Vigorous and Harpoon and sailing from Alexandria in the east and Gibraltar in the west, respectively, their sailing was timed with an effort by special forces teams to neutralize Axis ships and aircraft. Fellers efficiently reported all of that in his cable, No. 11119 dated June 11, which was intercepted in both Rome and by the German Military High Command Cipher Branch ("OKW Chiffrierabteilung"). It read, in part:


title: Bonner Fellers

text: NIGHTS OF JUNE 12TH JUNE 13TH BRITISH SABOTAGE UNITS PLAN SIMULTANEOUS STICKER BOMB ATTACKS AGAINST AIRCRAFT ON 9 AXIS AIRDROMES. PLANS TO REACH OBJECTIVES BY PARACHUTES AND LONG RANGE DESERT PATROL.


title: Bonner Fellers

text: British and Free French raiders went into action behind the lines in Libya and on the island of Crete. In most of the attacks, the raiders were met with accurate fire from the alerted garrisons and suffered heavy losses, but failed to inflict any damage upon the Luftwaffe. Their only success came when Fellers's unwitting early warnings were not received or were ignored or ineptly handled. Meanwhile, both convoys were located and came under attack. A day after leaving Gibraltar, Convoy Harpoon's six merchant ships and their escorts came under continuous air and surface attack. Only two of the merchant ships survived to reach Malta. Convoy Vigorous was the larger effort. Made up of 11 merchant ships, it suffered such serious losses that it was forced to turn back to Egypt.


title: Bonner Fellers

text: Debates continue on how the breaking of the code Fellers was assigned had impacted the overall battle for North Africa. For example, John Ferris argues that because Fellers sometimes reported imperfect information and assessments, the leaks also contributed to Rommel's ultimate defeat: "In its last days of life, after Tobruk fell, the 'Good Source' bolstered Rommel's decision to drive all-out on Alexandria, his native over-optimism reinforced by Bonner Fellers' belief that the British would crack under one last blow. Both men were wrong; this time the intelligence failure led to German defeat." Other authors, like Robin Lewin, write that breaking Fellers's code was "immensely fruitfull", though at tactical level Lewin also pointed to Rommel's Wireless Interception Center for the Axis successes on the ground in the summer of 1942, at least until this unit lost its commander and several operatives in action at Tel El Eisa on 10 July 1942.


title: Bonner Fellers

text: Ultra intercepts seen only by the British indicated the Germans were gaining information from a source in Egypt, and British intelligence had considered Fellers as a possible source. On June 10, 1942, the British became convinced Fellers's reports were compromised because an intercept had compared British tactics negatively to American tactics. The British informed the Americans on June 12, who, on June 14, confirmed the finding that Fellers's reports were the source. Fellers switched codes on June 29, which ended the leaks.


title: Bonner Fellers

text: Fellers was not found at fault for the interception of his reports, but he was transferred from Egypt on 7 July 1942. His successor as attaché used the US military cipher, which the Germans could not read. Upon returning to the United States, Fellers was decorated with the Distinguished Service Medal for his analysis and reporting of the North African situation. He was also promoted to brigadier general, the first in the West Point Class of 1918, on December 4, 1942.


title: Bonner Fellers

text: While assigned to the Office of Strategic Services (OSS) in Washington, he was, as recalled by a colleague, "the most violent anglophobe I have encountered." However, that comment may be colored by the context of the American-British intelligence situation of the time. Fellers' North African reports, which his Distinguished Service Medal citation characterized as "models of clarity and accuracy," were bluntly critical of British weapons, operations, and leadership: "The Eighth Army has failed to maintain the morale of its troops; its tactical conceptions were always wrong, it neglected completely cooperation between the various arms; its reactions to the lightning changes in the battlefield were always slow." Such assessments, meant for American officials, were deciphered by the Germans, then intercepted from the Germans by the British Ultra signals intelligence.


title: Bonner Fellers

text: Despite his anti-British attitude, Fellers and his reports influenced decisions to bring American supplies and troops to aid the British in North Africa. Throughout his tenure in North Africa, Fellers advocated for increased American support for the British in North Africa, which included both weapons and a commitment of American troops. This was at odds with the Joint Chiefs of Staff and the U.S. European Command as to the level of weapons support and an American troop landing. The military policy then was that saving the British in North Africa was not strategically required, especially not through a North Africa invasion (Operation Torch), which would divert focus from Operation Bolero, a plan for an early European invasion.


title: Bonner Fellers

text: President Roosevelt admired Fellers' reports and was influenced by them enough so that on June 29, General George C. Marshall wrote to Roosevelt, "Fellers is a very valuable observer but his responsibilities are not those of a strategist and his views are in opposition to mine and those of the entire Operations Division." The President invited Fellers to the White House upon his return from Cairo, and they met on July 30, 1942. "Consistent with his previous reporting through 1942, Fellers argued for robust and expeditious reinforcement of British forces in the Middle East." Thus, Fellers' blunt criticism and his analysis of the Middle East's strategic importance may well have influenced Roosevelt's decisions to reinforce the Eighth Army and to support Operation Torch.


title: Bonner Fellers

text: In the summer of 1943, Fellers left his job in the OSS, where he had played a role in planning psychological warfare, and he returned to the Southwest Pacific and resumed working under General Douglas MacArthur, who was then Commander of United States Army Forces in the Far East. Fellers served as military secretary and the Chief of Psychological Operations under MacArthur.


title: Bonner Fellers

text: During the liberation of the Philippines from the Japanese, Fellers had several assignments, including Director of Civil Affairs for the Philippines. For his efforts, Fellers received a second Philippine Distinguished Service Star.


title: Bonner Fellers

text: General Dwight D. Eisenhower had been at odds with Fellers since they served together in the 1930s under General MacArthur in the Philippines. In a recollection in her personal diary, the Countess of Ranfurly wrote of a comment made by Eisenhower when she expressed admiration for Fellers. Eisenhower reportedly replied, "Any friend of Bonner Fellers is no friend of mine!" Eisenhower apologized the next day for his rudeness. Eisenhower may have developed such a view because he was aware of the North Africa leaks that had strained British relations and because Fellers had been instrumental in getting presidential approval of increased support for the British in North Africa including Operation Torch, which was not supported by the U.S. military command, including Eisenhower.


title: Bonner Fellers

text: After the war, Fellers stayed on the staff of MacArthur, who was Supreme Commander for the Allied Powers in the occupation of Japan. Among his duties was liaison between HQ and the Imperial Household. Soon after occupation began, Fellers wrote several influential memoranda concerning why it would be advantageous for the occupation, reconstruction of Japan, and long-term US interests to keep Emperor Hirohito in place if he was not clearly responsible for war crimes.


title: Bonner Fellers

text: Fellers met with the major defendants of the Tokyo tribunal. Under an assignment with the codename "Operation Blacklist", Fellers allowed them to co-ordinate their stories to exonerate Hirohito and all members of his family of war crimes. This was done at the behest of MacArthur, who had decided that there was to be no criminal prosecution of the Emperor or his family.


title: Bonner Fellers

text: General Fellers, who came from a Religious Society of Friends family (commonly known as Quakers) and attended the Quaker-affiliated Earlham College, was instrumental in the selection of Elizabeth Vining, an American Quaker educator, as tutor to the Emperor's children.


title: Bonner Fellers

text: In 1971, Hirohito conferred on Fellers the Second Order of the Sacred Treasure "in recognition of your long-standing contribution to promoting friendship between Japan and the United States."


title: Bonner Fellers

text: Fellers' role in exonerating Hirohito is the main subject of the 2012 film "Emperor". Fellers was also featured as a protagonist in the 2022 alternative history novel "Atomic Sunrise" by R.M. Christianson.


title: Bonner Fellers

text: Fellers was also familiar with the writings of Lafcadio Hearn and became a friend of Hearn's descendants in Japan, the Koizumi family.


title: Bonner Fellers

text: In October 1946, Fellers reverted to the rank of colonel as part of a reduction in rank of 212 generals. He retired from the army on November 30, 1946. In 1948, his retirement rank was reinstated as brigadier general.


title: Bonner Fellers

text: After retiring from the Army, he worked for the Republican National Committee in Washington, D.C.. In 1952 Fellers was actively involved in promoting Robert A. Taft as a presidential candidate. Fellers was a member of the John Birch Society, which is named after a military intelligence officer, who was considered by its founding members to be the first casualty of the Cold War. In 1953 Fellers, wrote a book: "Wings for Peace: A Primer for a New Defense" (Chicago: Henry Regnery Co., 1953). In 1964, Fellers was actively involved in promoting Barry Goldwater for the presidency.


title: Chemical oxygen generator

text: A chemical oxygen generator is a device that releases oxygen via a chemical reaction. The oxygen source is usually an inorganic superoxide, chlorate, or perchlorate; ozonides are a promising group of oxygen sources. The generators are usually ignited by a firing pin, and the chemical reaction is usually exothermic, making the generator a potential fire hazard. Potassium superoxide was used as an oxygen source on early crewed missions of the Soviet space program, in submarines for use in emergency situations, for firefighters, and for mine rescue.


title: Chemical oxygen generator

text: Commercial aircraft provide emergency oxygen to passengers to protect them in case of loss of cabin pressure. Chemical oxygen generators are not used for the cockpit crew, who are typically supplied using compressed oxygen canisters, also known as oxygen bottles. In narrow body airliners, for each row of seats there were overhead oxygen masks and oxygen generators. In some wide-body airliners, such as the DC-10 and IL-96, the canisters and oxygen masks were mounted in the top portion of the seat backs, since the ceiling was too high above the passengers. If a decompression occurred, the panels were opened either by an automatic pressure switch or by a manual switch, and the masks were released. When the passengers pulled down on the mask they removed the retaining pins and triggered the production of oxygen.


title: Chemical oxygen generator

text: percent barium peroxide (BaO) and less than 1 percent potassium perchlorate (KClO). The explosives in the percussion cap are a lead styphnate and tetrazene explosive mixture. The chemical reaction is exothermic and the exterior temperature of the canister will reach . It will produce oxygen for 12 to 22 minutes. The two-mask generator is approximately in diameter and long. The three-mask generator is approximately in diameter and long.


title: Chemical oxygen generator

text: Accidental activation of improperly shipped expired generators, mistakenly labeled as empty, caused the ValuJet Airlines Flight 592 crash, killing all on board. An ATA DC-10, Flight 131, was also destroyed while parked at O'Hare Airport, on August 10, 1986. The cause was the accidental activation of an oxygen canister, contained in the back of a broken DC-10 seat, being shipped in the cargo compartment to a repair station. There were no fatalities or injuries because the plane contained no passengers when the fire broke out.


title: Chemical oxygen generator

text: A "chlorate candle", or an "oxygen candle", is a cylindrical chemical oxygen generator that contains a mix of sodium chlorate and iron powder, which when ignited smolders at about , producing sodium chloride, iron oxide, and at a fixed rate of about 6.5 man-hours of oxygen per kilogram of the mixture. The mixture has an indefinite shelf life if stored properly: candles have been stored for 20 years without decreased oxygen output. Thermal decomposition releases the oxygen. The burning iron supplies the heat. The candle must be wrapped in thermal insulation to maintain the reaction temperature and to protect surrounding equipment. The key reaction is:


title: Chemical oxygen generator

text: Potassium and lithium chlorate, and sodium, potassium and lithium perchlorates can also be used in oxygen candles.


title: Chemical oxygen generator

text: An explosion caused by one of these candles killed two Royal Navy sailors on , a nuclear-powered submarine, under the Arctic on 21 March 2007. The candle had become contaminated with hydraulic oil, which caused the mixture to explode rather than burn.


title: Chemical oxygen generator

text: In the Vika oxygen generator used on some spacecraft, lithium perchlorate is the source of oxygen. At 400 °C, it releases 60% of its weight as oxygen:


title: Chemical oxygen generator

text: Advances in technology have provided industrial oxygen generator systems for use where air is available and a higher concentration of oxygen is desired. Pressure swing adsorption (PSA) incorporates a material called molecular sieve for gas separation. In the case of oxygen generation a zeolite-based sieve forces preferential adsorption for nitrogen. Clean, dry air is passed through the sieve beds on the oxygen generator, producing an oxygen-enriched gas. Nitrogen separation membrane equipment is also used.


title: Chemical oxygen generator

text: Chemical oxygen generators are used in aircraft, breathing apparatus for firefighters and mine rescue crews, submarines, and everywhere a compact emergency oxygen generator with long shelf life is needed. They usually contain a device for absorption of carbon dioxide, sometimes a filter filled with lithium hydroxide; a kilogram of LiOH absorbs about half a kilogram of CO.


title: Negotiable instrument

text: A negotiable instrument is a document guaranteeing the payment of a specific amount of money, either on demand, or at a set time, whose payer is usually named on the document. More specifically, it is a document contemplated by or consisting of a contract, which promises the payment of money without condition, which may be paid either on demand or at a future date. The term has different meanings depending on the use of the term as it is used in the application of different laws, and depending in which country and context it is used.


title: Negotiable instrument

text: In the Commonwealth of Nations almost all jurisdictions have codified the law relating to negotiable instruments in a Bills of Exchange Act, e.g. Bills of Exchange Act 1882 in the UK, Bills of Exchange Act 1890 in Canada, Bills of Exchange Act 1908 in New Zealand, Bills of Exchange Act 1909 in Australia, the Negotiable Instruments Act, 1881 in India and the Bills of Exchange Act 1914 in Mauritius.


title: Negotiable instrument

text: Additionally most Commonwealth jurisdictions have separate Cheques Acts providing for additional protections for bankers collecting unendorsed or irregularly endorsed cheques, providing that cheques that are crossed and marked 'not negotiable' or similar are not transferable, and providing for electronic presentation of cheques in inter-bank cheque clearing systems.


title: Negotiable instrument

text: In India, during the Mauryan period in the 3rd century BCE, an instrument called adesha was in use, which was an order on a banker desiring him to pay the money of the note to a third person, which corresponds to the definition of a bill of exchange as we understand it today.


title: Negotiable instrument

text: The ancient Romans are believed to have used an early form of cheque known as "praescriptiones" in the 1st century BCE and 2,000-year-old Roman promissory notes have been found.


title: Negotiable instrument

text: Common prototypes of bills of exchanges and promissory notes originated in China, where special instruments called "fey tsien" which were used to safely transfer money over long distances during the reign of the Tang Dynasty in the 8th century.


title: Negotiable instrument

text: In about 1150 the Knights Templar issued an early form of bank notes to departing pilgrims in exchange for a deposit of valuables at a local Templar preceptory in a European country, which could be cashed by the pilgrim concerned on arrival in the Holy land, by presenting the note to a Templar preceptory there.


title: Negotiable instrument

text: In the mid-13th century, the Ilkhanid rulers of Persia printed the "cha" or "chap" which was used as paper money for limited use for transactions between the court and the merchants for about three years before it collapsed. The collapse was caused by the court accepting the "cha" only at progressive discount.


title: Negotiable instrument

text: Later, such documents were used for money transfer by Middle Eastern merchants, who had used the prototypes of bills of exchange ("suftadja" or "softa") from the 8th century to present. Such prototypes came to be used later by the Iberian and Italian merchants in the 12th century. In Italy in the 13–15th centuries, bills of exchange and promissory notes obtained their main features, while further phases of their development have been associated with France (16–18th centuries, where the endorsement had appeared) and Germany (19th century, formalization of Exchange Law). The first mention of the use of bills of exchange in English statutes dates from 1381, under Richard II; the statute mandates the use of such instruments in England, and prohibits the future export of gold and silver specie, in any form, to settle foreign commercial transactions. English exchange law was different than continental European law because of different legal systems; the English system was adopted later in the United States.


title: Negotiable instrument

text: 1. Carrying large amounts of coins from one place to the other was deemed unsafe, so the usage of negotiable instruments was to prevent merchants from being robbed off their coins either on land or by sea.


title: Negotiable instrument

text: 2. During the 1300s, there was an increase in the use of "counterfeit English money", so the aim of the English Crown was to eradicate the exchanges that were made between genuine English coins and "foreign debased coinage". As such, statutes such as the Statute of Money of 1335 and 1379 were implemented to prevent the importation of money that was deemed as counterfeit, and also to prevent the exportation of valuable items like gold and silver in the absence of any special licenses.


title: Negotiable instrument

text: The modern emphasis on negotiability may also be traced to Lord Mansfield. Germanic Lombards documents may also have some elements of negotiability.


title: Negotiable instrument

text: A negotiable instrument can serve to convey value constituting at least part of the performance of a contract, albeit perhaps not obvious in contract formation, in terms inherent in and arising from the requisite offer and acceptance and conveyance of consideration. The underlying contract contemplates the right to hold the instrument as, and to negotiate the instrument to, a "holder in due course", the payment on which is at least part of the performance of the contract to which the negotiable instrument is linked. The instrument, memorializing: (1) the power to demand payment; and, (2) the right to be paid, can move, for example, in the instance of a "bearer instrument", wherein the possession of the document itself attributes and ascribes the right to payment. Certain exceptions exist, such as instances of loss or theft of the instrument, wherein the possessor of the note may be a holder, but not necessarily a holder in due course. Negotiation requires a valid "endorsement" of the negotiable instrument.


title: Negotiable instrument

text: The consideration constituted by a negotiable instrument is cognizable as the value given up to acquire it (benefit) and the consequent loss of value (detriment) to the prior holder; thus, no separate consideration is required to support an accompanying contract assignment. The instrument itself is understood as memorializing the right for, and power to demand, payment, and an obligation for payment evidenced by the instrument itself with possession as a holder in due course being the touchstone for the right to, and power to demand, payment. In some instances, the negotiable instrument can serve as the writing memorializing a contract, thus satisfying any applicable statute of frauds as to that contract.


title: Negotiable instrument

text: The rights of a holder in due course of a negotiable instrument are qualitatively, as matters of law, superior to those provided by ordinary species of contracts:


title: Negotiable instrument

text: Negotiation often enables the transferee to become the party to the contract through a contract assignment (provided for explicitly or by operation of law) and to enforce the contract in the transferee-assignee's own name. Negotiation can be effected by endorsement and delivery (order instruments), or by delivery alone (bearer instruments).


title: Negotiable instrument

text: Promissory notes and bills of exchange are two primary types of negotiable instruments. The following chart shows the main differences:


title: Negotiable instrument

text: Although possibly non-negotiable, a promissory note may be a negotiable instrument if it is an unconditional promise in writing made by one person to another, signed by the maker, engaging to pay on demand to the "payee", or at fixed or determinable future time, a sum certain in money, to order or to bearer. The law applicable to the specific instrument will determine whether it is a negotiable instrument or a non-negotiable instrument.


title: Negotiable instrument

text: Bank notes are frequently referred to as promissory notes, a promissory note made by a bank and payable to bearer on demand. According to section 4 of India's Negotiable Instruments Act, 1881, "a Promissory Note is a writing (not being a bank note or currency note), containing an unconditional undertaking, signed by the maker to pay a certain sum of money only to or to the order of a certain person or the bearer of the instrument".


title: Negotiable instrument

text: A bill of exchange or "draft" is a written order by the "drawer" to the "drawee" to pay money to the "payee". A common type of bill of exchange is the cheque ("check" in American English), defined as a bill of exchange drawn on a banker and payable on demand. Bills of exchange are used primarily in international trade, and are written orders by one person to his bank to pay the bearer a specific sum on a specific date. Prior to the advent of paper currency, bills of exchange were a common means of exchange. They are not used as often today.


title: Negotiable instrument

text: A bill of exchange is essentially an order made by one person to another to pay money to a third person. A bill of exchange requires in its inception three parties—the drawer, the drawee, and the payee. The person who draws the bill is called the drawer. He gives the order to pay money to the third party. The party upon whom the bill is drawn is called the drawee. He is the person to whom the bill is addressed and who is ordered to pay. He becomes an acceptor when he indicates his willingness to pay the bill. The party in whose favor the bill is drawn or is payable is called the payee. The parties need not all be distinct persons. Thus, the drawer may draw on himself payable to his own order.


title: Negotiable instrument

text: A bill of exchange may be endorsed by the payee in favour of a third party, who may in turn endorse it to a fourth, and so on indefinitely. The "holder in due course" may claim the amount of the bill against the drawee and all previous endorsers, regardless of any counterclaims that may have disabled the previous payee or endorser from doing so. This is what is meant by saying that a bill is negotiable.


title: Negotiable instrument

text: In some cases a bill is marked "not negotiable"—see crossing of cheques. In that case it can still be transferred to a third party, but the third party can have no better right than the transferor.


title: Negotiable instrument

text: In the United States, Articles 3 and 4 of the Uniform Commercial Code (UCC) govern the issuance and transfer of negotiable instruments, unless the instruments are governed by Article 8 of the UCC. The various state law enactments of UCC §§ 3–104(a) through (d) set forth the legal definition of what is and what is not a "negotiable instrument":


title: Negotiable instrument

text: Thus, for a writing to be a negotiable instrument under Article 3, the following requirements must be met:


title: Negotiable instrument

text: The latter requirement is referred to as the "words of negotiability": a writing which does not contain the words "to the order of" (within the four corners of the instrument or in endorsement on the note or in allonge) or indicate that it is payable to the individual holding the contract document (analogous to the holder in due course) is not a negotiable instrument and is not governed by Article 3, even if it appears to have all of the other features of negotiability. The only exception is that if an instrument meets the definition of a cheque (a bill of exchange payable on demand and drawn on a bank) and is not payable to order (i.e. if it just reads "pay John Doe") then it is treated as a negotiable instrument.


title: Negotiable instrument

text: UCC Article 3 does not apply to money, to payment orders governed by Article 4A, or to securities governed by Article 8.


title: Negotiable instrument

text: Persons other than the original obligor and obligee can become parties to a negotiable instrument. The most common manner in which this is done is by "endorsing" (from Latin "dorsum", the back + "in"), that is placing one's signature on the back of the instrument—if the person who signs does so with the intention of obtaining payment of the instrument or acquiring or transferring rights to the instrument, the signature is called an "endorsement". There are five types of endorsements contemplated by the Code, covered in UCC Article 3, Sections 204–206:


title: Negotiable instrument

text: the transferee is a "holder in due course" and can enforce the instrument "without" being subject to defenses which the maker of the instrument would be able to assert against the original payee, except for certain "real defenses". These real defenses include (1) forgery of the instrument; (2) fraud as to the nature of the instrument being signed; (3) alteration of the instrument; (4) incapacity of the signer to contract; (5) infancy of the signer; (6) duress; (7) discharge in bankruptcy; and, (8) the running of a statute of limitations as to the validity of the instrument.


title: Negotiable instrument

text: The "holder-in-due-course rule" is a "rebuttable presumption" that makes the free transfer of negotiable instruments feasible in the modern economy. A person or entity purchasing an instrument in the ordinary course of business can reasonably expect that it will be paid when presented to, and not subject to dishonor by, the maker, without involving itself in a dispute between the maker and the person to whom the instrument was first issued (this can be contrasted to the lesser rights and obligations accruing to mere holders). Article 3 of the Uniform Commercial Code as enacted in a particular State's law contemplate "real defenses" available to purported holders in due course.


title: Negotiable instrument

text: The foregoing is the theory and application presuming compliance with the relevant law. Practically, the obligor-payor on an instrument who feels he has been defrauded or otherwise unfairly dealt with by the payee may nonetheless refuse to pay even a holder in due course, requiring the latter to resort to litigation to recover on the instrument.


title: Negotiable instrument

text: While bearer instruments are rarely created as such, a holder of commercial paper with the holder designated as payee can change the instrument to a bearer instrument by an endorsement. The proper holder simply signs the back of the instrument and the instrument becomes bearer paper, although in recent years, third party checks are not being honored by most banks unless the original payee has signed a notarized document stating such.


title: Negotiable instrument

text: Alternatively, an individual or company may write a check payable to "cash" or "bearer" and create a bearer instrument. Great care should be taken with the security of the instrument, as it is legally almost as good as cash.


title: Negotiable instrument

text: Under the Code, the following are not negotiable instruments, although the law governing obligations with respect to such items may be similar to or derived from the law applicable to negotiable instruments:


title: Negotiable instrument

text: Although often considered foundational in business law, the modern relevance of negotiability has been questioned. Negotiability can be traced back to the 1700s and Lord Mansfield, when money and liquidity was relatively scarce. The holder in due course rule has been limited by various statutes. Concerns have also been raised that the holder in due course rule does not align the incentives of the mortgage originators and the assignees efficiently.


title: 42nd Street (Manhattan)

text: 42nd Street is a major crosstown street in the New York City borough of Manhattan, spanning the entire breadth of Midtown Manhattan, from Turtle Bay at the East River, to Hell's Kitchen at the Hudson River on the West Side. The street hosts some of New York's best known landmarks, including (from east to west) the headquarters of the United Nations, the Chrysler Building, Grand Central Terminal, the New York Public Library Main Branch, Times Square, and the Port Authority Bus Terminal.


title: 42nd Street (Manhattan)

text: The street is known for its theaters, especially near the intersection with Broadway at Times Square, and as such is also the name of the region of the theater district (and, at times, the red-light district) near that intersection.


title: 42nd Street (Manhattan)

text: During the American Revolutionary War, a cornfield near 42nd Street and Fifth Avenue was where General George Washington angrily attempted to rally his troops after the British landing at Kip's Bay, which scattered many of the American militiamen. Washington's attempt put him in danger of being captured, and his officers had to persuade him to leave. The rout eventually subsided into an orderly retreat.


title: 42nd Street (Manhattan)

text: John Jacob Astor purchased a farm in 1803 that ran from 42nd Street to 46th Street west of Broadway to the Hudson River.


title: 42nd Street (Manhattan)

text: The street was designated by the Commissioners' Plan of 1811 that established the Manhattan street grid as one of 15 crosstown (east-west) streets that would be in width, while other streets were designated as in width.


title: 42nd Street (Manhattan)

text: In 1835, the city's Street Committee, after receiving numerous complaints about lack of access for development above 14th Street, decided to open up all lots which had already been plotted on the city grid up to 42nd Street, which thus became – for a time – the northern boundary of the city.


title: 42nd Street (Manhattan)

text: Cornelius Vanderbilt began the construction of Grand Central Depot in 1869 on 42nd Street at Fourth Avenue as the terminal for his Central, Hudson, Harlem and New Haven commuter rail lines, because city regulations required that trains be pulled by horse below 42nd Street. The Depot, which opened in 1871, was replaced by Grand Central Terminal in 1913.


title: 42nd Street (Manhattan)

text: Between the 1870s and 1890s, 42nd Street became the uptown boundary of the mainstream theatre district, which started around 23rd Street, as the entertainment district of the Tenderloin gradually moved northward.


title: 42nd Street (Manhattan)

text: 42nd Street was developed relatively late compared to other crosstown thoroughfares such as 14th Street and 23rd Street, which had grown during the American Civil War, and 57th Street, which became prominent in the 1890s. It was only after the beginning of the 20th century that the street saw entertainment venues being developed around Times Square and upscale office space around Grand Central Terminal.


title: 42nd Street (Manhattan)

text: The corner of 42nd Street and Broadway, at the southeast corner of Times Square, is the eastern terminus of the Lincoln Highway, the first road across the United States, which was conceived and mapped in 1913.


title: 42nd Street (Manhattan)

text: An elevated railroad line, running above East 42nd Street from Third Avenue to the Grand Central station, was closed in 1923, leading to the development of such structures as the Chanin Building and 110 East 42nd Street west of Lexington Avenue. The street east of Lexington Avenue continued to be made up of mostly low-rise buildings; these blocks were adjacent to the Second Avenue and Third Avenue elevated lines, and accordingly, initially considered unattractive for major development. By the 1920s, "The New York Times" reported that several high-rise developments were "radically changing the old-time conditions" along East 42nd Street, including the Chanin, Lincoln, Chrysler, and Daily News Buildings, as well as Tudor City.


title: 42nd Street (Manhattan)

text: West 42nd Street, meanwhile, prospered as a theater and entertainment district until World War II. According to historian Robert A. M. Stern, West 42nd Street's decline started in 1946, when the streetcars on 42nd Street were replaced by less efficient buses.


title: 42nd Street (Manhattan)

text: Lloyd Bacon and Busby Berkeley's 1933 film musical "42nd Street", starring 30s heartthrobs Dick Powell and Ruby Keeler, displays the bawdy and colorful mixture of Broadway denizens and lowlifes in Manhattan during the Depression. In 1980, it was turned into a successful Broadway musical which ran until 1989, and which was revived for a four-year run in 2001. In the words of the Al Dubin and Harry Warren title song, on 42nd Street one could find:


title: 42nd Street (Manhattan)

text: From the late 1950s until the late 1980s, 42nd Street, nicknamed the "Deuce", was the cultural center of American grindhouse theaters, which spawned an entire subculture. The book "Sleazoid Express", a travelogue of the 42nd Street grindhouses and the films they showed, describes the unique blend of people who made up the theater-goers:


title: 42nd Street (Manhattan)

text: depressives hiding from jobs, sexual obsessives, inner-city people seeking cheap diversions, teenagers skipping school, adventurous couples on dates, couples-chasers peeking on them, people getting high, homeless people sleeping, pickpockets...


title: 42nd Street (Manhattan)

text: phony drug salesman ... low-level drug dealers, chain snatchers ... [j]unkies alone in their heroin/cocaine dreamworld ... predatory chickenhawks spying on underage trade looking for pickups ... male prostitutes of all ages ... [t]ranssexuals, hustlers, and closety gays with a fetishistic homo- or heterosexual itch to scratch ... It was common to see porn stars whose films were playing at the adult houses promenade down the block. ... Were you a freak? Not when you stepped onto the Deuce. Being a freak there would get you money, attention, entertainment, a starring part in a movie. Or maybe a robbery and a beating.


title: 42nd Street (Manhattan)

text: For much of the mid and late 20th century, the area of 42nd Street near Times Square was home to activities often considered unsavory, including peep shows.


title: 42nd Street (Manhattan)

text: East 42nd Street was, for some time, spared from similar decline, especially east of Third Avenue, where the development of the United Nations supported a thriving business district and prompted the widening of that section of 42nd Street. The demolition of the Second and Third Avenue elevated lines by the 1950s led to increased development on East 42nd Street, such as annexes to the Chrysler and Daily News Buildings, as well as the construction of the Socony–Mobil and Ford Foundation Buildings. By the 1960s, East 42nd Street between Park and Second Avenues contained more headquarters of industries than any other place in the United States except Chicago or Pittsburgh. During this time, there was much development outside the rundown entertainment district of Times Square, somewhat offsetting the perception of that part of 42nd Street.


title: 42nd Street (Manhattan)

text: In the early 1990s, city government encouraged a cleanup of the Times Square area. In 1990, the city government took over six of the historic theatres on the block of 42nd Street between Seventh and Eighth Avenues, and New 42nd Street, a not-for-profit organization, was formed to oversee their renovation and reuse, as well as to construct new theatres and a rehearsal space. In 1993, Disney Theatrical Productions bought the New Amsterdam Theatre, which it renovated a few years later. Since the mid-1990s, the block has again become home to mainstream theatres and several multi-screen mainstream movie theatres, along with shops, restaurants, hotels, and attractions such as Madame Tussauds wax museum and Ripley's Believe It or Not that draw millions to the city every year. This area is now co-signed as "New 42nd Street" to signify this change.


title: 42nd Street (Manhattan)

text: In the 1990s, the renovation of Bryant Park between Fifth and Sixth Avenues, as well as the renovations of Times Square and Grand Central Terminal, led to increases in office occupancy along both sections of 42nd Street.


title: 42nd Street (Manhattan)

text: There are two subway lines under 42nd Street. The 42nd Street Shuttle () runs under 42nd Street between Broadway/Seventh Avenue (Times Square) and Park Avenue (Grand Central). The IRT Flushing Line () curves from Eleventh Avenue to 41st Street, under which it runs until Fifth Avenue; shifts to 42nd Street between Fifth and Madison Avenues; and continues under the East River to Queens. Each line stops at Times Square and Grand Central, though the Fifth Avenue station is also served by the .


title: 42nd Street (Manhattan)

text: A fifth station extended over 42nd Street as a western spur from the Third Avenue Line to Grand Central Depot, later Grand Central Station, and finally Grand Central Terminal.


title: 42nd Street (Manhattan)

text: MTA Regional Bus Operations's M42 bus runs the length of 42nd Street between the Circle Line Sightseeing Cruises ferry terminal on the Hudson River and the headquarters of the United Nations on the East River. Its predecessor, the 42nd Street Crosstown Line streetcar, had used 42nd Street. In 2019, bus lanes were installed along the length of the street.


title: 42nd Street (Manhattan)

text: In addition, "forty-deuce" is street slang for Manhattan's former live peep show district on 42nd Street. The following works reference the phrase "forty-deuce":


title: Outcome-based education

text: Outcome-based education or outcomes-based education (OBE) is an educational theory that bases each part of an educational system around goals (outcomes). By the end of the educational experience, each student should have achieved the goal. There is no single specified style of teaching or assessment in OBE; instead, classes, opportunities, and assessments should all help students achieve the specified outcomes. The role of the faculty adapts into instructor, trainer, facilitator, and/or mentor based on the outcomes targeted.


title: Outcome-based education

text: Australia and South Africa adopted OBE policies from the 1990s to the mid 2000s, but were abandoned in the face of substantial community opposition. The United States has had an OBE program in place since 1994 that has been adapted over the years. In 2005, Hong Kong adopted an outcome-based approach for its universities. Malaysia implemented OBE in all of their public schools systems in 2008. The European Union has proposed an education shift to focus on outcomes, across the EU. In an international effort to accept OBE, The Washington Accord was created in 1989; it is an agreement to accept undergraduate engineering degrees that were obtained using OBE methods. As of 2017, the full signatories are Australia, Canada, Taiwan, Hong Kong, India, Ireland, Japan, Korea, Malaysia, New Zealand, Russia, Singapore, South Africa, Sri Lanka, Turkey, the United Kingdom, Pakistan, China and the United States.


title: Outcome-based education

text: OBE can primarily be distinguished from traditional education method by the way it incorporates three elements: theory of education, a systematic structure for education, and a specific approach to instructional practice. It organizes the entire educational system towards what are considered essential for the learners to successfully do at the end of their learning experiences. In this model, the term "outcome" is the core concept and sometimes used interchangeably with the terms "competency, "standards, "benchmarks", and "attainment targets". OBE also uses the same methodology formally and informally adopted in actual workplace to achieve outcomes. It focuses on the following skills when developing curricula and outcomes:


title: Outcome-based education

text: In a regional/local/foundational/electrical education system, students are given grades and rankings compared to each other. Content and performance expectations are based primarily on what was taught in the past to students of a given age of 12-18. The goal of this education was to present the knowledge and skills of an older generation to the new generation of students, and to provide students with an environment in which to learn. The process paid little attention (beyond the classroom teacher) to whether or not students learn any of the material.


title: Outcome-based education

text: The focus on outcomes creates a clear expectation of what needs to be accomplished by the end of the course. Students will understand what is expected of them and teachers will know what they need to teach during the course. Clarity is important over years of schooling and when team teaching is involved. Each team member, or year in school, will have a clear understanding of what needs to be accomplished in each class, or at each level, allowing students to progress. Those designing and planning the curriculum are expected to work backwards once an outcome has been decided upon; they must determine what knowledge and skills will be required to reach the outcome.


title: Outcome-based education

text: With a clear sense of what needs to be accomplished, instructors will be able to structure their lessons around the student’s needs. OBE does not specify a specific method of instruction, leaving instructors free to teach their students using any method. Instructors will also be able to recognize diversity among students by using various teaching and assessment techniques during their class. OBE is meant to be a student-centered learning model. Teachers are meant to guide and help the students understand the material in any way necessary, study guides, and group work are some of the methods instructors can use to facilitate students learning.


title: Outcome-based education

text: OBE can be compared across different institutions. On an individual level, institutions can look at what outcomes a student has achieved to decide what level the student would be at within a new institution. On an institutional level, institutions can compare themselves, by checking to see what outcomes they have in common, and find places where they may need improvement, based on the achievement of outcomes at other institutions. The ability to compare easily across institutions allows students to move between institutions with relative ease. The institutions can compare outcomes to determine what credits to award the student. The clearly articulated outcomes should allow institutions to assess the student’s achievements rapidly, leading to increased movement of students. These outcomes also work for school to work transitions. A potential employer can look at records of the potential employee to determine what outcomes they have achieved. They can then determine if the potential employee has the skills necessary for the job.


title: Outcome-based education

text: Student involvement in the classroom is a key part of OBE. Students are expected to do their own learning, so that they gain a full understanding of the material. Increased student involvement allows students to feel responsible for their own learning, and they should learn more through this individual learning. Other aspects of involvement are parental and community, through developing curriculum, or making changes to it. OBE outcomes are meant to be decided upon within a school system, or at a local level. Parents and community members are asked to give input in order to uphold the standards of education within a community and to ensure that students will be prepared for life after school.


title: Outcome-based education

text: The definitions of the outcomes decided upon are subject to interpretation by those implementing them. Across different programs or even different instructors outcomes could be interpreted differently, leading to a difference in education, even though the same outcomes were said to be achieved. By outlining specific outcomes, a holistic approach to learning is lost. Learning can find itself reduced to something that is specific, measurable, and observable. As a result, outcomes are not yet widely recognized as a valid way of conceptualizing what learning is about.


title: Outcome-based education

text: When determining if an outcome has been achieved, assessments may become too mechanical, looking only to see if the student has acquired the knowledge. The ability to use and apply the knowledge in different ways may not be the focus of the assessment. The focus on determining if the outcome has been achieved leads to a loss of understanding and learning for students, who may never be shown how to use the knowledge they have gained. Instructors are faced with a challenge: they must learn to manage an environment that can become fundamentally different from what they are accustomed to. In regards to giving assessments, they must be willing to put in the time required to create a valid, reliable assessment that ideally would allow students to demonstrate their understanding of the information, while remaining objective.


title: Outcome-based education

text: Education outcomes can lead to a constrained nature of teaching and assessment. Assessing liberal outcomes such as creativity, respect for self and others, responsibility, and self-sufficiency, can become problematic. There is not a measurable, observable, or specific way to determine if a student has achieved these outcomes. Due to the nature of specific outcomes, OBE may actually work against its ideals of serving and creating individuals that have achieved many outcomes.


title: Outcome-based education

text: Parental involvement, as discussed in the benefits section can also be a drawback, if parents and community members are not willing to express their opinions on the quality of the education system, the system may not see a need for improvement, and not change to meet student’s needs. Parents may also become too involved, requesting too many changes, so that important improvements get lost with other changes that are being suggested. Instructors will also find that their work is increased; they must work to first understand the outcome, then build a curriculum around each outcome they are required to meet. Instructors have found that implementing multiple outcomes is difficult to do equally, especially in primary school. Instructors will also find their work load increased if they chose to use an assessment method that evaluates students holistically.


title: Outcome-based education

text: In the early 1990s, all states and territories in Australia developed intended curriculum documents largely based on OBE for their primary and secondary schools. Criticism arose shortly after implementation. Critics argued that no evidence existed that OBE could be implemented successfully on a large scale, in either the United States or Australia. An evaluation of Australian schools found that implementing OBE was difficult. Teachers felt overwhelmed by the amount of expected achievement outcomes. Educators believed that the curriculum outcomes did not attend to the needs of the students or teachers. Critics felt that too many expected outcomes left students with shallow understanding of the material. Many of Australia’s current education policies have moved away from OBE and towards a focus on fully understanding the essential content, rather than learning more content with less understanding.


title: Outcome-based education

text: Officially, an agenda to implement Outcomes Based Education took place between 1992 and 2008 in Western Australia. Dissatisfaction with OBE escalated from 2004 when the government proposed the implementation of an alternative assessment system using OBE 'levels' for years 11 and 12. With government school teachers not permitted to publicly express dissatisfaction with the new system, a community lobby group called PLATO as formed in June 2004 by high school science teacher Marko Vojkavi. Teachers anonymously expressed their views through the website and online forums, with the website quickly became one of the most widely read educational websites in Australia with more 180,000 hits per month and contained an archive of more than 10,000 articles on the subject of OBE implementation. In 2008 it was officially abandoned by the state government with Minister for Education Mark McGowan remarking that the 1990s fad "to dispense with syllabus" was over.


title: Outcome-based education

text: In December 2012, the European Commission presented a new strategy to decrease youth unemployment rate, which at the time was close to 23% across the European Union . The European Qualifications Framework calls for a shift towards learning outcomes in primary and secondary schools throughout the EU. Students are expected to learn skills that they will need when they complete their education. It also calls for lessons to have a stronger link to employment through work-based learning (WBL). Work-based learning for students should also lead to recognition of vocational training for these students. The program also sets goals for learning foreign languages, and for teachers continued education. It also highlights the importance of using technology, especially the internet, in learning to make it relevant to students.


title: Outcome-based education

text: Hong Kong’s University Grants Committee adopted an outcomes-based approach to teaching and learning in 2005. No specific approach was created leaving universities to design the approach themselves. Universities were also left with a goal of ensuring an education for their students that will contribute to social and economic development, as defined by the community in which the university resides. With little to no direction or feedback from the outside universities will have to determine if their approach is achieving its goals on their own.


title: Outcome-based education

text: OBE has been practiced in Malaysia since the 1950s; however, as of 2008, OBE is being implemented at all levels of education, especially tertiary education. This change is a result of the belief that the education system used prior to OBE inadequately prepared graduates for life outside of school. The Ministry of Higher Education has pushed for this change because of the number of unemployed graduates. Findings in 2006 state that nearly 70% of graduates from public universities were considered unemployed. A further study of those graduates found that they felt they lacked, job experience, communication skills, and qualifications relevant to the current job market. The Malaysian Qualifications Agency (MQA) was created to oversee quality of education and to ensure outcomes were being reached. The MQA created a framework that includes eight levels of qualification within higher education, covering three sectors; skills, vocational and technical, and academic. Along with meeting the standards set by the MQA, universities set and monitor their own outcome expectations for students


title: Outcome-based education

text: OBE was introduced to South Africa in the late 1990s by the post-apartheid government as part of its Curriculum 2005 program. , Initial support for the program derived from anti-apartheid education policies. The policy also gained support from the labor movements that borrowed ideas about competency-based education, and Vocational education from New Zealand and Australia, as well as the labor movement that critiqued the apartheid education system. With no strong alternative proposals, the idea of outcome-based education, and a national qualification framework, became the policy of the African National Congress government. This policy was believed to be a democratization of education, people would have a say in what they wanted the outcomes of education to be. It was also believed to be a way to increase education standards and increase the availability of education. The National Qualifications Framework (NQF) went into effect in 1997. In 2001 people realized that the intended effects were not being seen. By 2006 no proposals to change the system had been accepted by the government, causing a hiatus of the program. The program came to be viewed as a failure and a new curriculum improvement process was announced in 2010, slated to be implemented between 2012 and 2014.


title: Outcome-based education

text: In 1983, a report from the National Commission on Excellence in Education declared that American education standards were eroding, that young people in the United States were not learning enough. In 1989, President Bush and the nation’s governors set national goals to be achieved by the year 2000. Goals 2000: Educate America Act was signed in March 1994. The goal of this new reform was to show that results were being achieved in schools. In 2001, the No Child Left Behind Act took the place of Goals 2000. It mandated certain measurements as a condition of receiving federal education funds. States are free to set their own standards, but the federal law mandates public reporting of math and reading test scores for disadvantaged demographic subgroups, including racial minorities, low-income students, and special education students. Various consequences for schools that do not make "adequate yearly progress" are included in the law. In 2010, President Obama proposed improvements for the program. In 2012, the U.S. Department of Education invited states to request flexibility waivers in exchange for rigorous plans designed to improve students' education in the state.


title: Outcome-based education

text: India has become the permanent signatory member of the Washington Accord on 13 June 2014. India has started implementing OBE in higher technical education like diploma and undergraduate programmes. The National Board of Accreditation, a body for promoting international quality standards for technical education in India has started accrediting only the programmes running with OBE from 2013.


title: Outcome-based education

text: The National Board of Accreditation mandates establishing a culture of outcomes-based education in institutions that offer Engineering, Pharmacy, Management programs. Outcomes analysis and using the analytical reports to find gaps and carry out continuous improvement is essential cultural shift from how the above programs are run when OBE culture is not embraced. Outcomes analysis requires huge amount of data to be churned and made available at any time, anywhere. Such an access to scalable, accurate, automated and real-time data analysis is possible only if the institute adopts either excelsheet based measurement system or some kind of home-grown or commercial software system. It is observed that excelsheet based measurement and analysis system doesn't scale when the stakeholders want to analyse longitudinal data.


title: Couvade syndrome

text: Couvade syndrome, also called sympathetic pregnancy, is a proposed condition in which an expectant father experiences some of the same symptoms and behavior as his pregnant partner. These most often include major weight gain, altered hormone levels, morning nausea, and disturbed sleep patterns. In more extreme cases, symptoms can include labor pains, fatigue, postpartum depression, and nosebleeds. The labor pain symptom is commonly known as "sympathy pain".


title: Couvade syndrome

text: The source of Couvade Syndrome is a matter of debate. Some believe it to be a psychosomatic condition, while others believe it may have biological causes relating to hormone changes.


title: Couvade syndrome

text: Symptoms experienced by the partner can include stomach pain, back pain, indigestion, changes in appetite, weight gain, acne, diarrhea, constipation, headache, toothache, cravings, nausea, breast augmentation, breast growth, dry navel, hardening of the nipple, excessive earwax, and insomnia. A qualitative study listed 35 symptoms from Couvade literature, including gastrointestinal, genitourinary, respiratory, oral or dental, stiffening of the glutes, generalized aches and pains, and other symptoms.


title: Couvade syndrome

text: Psychological causes suggested have included anxiety, pseudo-sibling rivalry, identification with the fetus, ambivalence about fatherhood, or parturition envy. According to Osvlosky and Culp (1989), pregnancy causes the male counterpart to experience an emergence of ambivalence as well as a recurrence of Oedipal conflict. In 1920s France, Couvade was claimed to be more common in conditions where sex roles are flexible and the female is of a dominant status.


title: Couvade syndrome

text: Studies have shown that the male partner cohabitating with a pregnant female will experience hormonal shifts in his prolactin, cortisol, estradiol, and testosterone levels, typically starting at the end of the first trimester and continuing through several weeks post-partum.


title: Robert Monroe

text: Robert Allan Monroe (October 30, 1915 – March 17, 1995) was a radio broadcasting executive who became known for his research into altered consciousness and for founding The Monroe Institute. His 1971 book "Journeys Out of the Body" is credited with popularizing the term "out-of-body experience".


title: Robert Monroe

text: Assisted by specialists in psychology, medicine, biochemistry, psychiatry, electrical engineering, physics, and education, Monroe developed Hemi-Sync, a patented audio technology that is claimed to facilitate enhanced performance.


title: Robert Monroe

text: He is also notable as one of the founders of the Jefferson Cable Corporation, the first cable company to cover central Virginia.


title: Robert Monroe

text: Robert Allan Monroe was born, severely underweight at just two pounds, in 1915 in Indiana. He grew up in Lexington, Kentucky, and Columbus, Ohio; his mother, Georgia Helen Jordan Monroe, was a non-practicing medical doctor and cellist and piano player. His father, Robert Emmett Monroe, was a college professor of Romance Languages who led summer tours to Europe. Monroe had two older sisters, Dorothy and Peggy, and a younger brother, Emmett, who became a medical doctor.


title: Robert Monroe

text: According to his third book "Ultimate Journey", he dropped out of Ohio State University in his sophomore year due to a hospital stay for a facial burn that caused him to fall behind in his studies. During almost a year away from college, a desire to find work led him to become a hobo who rode freight trains. He returned to Ohio State to graduate after having studied pre-med, English, engineering, and journalism.


title: Robert Monroe

text: He had an early fascination with flying and music and had great mechanical aptitude. He displayed some ability to read music by age four without having studied the subject, perhaps by listening to his mother and sisters playing piano.


title: Robert Monroe

text: He married Jeanette, a graduate student and daughter of a lawyer, in 1937, and divorced her in 1938 or 1939. He married Mary Ashworth, a divorcee with a daughter Maria, in 1950 or 1951. They had Bob's only biological child together, daughter Laurie. They divorced in 1968. He then married Nancy Penn Honeycutt, a divorcee with four children. They remained married until her death from breast cancer on August 15, 1992.


title: Robert Monroe

text: Monroe developed ulcers in young adulthood and so was classified 4F (unfit for service) during World War II. He spent the war years working for a manufacturing company that designed a flight-simulator prototype. He wrote for an aviation column in "Argosy" magazine and was given a job with the National Aeronautic Association (NAA), for whom he produced a weekly radio show called "Scramble!", the primary purpose of which was to interest youth in aviation.


title: Robert Monroe

text: In 1953 Mr. Monroe formed RAM Enterprises, a corporation that produced network radio programs, as many as 28 programs monthly, principally in dramatic and popular quiz shows.


title: Robert Monroe

text: In 1956 the firm created a Research and Development division to study the effects of various sound patterns on human consciousness, including the sleep state. Monroe was especially attracted to the concept of sleep-learning. This was a natural direction to take, applying to this new area the audio production methods used in the firm's commercial activity. The purpose was to find more constructive uses for such knowledge than was ordinarily available, and the results of this research have become internationally known.


title: Robert Monroe

text: According to his own account, while experimenting with sleep-learning in 1958 Monroe experienced an unusual phenomenon, which he described as sensations of paralysis and vibration accompanied by a bright light that appeared to be shining on him from a shallow angle. Monroe went on to say that this occurred another nine times over the next six weeks, culminating in his first out-of-body experience (OBE). Monroe recorded his account in his 1971 book "Journeys Out of the Body" and went on to become a prominent researcher in the field of human consciousness. Monroe later authored two more books on his experiments with OBE, "Far Journeys" (1985) and "Ultimate Journey" (1994).


title: Robert Monroe

text: In 1962 the company moved to Virginia, and a few years later changed the corporate name to Monroe Industries. In this location it became active in radio station ownership, cable television, and later in the production and sale of audio cassettes. These cassettes were practical expressions of the discoveries made in the earlier and ongoing corporate research program.


title: Robert Monroe

text: In 1985 the company officially changed its name, once again, to Interstate Industries, Inc. This reflected Monroe's analogy of how the use of Hemi-Sync serves as a ramp from the "local road" to the "interstate" in allowing people to go "full steam ahead" in the exploration of consciousness, avoiding all of the stops and starts.


title: Robert Monroe

text: The research subsidiary was divested and established as an independent non-profit organization, The Monroe Institute, later in 1985. Interstate Industries, Inc. remains a privately held company, now doing business as Monroe Products.


title: Robert Monroe

text: Monroe's leadership of the entire program of development was supported for more than 50 years by many specialists who continue their participation to this day. His daughter, Laurie Monroe, continued her father's research into consciousness and the mind's potential until her death in 2006. Under the current direction of another of Monroe's daughters, Maria Monroe Whitehead, Monroe's stepson, A. J. Honeycutt, and Teresa West, president of Monroe Products, the company's objective is to continue to expand the Hemi-Sync line of products and their benefits into markets worldwide.


title: Robert Monroe

text: The Monroe Institute (TMI) is a nonprofit education and research organization devoted to the exploration of human consciousness, based in Faber, Virginia, United States. Upwards of 20,000 people are estimated to have attended TMI's residential Gateway program during its first thirty years, with consumers of the audio industry founded on its research running into millions. Currently, many tens of thousands of people have experienced the residential programs developed by the Monroe Institute at TMI's campus in Virginia as well as across the US and the world, including Australia, Brazil, Canada, Cyprus, the UK, France, Germany, Japan, Romania, and Spain. TMI claims a policy of no dogma or bias with respect to belief system, religion, political or social stance.


title: Robert Monroe

text: Monroe founded TMI after he started having what he called "out of body experiences", now also commonly referred to as OBEs. The institute is housed in several buildings on of land south of Charlottesville, Virginia, USA. One of its activities includes teaching various techniques, based on audio-guidance processes, in order to expand consciousness and explore areas of consciousness not normally available in the waking state.


title: Robert Monroe

text: In 1978, the U.S. military evaluated TMI and arranged to send officers there for OBE training. In 1983, it sent additional officers.


title: Robert Monroe

text: Controlled studies of the Institute's technology suggest that it is effective as an analgesic supplement and can reduce hospital discharge times. The Institute has an affiliated professional membership, and also publishes scientific papers on a subset of its own studies of altered states of consciousness. In its in-house laboratory, these states or focus levels are typically induced by delivering Hemi-Sync signals to subjects performing relaxation procedures inside a shielded, sense-depriving isolation tank. Progression through states is detected and monitored by measurement of peripheral skin temperature, galvanic skin response and DC skin potential voltage.


title: Robert Monroe

text: In 1994, a front-page article in "The Wall Street Journal" reported confirmation from the former director of the Intelligence and Security Command of the U.S. Army sending personnel to the institute. It also stated the opinion of the head of the Zen Buddhist temple in Vancouver British Columbia that "Gateway students can reach meditation states in a week that took [me] 30 years of sitting".


title: Robert Monroe

text: A reporter for "The Hook", weekly newspaper for Charlottesville, Virginia, who visited The Monroe Institute said, "...with a few exceptions, the only 'normal' people with whom I could fully identify were the trainers, who seemed remarkably well-grounded for people whose day-to-day experiences include astral projection and disembodied spirits".


title: Robert Monroe

text: The reporter also concluded that "there is something significant being developed at the Institute. Whether it's just a brilliant guided meditation complete with trance-inducing stereoscopic sound, or a doorway to a world of spirit entities, I cannot say".


title: Robert Monroe

text: In 1975, Monroe registered the first of several patents concerning audio techniques designed to stimulate brain functions until the left and right hemispheres became synchronized. Monroe held that this state, dubbed Hemi-Sync (hemispherical synchronization), could be used to promote mental well-being or to trigger an altered state of consciousness. Monroe's concept was based on an earlier hypothesis known as binaural beats and has since been expanded upon a commercial basis by the self-help industry.


title: Robert Monroe

text: Hemi-Sync is a trademarked brand name for a patented process used to create audio patterns containing binaural beats, which are commercialized in the form of audio CDs. Interstate Industries Inc., created by Hemi-Sync founder Robert Monroe, is the owner of the Hemi-Sync technology.


title: Robert Monroe

text: "Hemi-Sync" is short for "Hemispheric Synchronization", also known as "brainwave synchronization". Monroe indicated that the technique synchronizes the two hemispheres of one's brain, thereby creating a 'frequency-following response' designed to evoke certain effects. Hemi-Sync has been used for many purposes, including relaxation and sleep induction, learning and memory aids, helping those with physical and mental difficulties, and reaching altered states of consciousness through the use of sound.


title: Robert Monroe

text: The technique involves using sound waves to entrain brain waves. Wearing headphones, Monroe claimed that brains respond by producing a third sound (called binaural beats) that encouraged various brainwave activity changes. In 2002, a University of Virginia presentation at the Society for Psychophysiologial Research examined Monroe's claim. The presentation demonstrated that EEG changes did not occur when the standard electromagnetic headphones of Monroe's setup were replaced by air conduction headphones, which were connected to a remote transducer by rubber tubes. This suggests that the basis for the entrainment effects is electromagnetic rather than acoustical.


title: Robert Monroe

text: Replicated, double-blind, randomized trials on anesthetized patients have found Hemi-Sync effective as a partial replacement for fentanyl during surgery. A similar study found it ineffective at replacing propofol, however.


title: Rofecoxib

text: Rofecoxib is a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. Rofecoxib was approved in the US by the US Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx. Rofecoxib was available by prescription in both tablet-form and as an oral suspension.


title: Rofecoxib

text: Rofecoxib gained widespread use among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.


title: Rofecoxib

text: In September 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, allegedly resulting in between 88,000 and 140,000 cases of serious heart disease. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx.


title: Rofecoxib

text: In 2005 the FDA issued a memo concluding that risks for serious cardiovascular (CV) events seem to be as great for non-selective NSAIDs as for COX-2 selective agents such as rofecoxib, according to long-term controlled clinical trials. Based on data up to 2015, the FDA reasserted the likelihood of an increased risk of serious adverse cardiovascular events from COX-2 selective and non-selective NSAIDs, dependent on dose and duration.


title: Rofecoxib

text: In November 2017, Massachusetts-based Tremeau Pharmaceuticals announced its plan to return rofecoxib (TRM-201) to market as a treatment for hemophilic arthropathy (HA). Tremeau announced that the FDA had granted an orphan designation for TRM-201 (rofecoxib) for the treatment of HA, and that they had received FDA feedback on their development plan. HA is a degenerative joint disease caused by recurrent intra-articular bleeding. It is the largest cause of morbidity in patients with hemophilia and has no currently approved treatment options in the United States. Traditional NSAIDs are avoided in this population due to their effects on platelet aggregation and risk of gastrointestinal ulcers, and high potency opioids are the current standard of care in treating HA.


title: Rofecoxib

text: Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the synthesis of prostaglandins responsible for protection of the stomach lining, while COX-2 mediates the synthesis of prostaglandins responsible for pain and inflammation. By creating "selective" NSAIDs that inhibit COX-2, but not COX-1, the same pain relief as traditional NSAIDs is offered, but with greatly reduced risk of fatal or debilitating peptic ulcers. Rofecoxib is a selective COX-2 inhibitor, or "coxib".


title: Rofecoxib

text: Though the class of coxibs includes several agents, there are varying degrees of COX-2 selectivity among them, with celecoxib (Celebrex) being the least COX-2 selective, and rofecoxib (Vioxx), valdecoxib (Bextra), and etoricoxib (Arcoxia), being highly COX-2 selective.


title: Rofecoxib

text: At the time of its withdrawal, rofecoxib was the only coxib approved in the United States with clinical evidence of its superior gastrointestinal adverse effect profile over conventional NSAIDs. This was largely based on the VIGOR (Vioxx GI Outcomes Research) study, which compared the efficacy and adverse effect profiles of rofecoxib and naproxen.


title: Rofecoxib

text: The therapeutic recommended dosages were 12.5, 25, and 50 mg with an approximate bioavailability of 93%. Rofecoxib crossed the placenta and blood–brain barrier, and took 1–3 hours to reach peak plasma concentration with an effective half-life (based on steady-state levels) of approximately 17 hours. The metabolic products are cis-dihydro and trans-dihydro derivatives of rofecoxib which are primarily excreted through urine.


title: Rofecoxib

text: Rofecoxib was approved by the FDA to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. When it was marketed, it gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain.


title: Rofecoxib

text: A 2003 placebo-controlled small short-term study in India of 80 women with premenstrual acne vulgaris acne, were given rofecoxib or placebo for 2 cycles of 10 days suggest that "rofecoxib is effective in the management of premenstrual acne.


title: Rofecoxib

text: On March 11, 2009, Scott S. Reuben, former chief of acute pain at Baystate Medical Center, Springfield, Mass., revealed that data for 21 studies he had authored for the efficacy of the drug (along with others such as celecoxib) had been fabricated, overstating the analgesic effects of the drugs. There is no evidence that Reuben colluded with Merck in falsifying his data. Reuben was also a former paid spokesperson for the drug company Pfizer (which owns the intellectual property rights for marketing celecoxib in the United States). The retracted studies were not submitted to either the FDA or the European Union's regulatory agencies prior to the drug's approval. Drug manufacturer Merck had no comment on the disclosure.


title: Rofecoxib

text: In addition to the reduced incidence of gastric ulceration, rofecoxib exhibits no effect on bleeding time or platelet aggregation, even at supra-therapeutic doses.  Aside from these features, rofecoxib exhibits a similar adverse effect profile to other NSAIDs.


title: Rofecoxib

text: The VIGOR (Vioxx GI Outcomes Research) study, conducted by Bombardier, et al., compared the efficacy and adverse effect profiles of a supra-therapeutic dose of rofecoxib (50 mg/day) vs. a common dose of naproxen (500 mg/BID), had indicated a significant 4-fold increased risk of acute myocardial infarction (heart attack) in rofecoxib patients when compared with naproxen patients (0.4% vs 0.1%, RR 0.25) over a mean duration of 9-months. The elevated risk began during the second month on rofecoxib. There was no significant difference in the mortality from cardiovascular events between the two groups, nor was there any significant difference in the rate of myocardial infarction between the rofecoxib and naproxen treatment groups in patients without high cardiovascular risk. The difference in overall risk was by the patients at higher risk of heart attack, i.e. those meeting the criteria for low-dose aspirin prophylaxis of secondary cardiovascular events (previous myocardial infarction, angina, cerebrovascular accident, transient ischemic attack, or coronary artery bypass).


title: Rofecoxib

text: Merck's scientists interpreted the finding as a protective effect of naproxen, telling the FDA that the difference in heart attacks "is primarily due to" this protective effect. The Martin Report excused senior management by stating they believed they were victims of Pfizer's alleged manipulation of test results to promote their product as a safer alternative. Some commentators have noted that naproxen would have to be three times as effective as aspirin to account for all of the difference, and some outside scientists warned Merck that this claim was implausible before VIGOR was published. No evidence has since emerged for such a large cardioprotective effect of naproxen, although a number of studies have found protective effects similar in size to those of aspirin.


title: Rofecoxib

text: The results of the VIGOR study were submitted to the United States Food and Drug Administration (FDA) in February 2001. In September 2001, the FDA sent a warning letter to the CEO of Merck, stating, "Your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)." This led to the introduction, in April 2002, of warnings on Vioxx labeling concerning the increased risk of cardiovascular events (heart attack and stroke).


title: Rofecoxib

text: Months after the preliminary version of VIGOR was published in the "New England Journal of Medicine" in November 2000, the journal editors learned that certain data reported to the FDA were not included in the "NEJM" article. Several years later, when they were shown a Merck memo during the depositions for the first federal Vioxx trial, they realized that these data had been available to the authors months before publication. The editors wrote an editorial accusing the authors of deliberately withholding the data. They released the editorial to the media on December 8, 2005, before giving the authors a chance to respond. "NEJM" editor Gregory Curfman explained that the quick release was due to the imminent presentation of his deposition testimony, which he feared would be misinterpreted in the media. He had earlier denied any relationship between the timing of the editorial and the trial. Although his testimony was not actually used in the December trial, Curfman had testified well before the publication of the editorial.


title: Rofecoxib

text: The editors charged that "more than four months before the article was published, at least two of its authors were aware of critical data on an array of adverse cardiovascular events that were not included in the VIGOR article." These additional data included three additional heart attacks, and raised the relative risk of Vioxx from 4.25-fold to 5-fold. All the additional heart attacks occurred in the group at low risk of heart attack (the "aspirin not indicated" group) and the editors noted that the omission "resulted in the misleading conclusion that there was a difference in the risk of myocardial infarction between the aspirin indicated and aspirin not indicated groups." The relative risk for myocardial infarctions among the aspirin not indicated patients increased from 2.25 to 3 (although it remained statistically insignificant). The editors also noted a statistically significant (2-fold) increase in risk for serious thromboembolic events for this group, an outcome that Merck had not reported in the "NEJM", though it had disclosed that information publicly in March 2000, eight months before publication.