title: Apollo program

text: The problems with North American were severe enough in late 1965 to cause Manned Space Flight Administrator George Mueller to appoint program director Samuel Phillips to head a "tiger team" to investigate North American's problems and identify corrections. Phillips documented his findings in a December 19 letter to NAA president Lee Atwood, with a strongly worded letter by Mueller, and also gave a presentation of the results to Mueller and Deputy Administrator Robert Seamans. Meanwhile, Grumman was also encountering problems with the Lunar Module, eliminating hopes it would be ready for crewed flight in 1967, not long after the first crewed CSM flights.


title: Apollo program

text: Grissom, White, and Chaffee decided to name their flight Apollo1 as a motivational focus on the first crewed flight. They trained and conducted tests of their spacecraft at North American, and in the altitude chamber at the Kennedy Space Center. A "plugs-out" test was planned for January, which would simulate a launch countdown on LC-34 with the spacecraft transferring from pad-supplied to internal power. If successful, this would be followed by a more rigorous countdown simulation test closer to the February 21 launch, with both spacecraft and launch vehicle fueled.


title: Apollo program

text: The plugs-out test began on the morning of January 27, 1967, and immediately was plagued with problems. First, the crew noticed a strange odor in their spacesuits which delayed the sealing of the hatch. Then, communications problems frustrated the astronauts and forced a hold in the simulated countdown. During this hold, an electrical fire began in the cabin and spread quickly in the high pressure, 100% oxygen atmosphere. Pressure rose high enough from the fire that the cabin inner wall burst, allowing the fire to erupt onto the pad area and frustrating attempts to rescue the crew. The astronauts were asphyxiated before the hatch could be opened.


title: Apollo program

text: NASA immediately convened an accident review board, overseen by both houses of Congress. While the determination of responsibility for the accident was complex, the review board concluded that "deficiencies existed in command module design, workmanship and quality control". At the insistence of NASA Administrator Webb, North American removed Harrison Storms as command module program manager. Webb also reassigned Apollo Spacecraft Program Office (ASPO) Manager Joseph Francis Shea, replacing him with George Low.


title: Apollo program

text: To remedy the causes of the fire, changes were made in the Block II spacecraft and operational procedures, the most important of which were use of a nitrogen/oxygen mixture instead of pure oxygen before and during launch, and removal of flammable cabin and space suit materials. The Block II design already called for replacement of the Block I plug-type hatch cover with a quick-release, outward opening door. NASA discontinued the crewed Block I program, using the BlockI spacecraft only for uncrewed SaturnV flights. Crew members would also exclusively wear modified, fire-resistant A7L Block II space suits, and would be designated by the Block II titles, regardless of whether a LM was present on the flight or not.


title: Apollo program

text: On April 24, 1967, Mueller published an official Apollo mission numbering scheme, using sequential numbers for all flights, crewed or uncrewed. The sequence would start with Apollo 4 to cover the first three uncrewed flights while retiring the Apollo1 designation to honor the crew, per their widows' wishes.


title: Apollo program

text: In September 1967, Mueller approved a sequence of mission types which had to be successfully accomplished in order to achieve the crewed lunar landing. Each step had to be successfully accomplished before the next ones could be performed, and it was unknown how many tries of each mission would be necessary; therefore letters were used instead of numbers. The A missions were uncrewed Saturn V validation; B was uncrewed LM validation using the Saturn IB; C was crewed CSM Earth orbit validation using the Saturn IB; D was the first crewed CSM/LM flight (this replaced AS-258, using a single Saturn V launch); E would be a higher Earth orbit CSM/LM flight; F would be the first lunar mission, testing the LM in lunar orbit but without landing (a "dress rehearsal"); and G would be the first crewed landing. The list of types covered follow-on lunar exploration to include H lunar landings, I for lunar orbital survey missions, and J for extended-stay lunar landings.


title: Apollo program

text: The delay in the CSM caused by the fire enabled NASA to catch up on human-rating the LM and SaturnV. Apollo4 (AS-501) was the first uncrewed flight of the SaturnV, carrying a BlockI CSM on November 9, 1967. The capability of the command module's heat shield to survive a trans-lunar reentry was demonstrated by using the service module engine to ram it into the atmosphere at higher than the usual Earth-orbital reentry speed.


title: Apollo program

text: Apollo 5 (AS-204) was the first uncrewed test flight of the LM in Earth orbit, launched from pad 37 on January 22, 1968, by the Saturn IB that would have been used for Apollo 1. The LM engines were successfully test-fired and restarted, despite a computer programming error which cut short the first descent stage firing. The ascent engine was fired in abort mode, known as a "fire-in-the-hole" test, where it was lit simultaneously with jettison of the descent stage. Although Grumman wanted a second uncrewed test, George Low decided the next LM flight would be crewed.


title: Apollo program

text: This was followed on April 4, 1968, by Apollo 6 (AS-502) which carried a CSM and a LM Test Article as ballast. The intent of this mission was to achieve trans-lunar injection, followed closely by a simulated direct-return abort, using the service module engine to achieve another high-speed reentry. The Saturn V experienced pogo oscillation, a problem caused by non-steady engine combustion, which damaged fuel lines in the second and third stages. Two S-II engines shut down prematurely, but the remaining engines were able to compensate. The damage to the third stage engine was more severe, preventing it from restarting for trans-lunar injection. Mission controllers were able to use the service module engine to essentially repeat the flight profile of Apollo 4. Based on the good performance of Apollo6 and identification of satisfactory fixes to the Apollo6 problems, NASA declared the SaturnV ready to fly crew, canceling a third uncrewed test.


title: Apollo program

text: Apollo 7, launched from LC-34 on October 11, 1968, was the Cmission, crewed by Schirra, Eisele, and Cunningham. It was an 11-day Earth-orbital flight which tested the CSM systems.


title: Apollo program

text: Apollo 8 was planned to be the D mission in December 1968, crewed by McDivitt, Scott and Schweickart, launched on a SaturnV instead of two Saturn IBs. In the summer it had become clear that the LM would not be ready in time. Rather than waste the Saturn V on another simple Earth-orbiting mission, ASPO Manager George Low suggested the bold step of sending Apollo8 to orbit the Moon instead, deferring the Dmission to the next mission in March 1969, and eliminating the E mission. This would keep the program on track. The Soviet Union had sent two tortoises, mealworms, wine flies, and other lifeforms around the Moon on September 15, 1968, aboard Zond 5, and it was believed they might soon repeat the feat with human cosmonauts. The decision was not announced publicly until successful completion of Apollo 7. Gemini veterans Frank Borman and Jim Lovell, and rookie William Anders captured the world's attention by making ten lunar orbits in 20 hours, transmitting television pictures of the lunar surface on Christmas Eve, and returning safely to Earth.


title: Apollo program

text: The following March, LM flight, rendezvous and docking were successfully demonstrated in Earth orbit on Apollo 9, and Schweickart tested the full lunar EVA suit with its portable life support system (PLSS) outside the LM. The F mission was successfully carried out on Apollo 10 in May 1969 by Gemini veterans Thomas P. Stafford, John Young and Eugene Cernan. Stafford and Cernan took the LM to within of the lunar surface.


title: Apollo program

text: The G mission was achieved on Apollo 11 in July 1969 by an all-Gemini veteran crew consisting of Neil Armstrong, Michael Collins and Buzz Aldrin. Armstrong and Aldrin performed the first landing at the Sea of Tranquility at 20:17:40 UTC on July 20, 1969. They spent a total of 21 hours, 36 minutes on the surface, and spent 2hours, 31 minutes outside the spacecraft, walking on the surface, taking photographs, collecting material samples, and deploying automated scientific instruments, while continuously sending black-and-white television back to Earth. The astronauts returned safely on July 24.


title: Apollo program

text: In November 1969, Charles “Pete” Conrad became the third person to step onto the Moon, which he did while speaking more informally than had Armstrong:


title: Apollo program

text: Conrad and rookie Alan L. Bean made a precision landing of Apollo 12 within walking distance of the Surveyor 3 uncrewed lunar probe, which had landed in April 1967 on the Ocean of Storms. The command module pilot was Gemini veteran Richard F. Gordon Jr. Conrad and Bean carried the first lunar surface color television camera, but it was damaged when accidentally pointed into the Sun. They made two EVAs totaling 7hours and 45 minutes. On one, they walked to the Surveyor, photographed it, and removed some parts which they returned to Earth.


title: Apollo program

text: The contracted batch of 15 Saturn Vs was enough for lunar landing missions through Apollo 20. Shortly after Apollo 11, NASA publicized a preliminary list of eight more planned landing sites after Apollo 12, with plans to increase the mass of the CSM and LM for the last five missions, along with the payload capacity of the Saturn V. These final missions would combine the I and J types in the 1967 list, allowing the CMP to operate a package of lunar orbital sensors and cameras while his companions were on the surface, and allowing them to stay on the Moon for over three days. These missions would also carry the Lunar Roving Vehicle (LRV) increasing the exploration area and allowing televised liftoff of the LM. Also, the Block II spacesuit was revised for the extended missions to allow greater flexibility and visibility for driving the LRV.


title: Apollo program

text: The success of the first two landings allowed the remaining missions to be crewed with a single veteran as commander, with two rookies. Apollo 13 launched Lovell, Jack Swigert, and Fred Haise in April 1970, headed for the Fra Mauro formation. But two days out, a liquid oxygen tank exploded, disabling the service module and forcing the crew to use the LM as a "lifeboat" to return to Earth. Another NASA review board was convened to determine the cause, which turned out to be a combination of damage of the tank in the factory, and a subcontractor not making a tank component according to updated design specifications. Apollo was grounded again, for the remainder of 1970 while the oxygen tank was redesigned and an extra one was added.


title: Apollo program

text: About the time of the first landing in 1969, it was decided to use an existing Saturn V to launch the Skylab orbital laboratory pre-built on the ground, replacing the original plan to construct it in orbit from several Saturn IB launches; this eliminated Apollo 20. NASA's yearly budget also began to shrink in light of the successful landing, and NASA also had to make funds available for the development of the upcoming Space Shuttle. By 1971, the decision was made to also cancel missions 18 and 19. The two unused Saturn Vs became museum exhibits at the John F. Kennedy Space Center on Merritt Island, Florida, George C. Marshall Space Center in Huntsville, Alabama, Michoud Assembly Facility in New Orleans, Louisiana, and Lyndon B. Johnson Space Center in Houston, Texas.


title: Apollo program

text: The cutbacks forced mission planners to reassess the original planned landing sites in order to achieve the most effective geological sample and data collection from the remaining four missions. Apollo 15 had been planned to be the last of the H series missions, but since there would be only two subsequent missions left, it was changed to the first of three J missions.


title: Apollo program

text: Apollo 13's Fra Mauro mission was reassigned to Apollo 14, commanded in February 1971 by Mercury veteran Alan Shepard, with Stuart Roosa and Edgar Mitchell. This time the mission was successful. Shepard and Mitchell spent 33 hours and 31 minutes on the surface, and completed two EVAs totalling 9hours 24 minutes, which was a record for the longest EVA by a lunar crew at the time.


title: Apollo program

text: In August 1971, just after conclusion of the Apollo 15 mission, President Richard Nixon proposed canceling the two remaining lunar landing missions, Apollo 16 and 17. Office of Management and Budget Deputy Director Caspar Weinberger was opposed to this, and persuaded Nixon to keep the remaining missions.


title: Apollo program

text: Apollo 15 was launched on July 26, 1971, with David Scott, Alfred Worden and James Irwin. Scott and Irwin landed on July 30 near Hadley Rille, and spent just under two days, 19 hours on the surface. In over 18 hours of EVA, they collected about of lunar material.


title: Apollo program

text: Apollo 16 landed in the Descartes Highlands on April 20, 1972. The crew was commanded by John Young, with Ken Mattingly and Charles Duke. Young and Duke spent just under three days on the surface, with a total of over 20 hours EVA.


title: Apollo program

text: Apollo 17 was the last of the Apollo program, landing in the Taurus–Littrow region in December 1972. Eugene Cernan commanded Ronald E. Evans and NASA's first scientist-astronaut, geologist Dr. Harrison H. Schmitt. Schmitt was originally scheduled for Apollo 18, but the lunar geological community lobbied for his inclusion on the final lunar landing. Cernan and Schmitt stayed on the surface for just over three days and spent just over 23 hours of total EVA.


title: Apollo program

text: The Apollo program returned over of lunar rocks and soil to the Lunar Receiving Laboratory in Houston. Today, 75% of the samples are stored at the Lunar Sample Laboratory Facility built in 1979.


title: Apollo program

text: The rocks collected from the Moon are extremely old compared to rocks found on Earth, as measured by radiometric dating techniques. They range in age from about 3.2 billion years for the basaltic samples derived from the lunar maria, to about 4.6 billion years for samples derived from the highlands crust. As such, they represent samples from a very early period in the development of the Solar System, that are largely absent on Earth. One important rock found during the Apollo Program is dubbed the Genesis Rock, retrieved by astronauts David Scott and James Irwin during the Apollo 15 mission. This anorthosite rock is composed almost exclusively of the calcium-rich feldspar mineral anorthite, and is believed to be representative of the highland crust. A geochemical component called KREEP was discovered by Apollo 12, which has no known terrestrial counterpart. KREEP and the anorthositic samples have been used to infer that the outer portion of the Moon was once completely molten (see lunar magma ocean).


title: Apollo program

text: Almost all the rocks show evidence of impact process effects. Many samples appear to be pitted with micrometeoroid impact craters, which is never seen on Earth rocks, due to the thick atmosphere. Many show signs of being subjected to high-pressure shock waves that are generated during impact events. Some of the returned samples are of "impact melt" (materials melted near an impact crater.) All samples returned from the Moon are highly brecciated as a result of being subjected to multiple impact events.


title: Apollo program

text: From analyses of the composition of the returned lunar samples, it is now believed that the Moon was created through the impact of a large astronomical body with Earth.


title: Apollo program

text: Apollo cost $25.4 billion (or approximately $ in dollars when adjusted for inflation via the GDP deflator index).


title: Apollo program

text: Of this amount, $20.2 billion ($ adjusted) was spent on the design, development, and production of the Saturn family of launch vehicles, the Apollo spacecraft, spacesuits, scientific experiments, and mission operations. The cost of constructing and operating Apollo-related ground facilities, such as the NASA human spaceflight centers and the global tracking and data acquisition network, added an additional $5.2 billion ($ adjusted).


title: Apollo program

text: The amount grows to $28 billion ($ adjusted) if the costs for related projects such as Project Gemini and the robotic Ranger, Surveyor, and Lunar Orbiter programs are included.


title: Apollo program

text: Accurate estimates of human spaceflight costs were difficult in the early 1960s, as the capability was new and management experience was lacking. Preliminary cost analysis by NASA estimated $7 billion – $12 billion for a crewed lunar landing effort. NASA Administrator James Webb increased this estimate to $20 billion before reporting it to Vice President Johnson in April 1961.


title: Apollo program

text: Project Apollo was a massive undertaking, representing the largest research and development project in peacetime. At its peak, it employed over 400,000 employees and contractors around the country and accounted for more than half of NASA's total spending in the 1960s. After the first Moon landing, public and political interest waned, including that of President Nixon, who wanted to rein in federal spending. NASA's budget could not sustain Apollo missions which cost, on average, $445 million ($ adjusted) each while simultaneously developing the Space Shuttle. The final fiscal year of Apollo funding was 1973.


title: Apollo program

text: Looking beyond the crewed lunar landings, NASA investigated several post-lunar applications for Apollo hardware. The Apollo Extension Series ("Apollo X") proposed up to 30 flights to Earth orbit, using the space in the Spacecraft Lunar Module Adapter (SLA) to house a small orbital laboratory (workshop). Astronauts would continue to use the CSM as a ferry to the station. This study was followed by design of a larger orbital workshop to be built in orbit from an empty S-IVB Saturn upper stage and grew into the Apollo Applications Program (AAP). The workshop was to be supplemented by the Apollo Telescope Mount, which could be attached to the ascent stage of the lunar module via a rack. The most ambitious plan called for using an empty S-IVB as an interplanetary spacecraft for a Venus fly-by mission.


title: Apollo program

text: The S-IVB orbital workshop was the only one of these plans to make it off the drawing board. Dubbed Skylab, it was assembled on the ground rather than in space, and launched in 1973 using the two lower stages of a Saturn V. It was equipped with an Apollo Telescope Mount. Skylab's last crew departed the station on February 8, 1974, and the station itself re-entered the atmosphere in 1979 after development of the Space Shuttle was delayed too long to save it.


title: Apollo program

text: The Apollo–Soyuz program also used Apollo hardware for the first joint nation spaceflight, paving the way for future cooperation with other nations in the Space Shuttle and International Space Station programs.


title: Apollo program

text: In 2008, Japan Aerospace Exploration Agency's SELENE probe observed evidence of the halo surrounding the Apollo 15 Lunar Module blast crater while orbiting above the lunar surface.


title: Apollo program

text: Beginning in 2009, NASA's robotic Lunar Reconnaissance Orbiter, while orbiting above the Moon, photographed the remnants of the Apollo program left on the lunar surface, and each site where crewed Apollo flights landed. All of the U.S. flags left on the Moon during the Apollo missions were found to still be standing, with the exception of the one left during the Apollo 11 mission, which was blown over during that mission's lift-off from the lunar surface; the degree to which these flags retain their original colors remains unknown. The flags cannot be seen through a telescope from Earth.


title: Apollo program

text: The Apollo program has been described as the greatest technological achievement in human history. Apollo stimulated many areas of technology, leading to over 1,800 spinoff products as of 2015, including advances in the development of cordless power tools, fireproof materials, heart monitors, solar panels, digital imaging, and the use of liquid methane as fuel. The flight computer design used in both the lunar and command modules was, along with the Polaris and Minuteman missile systems, the driving force behind early research into integrated circuits (ICs). By 1963, Apollo was using 60 percent of the United States' production of ICs. The crucial difference between the requirements of Apollo and the missile programs was Apollo's much greater need for reliability. While the Navy and Air Force could work around reliability problems by deploying more missiles, the political and financial cost of failure of an Apollo mission was unacceptably high.


title: Apollo program

text: Technologies and techniques required for Apollo were developed by Project Gemini. The Apollo project was enabled by NASA's adoption of new advances in semiconductor electronic technology, including metal-oxide-semiconductor field-effect transistors (MOSFETs) in the Interplanetary Monitoring Platform (IMP) and silicon integrated circuit chips in the Apollo Guidance Computer (AGC).


title: Apollo program

text: The crew of Apollo 8 sent the first live televised pictures of the Earth and the Moon back to Earth, and read from the creation story in the Book of Genesis, on Christmas Eve 1968. An estimated one-quarter of the population of the world saw—either live or delayed—the Christmas Eve transmission during the ninth orbit of the Moon, and an estimated one-fifth of the population of the world watched the live transmission of the Apollo 11 moonwalk.


title: Apollo program

text: The Apollo program also affected environmental activism in the 1970s due to photos taken by the astronauts. The most well known include "Earthrise", taken by William Anders on Apollo 8, and "The Blue Marble", taken by the Apollo 17 astronauts. "The Blue Marble" was released during a surge in environmentalism, and became a symbol of the environmental movement as a depiction of Earth's frailty, vulnerability, and isolation amid the vast expanse of space.


title: Apollo program

text: According to "The Economist", Apollo succeeded in accomplishing President Kennedy's goal of taking on the Soviet Union in the Space Race by accomplishing a singular and significant achievement, to demonstrate the superiority of the free-market system. The publication noted the irony that in order to achieve the goal, the program required the organization of tremendous public resources within a vast, centralized government bureaucracy.


title: Apollo program

text: Prior to Apollo 11's 40th anniversary in 2009, NASA searched for the original videotapes of the mission's live televised moonwalk. After an exhaustive three-year search, it was concluded that the tapes had probably been erased and reused. A new digitally remastered version of the best available broadcast television footage was released instead.


title: Chronic traumatic encephalopathy

text: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse over time and can result in dementia. It is unclear if the risk of suicide is altered.


title: Chronic traumatic encephalopathy

text: Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, mixed martial arts, and Muay Thai—hence its original name "dementia pugilistica" (Latin for "fistfighter's dementia")—and contact sports such as American football, Australian rules football, professional wrestling, ice hockey, rugby, and association football (soccer), in semi-contact sports such as baseball and basketball, and military combat arms occupations. Other risk factors include being in the military, prior domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown, and as of 2022 definitive diagnosis can only occur at autopsy. The disease is classified as a tauopathy.


title: Chronic traumatic encephalopathy

text: There is no specific treatment for the disease. Rates of CTE have been found to be about 30% among those with a history of multiple head injuries; however, population rates are unclear. Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as "dementia pugilistica" or "fistfighter's dementia", "boxer's madness", or "punch drunk syndrome". It has been proposed that the rules of some sports be changed as a means of prevention.


title: Chronic traumatic encephalopathy

text: Symptoms of CTE, which occur in four stages, generally appear eight to ten years after an individual experiences repetitive mild traumatic brain injuries.


title: Chronic traumatic encephalopathy

text: First-stage symptoms are confusion, disorientation, dizziness, and headaches. Second-stage symptoms include memory loss, social instability, impulsive behavior, and poor judgment. Third and fourth stages include progressive dementia, movement disorders, hypomimia, speech impediments, sensory processing disorder, tremors, vertigo, deafness, depression and suicidality.


title: Chronic traumatic encephalopathy

text: Additional symptoms include dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis. The condition manifests as dementia, or declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under one's own power for a short time and/or Parkinsonism, or tremors and lack of coordination. It can also cause speech problems and an unsteady gait. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.


title: Chronic traumatic encephalopathy

text: Most documented cases have occurred in athletes with mild repetitive head impacts (RHI) over an extended period of time. Evidence indicates that repetitive concussive and subconcussive blows to the head cause CTE. Specifically contact sports such as boxing, American football, Australian rules football, wrestling, mixed martial arts, ice hockey, rugby, and association football. In association football (soccer), whether this is just associated with prolific headers or other injuries is unclear as of 2017. Other potential risk factors include military personnel (repeated exposure to explosive charges or large caliber ordnance), domestic violence, and repeated impact to the head. The exact amount of trauma required for the condition to occur is unknown although it is believed that it may take years to develop.


title: Chronic traumatic encephalopathy

text: The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimer's disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.


title: Chronic traumatic encephalopathy

text: The primary physical manifestations of CTE include a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe. The lateral ventricles and the third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle. Other physical manifestations of CTE include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra and locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum. As CTE progresses, there may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.


title: Chronic traumatic encephalopathy

text: On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus; the pathognomonic lesion must include p-tau in neurons to distinguish CTE from ARTAG. Supporting features of CTE are: superficial neurofibrillary tangles (NFTs); p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes (TSA) in the subpial region; p-tau dot-like neurites. Purely astrocytic perivascular p-tau pathology represents ARTAG and does not meet the criteria for CTE.


title: Chronic traumatic encephalopathy

text: A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS). Progressive muscle weakness and balance and gait problems (problems with walking) seem to be early signs of CTEM.


title: Chronic traumatic encephalopathy

text: Loss of neurons, scarring of brain tissue, collection of proteinaceous senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are implicated in the syndrome. Neurofibrillary tangles have been found in the brains of dementia pugilistica patients, but not in the same distribution as is usually found in people with Alzheimer's. One group examined slices of brain from patients having had multiple mild traumatic brain injuries and found changes in the cells' cytoskeletons, which they suggested might be due to damage to cerebral blood vessels.


title: Chronic traumatic encephalopathy

text: Increased exposure to concussions and subconcussive blows is regarded as the most important risk factor. This exposure can depend on the total number of fights, number of knockout losses, the duration of career, fight frequency, age of retirement, and boxing style.


title: Chronic traumatic encephalopathy

text: Diagnosis of CTE cannot be made in living individuals; a clear diagnosis is only possible during an autopsy. Though there are signs and symptoms some researchers associate with CTE, there is no definitive test to prove the existence in a living person. Signs are also very similar to that of other neurological conditions such as Alzheimer's.


title: Chronic traumatic encephalopathy

text: The lack of distinct biomarkers is the reason CTE cannot typically be diagnosed while a person is alive. Concussions are non-structural injuries and do not result in brain bleeding, which is why most concussions cannot be seen on routine neuroimaging tests such as CT or MRI. Acute concussion symptoms (those that occur shortly after an injury) should not be confused with CTE. Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years) and CTE symptoms can be difficult. Research studies are examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE. By the early 2010s, more progress in in-vivo diagnostic techniques for CTE had been made, using DTI, fMRI, MRI, and MRS imaging; however, more research needs to be done before any such techniques can be validated.


title: Chronic traumatic encephalopathy

text: PET tracers that bind specifically to tau protein are desired to aid diagnosis of CTE in living individuals. One candidate is the tracer , which is retained in the brain in individuals with a number of dementing disorders such as Alzheimer's disease, Down syndrome, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia, and Creutzfeldt–Jakob disease. In a small study of 5 retired NFL players with cognitive and mood symptoms, the PET scans revealed accumulation of the tracer in their brains. However, binds to beta-amyloid and other proteins as well. Moreover, the sites in the brain where the tracer was retained were not consistent with the known neuropathology of CTE. A more promising candidate is the tracer [F]-T807, which binds only to tau. It is being tested in several clinical trials.


title: Chronic traumatic encephalopathy

text: A putative biomarker for CTE is the presence in serum of autoantibodies against the brain. The autoantibodies were detected in football players who experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. The autoantibodies may enter the brain by means of a disrupted blood-brain barrier, and attack neuronal cells which are normally protected from an immune onslaught. Given the large numbers of neurons present in the brain (86 billion), and considering the poor penetration of antibodies across a normal blood-brain barrier, there is an extended period of time between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may constitute the earliest measurable event predicting CTE.


title: Chronic traumatic encephalopathy

text: According to 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE. Players still alive are not able to be tested.


title: Chronic traumatic encephalopathy

text: In order to help those suffering with possible CTE, the Patrick Risha CTE Awareness Foundation created this form to help patients identify symptoms and alert doctors for impactful care.


title: Chronic traumatic encephalopathy

text: Although the diagnosis of CTE cannot be determined by imaging, the effects of head trauma may be seen with the use of structural imaging. Imaging techniques include the use of magnetic resonance imaging, nuclear magnetic resonance spectroscopy, CT scan, single-photon emission computed tomography, Diffusion MRI, and Positron emission tomography (PET). One specific use of imaging is the use of a PET scan is to evaluate for tau deposition, which has been conducted on retired NFL players.


title: Chronic traumatic encephalopathy

text: The use of helmets and mouth-guards has been put forward as a possible preventative measure; though neither has significant research to support its use, both have been shown to reduce direct head trauma. Although there is no significant research to support the use of helmets to reduce the risk of concussions, there is evidence to support that helmet use reduces impact forces. Mouth guards have been shown to decrease dental injuries, but again have not shown significant evidence to reduce concussions. Because repeated impacts are thought to increase the likelihood of CTE development, a growing area of practice is improved recognition and treatment for concussions and other head trauma; removal from sport participation during recovery from these traumatic injuries is essential. Proper return-to-play protocol after possible brain injuries is also important in decreasing the significance of future impacts.


title: Chronic traumatic encephalopathy

text: Efforts are being made to change the rules of contact sports to reduce the frequency and severity of blows to the head. Examples of these rule changes are the evolution of tackling technique rules in American football, such as the banning of helmet-first tackles, and the addition of rules to protect defenseless players. Likewise, another growing area of debate is better implementation of rules already in place to protect athletes.


title: Chronic traumatic encephalopathy

text: Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport. Medical professionals have called for such a ban as early as the 1950s.


title: Chronic traumatic encephalopathy

text: No cure exists for CTE, and because it cannot be tested for until an autopsy is performed, people cannot know if they have it. Treatment is supportive as with other forms of dementia. Those with CTE-related symptoms may receive medication and non-medication related treatments.


title: Chronic traumatic encephalopathy

text: Rates of disease have been found to be about 30% among those with a history of multiple head injuries. Population rates, however, are unclear.


title: Chronic traumatic encephalopathy

text: Professional level athletes are the largest group with CTE, due to frequent concussions and sub-concussive impacts from play in contact sport. These contact-sports include American football, Australian rules football, ice hockey, Rugby football (Rugby union and Rugby league), boxing, kickboxing, mixed martial arts, association football, and wrestling. In association football, only prolific headers are known to have developed CTE.


title: Chronic traumatic encephalopathy

text: According to a 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE.


title: Chronic traumatic encephalopathy

text: Other individuals diagnosed with CTE were those involved in military service, had a previous history of chronic seizures, were domestically abused, or were involved in activities resulting in repetitive head collisions.


title: Chronic traumatic encephalopathy

text: CTE was originally studied in boxers in the 1920s as "punch-drunk syndrome." Punch-drunk syndrome was first described in 1928 by a forensic pathologist, Dr. Harrison Stanford Martland, who was the chief medical examiner of Essex County in Newark, New Jersey, in a "Journal of the American Medical Association" article, in which he noted the tremors, slowed movement, confusion and speech problems typical of the condition. The term "punch-drunk" was replaced with "dementia pugilistica" in 1937 by J.A. Millsbaugh, as he felt the term was condescending to former boxers. The initial diagnosis of "dementia pugilistica" was derived from the Latin word for boxer "pugil" (akin to "pugnus" 'fist', "pugnāre" 'to fight').


title: Chronic traumatic encephalopathy

text: Other terms for the condition have included chronic boxer's encephalopathy, traumatic boxer's encephalopathy, boxer's dementia, pugilistic dementia, chronic traumatic brain injury associated with boxing (CTBI-B), and punch-drunk syndrome.


title: Chronic traumatic encephalopathy

text: The seminal work on the disease came from British neurologist Macdonald Critchley, who in 1949 wrote a paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers". CTE was first recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. As evidence pertaining to the clinical and neuropathological consequences of repeated mild head trauma grew, it became clear that this pattern of neurodegeneration was not restricted to boxers, and the term chronic traumatic encephalopathy became most widely used.


title: Chronic traumatic encephalopathy

text: In 2002, American football player Mike Webster died following unusual and unexplained behavior. In 2005 Nigerian-American neuropathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published their findings in a paper titled "Chronic Traumatic Encephalopathy in a National Football League Player", followed by a paper on a second case in 2006 describing similar pathology.


title: Chronic traumatic encephalopathy

text: In June 2007 professional wrestler Chris Benoit murdered his wife and son before committing suicide days after appearing on television. His autopsy revealed he was in very advanced stages of CTE with his brain being said to resemble that of an 87-year-old with advanced Alzheimer's.


title: Chronic traumatic encephalopathy

text: In 2008, the Sports Legacy Institute joined with the Boston University School of Medicine (BUSM) to form the Center for the Study of Traumatic Encephalopathy (now the BU CTE Center). Brain Injury Research Institute (BIRI) also studies the impact of concussions.


title: Chronic traumatic encephalopathy

text: In 2014, Patrick Grange of Albuquerque was the first US soccer player with CTE at autopsy. He was well known for his heading and had died in 2012.


title: Chronic traumatic encephalopathy

text: In 2014, Patrick Risha was the first Dartmouth graduate diagnosed with CTE. His family started the website StopCTE.org and they spread awareness in his honor on CTE Awareness Day every January 30.


title: Chronic traumatic encephalopathy

text: On April 7, 2021, former National Football League player Phillip Adams was found to have shot and killed six people, before killing himself a day later. A subsequent autopsy revealed at that the time of the shooting, Adams had an "unusually severe" case of chronic traumatic encephalopathy.


title: Chronic traumatic encephalopathy

text: In October 2022. the United States National Institutes of Health formally acknowledged there was a causal link between repeated blows to the head and CTE.


title: Chronic traumatic encephalopathy

text: In 2005, forensic pathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published a paper, "Chronic Traumatic Encephalopathy in a National Football League Player", in the journal "Neurosurgery", based on analysis of the brain of deceased former NFL center Mike Webster. This was then followed by a paper on a second case in 2006 describing similar pathology, based on findings in the brain of former NFL player Terry Long.


title: Chronic traumatic encephalopathy

text: In 2008, the Center for the Study of Traumatic Encephalopathy at the BU School of Medicine (now the BU CTE Center) started the VA-BU-CLF Brain Bank at the Bedford Veterans Administration Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians. To date, the VA-BU-CLF Brain Bank is the largest CTE tissue repository in the world, with over 1000 brain donors.


title: Chronic traumatic encephalopathy

text: On 21 December 2009, the National Football League Players Association announced that it would collaborate with the BU CTE Center to support the center's study of repetitive brain trauma in athletes. Additionally, in 2010 the National Football League gave the BU CTE Center a $1 million gift with no strings attached. In 2008, twelve living athletes (active and retired), including hockey players Pat LaFontaine and Noah Welch as well as former NFL star Ted Johnson, committed to donate their brains to VA-BU-CLF Brain Bank after their deaths. In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the VA-BU-CLF Brain Bank.


title: Chronic traumatic encephalopathy

text: In 2010, 20 more NFL players and former players pledged to join the VA-BU-CLF Brain Donation Registry, including Chicago Bears linebacker Hunter Hillenmeyer, Hall of Famer Mike Haynes, Pro Bowlers Zach Thomas, Kyle Turley, and Conrad Dobler, Super Bowl Champion Don Hasselbeck and former pro players Lew Carpenter, and Todd Hendricks. In 2010, professional wrestlers Mick Foley, Booker T and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS player Taylor Twellman, who had to retire from the New England Revolution because of post-concussion symptoms, agreed to donate his brain upon his death. As of 2010, the VA-BU-CLF Brain Donation Registry consists of over 250 current and former athletes.


title: Chronic traumatic encephalopathy

text: In 2011, former North Queensland Cowboys player Shaun Valentine became the first Australian National Rugby League player to agree to donate his brain upon his death, in response to recent concerns about the effects of concussions on Rugby League players, who do not use helmets. Also in 2011, boxer Micky Ward, whose career inspired the film "The Fighter", agreed to donate his brain upon his death. In 2018, NASCAR driver Dale Earnhardt Jr., who retired in 2017 citing multiple concussions, became the first auto racing competitor agreeing to donate his brain upon his death.


title: Chronic traumatic encephalopathy

text: In related research, the Center for the Study of Retired Athletes, which is part of the Department of Exercise and Sport Science at the University of North Carolina at Chapel Hill, is conducting research funded by National Football League Charities to "study former football players, a population with a high prevalence of exposure to prior Mild Traumatic Brain Injury (MTBI) and sub-concussive impacts, in order to investigate the association between increased football exposure and recurrent MTBI and neurodegenerative disorders such as cognitive impairment and Alzheimer's disease (AD)".


title: Chronic traumatic encephalopathy

text: In February 2011, former NFL player Dave Duerson committed suicide via a gunshot to his chest, thus leaving his brain intact. Duerson left text messages to loved ones asking that his brain be donated to research for CTE. The family got in touch with representatives of the Boston University center studying the condition, said Robert Stern, the co-director of the research group. Stern said Duerson's gift was the first time of which he was aware that such a request had been made by someone who had committed suicide that was potentially linked to CTE. Stern and his colleagues found high levels of the protein tau in Duerson's brain. These elevated levels, which were abnormally clumped and pooled along the brain sulci, are indicative of CTE.


title: Chronic traumatic encephalopathy

text: In July 2010, NHL enforcer Bob Probert died of heart failure. Before his death, he asked his wife to donate his brain to CTE research because it was noticed that Probert experienced a mental decline in his 40s. In March 2011, researchers at Boston University concluded that Probert had CTE upon analysis of the brain tissue he donated. He was the second NHL player from the program at the BU CTE Center to be diagnosed with CTE postmortem.


title: Chronic traumatic encephalopathy

text: The BU CTE Center has also found indications of links between amyotrophic lateral sclerosis (ALS) and CTE in athletes who have participated in contact sports. Tissue for the study was donated by twelve athletes and their families to the VA-BU-CLF Brain Bank at the Bedford, Massachusetts VA Medical Center.


title: Chronic traumatic encephalopathy

text: In 2013, President Barack Obama announced the creation of the Chronic Effects of Neurotrauma Consortium or CENC, a federally funded research project devised to address the long-term effects of mild traumatic brain injury in military service personnel (SM's) and veterans. The CENC is a multi-center collaboration linking premiere basic science, translational, and clinical neuroscience researchers from the DoD, VA, academic universities, and private research institutes to effectively address the scientific, diagnostic, and therapeutic ramifications of mild TBI and its long-term effects.


title: Chronic traumatic encephalopathy

text: Nearly 20% of the more than 2.5 million U.S. service members (SMs) deployed since 2003 to Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have sustained at least one traumatic brain injury (TBI), predominantly mild TBI (mTBI), and almost 8% of all OEF/OIF Veterans demonstrate persistent post-TBI symptoms more than six months post-injury. Unlike those head injuries incurred in most sporting events, recent military head injuries are most often the result of blast wave exposure. After a competitive application process, a consortium led by Virginia Commonwealth University was awarded funding.<ref name="http://www.spectrum.vcu.edu"></ref><ref name="http://www.grpva.com"></ref><ref name="http://www.army-technology.com"></ref><ref name="http://www.army.mil"></ref><ref name="http://www.whitehouse.gov"></ref><ref name="http://www.news.vcu.edu"></ref>


title: Chronic traumatic encephalopathy

text: The project principal investigator for the CENC is David Cifu, chairman and Herman J. Flax professor of the Department of Physical Medicine and Rehabilitation (PM&R) at Virginia Commonwealth University (VCU) in Richmond, Virginia, with co-principal investigators Ramon Diaz-Arrastia, Professor of Neurology, Uniformed Services University of the Health Sciences, and Rick L. Williams, statistician at RTI International.


title: Chronic traumatic encephalopathy

text: In 2017, Aaron Hernandez, a former professional football player and convicted murderer, committed suicide at the age of 27 while in prison. His family donated his brain to the BU CTE Center. Ann McKee, the head of Center, concluded that "Hernandez had Stage 3 CTE, which researchers had never seen in a brain younger than 46 years old."


title: Chronic traumatic encephalopathy

text: Research into the genetic component of CTE is evolving, and well summarized in a recent review. Interestingly, the minor allele of TMEM106B has been found to be associated with a protective phenotype.


title: Lockheed C-5 Galaxy

text: The Lockheed C-5 Galaxy is a large military transport aircraft designed and built by Lockheed, and now maintained and upgraded by its successor, Lockheed Martin. It provides the United States Air Force (USAF) with a heavy intercontinental-range strategic airlift capability, one that can carry outsized and oversized loads, including all air-certifiable cargo. The Galaxy has many similarities to the smaller Lockheed C-141 Starlifter and the later Boeing C-17 Globemaster III. The C-5 is among the largest military aircraft in the world.


title: Lockheed C-5 Galaxy

text: The C-5 Galaxy's development was complicated, including significant cost overruns, and Lockheed suffered significant financial difficulties. Shortly after entering service, cracks in the wings of many aircraft were discovered and the C-5 fleet was restricted in capability until corrective work was completed. The C-5M Super Galaxy is an upgraded version with new engines and modernized avionics designed to extend its service life to 2040 and beyond.


title: Lockheed C-5 Galaxy

text: The USAF has operated the C-5 since 1969. In that time, the airlifter supported US military operations in all major conflicts including Vietnam, Iraq, Yugoslavia, and Afghanistan, as well as allied support, such as Israel during the Yom Kippur War and operations in the Gulf War. The Galaxy has also distributed humanitarian aid, provided disaster relief, and supported the US space program.


title: Lockheed C-5 Galaxy

text: In 1961, several aircraft companies began studying heavy jet transport designs that would replace the Douglas C-133 Cargomaster and complement Lockheed C-141 Starlifters. In addition to higher overall performance, the United States Army wanted a transport aircraft with a larger cargo bay than the C-141, whose interior was too small to carry a variety of their outsized equipment. These studies led to the "CX-4" design concept, but in 1962, the proposed six-engined design was rejected, because it was not viewed as a significant advance over the C-141. By late 1963, the next conceptual design was named CX-X. It was equipped with four engines, instead of six in the earlier CX-4 concept. The CX-X had a gross weight of , a maximum payload of , and a speed of Mach 0.75 (). The cargo compartment was wide by high and long with front and rear access doors. USAF studies showed that high-bypass turbofan engines were needed for thrust and fuel efficiency requirements.


title: Lockheed C-5 Galaxy

text: The criteria were finalized and an official request for proposal was issued in April 1964 for the "Heavy Logistics System" (CX-HLS) (previously CX-X). In May 1964, proposals for aircraft were received from Boeing, Douglas, General Dynamics, Lockheed, and Martin Marietta. General Electric, Curtiss-Wright, and Pratt & Whitney submitted proposals for the engines. After a downselect, Boeing, Douglas, and Lockheed were given one-year study contracts for the airframe, along with General Electric and Pratt & Whitney for the engines. All three of the designs shared a number of features. The cockpit was placed well above the cargo area to allow for cargo loading through a nose door. The Boeing and Douglas designs used a pod on the top of the fuselage containing the cockpit, while the Lockheed design extended the cockpit profile down the length of the fuselage, giving it an egg-shaped cross section. All of the designs had swept wings, as well as front and rear cargo doors, allowing simultaneous loading and unloading. Lockheed's design featured a T-tail, while the designs by Boeing and Douglas had conventional tails.


title: Lockheed C-5 Galaxy

text: The Air Force considered Boeing's design to be better than that of Lockheed, but Lockheed's proposal was the lowest total-cost bid. Lockheed was selected as the winner in September 1965, then awarded a contract in December 1965. General Electric's TF39 engine was selected in August 1965 to power the new transport plane. At the time, GE's engine concept was revolutionary, as all engines before had a bypass ratio less than two-to-one, while the TF39 promised and would achieve a ratio of eight-to-one, which had the benefits of increased engine thrust and lower fuel consumption. Boeing lost the military contract but went on to develop the successful 747 civilian airliner with over 1,500 aircraft built when manufacturing ended in 2022 after 54 years of production.


title: Lockheed C-5 Galaxy

text: The first C-5A Galaxy (serial number "66-8303") was rolled out of the manufacturing plant in Marietta, Georgia, on 2 March 1968. On 30 June 1968, flight testing of the C-5A began with the first flight, flown by Leo Sullivan, with the call sign "eight-three-oh-three heavy". Flight tests revealed that the aircraft exhibited a higher drag divergence Mach number than predicted by wind tunnel data. The maximum lift coefficient measured in flight with the flaps deflected 40° was higher than predicted (2.60 vs. 2.38), but was lower than predicted with the flaps deflected 25° (2.31 vs. 2.38) and with the flaps retracted (1.45 vs. 1.52).


title: Lockheed C-5 Galaxy

text: Aircraft weight was a serious issue during design and development. At the time of the first flight, the weight was below the guaranteed weight, but by the time of the delivery of the 9th aircraft, had exceeded guarantees. In July 1969, during a fuselage upbending test, the wing failed at 128% of limit load, which is below the requirement that it sustain 150% of limit load. Changes were made to the wing, but during a test in July 1970, it failed at 125% of limit load. A passive load-reduction system, involving uprigged ailerons, was incorporated, but the maximum allowable payload was reduced from . At the time, a 90% probability was predicted that no more than 10% of the fleet of 79 airframes would reach their fatigue life of 19,000 hours without cracking of the wing.


title: Lockheed C-5 Galaxy

text: Cost overruns and technical problems of the C-5A were the subject of a congressional investigation in 1968 and 1969. The C-5 program has the dubious distinction of being the first development program with a $1billion (equivalent to $ billion today) overrun. Due to the C-5's troubled development, the Department of Defense abandoned Total Package Procurement. In 1969, Henry Durham raised concerns about the C-5 production process with Lockheed, his employer. Subsequently, Durham was transferred and subjected to abuse until he resigned. The Government Accountability Office substantiated some of his charges against Lockheed. Later, the American Ethical Union honored Durham with the Elliott-Black Award. The Deputy Assistant Secretary of the Air Force for Management Systems, Ernest Fitzgerald, was another person whose fostering of public accountability was unwelcome.


title: Lockheed C-5 Galaxy

text: Upon completion of testing in December 1969, the first C-5A was transferred to the Transitional Training Unit at Altus Air Force Base, Oklahoma. Lockheed delivered the first operational Galaxy to the 437th Airlift Wing, Charleston Air Force Base, South Carolina, in June 1970. Due to higher than expected development costs, in 1970, public calls were made for the government to split the substantial losses that Lockheed was experiencing. Production was nearly brought to a halt in 1971 as Lockheed went through financial difficulties, due in part to the C-5 Galaxy's development, as well as a civilian jet liner, the Lockheed L-1011. The U.S. government gave loans to Lockheed to keep the company operational.


title: Lockheed C-5 Galaxy

text: In the early 1970s, NASA considered the C-5 for the Shuttle Carrier Aircraft role, to transport the Space Shuttle to Kennedy Space Center. However, they rejected it in favor of the Boeing 747, in part due to the 747's low-wing design. In contrast, the Soviet Union chose to transport its shuttles using the high-winged An-225, which derived from the An-124, which is similar in design and function to the C-5.


title: Lockheed C-5 Galaxy

text: During static and fatigue testing, cracks were noticed in the wings of several aircraft, and as a consequence, the C-5A fleet was restricted to 80% of maximum design loads. To reduce wing loading, load alleviation systems were added to the aircraft. By 1980, payloads were restricted to as low as for general cargo during peacetime operations. A $1.5 billion program (equivalent to $ billion today), known as H-Mod, to re-wing the 76 completed C-5As to restore full payload capability and service life began in 1976. After design and testing of the new wing design, the C-5As received their new wings from 1980 to 1987.


title: Lockheed C-5 Galaxy

text: In 1974, Iran, then having good relations with the United States, offered $160 million (equivalent to $ million today) to restart C-5 production to enable Iran to purchase aircraft for their own air force, in a similar climate as to their acquisition of F-14 Tomcat fighters. However, no C-5 aircraft were ever ordered by Iran, and the prospect was firmly halted by the Iranian Revolution in 1979.


title: Lockheed C-5 Galaxy

text: As part of President Ronald Reagan's military policy, funding was made available for expansion of the USAF's airlift capability. With the C-17 program still some years from completion, Congress approved funding for a new version of the C-5, the C-5B, in July 1982, to expand airlift capacity. The first C-5B was delivered to Altus Air Force Base in January 1986. In April 1989, the last of 50 C-5B aircraft was added to the 77 C-5As in the Air Force's airlift force structure. The C-5B includes all C-5A improvements and numerous additional system modifications to improve reliability and maintainability.


title: Lockheed C-5 Galaxy

text: In 1998, the Avionics Modernization Program (AMP) began upgrading the C-5's avionics to include a glass cockpit, navigation equipment, and a new autopilot system. Another part of the C-5 modernization effort is the Reliability Enhancement and Re-engining Program (RERP). The program replaced the engines with newer, more powerful ones.


title: Lockheed C-5 Galaxy

text: A total of 52 C-5s are contracted to be modernized, consisting of 49 B-, two C- and one A-model aircraft through the RERP. The program features over 70 changes and upgrades, including the newer General Electric engines. Three C-5s underwent RERP for testing purposes. Low-rate initial production started in August 2009 with Lockheed reaching full production in May 2011; 22 C-5M Super Galaxies have been completed as of August 2014. RERP upgrades were completed on 25 July 2018. The Air Force received the last modified aircraft on 1 August 2018.


title: Lockheed C-5 Galaxy

text: , Lockheed is investigating drag reduction by plasma-heating of turbulent transonic airflow in critical points, saving overall weight by reducing fuel consumption. The Air Force Research Laboratory is looking at shape-memory alloy for speed-dependent vortex generators.


title: Lockheed C-5 Galaxy

text: The C-5 is a large, high-wing cargo aircraft with a distinctive high T-tail fin (vertical) stabilizer, with four TF39 turbofan engines mounted on pylons beneath wings that are swept 25°. (The C-5M uses newer GE CF6 engines.) Similar in layout to its smaller predecessor, the C-141 Starlifter, the C-5 has 12 internal wing tanks and is equipped for aerial refueling. Above the plane-length cargo deck is an upper deck for flight operations and for seating 80 passengers in rear facing seats (unlike most commercial airplanes) and the embarked loadmaster crew in forward facing seats. Bay doors at both nose and tail open to enable "drive-through" loading and unloading of cargo.


title: Lockheed C-5 Galaxy

text: The cargo hold of the C-5 is longer than the entire length of the first powered flight by the Wright brothers at Kitty Hawk. For its voracious consumption of fuel and its maintenance and reliability issues the Galaxy's aircrews have nicknamed it "FRED", for Fucking Ridiculous, Economic/Environmental Disaster.


title: Lockheed C-5 Galaxy

text: Takeoff and landing distance requirements for the plane at maximum-load gross weight are and , respectively. Its high-flotation main landing gear provides 28 wheels to distribute gross weight on paved or earth surfaces. The rear main landing gear can be made to caster to make a smaller turning radius, and rotates 90° after takeoff before being retracted. "Kneeling" landing gear permits lowering the aircraft when parked, thereby presenting the cargo deck at truck-bed height to facilitate loading and unloading operations.


title: Lockheed C-5 Galaxy

text: The C-5 features a malfunction detection analysis and recording system to identify errors throughout the aircraft.


title: Lockheed C-5 Galaxy

text: The cargo compartment is long, high, and wide, or just over . It can accommodate up to 36 463L master pallets or a mix of palletized cargo and vehicles. The nose and aft cargo-bay doors open the full width and height of the cargo bay to maximize efficient loading of oversized equipment. Full-width ramps enable loading double rows of vehicles from either end of the cargo hold.


title: Lockheed C-5 Galaxy

text: The C-5 Galaxy is capable of moving nearly every type of military combat equipment, including such bulky items as the Army armored vehicle launched bridge, at , from the United States to any location on the globe; and of accommodating up to six Boeing AH-64 Apache helicopters or five Bradley Fighting Vehicles at one time.


title: Lockheed C-5 Galaxy

text: The first C-5A was delivered to the USAF on 17 December 1969. Wings were built up in the early 1970s at Altus AFB, Oklahoma; Charleston AFB, South Carolina; Dover AFB, Delaware; and Travis AFB, California. The C-5's first mission was on 9 July 1970, in Southeast Asia during the Vietnam War. C-5s were used to transport equipment and troops, including Army tanks and even some small aircraft, throughout the later years of the US action in Vietnam. In the final weeks of the war, prior to the Fall of Saigon, several C-5s were involved in evacuation efforts. During one such mission, a C-5A crashed while transporting a large number of orphans, with over 140 killed.


title: Lockheed C-5 Galaxy

text: C-5s have also been used to deliver support and reinforce various US allies over the years. During the Yom Kippur War in 1973, multiple C-5s and C-141 Starlifters delivered critical supplies of ammunition, replacement weaponry and other forms of aid to Israel, the US effort was named as Operation Nickel Grass. The C-5 Galaxy's performance in Israel was such that the Pentagon began to consider further purchases. The C-5 was regularly made available to support American allies, such as the British-led peacekeeper initiative in Zimbabwe in 1979.


title: Lockheed C-5 Galaxy

text: On 24 October 1974, the Space and Missile Systems Organization successfully conducted an air-launched ballistic missile test, where a C-5A Galaxy aircraft air dropped an Minuteman ICBM from over the Pacific Ocean. The missile descended to before its rocket engine fired. The 10-second engine burn carried the missile to again before it dropped into the ocean. The test proved the feasibility of launching an intercontinental ballistic missile from the air. Operational deployment was discarded due to engineering and security difficulties, though the capability was used as a negotiating point in the Strategic Arms Limitation Talks. Aircraft 69–0014, "Zero-One-Four" used in the test was retired to the Air Mobility Command Museum at Dover Air Force Base.


title: Lockheed C-5 Galaxy

text: The C-5 has been used for several unusual functions. During the development of the secretive stealth fighter, the Lockheed F-117 Nighthawk, Galaxies were often used to carry partly disassembled aircraft, leaving no exterior signs as to their cargo. The C-5 remains the largest aircraft to operate in the Antarctic, capable of operating from Williams Field near McMurdo Station. The C-5 Galaxy was a major supply asset in the international coalition operations in 1990–91 against Iraq in the Gulf War. C-5s have routinely delivered relief aid and humanitarian supplies to areas afflicted with natural disasters or crisis; multiple flights were made over Rwanda in 1994.


title: Lockheed C-5 Galaxy

text: The wings on the C-5As were replaced during the 1980s to restore full design capability. The USAF took delivery of the first C-5B on 28 December 1985 and the final one in April 1989. The reliability of the C-5 fleet has been a continued issue throughout its lifetime, however the C-5M upgrade program seeks in part to address this issue. Their strategic airlift capacity has been a key logistical component of U.S. military operations in Afghanistan and Iraq. Following an incident during Operation Iraqi Freedom where one C-5 was damaged by a projectile, the installation of defensive systems has become a stated priority.


title: Lockheed C-5 Galaxy

text: The C-5 AMP and RERP modernization programs plan to raise mission-capable rate to a minimum goal of 75%. Over the next 40 years, the U.S. Air Force estimates the C-5M will save over $20 billion. The first C-5M conversion was completed on 16 May 2006 and C-5Ms began test flights at Dobbins Air Reserve Base in June 2006. In 2008, the USAF decided to convert remaining C-5Bs and C-5Cs into C-5Ms with avionics upgrades and re-engining. The C-5As will receive only the avionics upgrades. The last of 52 C-5Ms was delivered to Air Mobility Command in August 2018.


title: Lockheed C-5 Galaxy

text: In response to Air Force plans to retire older C-5 aircraft, Congress implemented legislation that set limits on retirement plans for C-5As in 2003. As of November 2013, 45 C-5As have been retired, 11 have been scrapped, parts of one (A/C 66-8306) are now a cargo load trainer at Lackland AFB, Texas and one was sent to the Warner Robins Air Logistics Center (WR-ALC) for tear down and inspection to evaluate structural integrity and estimate the remaining life for the fleet.


title: Lockheed C-5 Galaxy

text: The U.S. Air Force began to receive refitted C-5M aircraft in December 2008. Full production of C-5Ms began in the summer of 2009. In 2009, the Congressional ban on the retirement of C-5s was overturned. The Air Force seeks to retire one C-5A for every 10 new C-17s ordered. In October 2011, the 445th Airlift Wing based at Wright-Patterson Air Force Base replaced all remaining C-5s with C-17s. The C-5M reached initial operating capability (IOC) on 24 February 2014 with 16 aircraft delivered.


title: Lockheed C-5 Galaxy

text: On 13 September 2009, a C-5M set 41 new records and flight data was submitted to the National Aeronautic Association for formal recognition. The C-5M had carried a payload of to over in 23 minutes, 59 seconds. Additionally, 33 time to climb records at various payload classes were set, and the world record for greatest payload to was broken. The aircraft was in the category of with a takeoff weight of including payload, fuel, and other equipment.


title: Lockheed C-5 Galaxy

text: On 18 July 2017, C-5s based at Dover were ordered to stand down so maintenance crews could determine the cause for some nose landing gear failing. The last TF39-powered C-5 flew in late 2017.


title: Lockheed C-5 Galaxy

text: The C-5A is the original version of the C-5. From 1969 to 1973, 81 C-5As were delivered to the Military Airlift Command of the U.S. Air Force. Due to cracks found in the wings in the mid-1970s, the cargo weight was restricted. To restore the C-5's full capability, the wing structure was redesigned. A program to install new strengthened wings on 77 C-5As was conducted from 1981 to 1987. The redesigned wing made use of a new aluminum alloy that did not exist during the original production. As of August 2016, there were 10 A-models in service flown by the Air Force Reserve Command's 433d Airlift Wing at Lackland AFB / Kelly Field, Texas, and 439th Airlift Wing at Westover ARB, Massachusetts. The last operational C-5A was retired on 7 September 2017.


title: Lockheed C-5 Galaxy

text: The C-5B is an improved version of the C-5A. It incorporated all modifications and improvements made to the C-5A with improved wings, simplified landing gear, upgraded TF-39-GE-1C turbofan engines and updated avionics. Fifty examples of the new variant were delivered to the U.S. Air Force from 1986 to 1989.


title: Lockheed C-5 Galaxy

text: The C-5C is a specially modified variant for transporting large cargo. Two C-5As (68-0213 and 68-0216) were modified following major accidents to have a larger internal cargo capacity to accommodate large payloads, such as satellites. The major modifications were the removal of the rear passenger compartment floor, splitting the rear cargo door in the middle, and installing a new movable aft bulkhead further to the rear. The official C-5 technical manual refers to the version as C-5A(SCM) "Space Cargo Modified". Modifications also included adding a second inlet for ground power, which can feed any power-dependent equipment that may form part of the cargo. The two C-5Cs are operated by U.S. Air Force crews for DOD spacecraft programs and NASA, and are stationed at Travis AFB, California. Both C-5Cs #68-0213 and #68-0216 have been modified into C-5Ms as of 2017.


title: Lockheed C-5 Galaxy

text: Following a study showing that 80% of the C-5 airframe's service life was remaining, Air Mobility Command (AMC) began an aggressive program to modernize all remaining C-5Bs and C-5Cs and many of the C-5As. The C-5 Avionics Modernization Program (AMP) began in 1998 and includes upgrading the avionics to comply with Global Air Traffic Management standards, improving communications, fitting new flat-panel displays, improving navigation and safety equipment, and installing a new autopilot system. The first flight of a C-5 with AMP (85-0004) occurred on 21 December 2002.


title: Lockheed C-5 Galaxy

text: The Reliability Enhancement and Re-engining Program (RERP) began in 2006. It includes fitting new General Electric F138-GE-100 (CF6-80C2) engines, pylons and auxiliary power units, and upgrades to aircraft skin and frame, landing gear, cockpit and pressurization systems. Each CF6 engine produces 22% more thrust (), providing a 30% shorter takeoff, a 38% higher climb rate to initial altitude, an increased cargo load and a longer range. Upgraded C-5s are designated "C-5M Super Galaxy".


title: Lockheed C-5 Galaxy

text: Lockheed also planned a civilian version of the C-5 Galaxy, the "L-500", the company designation also used for the C-5 itself. Both passenger and cargo versions of the L-500 were designed. The all-passenger version would have been able to carry up to 1,000 travelers, while the all-cargo version was predicted to be able to carry typical C-5 volume for as little as 2 cents per ton-mile (in 1967 dollars). Although some interest was expressed by carriers, no orders were placed for either L-500 version, due to operational costs caused by low fuel efficiency, a significant concern for a profit-making carrier, even before the oil crisis of the 1970s, keen competition from Boeing's 747, and high costs incurred by Lockheed in developing the C-5, and later the L-1011, which led to the governmental rescue of the company.


title: Lockheed C-5 Galaxy

text: Lockheed proposed a twin body C-5 as a Shuttle Carrier Aircraft to counter the Conroy Virtus, but the design was turned down in favor of the Boeing 747.


title: Lockheed C-5 Galaxy

text: Three C-5 Galaxy aircraft have been lost in crashes along with two class-A losses resulting from ground fire, with a combined total of 169 fatalities. At least two other C-5 crashes have resulted in major airframe damage, but the aircraft were repaired and returned to service.


title: Prince Andrew of Greece and Denmark

text: Prince Andrew of Greece and Denmark (; ; – 3 December 1944) of the House of Schleswig-Holstein-Sonderburg-Glücksburg, was the seventh child and fourth son of King George I of Greece and Olga Constantinovna of Russia. He was a grandson of Christian IX of Denmark, and the father of Prince Philip, Duke of Edinburgh. He was a prince of both Denmark and Greece by virtue of his patrilineal descent.


title: Prince Andrew of Greece and Denmark

text: A career soldier, he began military training at an early age, and was commissioned as an officer in the Greek army. His command positions were substantive appointments rather than honorary, and he saw service in the Balkan Wars. In 1913, his father was assassinated and Andrew's elder brother, Constantine, became king. The king's neutrality policy during World War I led to his abdication, and most of the royal family, including Andrew, was exiled. On their return a few years later, Andrew saw service as Major General in the Greco-Turkish War (1919–1922), but the war went badly for Greece, and Andrew was blamed, in part, for the loss of Greek territory. He was exiled for a second time in 1922, and spent most of the rest of his life in France.


title: Prince Andrew of Greece and Denmark

text: By 1930, he was estranged from his wife, Princess Alice of Battenberg. His only son, Prince Philip, served in the British navy during World War II, while all four of his daughters were married to Germans, three of whom had Nazi connections. Separated from his wife and son by the effects of the war, Andrew died in Monte Carlo in 1944. He had seen neither of them since 1939.


title: Prince Andrew of Greece and Denmark

text: Prince Andrew was born at the Tatoi Palace just north of Athens on 2 February 1882, the fourth son of George I of Greece. A member of the House of Schleswig-Holstein-Sonderburg-Glücksburg, he was a prince of both Greece and Denmark, as his father was a younger son of Christian IX of Denmark. He was in the line of succession to the Greek and more distantly to the Danish throne.


title: Prince Andrew of Greece and Denmark

text: In addition to his native Greek he learned Danish, German, French, English and Russian; In conversations with his parents he refused to speak anything but Greek. He attended cadet school and staff college at Athens, and was given additional private tuition in military subjects by Panagiotis Danglis, who recorded that he was "quick and intelligent". He "became quite friendly" with fellow student Theodore Pangalos.


title: Prince Andrew of Greece and Denmark

text: In 1902, Prince Andrew met Princess Alice of Battenberg during his stay in London on the occasion of the coronation of Edward VII, who was his uncle-by-marriage and her grand-uncle. Princess Alice was a daughter of Prince Louis of Battenberg and Princess Victoria of Hesse and by Rhine, King Edward's niece. They fell in love, and the following year, on 6 October 1903, Andrew married Alice in a civil wedding at Darmstadt. The following day two religious wedding services were performed: one Lutheran in the Evangelical Castle Church, and another Greek Orthodox in the Russian Chapel on the Mathildenhöhe. Prince and Princess Andrew had five children, all of whom later had children of their own.


title: Prince Andrew of Greece and Denmark

text: In 1909, the political situation in Greece led to a "coup d'état", as the Athens government refused to support the Cretan parliament, which had called for the union of Crete (still nominally part of the Ottoman Empire) with the Greek mainland. A group of dissatisfied officers formed a Greek nationalist Military League and demanded, among other reforms, the removal of royal princes from the army, which led to Prince Andrew's resignation from the army and the rise to power of Eleftherios Venizelos.


title: Prince Andrew of Greece and Denmark

text: A few years later, at the outbreak of the Balkan Wars in 1912, Andrew was reinstated in the army as a lieutenant colonel in the 3rd Cavalry Regiment, and placed in command of a field hospital. During the war, his father was assassinated and Andrew inherited a villa on the island of Corfu, Mon Repos. In 1914, Andrew (like many European princes) held honorary military posts in both the German and Russian empires, as well as Prussian, Russian, Danish and Italian knighthoods.


title: Prince Andrew of Greece and Denmark

text: During World War I, he continued to visit Britain, despite veiled accusations in the British House of Commons that he was a German agent. His brother, King Constantine, who was the Kaiser's brother-in-law, followed a neutrality policy, but the democratically elected government of Venizelos supported the Allies. By June 1917, the King's neutrality policy had become so untenable that he abdicated and the Greek royal family were forced into exile. For the next few years, most of the Greek royal family lived in Switzerland.


title: Prince Andrew of Greece and Denmark

text: For three years, Constantine's second son, Alexander, was king of Greece, until his early death from an infection due to a monkey bite. Constantine was restored to the throne, and Andrew was once again reinstated in the army, this time as a major-general. The family took up residence at Mon Repos.


title: Prince Andrew of Greece and Denmark

text: Andrew was given command of the II Army Corps during the Battle of the Sakarya, which effectively stalemated the Greco-Turkish War (1919–1922). Andrew had little respect for his superior officers, whom he considered incompetent. He was ordered to attack the Turkish positions, which he considered a desperate move little short "of ill-concealed panic". Refusing to put his men in undue danger (suffering lack of food and ammunition), Andrew followed his own battle plan, much to the dismay of the commanding general, Anastasios Papoulas. Relieved of his chief of staff, and given a dressing-down by Papoulas, in September Andrew asked to be removed from command but Papoulas refused. Andrew's troops were forced to retreat. He was placed on leave for two months, until he was transferred to the Supreme Army Council. In March 1922, he was appointed as commander of the V Army Corps in Epirus and the Ionian Islands. Papoulas was replaced by General Georgios Hatzianestis.


title: Prince Andrew of Greece and Denmark

text: The Greek defeat in Asia Minor in August 1922 led to the 11 September 1922 Revolution, during which Prince Andrew was arrested, court-martialed, and found guilty of "disobeying an order" and "acting on his own initiative" during the battle of the previous year. Many defendants in the treason trials that followed the coup were shot, including Hatzianestis and five senior politicians. British diplomats assumed that Andrew was also in mortal danger. Andrew, though spared, was banished for life and his family fled into exile aboard a British cruiser, HMS "Calypso". The family settled at Saint-Cloud on the outskirts of Paris, in a small house loaned to them by Andrew's wealthy sister-in-law, Princess George of Greece. He and his family were stripped of their Greek nationality, and traveled under Danish passports.


title: Prince Andrew of Greece and Denmark

text: In 1930, Andrew published a book entitled "Towards Disaster: The Greek Army in Asia Minor in 1921", in which he defended his actions during the Battle of the Sakarya, but he essentially lived a life of enforced retirement, despite only being in his forties. During their time in exile the family became more and more dispersed. Alice suffered a nervous breakdown and was institutionalized in Switzerland. Their daughters married and settled in Germany, separated from Andrew, and Philip was sent to school in Britain, where he was brought up by his mother's British relatives. Andrew went to live in the South of France.


title: Prince Andrew of Greece and Denmark

text: On the French Riviera, Andrew lived in a small apartment, or hotel rooms, or on board a yacht with Countess Andrée de La Bigne. His marriage to Alice was effectively over, and after her recovery and release, she returned to Greece. In 1936, his sentence of exile was quashed by emergency laws, which also restored land and annuities to the King. Andrew returned to Greece for a brief visit that May. The following year, his pregnant daughter Cecilie, his son-in-law and two of his grandchildren were killed in an air accident at Ostend; he met Alice for the first time in six years at the funeral, which was also attended by Andrew's sixteen-year-old son Prince Philip.


title: Prince Andrew of Greece and Denmark

text: During World War II, he found himself essentially trapped in Vichy France, while his son, Prince Philip, fought on the side of the British. They were unable to see or even correspond with one another. Andrew's three surviving sons-in-law fought on the German side: Prince Christoph of Hesse was a member of the Nazi Party and the Waffen-SS; Berthold, Margrave of Baden, was invalided out of the Wehrmacht in 1940 after an injury in France; Prince Gottfried of Hohenlohe-Langenburg served on the Eastern Front and was dismissed after the 20 July plot. For five years, Andrew saw neither his wife nor his son.


title: Prince Andrew of Greece and Denmark

text: He died in the Hotel Metropole, Monte Carlo, Monaco, of heart failure and arteriosclerosis in the closing months of the war in Europe. Andrew was at first buried in the Russian Orthodox church in Nice, but in 1946 his remains were transferred, by the Greek cruiser "Averof", to the royal cemetery at Tatoi Palace, near Athens. Prince Philip and then-private secretary, Mike Parker, traveled to Monte Carlo to collect items belonging to his father from Andrée de La Bigne; among these items: a signet ring which the Prince wore from then onwards, an ivory shaving brush he took to using, and some clothes he had adapted to fit him. Prince Andrew left to his only son seven-tenths of his estate, but he also left behind a debt of £17,500, leading Philip's maternal grandmother, Victoria, Marchioness of Milford Haven, to complain bitterly of the extravagance the Greek prince had been led into by his French mistress.


title: Metronidazole

text: Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. It is an option for a first episode of mild-to-moderate "Clostridium difficile" colitis if vancomycin or fidaxomicin is unavailable. Metronidazole is available by mouth, as a cream, and by injection into a vein.


title: Metronidazole

text: Common side effects include nausea, a metallic taste, loss of appetite, and headaches. Occasionally seizures or allergies to the medication may occur. Some state that metronidazole should not be used in early pregnancy, while others state doses for trichomoniasis are safe. Metronidazole is generally considered compatible with breastfeeding.


title: Metronidazole

text: Metronidazole began to be commercially used in 1960 in France. It is on the World Health Organization's List of Essential Medicines. It is available in most areas of the world. In 2020, it was the 222nd most commonly prescribed medication in the United States, with more than 2million prescriptions.


title: Metronidazole

text: Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, periodontitis, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as "Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus", and "Prevotella" species. It is also often used to eradicate "Helicobacter pylori" along with other drugs and to prevent infection in people recovering from surgery.


title: Metronidazole

text: Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum.


title: Metronidazole

text: Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin. The treatment of choice for bacterial vaginosis in nonpregnant women include metronidazole oral twice daily for seven days, or metronidazole gel intravaginally once daily for five days, or clindamycin intravaginally at bedtime for seven days. For pregnant women, the treatment of choice is metronidazole oral three times a day for seven days. Data does not report routine treatment of male sexual partners.


title: Metronidazole

text: The 5-nitroimidazole drugs (metronidazole and tinidazole) are the mainstay of treatment for infection with "Trichomonas vaginalis". Treatment for both the infected patient and the patient's sexual partner is recommended, even if asymptomatic. Therapy other than 5-nitroimidazole drugs is also an option, but cure rates are much lower.


title: Metronidazole

text: Oral metronidazole is a treatment option for giardiasis, however, the increasing incidence of nitroimidazole resistance is leading to the increased use of other compound classes.


title: Metronidazole

text: In the case of "Dracunculus medinensis" (Guinea worm), metronidazole just eases worm extraction rather than killing the worm.


title: Metronidazole

text: Initial antibiotic therapy for less-severe "Clostridioides difficile infection" colitis (pseudomembranous colitis) consists of metronidazole, vancomycin, or fidaxomicin by mouth. In 2017, the IDSA generally recommended vancomycin and fidaxomicin over metronidazole. Vancomycin by mouth has been shown to be more effective in treating people with severe "C. difficile" colitis.


title: Metronidazole

text: "Entamoeba histolytica" invasive amebiasis is treated with metronidazole for eradication, in combination with diloxanide to prevent recurrence. Although it is generally a standard treatment it is associated with some side effects.


title: Metronidazole

text: Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). Metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women (selected by history and a positive fFN test) and, conversely, the incidence of preterm delivery was found to be higher in women treated with metronidazole.


title: Metronidazole

text: In addition to its anti-biotic properties, attempts were also made to use a possible radiation-sensitizing effect of metronidazole in the context of radiation therapy against hypoxic tumors. However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy. However, other nitroimidazoles derived from metronidazole such as nimorazole with reduced electron affinity showed less serious neuronal side effects and have found their way into radio-onological practice for head and neck tumors in some countries.


title: Metronidazole

text: "Canadian Family Physician" has recommended topical metronidazole as a third-line treatment for the perioral dermatitis either along with or without oral tetracycline or oral erythromycin as first and second line treatment respectively.


title: Metronidazole

text: Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic metronidazole therapy include: nausea, diarrhea, weight loss, abdominal pain, vomiting, headache, dizziness, and metallic taste in the mouth. Intravenous administration is commonly associated with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and paraesthesia. High doses and long-term systemic treatment with metronidazole are associated with the development of leucopenia, neutropenia, increased risk of peripheral neuropathy, and central nervous system toxicity. Common adverse drug reaction associated with topical metronidazole therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes). Metronidazole has been associated with cancer in animal studies. In rare cases, it can also cause temporary hearing loss that reverses after cessation of the treatment.


title: Metronidazole

text: Some evidence from studies in rats indicates the possibility it may contribute to serotonin syndrome, although no case reports documenting this have been published to date.


title: Metronidazole

text: In 2016 metronidazole was listed by the U.S. National Toxicology Program (NTP) as reasonably anticipated to be a human carcinogen. Although some of the testing methods have been questioned, oral exposure has been shown to cause cancer in experimental animals and has also demonstrated some mutagenic effects in bacterial cultures. The relationship between exposure to metronidazole and human cancer is unclear. One study found an excess in lung cancer among women (even after adjusting for smoking), while other studies found either no increased risk, or a statistically insignificant risk.


title: Metronidazole

text: Metronidazole is listed as a possible carcinogen according to the World Health Organization (WHO) International Agency for Research on Cancer (IARC). A study in those with Crohn's disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole.


title: Metronidazole

text: Metronidazole alone rarely causes Stevens–Johnson syndrome, but is reported to occur at high rates when combined with mebendazole.


title: Metronidazole

text: Consuming alcohol while taking metronidazole has been suspected in case reports to cause a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia, and shortness of breath. People are often advised not to drink alcohol during systemic metronidazole therapy and for at least 48 hours after completion of treatment. However, some studies call into question the mechanism of the interaction of alcohol and metronidazole,


title: Metronidazole

text: and a possible central toxic serotonin reaction for the alcohol intolerance is suggested. Metronidazole is also generally thought to inhibit the liver metabolism of propylene glycol (found in some foods, medicines, and in many electronic cigarette e-liquids), thus propylene glycol may potentially have similar interaction effects with metronidazole.


title: Metronidazole

text: Metronidazole is a moderate CYP2C9 inhibitor. CYP2C9 is an enzyme of cytochrome P450 family. Therefore, metronidazole may interact with medications metabolized by this enzyme. Examples of such medications are lomitapide, warfarin, etc.


title: Metronidazole

text: Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells. This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic bacteria and protozoans, it has relatively little effect upon human cells or aerobic bacteria.


title: Metronidazole

text: Oral metronidazole is approximately 80% bioavailable via the gut and peak blood plasma concentrations occur after one to two hours. Food may slow down absorption but does not diminish it. Of the circulating substance, about 20% is bound to plasma proteins. It penetrates well into tissues, the cerebrospinal fluid, the amniotic fluid and breast milk, as well as into abscess cavities.


title: Metronidazole

text: About 60% of the metronidazole is metabolized by oxidation to the main metabolite hydroxymetronidazole and a carboxylic acid derivative, and by glucuronidation. The metabolites show antibiotic and antiprotozoal activity "in vitro". Metronidazole and its metabolites are mainly excreted via the kidneys (77%) and to a lesser extent via the faeces (14%). The biological half-life of metronidazole in healthy adults is eight hours, in infants during the first two months of their lives about 23 hours, and in premature babies up to 100 hours.


title: Metronidazole

text: The biological activity of hydroxymetronidazole is 30% to 65%, and the elimination half-life is longer than that of the parent compound. The serum half-life of hydroxymetronidazole after suppository was 10 hours, 19 hours after intravenous infusion, and 11 hours after a tablet.


title: Metronidazole

text: The drug was initially developed by Rhône-Poulenc in the 1950s and licensed to G.D. Searle. Searle was acquired by Pfizer in 2003. The original patent expired in 1982, but evergreening reformulation occurred thereafter.


title: Metronidazole

text: In India, it is sold under the brand name Metrogyl and Flagyl. In Bangladesh, it is available as Amodis, Amotrex, Dirozyl, Filmet, Flagyl, Flamyd, Metra, Metrodol, Metryl, etc. In Pakistan, it is sold under the brand name of Flagyl and Metrozine.


title: Metronidazole

text: 2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2-Methylimidazole is nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in turn alkylated with ethylene oxide or 2-chloroethanol to give metronidazole (3):


title: Metronidazole

text: Metronidazole is used to treat infections of "Giardia" in dogs, cats, and other companion animals, although it does not reliably clear infection with this organism and is being supplanted by fenbendazole for this purpose in dogs and cats. It is also used for the management of chronic inflammatory bowel disease in cats and dogs. Another common usage is the treatment of systemic and/or gastrointestinal clostridial infections in horses. Metronidazole is used in the aquarium hobby to treat ornamental fish and as a broad-spectrum treatment for bacterial and protozoan infections in reptiles and amphibians. In general, the veterinary community may use metronidazole for any potentially susceptible anaerobic infection. The U.S. Food and Drug Administration (FDA) suggests it only be used when necessary because it has been shown to be carcinogenic in mice and rats, as well as to prevent antimicrobial resistance.


title: Intercontinental ballistic missile

text: An intercontinental ballistic missile (ICBM) is a ballistic missile with a range greater than , primarily designed for nuclear weapons delivery (delivering one or more thermonuclear warheads). Conventional, chemical, and biological weapons can also be delivered with varying effectiveness, but have never been deployed on ICBMs. Most modern designs support multiple independently targetable reentry vehicles (MIRVs), allowing a single missile to carry several warheads, each of which can strike a different target. Russia, the United States, China, France, India, the United Kingdom, and North Korea are the only countries known to have operational ICBMs.


title: Intercontinental ballistic missile

text: Early ICBMs had limited precision, which made them suitable for use only against the largest targets, such as cities. They were seen as a "safe" basing option, one that would keep the deterrent force close to home where it would be difficult to attack. Attacks against military targets (especially hardened ones) still demanded the use of a more precise, manned bomber. Second- and third-generation designs (such as the LGM-118 Peacekeeper) dramatically improved accuracy to the point where even the smallest point targets can be successfully attacked.


title: Intercontinental ballistic missile

text: ICBMs are differentiated by having greater range and speed than other ballistic missiles: intermediate-range ballistic missiles (IRBMs), medium-range ballistic missiles (MRBMs), short-range ballistic missiles (SRBMs) and tactical ballistic missiles (TBMs). Short and medium-range ballistic missiles are known collectively as the theatre ballistic missiles.


title: Intercontinental ballistic missile

text: The first practical design for an ICBM grew out of Nazi Germany's V-2 rocket program. The liquid-fueled V-2, designed by Wernher von Braun and his team, was widely used by Nazi Germany from mid-1944 until March 1945 to bomb British and Belgian cities, particularly Antwerp and London.


title: Intercontinental ballistic missile

text: Under "Projekt Amerika," von Braun's team developed the A9/10 ICBM, intended for use in bombing New York and other American cities. Initially intended to be guided by radio, it was changed to be a piloted craft after the failure of Operation Elster. The second stage of the A9/A10 rocket was tested a few times in January and February 1945.