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/index.php/Wheeze_medical_therapy

# Wheeze medical therapy All patients with COPD should be on a short-acting bronchodilator to be used on as-needed basis for intermittent increases in dyspnea. The purpose of the short-acting bronchodilator is to reduce symptoms and improve lung function. It is recommended to use a short-acting beta agonist plus a short-acting anticholinergic, rather than either alone, to achieve greater benefit. However, monotherapy with either is acceptable. For patients in whom intermittent short-acting bronchodilators are insufficient to control symptoms, a regularly scheduled long-acting inhaled bronchodilator is recommended. The purpose of the long-acting inhaled bronchodilator is to improve symptoms, improve lung function, and reduce the frequency of exacerbations. The effects of the currently available once daily long acting anticholinergic are superior to the effects of the twice daily long acting beta agonists that are available. Theophylline is the least preferred long-acting bronchodilator option because its effects are modest and toxicity is a concern. For patients who continue to have symptoms or repeated exacerbations despite an optimal long-acting inhaled bronchodilator regimen, adding an inhaled glucocorticoid is recommended. All patients with COPD should be advised to quit smoking, educated about COPD, and given a yearly influenza vaccination. In addition, the pneumococcal polysaccharide vaccine should be given to patients who are ≥ 65 years old, or who are younger than 65 years with a forced expiratory volume in one second (FEV1) less than 40 percent. Asthma severity is based upon current level of symptoms, FEV1 or PEFR values, and the number of exacerbations requiring oral glucocorticoids per year. Medications include: quick-acting inhaled beta-2-selective adrenergic agonists, long-acting inhaled beta agonists, inhaled glucocorticoids, leukotriene receptor antagonists, theophylline, cromoglycates, anti-IgE therapy (omalizumab), and oral glucocorticoids on a daily or alternate-day basis.

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/index.php/Wheeze_overview

# Wheeze overview A wheeze is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed, or airflow velocity within the respiratory tree must be heightened. Wheezing is commonly experienced by persons with a lung disease; the most common cause of recurrent wheezing is asthma, a form of reactive airway disease.

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/index.php/Whey_protein

# Whey protein Whey protein is the name for a collection of globular proteins that can be isolated from whey, a by-product of cheese manufactured from cow's milk. It is typically a mixture of beta-lactoglobulin (~65%), alpha-lactalbumin (~25%), and serum albumin (~8%), which are soluble in their native forms, independent of pH. Whey has the highest Biological Value (BV) of any known protein. Whey is a lactose-free or reduced lactose protein containing a variety of nutrients and essential amino acids. Whey comprises four major protein fractions and six minor protein fractions. The major protein fractions in whey are beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin and immunoglobulins. Each of these components have important disease-fighting effects. In addition, whey protein is easily digestible. Native whey protein does not aggregate upon renneting or acidification of milk. Prolonged heat-treatment at sufficiently high temperatures and long duration will denature (i.e. partly unfold) the whey protein, triggering hydrophobic interactions with other proteins, and the formation of disulfide bonds between whey proteins and casein micelles, leading to aggregation with other milk proteins at low pH. Whey protein can be denatured (irreversibly changed) by heat — similar to the protein in egg whites which, when cooked, permanently changes from a clear liquid to a white solid. When subjected to high heat (like the sustained high temperatures above 72 degrees Celsius (160 degrees Fahrenheit) associated with the pasteurization process) whey proteins become denatured and lose some bioactive compounds like cysteine, an amino acid that is a precursor to glutathione, an antioxidant. Whey protein typically comes in three major forms: concentrate, isolate and hydrolysate. Whey protein concentrates contain a low level of fat and cholesterol but generally have higher levels of bioactive compounds, and carbohydrates in the form of lactose — they are 29%-89% protein by weight. Isolates are processed to remove the fat, and lactose, but are usually lower in bioactive compounds as well — they are 90%+ protein by weight. Hydrolysates are predigested, partially hydrolyzed whey proteins which consequently are more easily absorbed, but their cost is generally higher. Whey protein contains high levels of both essential and non-essential amino acids, and pregnant mothers are sometimes advised by their obstetricians to supplement their diets with whey protein to ensure that their developing babies get all the basic amino acids they might need.[citation needed] More than other protein supplements, whey protein powder is commonly used by bodybuilders and other athletes to accelerate muscle development and aid in recovery. Some individuals with suppressed or otherwise abnormal immune systems or degenerative diseases use undenatured bioactive whey proteins to increase their antioxidant levels. Undenatured whey proteins are a good source of cysteine, a conditionally essential amino acid which is the rate limiting factor for the body's production of glutathione, an important antioxidant. Examples of commercial whey proteins include those available in most health food stores and supermarket health sections; they typically consist of isolate/concentrate or isolate/concentrate/hydrolysate mixtures and they are usually flavored so they can be mixed with water or milk and consumed as a drink or shake. It is not always as expensive as you would think, it can be purchased cheaply from any good sports store.

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/index.php/Whiplash_(medicine)

# Whiplash (medicine) Whiplash is the common name for neck sprains, such as those caused by hyper extension/flexion injury to the cervical, thoracic or lumbar spines. The injury is referred to as "whiplash" due to the neck or back being thrown forwards and/or backwards at a rapid speed. This may cause the fibres of the neck muscles to tear, resulting in pain and often a decreased range of movement. Whiplash and whiplash-associated disorders (WAD) represent a range of injuries to the neck caused by or related to a sudden distortion of the neck. Whiplash is commonly associated with motor vehicle accidents, usually when the vehicle has been hit in the rear, however the injury can be sustained in many other ways, including falls from bicycles or horses. The exact injury mechanism that causes whiplash injuries is unknown. A whiplash injury may be the result of impulsive stretching of the spine, mainly the ligament: anterior longitudinal ligament which is stretched or tears, as the head snaps forward and then back again causing a whiplash injury. Whiplash may be caused by any motion similar to a rear-end collision in a motor vehicle, such as may take place on a roller coaster or other rides at an amusement park, sports injuries such as skiing accidents, other modes of transportation such as airplane travel, or from being hit or shaken. Shaken baby syndrome can result in a whiplash injury. Symptoms reported by sufferers include: pain and aching to the neck and back, referred pain to the shoulders, sensory disturbance (such as pins and needles) to the arms & legs and headaches. Symptoms can appear directly after the injury, but often are not felt until days afterwards. Whiplash is usually confined to the spinal cord (neck to pubic bone), and the most common areas of the spinal cord affected by whiplash are the neck, and the mid-back (middle of the spine). Reliably diagnosing a whiplash injury or disorder is not difficult for a trained doctor. If a patient cannot achieve the full motion, or has excessive range of motion,or chronic pain, the probable ultimate cause is the whiplash motion.[citation needed]Because whiplash may be caused by damage to the soft tissues of the spine (ex: tearing of a disk), these injuries often cannot be seen on an X-ray machine, and an alternative type of scanning machine such as an MRI is used instead. Certain severe injuries caused by whiplash movement, such as torn ligaments of the head-neck-joint system (e.g. the alar ligaments) cannot be displayed with non-functional imaging techniques. For showing ligamental damage functional imaging is essential. The Québec Task Force (QTF) was a task force sponsored by the Société de l'assurance automobile du Québec, the public auto insurer in Quebec, Canada. The QTF submitted a report on whiplash-associated disorders in 1995, which made specific recommendations on prevention, diagnosis and treatment of WAD. These recommendations have become the base for Guideline on the Management of Claims Involving Whiplash-Associated, a guide to classifying WAD and guidelines on managing the disorder. The full report titled Redefining "Whiplash" was published in the April 15, 1995 issue of Spine. An update was published in January of 2001. The QTF grading system is remarkably similar to the one developed by Dr. AC Croft in 1992 and subsequently published in 1993. However, the QTF Guidelines, published some 2 years later, fail to cite Dr. Croft's work. Croft AC: Treatment paradigm for cervical acceleration/deceleration injuries (whiplash). ACA J Chiro 30(1):41-45, 1993. The consequences of whiplash range from mild pain for a few days (which is the case for most people) , to severe disability caused by restricted head movement or of the cervical spine, sometimes with persistent pain. The injury can exacerbate pre-existing conditions, such as spondylosis and other degenerative changes.[citation needed] Protection efforts are hampered by lack of knowledge about the causes of whiplash injuries. The focus of preventive measures to date has been on the design of car seats, primarily through the introduction of headrestraints, often incorrectly called headrests. This approach is potentially problematic given the underlying assumption that purely mechanical factors cause whiplash injuries - an unproven theory. So far the injury reducing effects of head restraints appears to have been low, approximately 5-10%, because car seats have become stiffer in order to increase crash-worthiness of cars in high-speed rear-end collisions which in turn could increase the risk of whiplash injury in low-speed rear impact collisions. Improvements in the geometry of car seats through better design and energy absorption could offer additional benefits. Active devices move the body in a crash in order to shift the loads on the car seat. Some car manufacturers have begun to implement various whiplash protection devices in their products in order to reduce the risk for and severity of injury, such as Whether or not such devices offer a substantial benefit over vehicles without them remains controversial. In a test undertaken by the Swedish National Road Administration and an insurance company (Folksam), one test showed that a whiplash protection device was no guarantee against injury and that the degree of protection varies between vehicles both with and without whiplash protection devices. Yet The Journal of TRAUMA, Volume 51, No 5, November 2001 found that an Active Head Restraint helps reduce the risk of neck injuries by up to 75% in rear-end collisions.

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/index.php/Whisper_triangle

# Whisper triangle The Whispering Triangle is an opening in the larynx which allows air to pass from the lungs to the mouth even though the vocal folds are adducted (i.e. closed). It is opened if the back part of the Arytenoid catilage is pulled apart while the front part is close together in order to facilitate closed vocal folds. Because the opening of the Whisper Triangle is quite small, air rushing through it creates turbulence in the air stream, which can be perceived as acoustic noise. This noise is used for the production of vowels in (unvoiced) whispering.

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/index.php/Whistle_register

# Whistle register The whistle register (also called the flageolet register and in Speech Level Singing the super-head register) is the highest register of the human voice. The register is so called because the timbre of the notes that are produced from this register is similar to that of a whistle. The physiology of the whistle register is the least understood of the vocal registers. It is known that when producing pitches in this register, vibration occurs only in some anterior portion of the vocal folds. This shorter vibrating length naturally allows for easier production of high pitches. The physiological process that causes this is not currently known. The whistle register is most commonly used to produce pitches around and above the soprano C. By the physiological definition just detailed, it is a configuration of the vocal folds and is a range of pitches. However, there is no universally agreed-upon scheme for classifying vocal registers, so it is common to see other definitions. In European classical music, the whistle register is rarely called for. When it is, it is exclusively used by coloratura sopranos to produce pitches above C6. Probably the best-known example of the whistle register in European classical music is in the "Queen of the Night" aria (properly titled "Der Hölle Rache kocht in meinem Herzen") from the Mozart opera Die Zauberflöte; it calls for pitches up to F6. In Western popular music, the whistle register is used with more variety and to produce much higher pitches than are called for in classical music. While it is mostly used by females, such as Mariah Carey and Minnie Riperton, there are a few male singers who use it. Georgia Brown holds the record for highest note ever reached. Among male singers, the one who holds the Guinness Book of Records record (C#8) for highest vocal note by a male, Adam Lopez, makes extensive use of the whistle register.

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/index.php/White_cane

# White cane A white cane is used by many people who are blind or visually impaired, both as a mobility tool and as a courtesy to others. Not all modern white canes are designed to fulfill the same primary function, however: There are at least five different varieties of this tool, each serving a slightly different need. Blind people have used canes as mobility tools for centuries, but it was not until after World War I that the white cane was introduced. In 1921 James Biggs, a photographer from Bristol who became blind after an accident and was uncomfortable with the amount of traffic around his home, painted his walking stick white to be more easily visible. In the United States, the introduction of the white cane is attributed to George A. Bonham of the Lions Clubs International . In 1930, a Lions Club member watched as a man who was blind attempted to cross the street with a black cane that was barely visible to motorists against the dark pavement. The Lions decided to paint the cane white to make it more visible. In 1931, Lions Clubs International began a program promoting the use of white canes for people who are blind. The first special White Cane Ordinance was passed in December 1930 in Peoria, Illinois granting blind pedestrians protections and the right-of-way while carrying a white cane. On October 6, 1964, a joint resolution of the Congress, HR 753, was signed into law authorizing the President of the United States to proclaim October 15 of each year as "White Cane Safety Day". President Lyndon Johnson was the first to make this proclamation. While the white cane is commonly accepted as a "symbol of blindness", different countries still have different rules concerning what constitutes a "cane for the blind". In the United Kingdom, for example, the white cane is recognised as being used by visually impaired persons; with two red bands added it indicates that the user is deafblind. In the United States, laws vary from state to state, but in all cases, those carrying white canes are afforded the right-of-way when crossing a road. They are afforded the right to use their cane in any public place as well. In some cases, it is illegal for a non-blind person to carry a white cane. There is much debate among blind people about issues relating to white canes. Though most blind people who use canes support using the long white cane, there is much disagreement over whether canes should be collapsible or not. During the 1970s, the National Federation of the Blind started a campaign to promote the use of noncollapsible, straight canes. Though they are harder to store, the NFB and some others believe that the lightness and greater length of the straight canes allows greater mobility and safety. Those who support the collapsible canes, which can be folded for storage, say that the benefits of the straight cane do not outweigh the inconvenience of having to store them carefully in crowded areas such as classrooms and public events. There is also a movement among blind people which believes that guide dogs, the other major mobility tool for blind people, should be used by blind adults. They claim that canes are not safe enough to cross streets and go in other insecure places with, because the dog can interactively warn the user. Despite the high profile of guide dogs, however, most blind people still use canes at least sometimes, and many still use canes entirely. Additionally, some people are allergic to dogs which may make them unsuitable for certain blind people. Some educators of blind people, particularly those who are not totally blind, have been reluctant to have children use canes until they are older. Many organizations, such as the National Federation of the Blind, have attempted to change this, largely with success.[citation needed]

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/index.php/White_coat

# White coat A white coat or laboratory coat (abbreviated lab coat) is a knee-length overcoat/smock worn by professionals in the medical field or by those involved in laboratory work to protect their street clothes. The garment is made from white cotton or linen to allow it to be washed at high temperature and make it easy to see if it is clean. Similar coats are a symbol of learning in Argentina, where they are worn by students. When used in the laboratory, they protect against accidental spills, e.g. acids. In this case they have to have long sleeves and be made of an absorbent material, such as cotton, so that the user can be protected from the chemical. Some lab coats have buttons at the end of the sleeves, to secure them around the wrist so that they do not hang into beakers of chemicals. Like the word "suit", the phrase, "white coat", is sometimes used to denote the wearer, i.e. the scientific personnel in a biotechnology or chemical company. White coats are sometimes seen as the distinctive dress of physicians, who have worn them for over 100 years. Recently, white coat ceremonies have become popular amongst those starting medical school. The white coat was introduced to medicine in Canada by Dr. George Armstrong (1855-1933) who was a surgeon at the Montreal General Hospital and President of the Canadian Medical Association. Some doctors in institutions such as the Mayo Clinic are instructed to wear business attire, to convey professionalism, as the clinic dislikes the message that white coats represent to the patient. An earlier study found that the majority of patients prefer their doctors to wear white coats, but the majority of doctors prefer other clothing, such as scrubs The study found that psychiatrists were among the least likely to wear white coats, perhaps in part due to the stereotyping that the pop culture phrase suggests. Some medical doctors view the coats as hot and uncomfortable, and many feel that they spread infection. Some patients who have their blood pressure measured in a clinical setting have higher readings than they do when measured in a home setting. This is sometimes called "white coat hypertension", in reference to the traditional white coats worn in a clinical setting, though the coats themselves may have nothing to do with the elevated readings. The term is also used as verbal shorthand for psychiatric orderlies or other personnel and may be used, in a usually jocular manner, to imply someone's lunacy. In the 1966 song, They're Coming to Take Me Away Ha-Haaa!, Napoleon XIV fictionalized the public's view of the symbolic relationship between such institutions and white coats in the following lyrics: They're coming to take me away ho ho hee hee ha haaa! To the funny farm, Where life is beautiful all the time. And I'll be happy to see those nice young men In their clean white coats, And they're coming to take me away ha haaa! Until the mid 1920's, students who were examining cadavers would wear black lab coats to show respect for the dead. Black lab coats were used in early biomedical and microbiology laboratories because any dust (i.e. contamination) that settled on them was easily visible. A white coat ceremony (WCC) is a relatively new ritual that marks one's entrance into medical school and, more recently, into a number of related health-related schools and professions. It originated in Columbia University's College of Physicians and Surgeons in 1993 and involves a formal "robing" or "cloaking" in white lab coats.

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/index.php/White_matter

# White matter White matter is one of the three main solid components of the central nervous system designated by color. The other two are gray matter and substantia nigra. It is composed of myelinated nerve cell processes, or axons, which connect various gray matter areas (the locations of nerve cell bodies) of the brain to each other and carry nerve impulses between neurons. Cerebral and spinal white matter do not contain dendrites, which can only be found in gray matter along with neural cell bodies and shorter axons. The white matter is the tissue through which messages pass between different areas of gray matter within the nervous system. Using a computer network as an analogy, the gray matter can be thought of as the actual computers themselves, whereas the white matter represents the network cables connecting the computers together. The white matter is white because of the fatty substance (myelin) that surrounds the nerve fibers (axons). This myelin is found in almost all long nerve fibers as the insulation is important for allowing the messages to pass quickly from place to place. The brain in general (and especially a child's brain) can adapt to white matter damage by finding alternative routes which bypass the damaged areas of white matter and can therefore maintain good connections between the various areas of gray matter. White matter forms the bulk of the deep parts of the brain and the superficial parts of the spinal cord. Aggregates of grey matter such as the basal ganglia (caudate nucleus, putamen, globus pallidus, subthalamic nucleus, nucleus accumbens) and brain stem nuclei (red nucleus, substantia nigra, cranial nerve nuclei) are spread within the cerebral white matter. The cerebellum is structured in a similar manner as the cerebrum, with a superficial mantle of cerebellar cortex, deep cerebellar white matter (called the "arbor vitae") and aggregates of grey matter surrounded by deep cerebellar white matter (dentate nucleus, globose nucleus, emboliform nucleus, and fastigial nucleus). The fluid-filled cerebral ventricles (lateral ventricles, third ventricle, cerebral aqueduct, fourth ventricle) are also located deep within the cerebral white matter.and suppl Leukoaraiosis is "non-specific white matter changes in the brain, often seen after age 65". The prevalence of these changes is 20% among patients over age 60. These lesions are associated with a doubling of risk of dementia , stroke , and death . Multiple Sclerosis is one of the most common disease which affects white matter. In MS lesions, the myelin shield around the axons has been destroyed by inflammation. Changes in white matter known as amyloid plaques are associated with Alzheimer's disease and other neurodegenerative diseases. White matter injuries ("axonal shearing") may be reversible, while gray matter regeneration is less likely.

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/index.php/White_spot_syndrome

# White spot syndrome White spot syndrome (WSS) is a viral infection of penaeid shrimp. The disease is highly lethal and contagious, killing shrimps quickly. Outbreaks of this disease have wiped out within a few days the entire populations of many shrimp farms throughout the world. The disease is caused by a family of related viruses subsumed as the White Spot Syndrome Baculovirus Complex (WSSV)  and the disease caused by them as white spot syndrome (WSS)  . The first reported epidemic due to this virus is from Taiwan in 1992  , however, reports of losses due to white spot disease came from China in 1993  , where it led to a virtual collapse of the shrimp farming industry. This was followed by outbreaks in Japan and Korea in the same year, Thailand, India and Malaysia in 1994 and by 1996 it had severely affected East Asia and South Asia. In late 1995, it was reported in the USA, 1998 in Central and South America, 1999 in Mexico and in 2000 in the Philippines. Presently it is known to be present in all shrimp growing regions except Australia. The virus has a wide host range and is highly virulent and leads to mortality rates of 100% within days in the case of cultured penaeid shrimps. Most of the cultured penaeid shrimps (Penaeus monodon, Marsupenaeus japonicus, Litopenaeus vannamei, Fenneropenaeus indicus, etc.) are natural hosts of the virus. Several non-penaeid shrimps were also found to be severely infected during experimental challenges. Many crustaceans like crabs (Scylla spp., Portunus spp.), spiny lobsters (Panulirus spp.), crayfish (Astacus spp., Cherax spp., etc.) and freshwater prawn (Macrobrachium spp.) are reported to get infected with variable severities depending on the life stage of the host and presence of external stressors (temperature, salinity, bacterial diseases, pollutants, etc.). Clinical signs of WSSV include a sudden reduction in food consumption, lethargy, loose cuticle and often reddish discolouration, and the presence of white spots of 0.5 to 2.0 mm in diameter on the inside surface of the carapace, appendages and cuticle over the abdominal segments. WSSV is a rod-shaped double-stranded DNA virus, and the size of the enveloped viral particles have been reported to be 240-380 nm long and 70-159 nm dia and nucleocapsid core is 120-205 nm long and 95-165 nm dia. The virus has an outer lipid bilayer membrane envelope, sometimes with a tail like appendage at one end of the virion. The nucleocapsid consists of 15 conspicuous vertical helices located along the long axis, each helix has two parallel striations, composed of 14 globular capsomers, each of which is 8 nm in diameter  . White spots on the shell of infected shrimp under scanning electron microscope appear as large dome shaped spots on the carapace measuring 0.3 to 3 mm in diameter. Smaller white spots of 0.02 to 0.1 mm appear as linked spheres on the cuticle surface. Chemical composition of the spots is similar to the carapace, calcium forming 80-90% of the total material and it is suggested to have derived from abnormalities of the cuticular epidermis  . The complete DNA sequence of WSSV genome has been assembled into a circular sequence of 292,967 bp  . Transmission of the virus is mainly through oral ingestion and water borne routes in farms (horizontal transmission) and vertical transmission (from infected mother prawns) in case of shrimp hatcheries. The virus is present in the wild stocks of shrimp, especially in the coastal waters adjacent to shrimp farming regions in Asian countries, but mass mortalities of wild shrimps are yet to be observed. Rapid and specific diagnosis of the virus is presently carried out using two step-nested polymerase chain reaction (PCR). Histopathological changes in infected shrimps include prominent intranuclear eosinophilic to basophilic inclusions in the infected cells and cellular degeneration with hypertrophied nuclei and chromatin margination in the cuticular epidermis, gill epithelium, antennal gland, haematopoeitic tissue, nervous tissue and connective tissue and cellular necrosis and detachment of intestinal epithelial tissue  . There are no available treatments for WSS, although a large number of disinfectants are widely used in shrimp farms and hatcheries to prevent an outbreak. Stocking of uninfected shrimp seeds and rearing them away from environmental stressors with extreme care to prevent contamination are useful management measures. White spot syndrome virus (WSSV) does not infect human beings and eating infected shrimp (in any form) does not pose any hazard to human health.

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/index.php/Whitey_(drugs)

# Whitey (drugs) Template:Articleissues Whitey is a slang term for when a recreational drug user, as a direct or indirect result of drug use (usually cannabis), begins to faint and usually faints. The term comes from the way one's skin turns pale during and after a fainting episode. While fainting is usually only a problem for those with low blood pressure, it can become possible for those without hypotension to faint after using cannabis or other drugs which have the short-term effect of lowering the blood pressure. Whiteying is perceived by the stoner subculture as the result of using too much cannabis within too short a period of time. In fact the factors that usually facilitate fainting, such as tiredness, lack of fluids and food, and a hot and humid environment, as well as natural hypotension, are just as important as the amount of cannabis involved. Therefore, one can experience a whitey having used only what may be regarded as a perfectly moderate dosage. The experience of whiteying involves first a declining ability to walk or stand up straight, or at all, and feelings of light-headedness. The victim will be physically unable to stand up if the whitey is not treated and may have no choice but to sit or lie down in an appropriate place. If no treatment is available, a whitey can be overcome by lying down until it passes. However, this can take upwards of ten minutes, and afterwards the victim will probably still feel ill. If one wishes to use cannabis, one can avoid the unpleasant and potentially embarrassing experience of whiteying by taking appropriate steps hours or days before using the drug. Those with naturally low blood pressure should be particularly aware of this. Regular meals with enough carbohydrates should be eaten, and enough fluids (preferably plain water) should be consumed. Tiredness can be avoided by getting enough sleep. However, the amount of cannabis used is a factor also, so it is possible to whitey, despite not behaving in a way that facilitates it, by simply using a relatively excessive amount of cannabis. During your whitey, if you manage to distract yourself from the faintness and mind indulging high it may be overpassed. If sat down or lying you will sink into a deep trance from which sooner or later you will rapidly come out of and either vomit or faint. Lightweight/ first time stoners may also expierience a shortness of breath. In the UK cannabis television documentary, Stoned in Suburbia, former international cannabis smuggler Howard Marks refers to an episode where he whiteyed after engaging in a smoking competition with some Germans on a book-promoting visit to Germany.

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/index.php/Whole_Number_Rule

# Whole Number Rule ## See also The Whole Number Rule states that the masses of the elements are whole number multiples of the mass of the hydrogen atom. The rule can be formulated from Prout's hypothesis put forth in 1815. In 1920, Francis W. Aston demonstrated through the use of a mass spectrometer that apparent deviations from the rule were due to the existence of isotopes.

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/index.php/Whole_bowel_irrigation

# Whole bowel irrigation ## Contents Whole bowel irrigation (WBI) is a medical process involving the rapid administration of large volumes of an osmotically balanced polyethylene glycol solution (GoLYTELY®, CoLyte®), either orally or via a nasogastric tube, to flush out the entire gastrointestinal tract. ## History Whole bowel irrigation was originally developed to cleanse the large bowel before surgery or colonoscopy. Initially a solution of sodium chloride, potassium chloride, and sodium bicarbonate was used but this electrolyte solution was shown to be absorbed by the body, sometimes leading to complications. To solve this problem a specialized irrigation fluid was developed consisting mainly of an iso-osmolar solution of polyethylene glycol. With the polyethylene glycol solution there is negligible fluid or electrolyte absorption and several studies have shown the overall safety of the procedure. Whole bowel irrigation was also suggested as a possible treatment for toxic ingestions. WBI has the effect of mechanically flushing the ingested poison out of the gastrointestinal tract before it can be absorbed into the body. A study provided evidence that whole bowel irrigation is an effective and safe gastrointestinal decontamination procedure for acute poisoning. ## Technique Whole bowel irrigation is undertaken either by having the patient drink the solution or a nasogastric tube is inserted and the solution is delivered down the tube into the stomach. The solution is administered at a rate of 500 mL/h in children 9 months to 6 years, 1000 mL/h in children 6 to 12 years, and 1500 to 2000 mL/h in adolescents and adults. The patient is usually seated on a toilet and the procedure continues until the rectal effluent is clear. The entire procedure usually takes 4 to 6 hours. Often patients vomit (especially if ipecac was given prior to the procedure or following ingestion of a drug that produces vomiting such as aspirin or theophylline), indicating that the rate of infusion may need to be slowed or an antiemetic such as metoclopramide given. ## Indications Whole bowel irrigation is indicated prior to surgery, colonoscopy, or a barium enema to cleanse the bowel. Whole bowel irrigation is not used routinely in poisoning situations. It is usually reserved for patients who have ingested toxic doses of medications not absorbed by activated charcoal (such as iron and lithium), potentially toxic ingestions of sustained-release or enteric-coated drugs, or in the situation of packaged drug ingestion (body packing/stuffing). ## Contraindications Major gastrointestinal dysfunction precludes the use of whole bowel irrigation. WBI is specifically contraindicated in the presence of ileus, significant gastrointestinal hemorrhage, hemodynamic instability, uncontrollable intractable vomiting, bowel obstruction, bowel perforation, and in patients with a decreased level of consciousness with a compromised unprotected airway. ## Complications Minor complications include nausea, vomiting, abdominal cramps, and bloating. Patients with altered mental status or a compromised and unprotected airway are at risk for pulmonary aspiration.

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/index.php/Whole_food_supplements

# Whole food supplements Template:Tfd Template:Cleanup Whole food supplements comprise a unique class within the food supplement industry. But the distinction must be made to avoid confusion over the differences between foods, food supplements, whole food supplements, vitamins, multivitamins and herbs. Few consumers Template:Whorecognize the difference and are more swayed by promotion and advertising than by demonstrable evidence. By definition, whole food supplements are foods that have been compressed into tablet form, poured into capsules or powdered. The word "whole" indicates that the end product — a supplement — does not contain parts of foods, or synthetic or isolated vitamins. Ideally, the foods comprising these supplements have not been subjected to irradiation, contain no pesticide or herbacide residues, contain no GMO (genetically modified organisms), have not been sterilized, and do not contain animal products that have been subjected to steroids, antibiotics or other drugs. The belief being, the closer to nature, the more benefit foods provide the consumer. Further, whole food supplements should not contain isolated minerals, amino acids, carotenes or any other substance that is not native to, and still intact within, the original food. Thus, a supplement that contains foods plus a mixture of isolated (also called "fractionated") vitamins, minerals, amino acids and other substances, does not constitute a whole food supplement. Examples of whole food supplement ingredients may include carrots, broccoli, kale, alfalfa, wheat grass, acerola cherry, cauliflower, kelp, wild pansy, spirulina, bovine liver, bovine kidney, radishes and quinoa. Since the above types of food ingredients are natural, they contain a host of nutrients that exist within a "complex." A food complex includes not only vitamins and minerals, but also many cofactors (helper nutrients) that are found in nature's foods as a result of the evolutionary process. Cofactors and food complexes therefore cannot be made in a laboratory nor can they be duplicated by scientists. Many nutritional doctors and researchers conclude that cofactors are often more valuable than vitamins and minerals, and that food cannot be duplicated due to its complexity, dynamism and energy. Cofactors within nature's foods (which are found also in whole food supplements) include, but are not limited to: vitamins, minerals, terpenes, trace mineral activators, enzymes, co-enzymes, chlorophyll, lipids, essential fatty acids, fiber, carotenoids, antioxidants, flavonoids, pigments, amino acids, whole proteins and more. The human organism is biologically suited to ingest and utilize nature's whole foods for its sustenance, including the optimal functioning of cells, and for the processes of healing and prevention. Because vitamin and mineral pills are merely comprised of isolated chemicals, the body often regards these as foreign invaders. Many vitamins, minerals and amino acids produce toxic side effects ranging from skin itching and flushing (niacin, for example) to liver impairment (vitamin A palmitate, for example). The ingredients within foods operate on a system of synergism; in other words they work as 'teams' to feed cells. The interwoven, interrelated and complementary functions of food particles represent some of Nature's most wonderful properties of synergistic power and function. Synergism is defined as 'the interaction of two or more agents or forces so that their combined effect is greater than the sum of their individual effects: working together.' Where marketing interferes with health. Although the term "whole food supplement" should denote that the product's ingredients are only made of whole, natural foods, this is not always the case.[verification needed] Instead, many products on the market contain not only foods, but are also infused with isolated vitamins, minerals and amino acids. Therefore, mixed in with the foods such as broccoli, et.al, (as indicated on the label) would also be mentioned —for example — zinc chelate, ascorbic acid, vitamin A palmitate, d-tocopherol, mixed tocopherols, vitamin C ascorbic acid, ester C, pyridoxine, thiamin, riboflavin, rutin, pantothenic acid, potassium, glutamic acid, beta carotene, iron, folic acid, etc. Wherein real, whole foods contain these nutrients naturally, some supplement manufacturers add the isolates to the foods, yet paradoxically claim their products are "whole foods." This amounts to a contradiction of philosophy.[verification needed] Essentially, these manufacturers mislead the public and are involved in the practice of "standardization," which is a term used to mean that a certain amount of a vitamin or food chemical is infused into the formula to ensure pharmacological potency.[verification needed] This is a very common practice among food supplements and herbs. Amino acid researchers Eric Braverman, MD and Carl Pfeiffer, MD explain the potential side effects of consuming amino acids (the building blocks of proteins found in foods) as isolates (not contained within their original food complexes): Because many of the amino acids are absorbed and metabolized in a similar fashion, there is a great deal of competition between molecules. Sometimes, one amino acid can cancel the effect of others. This adds to the overall complexity of prescribing amino acids to treat disease. For example, amino acids compete for absorption with others in the same group, e.g., the aromatic amino acid group (tryptophan, tyrosine and phenylalanine) and can inhibit one another's passage into the brain. Similarly, in defense of the wholistic approach to food nutrients, James Duke, PhD, herbalist, researcher, author and inventor of the USDA database on food nutrients, wrote, For years I worked with the National Cancer Institute (NCI) and the United States Department of Agriculture (USDA) collaborative cancer screening and collaborated with the National Institutes of Health (NIH) AIDS and Designer Food programs. I watched their scientists and contractors futilely follow their directed fractionations in search of the single super silver bullet compound in the herbal potpourri. It became clear that there were almost always, not one, but many closely related chemicals in a species, each of which contributed in slightly different ways to the activitly of the whole herb. More often than not, these chemicals and their activities were synergistic, the whole herb being more active proportionately, than even the strongest single isolated ingredient…[I]t adds up to the whole plant being better than the sum of its known parts…Silver bullets, single solitary chemicals, are still even more likely to upset our genetic phytochemical ratios, and that's why they are more liable to have serious side effects than natural remedies our genes have experienced over the millennia. Vitamins will be found to exist — and this is the important point — in the foods made in nature's laboratory, in quantities and combinations adequate for the due digestion and assimilation of the natural foodstuffs with which they are associated in nature. The subdivision of vitamins into many classes is not without the risks attendant on decentralization. Vitamins, like other essential constituents of food, are not to be regarded as independent of the assistance derivable from their associates in the maintenance of nutritional harmony. Each vitamin is but a member of a team, and the team itself but a part of the co-ordinated whole. Wherein a vitamin pill or a multi-vitamin may contain a host of vitamins, minerals and amino acids, they never contain the aforementioned food cofactors/complex. Instead they contain groups of isolated (singular) nutrients that are either extracted from foods (fractionated) or are synthetic (wholly laboratory-made). By their very chemical makeup, vitamins and multivitamins, as well as minerals, are regarded by the human organism as incomplete chemicals that can only be best utilized if the body is concomitantly supplied with the cofactors that allow them to work. In this way, consuming vitamins, minerals and amino acids may cause biochemical imbalances and, over time, rob the body from existing nutrients (which are borrowed to make the isolated substances viable). Herbs are used more medicinally than are foods, in most cases. Because they are more potent than most foods, herbs are not used on a long term basis to supply the body with the building blocks of health. Rather, they are used by practitioners (herbalists and naturopaths) to rebalance the biochemistry with natural plants. Yet, many herb manufacturers not only include the whole herb in their end products, but also infuse them with isolated active ingredients to increase their potency. One example of many would be the herb milk thistle, known to improve liver health. While some herb formulators use the whole milk thistle plant, others will add to the plant substance the active ingredient (the isolated chemical) silymarin to increase its potency. The term "food supplement" has little meaning in and of itself other than to denote that the product is meant to "supplement" or be added to the diet. Thus, the word "food" in this instance may be very misleading, because quite often food supplements contain no food at all. Whether this confusing term is used to purposefully mislead the consumer or is merely an accurate description is difficult to tell, prima facia. Food supplements usually are simply vitamin and multi-vitamin products or isolated chemicals, and may be either natural Whole food supplements are one step away from fresh foods. Since they are somewhat processed to be converted into supplement form, they are not as potent as or as nutrient-rich as fresh produce that can be found in one's garden, fresh off the farm or in the grocery produce section. Dr Shayne writes, "Yet, because they are whole and contain a variety of nutrient-dense foods with phytochemicals and the complexes only known to natural foods, they are used clinically to reverse diseases and symptoms, to increase energy, and to foster immune system function."[verification needed] Food science researchers have, in keeping with traditional medicine, discovered that certain foods exert a positive effect on certain bodily systems. Thus, specific whole food supplement formulas are used to feed very specific functions, targeting, for example, the nervous, cardiovascular, respiratory, digestive, eliminatory, immune, skin, musculoskeletal, energy and glandular systems of the body. Further, there are some foods that offer protection and immune system enhancement with their ability to remove toxins from the body. The sulfur-containing plants — cabbage, cauliflower, broccoli, radish and Brussels' sprouts — are one example. These vegetables have the ability to convert fat-soluble toxins into water soluble versions that can be eradicated from fat cells and removed from the body through the kidneys. Still other natural, whole foods offer antioxidant benefits to offset the damage caused by "free radical" molecules that rob the body of oxygen. Fruits and vegetables supply antioxidants other than those you can get from pills, say researchers at the USDA's Jean Mayer Human Nutrition Research Center on Aging at Tufts University in Boston. Ron Prior and co-workers fed 36 men and women aged 20 to 40 or 60 to 80 a diet containing ten servings of fruits and vegetables a day. Then they measured the 'antioxidant capacity' of the participants' blood samples by seeing how well the blood deactivated damaging oxidized free radicals in a test tube. After two weeks, the antioxidant capacity of the participants' blood rose in both groups, though more consistently in the older people. "Based on this and other studies, it appears that compounds other than vitamins C and E and carotenoids contribute a major portion of the increase in antioxidant capacity," says Prior. Among the foods with the highest antioxidant capacity were oranges, cauliflower, and peas. A fact of modern life is that most people do not regularly eat real, whole, raw, nutrient-dense foods. Instead, most diets consist of cooked and processed foods that are full of artificial ingredients and toxic substances and contain very little in the way of vitamins or other vital biochemicals. Wherein an ideal diet would contain raw spinach, kale, broccoli, poultry, fish, zucchini, squash, seeds, nuts and fruits, etc., the actual diet of most Western peoples contain few of these real whole foods. Instead, the diet consists of hamburgers, fast foods, french fries, boxed cereal, table sugar, potato chips, bagels, cheese spreads, ice cream, muffins, cakes, fish sticks, trans fats, margarine and pasteurized milk and juice. This Western diet has been called SAD (Standard American Diet). The SAD diet is so named because its ingredients not only fail to provide people with the nutrients necessary for cellular health and function, but it also is active in destroying health, and thereby creates disease as well as a lack of resistance to disease (also called an impaired immune system). Due to the SAD diet, whole food supplements may be used to bolster health by supplying the nutrients that are not consumed on a regular basis. In this way, consumers of whole food supplements may eat a wide variety of foods in tablet, powder or capsule form without having to even "enjoy" the flavor. The convenience and benefits of whole food supplementation make up, at least in part, for the failings of the daily diet. And in many cases, whole food supplementation has reversed symptoms and restored quality of life to those with impaired health. Braverman, MD, Eric, Carl Pfeiffer, MD, The Healing Nutrients Within: Facts, Findings and New Research on Amino Acids, Keats Publishing, New Canaan, CT, 1987 ISBN 978-1-59120-037-6

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/index.php/Wide_Range_Achievement_Test

# Wide Range Achievement Test The Wide Range Achievement Test or WRAT is an achievement test which measures an individual's ability to read words, comprehend sentences, spell, and compute solutions to math problems. The test is currently in its fourth revision.

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/index.php/Wide_complex_tachycardia_resident_survival_guide

# Wide complex tachycardia resident survival guide Wide complex tachycardia is characterized by a heart rate more than 100 beats per minute associated with a QRS interval of more than 120 ms. When wide complex tachycardia is present, it is important to determine whether the tachycardia is ventricular tachycardia or supraventricular tachycardia with aberrancy. The diagnosis of wide complex tachycardia is very challenging as there is no fixed criteria to accurately determine the cause and type of the wide complex tachycardia. Hemodynamically unstable patients should receive urgent synchronized cardioversion unless the patient has polymorphic ventricular tachycardia for which unsynchronized cardioversion should be performed. If the QRS complex and the T wave can't be distinguished in unstable patients, then the patient should receive unsynchronized cardioversion. Abbreviations: Afib: Atrial fibrillation; AP: Accessory pathway; AT: Atrial tachycardia; AVRT: Atrioventricular reentrant tachycardia; BPM: Beat per minute; ECG: Electrocardiogram; ICD: Implantable cardioverter defibrillator; LBBB: Left bundle branch block; RBBB: Right bundle branch block; S1: First heart sound; SVT: Supraventricular tachycardia; SR: Sinus rhythm; VT: Ventricular tachycardia; VF: Ventricular fibrillation Afib: Atrial fibrillation; BBB: Bundle branch block; CAB: Circulation, airway and breathing; LV: Left ventricle; SVT: Supraventricular tachycardia; VT: Ventricular tachycardia; WPW: Wolff Parkinson White

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/index.php/Widow%27s_peak

# Widow's peak A widow's peak (widow's brow) is a descending V-shaped point in the middle of the hairline (above the forehead). The trait is inherited genetically and is dominant. The term comes from English folklore, where it was believed that this hair formation was a sign of a woman who would outlive her husband. The peak refers to the beak or bill of a headdress, particularly a widow's hood, making people think a woman was being given a mourning hood for her husband's soon-to-be passing.

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/index.php/Wiggers_diagram

# Wiggers diagram It is named after Carl J. Wiggers. (The diagram is frequently incorrectly called a "Wigger's diagram". Although "Wiggers' diagram" would be grammatically correct, it is more frequently rendered "Wiggers diagram", with no apostrophe.)

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/index.php/Wigglesworthia_glossinidia_brevipalpis

# Wigglesworthia glossinidia brevipalpis Wigglesworthia glossinidia brevipalpis is a Gram-negative bacterium in the family Enterobacteriaceae, related to E. coli, which lives in the gut of the tsetse fly. The bacterium bears the name of the British entomologist who first described it, Sir Vincent Brian Wigglesworth. Wigglesworthia has symbiotically co-evolved with the tsetse fly for millions of years, and is a text book example of a bacterial endosymbiont. Because of this relationship, Wigglesworthia has lost a large part of its genome and has one of the smallest known genomes of any living organism. Together with Buchnera aphidicola, Wigglesworthia has been the subject of genetic research into the minimal genome necessary for any living organism. Wigglesworthia also synthesizes key vitamins which the tsetse fly does not get from its diet of blood. Without the vitamins Wigglesworthia produces, the tsetse fly cannot reproduce. Since the tsetse fly spreads african sleeping sickness, Wigglesworthia may one day be used to control the spread of this terrible disease.

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/index.php/Wikispecies

# Wikispecies Template:Infobox Website Wikispecies is a wiki-based online project supported by the Wikimedia Foundation that aims to create a comprehensive free content catalogue of all species (including animalia, plantae, fungi, bacteria, archaea, and protista). It is aimed at scientists, rather than at the general public. Jimmy Wales, chairman emeritus of the Wikimedia Foundation, has said that editors are not required to fax in their degrees, but that submissions will have to pass muster with a technical audience. Started in August 2004, with biologists across the world invited to contribute, the project had grown a framework encompassing the Linnaean taxonomy with links to Wikipedia articles on individual species by April 2005.

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/index.php/Wild_carrot

# Wild carrot Wild carrot, bishop's lace, or queen anne's lace (Daucus carota) is a flowering plant in the family Apiaceae, native to temperate regions of Europe and southwest Asia; domesticated carrots are cultivars of a subspecies, Daucus carota subsp. sativus. Daucus carota is a variable biennial plant, usually growing up to 1 m tall and flowering from June to August. The umbels are claret-coloured or pale pink before they open, then bright white and rounded when in full flower, measuring 3-7cm wide with a festoon of bracts beneath; finally, as they turn to seed, they contract and become concave like a bird's nest. This has given the plant its British common or vernacular name, Bird's Nest. Very similar in appearance to the deadly poison hemlock, it is distinguished by a mix of bi-pinnate and tri-pinnate leaves, fine hairs on its stems and leaves, a root that smells like carrots, and occasionally a single dark red flower in its center. Like the cultivated carrot, the wild carrot root is edible while young, but quickly becomes too woody to consume. A teaspoon of crushed seeds has long been used as a form of natural birth control – its use for this purpose was first described by Hippocrates over 2,000 years ago. Research conducted on mice has offered a degree of confirmation for this use – it was found that wild carrot disrupts the implantation process, which reinforces its reputation as a contraceptive. Chinese studies have also indicated that the seeds block progesterone synthesis, which could explain this effect. It is recommended that, as with all herbal remedies and wild food gathering, one should use appropriate caution. Extra caution should be used in this case, as it bears close resemblance to a dangerous species (see Water Hemlock). The leaves of the wild carrot can be a skin irritant, so caution should also be used when handling the plant. Wild carrot was introduced and naturalised in North America, where it is often known as "Queen Anne's lace". It is so called because the flower resembles lace; the red flower in the center represents a blood droplet where Queen Anne pricked herself with a needle when she was making the lace. The function of the tiny red flower, coloured by anthocyanin, is to attract insects.

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/index.php/Wilderness_Emergency_Medical_Technician

# Wilderness Emergency Medical Technician Wilderness Emergency Medical Technician, or WEMT, is the second highest level of wilderness emergency medical training available in the USA (second to Wilderness Advanced Life Support (WALS)), or other courses for advanced providers such as AWLS, and RMAP (Remote Medicine for Advanced Providers). In addition to an urban EMT-Basic course, WEMT places a greater emphasis on long term patient care in the backcountry where conventional hospital care can take days to reach. Some of the main providers of Wilderness EMT training in the United States include Wilderness Medical Associates (WMA), NOLS' Wilderness Medicine Institute, SOLO, and Remote Medical International. Near the end of the 19th century, volunteer organizations such as St. John Ambulance began teaching the principles of first aid at mining sites and near large railway centers. By the dawn of the 20th century, additional organizations such as the Boy Scouts and the American Red Cross began teaching first aid to lay people. Over the years, these organizations trained hundreds of thousands of people in the elements of providing assistance until definitive care could be arranged. The training in these courses assumed that definitive care was nearby and could be delivered quickly. Eventually there was a realization that this training, while valuable, needed to be supplemented and/or revised to deal with the extended time and limited resources inherent when a medical crisis occurs in a wilderness setting. In the 1950's organizations such as The Mountaineers began developing training programs that addressed these special needs. In 1966, the US Government, through the National Traffic and Motor Vehicle Safety Act, gave the Department of Transportation (DOT) reponsibility for creating a national Emergency management System (EMS). From this program came the standarized curriculum for the position of Emergency Medical Technician (EMT). The first Wilderness EMT course was taught in 1976 to help EMTs in Colorado adapt their skills and knowledge when working with Search and Rescue teams. By 1977 organizations such as Stonehearth Open Learning Opportunities (SOLO) and Wilderness Medical Associates were offering specialized Wilderness First Aid training to their instructors. Meanwhile the DOT EMS program recognized a need to develop standardized training for "first responders" such as truck drivers, policemen and fireman who could lend assistance during the initial part of "golden hour" until an ambulance with an EMT arrived. In 1984 SOLO developed and taught the first Wilderness First Responder course. The purpose of creating the course was to provide Rangers, outdoor leaders, and guides the necessary knowledge to provide care in crisis situations in the wilderness. In 1985, SOLO began providing WFR training to Outward Bound instructors in Florida. Today WFR certification is frequently a pre-requisite for professional positions that involve work in the outdoors. The largest providers of this training today are SOLO, Wilderness Medicine Institute (WMI) - affliated with NOLS, Wilderness Medical Associates (WMA) - frequently associated with Outward Bound, and Remote Medical International. WEMT training is not standardized and varies by state and school but typically involves around 50 hours of wilderness medicine training in addition to traditional EMT-B certification. All WEMTs have valid National Registry EMT or state certified EMTs before joining a course, unless the course also incorporates the urban Emergency Medical Technician curriculum. Most schools also allow for other health care professionals, such as RNs, MDs, or Paramedics, to become wilderness certified, but the curriculum is the same. Often a student will have to travel a long distance to attend a WEMT class, and as a result, most WEMT classes involve taking classes 8-10 hours per day for one or more weeks (depending on whether the student is already an EMT). There is a strong focus on rendering aid with improvised means (for instance, using a branch and some rope to splint an injured extremity rather than using commercially available splinting devices). In wilderness settings it is unlikely that the specialized equipment found in an ambulance will be available, so the focus is on using only what is at hand in your assessment and care for a patient. There is also a greater focus on long-term care, since a WEMT may have to be with a patient for many hours, while most urban EMTs are with each patient for no more than an hour (at the most). Providing care in the wild can be a daunting task, since the golden hour is usually out of the question, and one may have to treat or stabilize a critical patient for hours until help arrives or you can get them the care they need. Backcountry medicine often speaks of the golden day -- a patient's survival chances for critical injuries drastically drop off around 24 hours without hospital care. WEMT's can perform all of the Wilderness First Responder Skills in addition to more advanced interventions, such as traction on a fractured femur, or assisting patients with their prescribed medications.

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/index.php/Wilderness_First_Responder

# Wilderness First Responder Wilderness First Responders are individuals who are trained to respond to emergency situations in remote settings. They are part of a wide variety of wilderness medical professionals who work to deal with medical emergencies that occur in wilderness settings. Near the end of the 19th century, volunteer organizations such as St. John Ambulance began teaching the principles of first aid at mining sites and near large railway centers. By the dawn of the 20th Century additional organizations such as the Boy Scouts and the American Red Cross began teaching first aid to lay people. Over the years, these organizations trained hundreds of thousands of people in the elements of providing assistance until definitive care could be arranged. The training in these courses assumed that definitive care was nearby and could be delivered quickly. Eventually there was a realization that this training, while valuable, needed to be supplemented and/or revised to deal with the extended time and limited resources inherent when a medical crisis occurs in a wilderness setting. In the 1950's organizations such as The Mountaineers began developing training programs that addressed these special needs. In 1966, the US Government, through the National Traffic and Motor Vehicle Safety Act, gave the Department of Transportation (DOT) reponsibility for creating a national Emergency management System (EMS). From this program came the standarized curriculum for the position of Emergency Medical Technician (EMT). The first Wilderness EMT course was taught in 1976 to help EMTs in Colorado adapt their skills and knowledge when working with Search and Rescue teams. By 1977 organizations such as Stonehearth Open Learning Opportunities (SOLO)and National Outdoor Leadership School (NOLS) were offering specialized Wilderness First Aid training to their instructors. Meanwhile the DOT EMS program recognized a need to develop standardized training for "first responders" such as truck drivers, policemen and fireman who could lend assistance during the initial part of "golden hour" until an ambulance with an EMT arrived. In 1984 SOLO developed and taught the first Wilderness First Responder course. The purpose of creating the course was to provide Rangers, outdoor leaders, and guides the necessary knowledge to provide care in crisis situations in the wilderness. In 1985, SOLO began providing WFR training to Outward Bound instructors in Florida. Today WFR certification is frequently a pre-requisite for professional positions that involve work in the outdoors. The largest providers of this training today are SOLO, Wilderness Medicine Institute (WMI) - affliated with NOLS, Wilderness Medical Associates (WMA) - frequently associated with Outward Bound,. A wilderness first responder is trained to deal with any situation that may be encountered in the wilderness. While a standard Department of Transportation defined First Responder course as taught by an organization such as the American Red Cross may require 40 hours of training, the typical Wilderness First Responder Course involves 80 hours of training. Wilderness first responder training courses focus on teaching the students to assess a situation, improvise solutions using available resources to stablize the patient and identify the best way to get the patient to definitive medical treatment. In many courses, students are encouraged to develop the habit of systematically thinking through and documenting their assessment decisions/plans using a SOAP note. Topics covered usually include, but are not limited to, the following principles

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/index.php/Wildlife

# Wildlife Wildlife refers to all non-domesticated plants, animals, and other organisms. Domesticated organisms are those that have adapted to survival with the help of (or under the control of) humans, after many generations. Domesticating wild plant and animal species for human benefit has occurred many times all over the planet, and has had a major impact on the environment, both positive and negative. Wildlife can be found in all ecosystems. Deserts, rainforests, plains, and other areas—including the most developed urban sites—all have distinct forms of wildlife. While the term in popular culture usually refers to animals that are untouched by human factors, most scientists agree that wildlife around the world is impacted by human activities. Humans have historically tended to separate civilization from wildlife in a number of ways including the legal, social, and moral sense. This has been a reason for debate throughout recorded history. Religions have often declared certain animals to be sacred, and in modern times concern for the environment has provoked activists to protest the exploitation of wildlife for human benefit or entertainment. Literature has also made use of the traditional human separation from wildlife. Anthropologists believe that the Stone Age peoples and hunter-gatherers relied on wildlife, both plant and animal, for their food. In fact, some species may have been hunted to extinction by early human hunters. Today, hunting, fishing, or gathering wildlife is still a significant food source in some parts of the world. In other areas, hunting and non-commercial fishing are mainly seen as a sport or recreation, with the edible meat as mostly a side benefit.[citation needed] Meat sourced from wildlife that is not traditionally regarded as game is known as bushmeat. The increasing demand for wildlife as a source of traditional food in East Asia is decimating populations of sharks, primates, pangolins and other animals, which they believe have aphrodisiac properties. Many wildlife species have spiritual significance in different cultures around the world, and they and their products may be used as sacred objects in religious rituals. For example, eagles, hawks and their feathers have great cultural and spiritual value to Native Americans as religious objects.inu Wildlife has long been a common subject for educational television shows. National Geographic specials appeared on CBS beginning in 1965, later moving to ABC and then PBS. In 1963, NBC debuted Wild Kingdom, a popular program featuring zoologist Marlin Perkins as host. The BBC natural history unit in the UK was a similar pioneer, the first wildlife series LOOK presented by Sir Peter Scott, was a studio-based show, with filmed inserts. It was in this series that David Attenborough first made his appearance which led to the series Zoo Quest during which he and cameraman Charles Lagus went to many exotic places looking for elusive wildlife -- notably the Komodo dragon in Indonesia and lemurs in Madagascar. Since 1984, the Discovery Channel and its spinoff Animal Planet in the USA have dominated the market for shows about wildlife on cable television, while on PBS the NATURE strand made by WNET-13 in New York and NOVA by WGBH in Boston are notable. See also Nature documentary. Wildlife television is now a multi-million dollar industry with specialist documentary film-makers in many countries including UK, USA, New Zealand NHNZ, Australia, Austria, Germany, Japan, and Canada. Fuelled by media coverage and inclusion of conservation education in early school curriculum, Wildlife tourism & Ecotourism has fast become a popular industry generating substantial income for poor nations with rich wildlife specially in Africa and India. This ever growing and ever becoming more popular form of tourism is providing the much needed incentive for poor nations to conserve their rich wildlife heritage and it's habitat. Exploitation of wild populations has been a characteristic of modern man since our exodus from Africa 130,000 – 70,000 years ago. The rate of extinctions of entire species of plants and animals across the planet has been so high in the last few hundred years it is widely considered that we are in the sixth great extinction event on this planet; the Holocene Mass Extinction. Destruction of wildlife does not always lead to an extinction of the species in question, however, the dramatic loss of entire species across Earth dominates any review of wildlife destruction as extinction is the level of damage to a wild population from which there is no return. The four most general reasons that lead to destruction of wildlife include overkill, habitat destruction and fragmentation, impact of introduced species and chains of extinction. Overkill occurs whenever hunting occurs at rate greater than the reproductive capacity of the population being exploited. The effects of this are often noticed much more dramatically in slow growing populations such as many larger species of fish. Initially when a portion of a wild population is hunted, an increased availability of resources (food, etc) is experienced increasing growth and reproduction as Density dependent inhibition is lowered. Hunting, fishing and so on, has lowered the competition between members of a population. However, if this hunting continues at rate greater than the rate at which new members of the population can reach breeding age and produce more young, the population will begin to decrease in numbers. Populations in confined to islands – whether literal islands or just areas of habitat that are effectively an "island" for the species concerned – have also been observed to be at greater risk of dramatic population declines following unsustainable hunting.Overkill is really very very dangerous to our animals. The habitat of any given species is considered its preferred area or territory. Many processes associated human habitation of an area cause loss of this area and the decrease the carrying capacity of the land for that species. In many cases these changes in land use cause a patchy break-up of the wild landscape. Agricultural land frequently displays this type of extremely fragmented, or relictual, habitat. Farms sprawl across the landscape with patches of uncleared woodland or forest dotted in-between occasional paddocks. Examples of habitat destruction include grazing of bushland by farmed animals, changes to natural fire regimes, forest clearing for timber production and wetland draining for city expansion. Rats, cats, rabbits, dandelions and poison ivy are all examples of species that have become invasive threats to wild species in various parts of the world. Frequently species that are uncommon in their home range become out of control invasions in distant but similar climates. The reasons for this have not always been clear and Charles Darwin felt it was unlikely that exotic species would ever be able to grow abundantly in a place they had not evolved in. The reality is that the vast majority of species exposed to a new habitat do not reproduce successfully. However occasionally some populations do take hold and after a period of acclimation can increase in numbers significantly having destructive effects on many elements of the native environment they have become part of. This final group is one of secondary effects. All wild populations of living things have many complex intertwining links with other living things around them. Large herbivorous animals such as the hippopotamus have populations of insectivorous birds that feed off the many parasitic insects that grow on the hippo. Should the hippo die out so to will these groups of birds, leading to further destruction as other species dependant on the birds are affected. Also referred to as a Domino effect, this series of chain reactions is by far the most destructive process that can occur in any ecological community.

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/index.php/Wiley_Protocol

# Wiley Protocol The Wiley Protocol is a controversial form of bioidentical hormone replacement therapy (BHRT) devised and advocated by T. S. Wiley. Wiley promotes the Wiley Protocol as a means of restoring or preserving health, which is a step beyond the symptomatic treatment of conventional hormone replacement therapy. The protocol is an attempt to relieve the symptoms of menopause and increase health through the recreation of a pre-menopausal woman's monthly hormonal cycle using rhythmic doses of hormones standardized to a uniform purity. The protocol has been criticized by members of the medical community for lacking proof. In addition there are criticisms about the dosages of the hormones used, and about Wiley's lack of qualifications to design the protocol. The protocol has not been empirically verified as safe or effective. The Wiley Protocol uses bioidentical hormones, specifically estradiol and progesterone. Hormones are applied transdermally, using an oil-based skin cream for topical administration. Doses of the hormones vary throughout a 28-day cycle that is designed to mimic the hormone levels and changes of a young woman who experiences regular menstruation, with each hormone cycling and peaking at separate times throughout the period. The protocol is promoted as differing from conventional hormone replacement therapy in several ways: Wiley has stated that in her opinion, the most important aspect of the protocol is the specific schedule and levels of the hormone doses rather than their bioidentical nature. Concerns have been raised that serum levels may not be an acceptable marker for transdermally administered hormones, that some women have experienced significant side effects while following the protocol and have stopped using it, and that the dosages used are too high and not physiologic. T. S. Wiley and Suzanne Somers have been criticized by some physicians for their advocacy of the Wiley Protocol. A group of seven doctors issued a public letter to Somers and her publisher, Crown, in which they state that the protocol is "scientifically unproven and dangerous" and cite Wiley's lack of medical and clinical qualifications. Somers is acting as a spokesperson for the protocol and was not involved in the development of the Wiley Protocol or its ongoing development.

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/index.php/Wilhelm_His,_Jr.

# Wilhelm His, Jr. Wilhelm His, Jr. (born December 29, 1863, died November 10, 1934) was a Swiss-born cardiologist and anatomist. In 1893, he discovered the bundle of His, which is a specialized tissue in the heart that transmits the electrical impulses and helps synchronize contraction of the cardiac muscles. Later in life, as a professor of medicine at the University of Berlin, His was one of the first to recognize that "the heartbeat has its origin in the individual cells of heart muscle." Werner-His disease (or trench fever) was also named after him.

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/index.php/William_Broadbent

# William Broadbent Sir William Henry Broadbent, 1st Baronet (January 23, 1835 - July 10, 1907) was an English neurologist who was born in Lindley, West Yorkshire. He studied medicine at Owens College and the Royal School of Medicine in Manchester. For most of his career he was associated with St Mary's Hospital, London (1859-1896), and also the London Fever Hospital (1860-1879). Broadbent was a leading British authority in the field of cardiology as well as neurology. He also performed research involving diseases such as tuberculosis and cancer. In 1876 he was the first to describe a type of stroke caused by a cerebral hemorrhage into the ventricular system, that was later to be named Broadbent apoplexy.

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/index.php/William_Coley

# William Coley Dr. William Coley (1862–1936) was an American bone surgeon and cancer researcher, pioneer of cancer immunotherapy. He developed a treatment based on provoking an immune response to bacteria. Dr. William Coley worked as a bone surgeon at New York Cancer Hospital (which later became part of the Memorial Sloan-Kettering Cancer Center). He looked into the success rates of cancer treatment in the past compared to his day. He found that surgery had been much more effective in the past, before the use of antiseptics when infection was a normal side effect of surgery. For example, one surgeon in the 1770s purportedly cured six out of every seven patients. Coley also learned of the case of a patient at his own hospital seven years earlier, who had throat and tonsil cancer. After surgery, there was not much hope for him. Then he came down with erysipelas, a bacterial infection caused by Streptococcus pyogenes. His cancer disappeared, and Coley found that he was still alive, seven years later. He discovered that the human immune system could be stimulated through the administration of killed bacterial infusions. Once stimulated, he observed, the immune system would capable of tackling cancerous cells along with the infection. The cancerous cells would then slough off. His clinical tests achieved a number of remissions, in patients with severe or terminal tumours. His work was however marginalised, by the advent of radiology and radiation treatment. The infusions of killed bacteria are now known as Coley's Toxins. They are currently not generally available to patients suffering from cancer. One reformulation of Coley's Toxins persists under the name Coley Fluid. Coley developed the theory that it was the infections which had helped patients in the past to recover from their cancer. So he began to treat patients by injecting a brew of Streptococcus pyogenes directly into inoperable tumors. This met with much success, even after metastasis. The treatment was most effective when it provoked a fever and a full-blown infection. Later, Coley decided to use a mixture of dead Streptococcus pyogenes and dead Serratia marcescens bacteria. According to Stephen Hoption Cann of the University of British Columbia, "He had successes you simply couldn't hope for today, curing even extensive metastatic disease." The first patient to receive Coley Vaccine was a sixteen-year-old boy with a massive abdominal tumor. Every few days, Coley injected his vaccine directly into the tumor mass and produced the symptoms of an infectious disease, but did not produce the disease itself. On each injection, there was a dramatic rise in body temperature and chills. The tumour gradually diminished in size. By May 1893, after four months of intensive treatment, the tumour was a fifth its original size. By August, the remains of the growth were barely perceptible. The boy received no further anticancer treatment and remained in good health until he died of a heart attack 26 years later. Coley published his results and by the turn of the century 42 physicians from Europe and North America had reported cases of cancer that had been successfully treated with Coley Vaccine. By 1901, the development of x-rays as a cancer treatment showed great promise. In particular, the therapy resulted in immediate tumor destruction and pain relief. Although Coley successfully treated hundreds of patients, his superiors decided to put the emphasis on the newly invented radiation therapy. At the time, it was thought that radiation therapy could be improved into an effective cure for cancer. But, as we now know, radiation is not successful after metastasis. Coley arranged for a wealthy friend to provide funds to purchase two x-ray machines for his use. However, after several years of experience, Coley came to the conclusion that the effect of x-ray therapy was localized, temporary and not curative. Others disagreed and cited the dangerous and unpredictable effects, predominantly the fever caused by the bacteria, that the vaccine had upon individuals weakened by cancer. Furthermore the creation of the vaccine had to be made to a patient's exact needs, making the Coley Vaccine more labour intensive, time consuming and expensive. Coley died in 1936, and his treatment method more or less died with him. There is only now a renewed interest in his ideas.[verification needed] There were, however, many different formulations of Coley Vaccine. These varied greatly in effectiveness, and there were many different treatment protocols that also varied greatly in effectiveness.

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/index.php/William_Dameshek

# William Dameshek William Dameshek (1900-1969) was an American hematologist. Trained at Harvard, he was the founder of Blood, the prime core clinical journal of hematology, in 1946. He is also credited with describing the concept of myeloproliferative diseases in 1951. In addition, he participated in the first studies of nitrogen mustard in various hematological malignancies, widely considered the first uses of chemotherapy in malignant diseases.

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/index.php/William_DeVries

# William DeVries William C. DeVries (December 19, 1943 - ) is an American cardiothoracic surgeon, who performed the first successful permanent artificial heart implantation (on Barney Clark), using the Jarvik-7 model. DeVries was the son of a Dutch immigrant father who served as a surgeon in the U.S. Navy during World War II. He was born at the Brooklyn Navy Yard. His father, Henry DeVries, died in combat in 1944 aboard the destroyer USS Kalk during the Battle of Hollandia. DeVries became an Eagle Scout in his youth and a brother of the Sigma Chi Fraternity in college. DeVries was on the cover of Time magazine on December 10, 1984. He obtained his Bachelor's and MD degrees from the University of Utah, and then took an internship and became a resident at Duke University Medical Center. In 2000, he joined the United States Army Reserve as a lieutenant colonel, becoming at age 57 one of the oldest people to enter and complete the Officer Basic Course. After completion of that course, he was stationed at Walter Reed Army Medical Center in Washington D.C. teaching surgical residents there and medical students from the Uniformed Services University of the Health Sciences and the George Washington University School of Medicine.

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/index.php/William_H._Tucker

# William H. Tucker Tucker received his bachelor's degree from Bates College in 1967, and his master's and doctorate from Princeton University. He joined the faculty at Rutgers University in 1970 and has been there since. Tucker was a Psychometric Fellow for three years at Princeton, a position subsidized by Educational Testing Service. The majority of Tucker's scholarship has been about psychometrics, not in it. He currently sits on the advisory board of the Institute for the Study of Academic Racism. He has written critical commentaries on several hereditarian psychologists known for their controversial work on race and intelligence. He has received awards for his research on Cyril Burt and the Pioneer Fund. According to his website, "My research interests concern the use—or more properly the misuse—of social science to support oppressive social policies, especially in the area of race. I seek to explore how scientists in general, and psychologists in particular, have become involved with such issues and what effect their participation has produced."

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/index.php/William_Hewson

# William Hewson William Hewson (1739-1774) was an 18th Century surgeon, anatomist and physiologist who has sometimes been referred to as the 'father of haematology'. He was born on 14th November 1739 in Hexham. He initially studied in 1753 in at the Newcastle Infirmary, Newcastle upon Tyne (which later became the Royal Victoria Infirmary) under its founder Richard Lambert and much later in the winter of 1761/1762 in Edinburgh and was a student, and later an assistant, of William Hunter. He was elected to the Royal Society in 1770. His major contribution was in isolating fibrin, a key protein in the blood coagulation process. He also contributed work on the lymphatic system by showing the existence of lymph vessels in animals and explaining their function (work for which he was awarded the Copley Medal by the Royal Society in 1769), and demonstrated that red blood cells were flat rather than spherical as had been previously supposed by Anton van Leeuwenhoek. In 1773 he produced evidence for the concept of a cell membrane in red blood cells - however, this last work was largely ignored. On 10th July 1770 he married Mary Stevenson (better known as Polly), a London friend of Benjamin Franklin. From September 1772 he ran an anatomy school at 36 Craven Street, where Franklin lodged in London (which is now the Benjamin Franklin House museum). In 1998, workmen restoring the London home (Benjamin Franklin House) dug up the remains of six children and four adults hidden below the home. The Times reported on February 11, 1998: Initial estimates are that the bones are about 200 years old and were buried at the time Franklin was living in the house, which was his home from 1757 to 1762 and from 1764 to 1775. Most of the bones show signs of having been dissected, sawn or cut. One skull has been drilled with several holes. Paul Knapman, the Westminster Coroner, said yesterday: "I cannot totally discount the possibility of a crime. There is still a possibility that I may have to hold an inquest." The Friends of Benjamin Franklin House (the organization responsible for the restoration of Franklin's house at 36 Craven Street in London) note that the bones were likely placed there by William Hewson, who lived in the house for 2 years. They note that Franklin likely knew what Hewson was doing. Hewson's work was continued after his death by Magnus Falconar, who had married Hewson's sister Dorothy in September 1774. Falconar repeated Hewson's experiments on the spleen and thymus and as a result re-published Hewson's work on red blood cells in 1777 together with his corroboration.

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/index.php/William_Hurwitz

# William Hurwitz William E. Hurwitz, M.D., is a Virginia based pain management physician who was aggressively prosecuted and convicted by the United States Government in 2004 for prescribing pain medication to patients, some of whom subsequently abused and redistributed it on the black market. Before his conviction, Dr. Hurwitz had had a series of running battles with the Virginia Board of Medicine which, in 2003 found fault with some of his prescriptions but also held that all were written "in good faith". William E. Hurwitz is a graduate of Columbia College, completing the BA in three years. He then spent a period at the Harvard University School of Education before attending Stanford University's Medical School. While at Stanford he also earned a Masters in Sociology. He served as a staff physician in Brazil with the Peace Corps upon completing his medical degree. In 2004 Hurwitz was convicted of over 50 counts of distribution of narcotics originally sentenced to four 25-year sentences and forty-six 15-year sentences, all of which were to be served concurrently, and was fined more than $1 million (U.S.). During the prosecution of the first case, all of Dr. Hurwitz's property was seized. Dr. Hurwitz maintains that he was duped by his patients, and that the enforcement tactics being applied in the War on Drugs unfairly target law-abiding doctors, leading to a situation where doctors must choose between providing compassionate care and accepting personal liability for what their patients do with prescribed medications. His case has potentially serious ramifications among all practitioners of pain medicine, and is considered by many to be a drastic example of the overreach of anti-drug law enforcement efforts. His conviction was overturned by the U.S. Court of Appeals for the Fourth Circuit on August 22, 2006, due to errors by the trial judge that essentially prevented the jury from considering Hurwitz's defense -- that he was prescribing the medication in good faith as part of the regular practice of medicine. His re-trial began on March 26, 2007 in federal district court for the Eastern District of Virginia. Dr. Hurwitz's entire defense team -- including four expert witnesses and every attorney -- worked on the matter pro bono, i.e. for free. On April 28, 2007 jurors found William E. Hurwitz guilty of 16 counts of drug trafficking and determined that he prescribed massive quantities of medicine to patients in chronic pain. The 12-member jury acquitted Hurwitz on 17 other trafficking counts. District Judge Leonie Brinkema dismissed the remaining 12 counts. His two lead trial attorneys for the second trial were Lawrence Robbins and Richard Sauber, of Robbins, Russell, Englert, Orseck & Untereiner, and Fried, Frank, Harris, Shriver & Jacobson, respectively. On July 13, 2007 Judge Brinkema sentenced Hurwitz to four years and nine months. The judge said that most of Hurwitz's practice was legitimate medicine that saved patients' lives and that medical literature increasingly supports his theories on the propriety of massive drug doses to treat patients in chronic pain. "An increasing body of respectable medical literature and expertise supports those types of high-dosage, opioid medications," the judge said. The judge added that Hurwitz had undermined his own cause by ignoring that some patients were clearly drug dealers and Hurwitz admitted before sentencing that he had deceived himself about some patients who in retrospect were clearly criminals.

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/index.php/William_Sands_Cox

# William Sands Cox William Sands Cox was a surgeon in Birmingham, England. He founded Birmingham's first medical school in 1828 as a residential Anglican-based college in Temple Row, where a blue plaque commemorates him on the House of Fraser department store, and in Brittle Street (now obliterated by Snow Hill Station). Cox went on to found the Queen's Hospital in Bath Row (Drury & Bateman, opened 1841) as a practical resource for his medical students. The 1828 Medical School became the Birmingham Royal School of Medicine in 1836 and then the Queen's College in 1843 by Royal Charter. Cox's ambition was for the college to teach arts, law, engineering, architecture and general science as well as medicine, surgery and theology. However, after a major split in the organisation, the non-theological departments moved off into Mason Science College which later became the University of Birmingham leaving the name Queen's College as a theological institution.

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/index.php/Willy_Burgdorfer

# Willy Burgdorfer Willy Burgdorfer, an American scientist born and educated in Basel, Switzerland, is an international leader in the field of medical entomology. He is famous for his discovery of the bacterial pathogen that causes Lyme disease, a spirochete named Borrelia burgdorferi in his honor. As a research subject for his thesis he chose to study the development of the African relapsing fever spirochete, Borrelia duttonii in its tick vector Ornitnodoros moubata, and to evaluate this tick's efficiency in transmitting spirochetes during feeding on animal hosts. During his college years he was a member of a research team investigating outbreaks of Q fever in various parts of Switzerland and became interested in similar research activities carried out at the Rocky Mountain Laboratory (RML) in Hamilton, Montana, a U.S. National Institutes of Health research facility. He joined RML in 1952 as a Research Fellow, and later became a Research Associate in the USPHS's Visiting Scientist Program. In 1957, he became a U.S. citizen and shortly thereafter joined the RML staff as a Medical Entomologist. Dr. Burgdorfer's research concerned the interactions between animal and human disease agents and their transmitting arthropod vectors, particularly ticks, fleas and mosquitoes. His research contributions are published in more than 225 papers and books, and cover a wide field of investigations including those on relapsing fevers, plague, tularemia, Colorado tick fever, Rocky Mountain spotted fever and other bacterial and viral diseases. Dr. Burgdorfer gained world-wide recognition for his 1982 discovery of a tick-borne spirochete as the long-sought cause of Lyme disease and related disorders in the U.S. and Europe. The agent was named after him — Borrelia burgdorferi. From 1967-1972, he served as Associate Member on the Rickettsial Commission of the Armed Forces Epidemiology Board. For several years (1968-1971) he was also Co-Project Officer of the PL 480-sponsored Research Project on Rickettsial Zoonoses in Egypt and adjacent areas, and from 1979 to 1986, he directed the WHO-sponsored Reference Center for Rickettsial Diseases at RML in Montana, U.S. Although retired since 1986, Dr. Burgdorfer continues his association with the Rocky Mountain Laboratories' Laboratory of Human Bacterial Pathogenesis as Scientist Emeritus. He is also active on the Scientific/Medical Advisory Committee of the Lyme Disease Foundation. In 1999, he delivered the keynote address at the 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders .

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/index.php/Wilson_disease_protein

# Wilson disease protein Wilson disease protein (WND), also known as ATP7B protein, is a copper-transporting P-type ATPase which is encoded by the ATP7B gene. The ATP7B protein is located in the trans-Golgi network of the liver and brain and balances the copper level in the body by excreting excess copper into bile and plasma. Genetic disorder of the ATP7B gene may cause Wilson's disease, a disease in which copper accumulates in tissues, leading to neurological or psychiatric issues and liver diseases. Wilson disease protein is associated with ATP7B gene,approximate 80 Kb, located on human chromosome 13 and consists of 21 exons.The mRNA transcribed by ATP7B gene has a size of 7.5 Kb, and which encodes a protein of 1465 amino acids. The gene is a member of the P-type cation transport ATPase family and encodes a protein with several membrane-spanning domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least two putative copper-binding sites. This protein functions as a monomer, exporting copper out of the cells, such as the efflux of hepatic copper into the bile. Alternate transcriptional splice variants, encoding different isoforms with distinct cellular localizations, have been characterized. Wilson disease is caused by various mutations. One of the common mutations is single base pair mutation,H1069Q. ATP7B protein is a copper-transporting P-type ATPase, synthesized as a membrane protein of 165 KDa in human hepatoma cell line, and which is 57% homologous to menkes disease associated protein ATP7A. The copper binding motif also shows a high affinity to other transition metal ions like zinc Zn(II), cadmium Cd(II), gold Au(III), and mercury Hg(II). However, copper is able to decrease the zinc binding affinity at low concentration and increase copper binding affinity dramatically with increasing concentration to ensure a strong binding between the motif and copper. As a P-type ATPases, ATP7B undergoes auto-phosphorylation of a key conserved aspartic acid (D) residue in the DKTGT motif. The ATP binding to the protein initiates the reaction and copper binds to the transmembrane region. Then phosphorylation occurs at the aspartic acid residue in the DKTGT motif with Cu release. Then dephosphorylation of the aspartic acid residue recovers the protein to ready for the next transport. Most of ATP7B protein is located in the trans-Golgi network (TGN) of hepatocytes, which is different from its homologous protein ATP7A. Small amount of ATP7B is located in the brain. As a copper-transporting protein, one major function is delivering copper to copper dependent enzymes in Golgi apparatus(e.g.holo-ceruloplasmin(CPN)). In the human body, liver plays an important role in copper regulation including removal of extra copper. ATP7B participates in the physiological pathway in the copper removal process in two ways: secreting copper into plasma and excreting copper into bile. ATP7B receives copper from cytosolic protein Antioxidant 1 copper chaperone (ATOX1). This protein targets ATP7B directly in liver in order to transport copper. ATOX1 transfers copper from cytosol to the metal binding domain of ATP7B which control the catalytic activity of ATP7B. Wilson disease happens when accumulation of copper inside the liver causes mitochondrial damage and cell destruction and shows symptoms of hepatic disease. Then, the loss of excretion of copper in bile leads to an increasing concentration of copper level in urine and causes kidney problems. Therefore, symptoms of Wilson disease could be various including kidney disease and neurological disease. The major cause is the malfunction of ATP7B by single base pair mutations, deletions, frame-shifts, splice errors in ATP7B gene.

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/index.php/Window_period

# Window period In medicine, the window period for a test designed to detect a specific disease (particularly infectious disease) is the time between first infection and when the test can reliably detect that infection. In antibody-based testing, the window period is dependent on the time taken for seroconversion. The window period is important to epidemiology and safe sex strategies, and in blood and organ donation, because during this time, an infected person or animal cannot be detected as infected but may still be able to infect others. For this reason, the most effective disease-prevention strategies combine testing with a waiting period longer than the test's window period.

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/index.php/Winpepi

# Winpepi WinPepi is a freeware package of statistical programs for epidemiologists, comprising seven programs with over 100 modules. WinPepi is not a complete compendium of statistical routines for epidemiologists. but it provides a very wide range of procedures, including those most commonly used and many that are not easy to find elsewhere. This has repeatedly led reviewers to use a "Swiss army knife" analogy. Each program has a comprehensive fully-referenced manual. WinPepi had its origins in 1983 in a book of programs for hand-held calculators, which in 1993 developed into a set of DOS-based computer programs that came to be called Pepi (an acronym for "Programs for EPIdemiologists") and evolved, after its fourth version in 2001, into WinPepi (Pepi-for-Windows). WinPepi is still a work in progress, and new expanded versions are issued at frequent intervals. The programs are notable for their user-friendliness. A portal provides immediate access to all the programs and manuals, and to an alphabetical index that pinpoints the programs and modules to be used for specific purposes. Menus, buttons, on-screen instructions, help screens, pop-up hints, and built-in error traps make the programs easy to use. WinPepi does not provide data management facilities. With some exceptions, it requires the entry (at the keyboard or by pasting) of data that have already been counted or summarized.

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/index.php/Winstein_reaction

# Winstein reaction The Wittig reaction is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide (often called a Wittig reagent) to give an alkene and triphenylphosphine oxide. The Wittig reaction was discovered in 1954 by Georg Wittig, for which he was awarded the Nobel Prize in Chemistry in 1979. It is widely used in organic synthesis for the preparation of alkenes. It should not be confused with the Wittig rearrangement. Wittig reactions are most commonly used to couple aldehydes and ketones to singly substituted phosphine ylides. With simple ylides this results in almost exclusively the Z-alkene product. In order to obtain the E-alkene, the Schlosser modification of the Wittig reaction can be performed. The steric bulk of the ylide 1 influences the stereochemical outcome of nucleophilic addition to give a predominance of the betaine 3. Carbon-carbon bond rotation gives the betaine 4, which then forms the oxaphosphatane 5. Elimination gives the desired Z-alkene 7 and triphenylphosphine oxide 6. With simple Wittig reagents, the first step occurs easily with both aldehydes and ketones, and the decomposition of the betaine (to form 5) is the rate-determining step. However with stabilised ylides (where R1 stabilises the negative charge) the first step is the slowest step, so the overall rate of alkene formation decreases and a bigger proportion of the alkene product is the E-isomer. This also explains why stabilised reagents fail to react well with sterically hindered ketones. Recent research has shown that the reaction mechanism presented above does not account for all experimental results. Mechanistic studies have been done mostly on unstablilized ylides, because the intermediates can be followed by NMR spectroscopy. The existence and interconversion of the betaine (3a and 3b) is still under debate and a subject of ongoing research. There is evidence that phosphonium ylides 1 can react with carbonyl compounds 2 via a π²s/π²a [2+2] cycloaddition to directly form the oxaphosphatanes 4a and 4b. The stereochemistry of the product 5 is due to the addition of the ylide 1 to the carbonyl 2 and to the ability of the intermediates to equilibrate. Maryanoff and Reitz identified the issue about equilibration of Wittig intermediates and termed the process "stereochemical drift". For many years, the stereochemistry of the Wittig reaction, in terms of carbon-carbon bond formation, had been assumed to correspond directly with the Z/E stereochemistry of the alkene products. However, certain reactants do not follow this simple pattern. Lithium salts can also exert a profound effect on the stereochemical outcome. There are distinct differences in the mechanisms of aliphatic and aromatic aldehydes and of aromatic and aliphatic phosphonium ylides. Vedejs et al. have provided evidence that the Wittig reaction of unbranched aldehydes under lithium-salt-free conditions do not equilibrate and are therefore under kinetic reaction control. Vedejs has put forth a theory to explain the stereoselectivity of stabilized and unstabilized Wittig reactions. The Wittig reagent is usually prepared from a phosphonium salt, which is in turn made by the reaction of triphenylphosphine with an alkyl halide. To form the Wittig reagent (ylide), the phosphonium salt is suspended in a solvent such as diethyl ether or THF and a strong base such as phenyllithium or n-butyllithium is added. The simplest ylide used is methylenetriphenylphosphorane (Ph3P+−C−H2), and this is also the basis of an alternative synthesis of Wittig reagents. Substituted ylides can be made by alkylation of Ph3P=CH2 with a primary alkyl halide R−CH2−X, to produce a substituted phosphonium salt: These contain groups that can stabilise the negative charge from the carbanion-like carbon, for example Ph3P=CH−COOR, Ph3P=CH−Ph. These are less reactive than simple ylides, and so they usually fail to react with ketones, necessitating the use of the Horner-Wadsworth-Emmons reaction as an alternative. They can be prepared from the phosphonium salts using weaker bases than butyllithium such as alkoxides and (in some cases) sodium hydroxide. They usually give rise to an E-alkene product when they react, rather than the more usual Z-alkene. However the phosphorane resonance requires expansion of the octet on phosphorus. This hypervalency cannot (yet) be explained well in terms of standard bonding theory, and this resonance is rather less favoured than the more familiar p–p overlap seen in π-bonded compounds as alkenes or imines. This means that the ylide form is a significant contributor, and the carbon is quite nucleophilic. The Wittig reaction has become a popular method for alkene synthesis precisely because of its wide applicability. Unlike elimination reactions (such as dehydrohalogenation of alkyl halides), which produce mixtures of alkene regioisomers determined by Zaitsev's rule, the Wittig reaction forms the double bond in one position with no ambiguity. A large variety of ketones and aldehydes are effective in the reaction, though carboxylic acid derivatives such as esters fail to react usefully. Thus mono-, di- and trisubstituted alkenes can all be prepared in good yield in most cases. The carbonyl compound can tolerate several groups such as OH, OR, aromatic nitro and even ester groups. There can be a problem with sterically hindered ketones, where the reaction may be slow and give poor yields, particularly with stabilised ylides, and in such cases the Horner-Wadsworth-Emmons (HWE) reaction (using phosphonate esters) is preferred. Another reported limitation is the often labile nature of aldehydes which can oxidize, polymerize or decompose. In a so-called Tandem Oxidation-Wittig Process the aldehyde is formed in situ by oxidation of the corresponding alcohol. As mentioned above, the Wittig reagent itself is usually derived from a primary alkyl halide, because with most secondary halides the phosphonium salt is formed in poor yield. This means that most tetrasubstituted alkenes are best made by other means. However the Wittig reagent can tolerate many other variants. It may contain alkenes and aromatic rings, and it is compatible with ethers and even ester groups. Even C=O and nitrile groups can be present if conjugated with the ylide- these are the stabilised ylides mentioned above. Bis-ylides (containing two P=C bonds) have also been made and used successfully. One limitation relates to the stereochemistry of the product. With simple ylides, the product is usually mainly the Z-isomer, although a lesser amount of the E-isomer is often formed also- this is particularly true when ketones are used. If the reaction is performed in DMF in the presence of LiI or NaI, the product is almost exclusively the Z-isomer. If the E-isomer is the desired product, the Schlosser modification may be used. With stabilised ylides the product is mainly the E-isomer, and this same isomer is also usual with the HWE reaction. The major limitation of the traditional Wittig reaction is that the reaction goes mainly via the erythro betaine intermediate, which leads to the Z-alkene. However Schlosser & Christmann found that the erythro betaine can be converted to the threo betaine using phenyllithium at low temperature (forming a betaine) followed by HCl. Upon workup this leads to the E-alkene product as shown. E. J. Corey and H. Yamamoto found that the utility can be extended to a stereoselective synthesis of allylic alcohols, by reaction of the betaine ylid with a second aldehyde. For example: The most popular use of the Wittig reaction is for the introduction of a methylene group using methylenetriphenylphosphorane (Ph3P=CH2). In the example shown, even a sterically hindered ketone such as camphor can be successfully converted to its methylene derivative by heating with methyltriphenylphosphonium bromide and potassium tert-butoxide, which generate the Wittig reagent in situ. In another example, the phosphorane is produced using sodium amide as a base, and this successfully converts the aldehyde shown into alkene I in 62% yield. The reaction is performed in cold THF, and the sensitive nitro, azo and phenoxide groups all survive intact. The product can be used to incorporate a photostabiliser into a polymer, to protect the polymer from damage by UV radiation. Another example of its use is in the synthesis of leukotriene A methyl ester. The first step uses a stabilised ylide, where the carbonyl group is conjugated with the ylid preventing self condensation, although unexpectedly this gives mainly the cis product. The second Wittig reaction uses a non-stabilised Wittig reagent, and as expected this gives mainly the cis product. Note that the epoxide and ester functional groups survive intact.

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/index.php/Winters%27_formula

# Winters' formula Winters' formula, named after Robert W. Winters, is a formula used to evaluate respiratory compensation when analyzing acid-base disorders and a metabolic acidosis is present.

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/index.php/Wireless_capsule_endoscopy

# Wireless capsule endoscopy Wireless capsule endoscopy, also known as the capsule camera or video pill or Miniature ingestible Capsule or Capsule Endoscopy is a camera with the size and shape of pill used to visualize the gastrointestinal tract . This device is being promoted as an alternative to an endoscopy and has become a valuable tool to gastroenterologists all over the world with sales over 135 million dollars per year with over half million Capsules already sold. The camera assists in detecting cancer, ulcer,Small Bowel and other types of internal Gastrointestinal or Digestive ailments. Currently there are two key patents. The main System patent 7039453 for Capsule Endoscopy System was issued based on long review by the US Patent Office to Tarun Mullick,Ram Nair,Sudhir Dutta et el based on "First to Invent" criteria and not "First to File" issued to Gavriel Iddan and Doron Sturlesi. Their patent # 5604531 has subsequently been changed with Key Claims 1,2,3 and 11 rejected by US Patent office in April,2006 based on an appeal by Olympus Corp. in 2003. These claims for Capsule Endoscopy System are crucial as other claims 4 to 10 and 12 to 17 are dependent on them. Moreover,the US Patent laws give top priority to "First to Invent" and not "First to File" to protect the rights of small inventors.Currently Given Imaging Ltd. and Olympus Corp.are producing these products outlined in this system patent.According to these inventors,Tarun Mullick conceived CAPSULE ENDOSCOPY in 1985 and had developed it by 1989,but chose to wait for more features and finally filed a provisional patent followed by a complete 157 claims patents which the US Patent office reviewed carefully as "First to Invent" documents were examined by them over 5 years and complete System patent for Capsule Endoscopy was issued in 2006 at the same time to Tarun Mullick et el. while US Patent office rejected Iddan's 4 main claims relating to the system(Claims 1,2,3 and 11 have been rejected) in 2006.Olympus Corp.is trying to prove the invalidity of this patent by Iddan as they filed their patent after Tarun Mullick et el. So now there are three patents and Law Judges/Jury will decide who the first inventors are and whose patent is basic and more powerful.Olympus Corp. has spent close to 3 million$ in legal battle and Given Imaging has spent close to 2 mil.$ and in the next 18 months,they may spend another 6 to 8 million dollars each.Both corporations could spend 16 to 20 million$ in total in 2007 and 2008.These estimates are based on Given Imaging statements on Aug.2,2007 that their 2007 litigation expenses for 2007 are likely to be 4 million$. An Israeli Patent attorney Dr.Michael Factor reported in a blog in 2006 that in Israel,if main claims are rejected on appeal,the patent becomes less effective based on a recent ruling by the Israel patent office that where an independent claim is disqualified,all the dependent claims are disqualified as well.Because of high stakes,this legal case could take 4 years to settle as the main inventor has not announced their legal moves.US District Judge James Knoll Gardner has ordered JURY TRIAL from November 3,2008 in Allentown,Pennsylvania in Eastern District Court of Pennsylvania which is close to Olympus USA headquarters.Both companies(Given Imaging,Olympus Corp.) are gathering information and witnesses to defend that they are not infringing patents in the discovery phase and each spending close to 300,000 to 400,000$ per month in legal costs.At some point,MicroGizzmos 's CEO/Inventors Tarun Mullick ,Sudhir Dutta are going to file their lawsuit against Given Imaging and Olympus Corp.which could push the final verdict timing to 2010/2011.Details of this legal case 2:06-cv-02132 are available thru www.Pacer.com . US Judges in the past have imposed severe penalties for willful infringement of patents of small inventors by big companies and US Supreme Court has sided with the small inventors like Late Thomas Campana Jr. and David Stout of NTP,Inc. a patent holding company . US Supreme Court refused to hear Research in Motion case and sent the case back to US District Court Judge James R.Spencer who issued stern warnings to RIM and RIM finally paid 612.5 million$ to NPT,Inc in Jan.2006.Nokia,Visto and Good Technology decided to license in 2005 fearing big penalties. For this reason,it is premature for readers to think that Iddan et el. has the first basic patent based on publicity by Given Imaging. The US patent law clearly states that "Patents are governed by "FIRST TO INVENT" principle and not "First to File" rule".This is why the US Patent office took 5 years 4 months to approve Patent#7039453 to Tarun Mullick et el as their claims are very broad.The provisional patent was filed in 1999 and approved on Feb.8,2000 but the 157 claims patent was filed on January 12,2001. The USPTO approved 17 claims out of 157 claims of Tarun Mullick et el.The other 140 claims have been refiled in July,2006 as they are for much larger functions pertaining to Endoscopy.Only the Judge and Jury will determine this in United States.Olympus Corp.is contesting in Eastern Dist.of Pennsylvania Court in Allentown that it also has a patent for Capsule Endoscope .Readers can examine the wordings of Patent# 6939292 issued to Olympus corp.This patent was filed after Patent# 7039453.That is why ,it is premature to declare the first inventor of Capsule Endoscopy. At the present time, the capsule camera is primarily used to visualize the small intestine. Whereas the upper gastrointestinal tract (esophagus, stomach, and duodenum) and the colon (large intestine) can be very adequately visualized with scopes (cameras placed at the ends of thin flexible tubes), the small intestine is very long (average 20-25 feet) and very convoluted. The capsule camera travels through the length of the small intestine in about 4 hours, and wirelessly transmits two images every second to a receiver carried by the patient. The images are of very good quality, comparable to those from scopes. The test carries a high sensitivity and specificity for detecting lesions. The main uses today are for detecting the cause of gastrointestinal bleeding, and for inflammatory bowel disease, such as Crohn's disease. Capsule Endoscopy is currently a favorite of many research Gastroenterologists for Small Bowel .At DDW 2007,Olympus EndoCapsule was compared to Given Imaging PillCam for picture quality in a study presented at this meeting.Olympus EndoCapsule picture quality was deemed to be better.Click on Image quality on the Olympus website to see the high resolution image of EndoCapsule. EndoCapsule uses CCD chip and PillCam uses CMOS chip. Given Imaging is going to sell Colon Capsules or Pills in the second half of 2007 in Europe and possibly in the USA after FDA approval.At this meeting,new advanced Endoscopy Capsule concepts for Colon Screening were discussed.These concepts are part of 140 claims refiled by Tarun Mullick ,Sudhir Dutta et el with the US Patent Office. The Capsule Endoscopy is going to be used for many more active procedures and functions like the Current Endoscopes very soon and Capsule Endoscopy is likely to become a first line procedure by Gastroenterologists to detect and treat Gastrointestinal problems based on many papers presented at DDW 2007 in May in Washington,DC.Stanford Univ.aeronautics dept. and many other Japanese co.like Sayaka are also working on similar advancements. Sayaka Promo Video is interesting to watch for those unfamiliar with the Capsule Endoscopy .Stanford Univ.inventors have filed a patent in the US and Europe. In addition,its use is likely to spread to every country in the world.This June,2007,Capsule Endoscopy was approved in Japan with reimbursement from Oct.2007 due to the great efforts of Given Imaging.Given imaging website provides regular news releases on FDA approvals,worldwide acceptance and reimbursement and new studies worldwide supporting Capsule Endoscopy as an accepted diagnostic procedure. , Olympus corp. announced on Sept.21,2007 that they are launching their EndoCapsule in Oct.2007 in USA as a new technology which is going to grow rapidly for many applications. Dr.Oz investigated Food Myths on Oprah show on sept.17,2007 using PillCam.This Capsule is now being used by researchers for all kinds of foods digestion in our body along with stress affect on our digestion system for London Cab drivers by Dr.Oz.

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/index.php/Wisconsin_card_sort

# Wisconsin card sort The Wisconsin Card Sorting Test® (WCST) is a neuropsychological test of "set-shifting", i.e. the ability to display flexibility in the face of changing schedules of reinforcement. Initially, a number of stimulus cards are presented to the participant. He or she is then given a stack of additional cards and asked to match each one to one of the stimulus cards, thereby forming separate piles of cards for each. The participant is not told how to match the cards; however, he or she is told whether a particular match is right or wrong. The original WCST used paper cards and was carried out with the experimenter on one side of the desk facing the participant on the other. Since the early 1990s, however, computerized versions of the task have been available, the most recent version being the windows-compatible version 4.0. The latter has the advantage of automatically scoring the test, which was quite complex in the manual version. The test takes approximately 12-20 minutes to carry out and generates a number of psychometric scores, including numbers, percentages, and percentiles of: categories achieved, trials, errors, and perseverative errors. Clinically, the test is widely used by psychiatrists, neurologists and neuropsychologists in patients with acquired brain injury, neurodegenerative disease, or mental illness such as schizophrenia. Although successful completion of the test relies upon a number of intact cognitive functions including attention, working memory, and visual processing, it is loosely termed a "frontal lobe" test on the basis that patients with any sort of frontal lobe lesion generally do poorly at the test. In particular, patients with lesions of the dorsolateral frontal lobe make a higher number of perseverative errors than control participants. Having achieved the first category they often continue to sort the cards according to the first rule long after that rule has been superseded. A recent factor analysis of the WCST has shown these perseverative errors to be the most useful outcome measure in assessing caseness. A more sophisticated description of deficits of this type is "executive dysfunction". The WCST has been used in neuroimaging paradigms such as PET and MRI. As predicted by the acquired brain injury literature, completing the task involves activation primarily of the dorsolateral prefrontal cortex. The test's use in neurodegenerative diseases such as motor neurone disease has identified at least a subgroup of these patients for whom there is some subtle degree of cognitive dysfunction, in contrast to the traditional view that these were pure disorders of the motor system. The trademark "Wisconsin Card Sorting Test" was registered in the year 2000 with the United States patent and Trademark Office (Reg. #2320931, Ser # 75-588988) by Wells Printing and Digital Services of Madison, Wisconsin. Although filed in 1998, the trademark application states the mark has been in use in commerce since at least 1970. The trademark covers "psychological testing materials, namely printed tests, printed cards, and printed instruction manuals in the field of psychological evaluation." This trademark does not cover the computer implementation of the test, distributed by PAR Inc., sometimes referred to as simply WCST.

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/index.php/Wisdom_teeth

# Wisdom teeth Wisdom teeth are third molars that usually appear between the ages of 16 and 24. They are commonly extracted when they affect other teeth—this impaction is colloquially known as "coming in sideways." Most people have four wisdom teeth, but it is possible to have more or fewer. Absence of one or more wisdom teeth is an example of hypodontia. Any extra teeth are referred to as supernumerary teeth. They are generally thought to be called wisdom teeth because they appear so late—much later than the other teeth, at an age where people are arguably wiser than as a child, when the other teeth erupt. The English wisdom tooth is derived from Latin dens sapientiae. The same root is shared by the following languages: There exists an interesting Dutch folk etymology that the Dutch word verstandskies is derived from "far-standing" (ver-staand) molar, and that mistranslations of the Dutch word (in which verstand translates to wisdom) are the root for corresponding words in other European languages. Turkish refers directly to the age at which wisdom teeth appear and calls it 20 yaş dişi (20th year tooth). In Arabic, its name is Ders-al-a'qel (ضرس العقل), literally meaning "The tooth of the mind" and hence similar to occidental names. In Korean, its name is Sa-rang-nee (사랑니, love teeth) referring to the young age and the pain of the first love. In Japanese, its name is Oyashirazu (親知らず), literally meaning "unknown to the parents," from the idea that they erupt after a child has moved away. The Indonesian term gigi bungsu for the latest teeth a person cuts refers to bungsu "youngest child". In Thailand the wisdom tooth is described fan-khut (ฟันคุด) "huddling tooth" due to its shortage of place. Impacted wisdom teeth fall into one of several categories. Mesioangular impaction is the most common form (43%), and means the tooth is angled forward, towards the front of the mouth. Vertical impaction (38%) occurs when the formed tooth does not erupt fully through the gum line. Distoangular impaction (6%) means the tooth is angled backward, towards the rear of the mouth. And finally, Horizontal impaction (3%) is the least common form, which occurs when the tooth is angled fully ninety degrees forward, growing into the roots of the second molar. Typically distoangular impactions are the easiest to extract in the maxilla and most difficult to extract in the mandible, while mesioangular impactions are the most difficult to extract in the maxilla and easiest to extract in the mandible. Impacted wisdom teeth may also be categorized on whether they are still completely encased in the jawbone. If it is completely encased in the jawbone, it is a bony impaction. If the wisdom tooth has erupted out of the jawbone but not through the gumline, it is called a soft tissue impaction. Sometimes the wisdom tooth fails to erupt completely through the gum bed and the gum at the back of the wisdom tooth extends over the biting surface, forming a soft tissue flap or lid around the tooth called an operculum. Teeth covered by an operculum can be difficult to clean with a toothbrush. Additional cleaning techniques can include using a needle-less plastic syringe to vigorously wash the tooth with moderately pressured water or to softly wash it with hydrogen peroxide. However, debris and bacteria can easily accumulate under an operculum, which may cause pericoronitis, a common infection problem in young adults with partial impactions that is often exacerbated by occlusion with opposing 3rd or 2nd molars. Common symptoms include a swelling and redness of the gum around the eruption site, difficulty in opening the mouth, a bad odor or taste in the mouth, and pain in the general area which may also run down the entire lower jaw or possibly the neck. Untreated pericoronitis can progress to a much more severe infection. If the operculum does not disappear, recommended treatment is extraction of the wisdom tooth. An alternative treatment involving removal of the operculum, called operculectomy, has been advocated. There is a high risk of permanent or temporary numbness of the tongue due to damage of the nerve with this treatment and it is no longer recommended as a standard treatment in oral surgery. A wisdom tooth is extracted to correct an actual problem or to prevent problems that may come up in the future. Wisdom teeth are extracted for two general reasons: either the wisdom teeth have already become impacted, or the wisdom teeth could potentially become problematic if not extracted. Potential problems caused by the presence of properly grown-in wisdom teeth include infections caused by food particles easily trapped in the jaw area behind the wisdom teeth where regular brushing and flossing is difficult and ineffective. Such infections may be frequent, and cause considerable pain and medical danger. Another reason to have a wisdom tooth removed is if the tooth has grown in improperly, causing the tongue to brush up against it. The tongue can tolerate it for a limited time, until it causes a painful sensation, to the point where the sheer pain can numb the tongue affected, and the area around it (part of the lips, and the cheek). The numbness feels similar to the feeling of anesthesia, possibly meaning a nerve can be affected by the wisdom tooth improperly growing in. Also, it is a wise choice to have them removed if undergoing extensive orthodontic work because once the teeth have come in they could inflict some damage on expensive straightening. The extraction of wisdom teeth should only be performed by dental professionals with proper training and experience performing such extractions. The precise reasons why an individual's wisdom teeth need to be extracted should be explained to them by their dentist, after an examination which almost certainly will need to include x-rays. A panoramic x-ray (aka "panorex") is the best x-ray to view wisdom teeth and diagnose their problems. There are several problems that can manifest themselves after the extraction(s) have been completed. Some of these problems are unavoidable and natural, while others are under the control of the patient. The suggestions contained in the sections below are general guidelines that a patient will be expected to abide by, but the patient should follow all directions that are given by the surgeon in addition to the following guidelines. Above all, the patient must not disregard the given instructions; doing so is extremely dangerous and could result in any number of problems ranging in severity from being merely inconvenient (dry socket) to potentially life-threatening (serious infection of the extraction sites). Bleeding and oozing is inevitable and should be expected to last up to three days (although by day three it should be less noticeable). Rinsing out one's mouth during this period is counter-productive, as the bleeding stops when the blood forms clots at the extraction sites, and rinsing out the mouth will most likely dislodge the clots. The end result will be a delay in healing time and a prolonged period of bleeding. However, after about 24 hours post-surgery, it is best to rinse with lukewarm saltwater to promote healing. This should be done every 2 hours until the swelling goes down and every 4-6 hours after that for at least a week. Gauze pads should be placed at the extraction sites, and then should be bitten down on with firm and even pressure. This will help to stop the bleeding, but should not be overdone as it is possible to irritate the extraction sites and prolong the bleeding. The bleeding should decrease gradually and noticeably upon changing the gauze. If the bleeding lasts for more than a day without decreasing despite having followed the surgeon's directions, the surgeon should be contacted as soon as possible. This is not supposed to happen under normal circumstances and signals that a serious problem is present. A wet tea bag can replace the gauze pads. Tannic acid contained in tea can help reduce the bleeding. Due to the blood clots that form in the exposed sockets as well as the abundant bacterial flora in the mouth, an offensive smell may be noticeable a short time after surgery. The persistent odour often is accompanied by an equally rancid-tasting fluid seeping from the wounds. These symptoms will diminish over an indefinite amount of time, although one to two weeks is normal. While not a cause for great concern, a post-operative appointment with your surgeon seven to ten days after surgery is highly recommended to make sure that the healing process has no complications and that the wounds are relatively clean. If infection does enter the socket, a qualified dental professional can gently plunge a plastic syringe (minus the hypodermic needle) full of a mixture of equal parts hydrogen peroxide and water or chlorohexidine gluconate into the sockets to remove any food or bacteria that may collect in the back of the mouth. This is less likely if the person has his wisdom teeth removed at an early age. A dry socket is not an infection; it is the event where the blood clot at an extraction site is dislodged, falls out prematurely, or fails to form. It is still not known how they form or why they form. In some cases, this is beyond the control of the patient. However, in other cases this happens because the patient has disregarded the instructions given by the surgeon. Smoking, spitting, or drinking with a straw in disregard to the surgeon's instructions can cause this, along with other activities that change the pressure inside of the mouth, such as playing a musical instrument. The risk of developing a dry socket is greater in smokers, if the patient has had a previous dry socket, in the lower jaw, and following complicated extractions. The extraction site will become irritated and pain is due to the bone lining the tooth socket becoming inflamed (osteitis). The symptoms are made worse when food debris is trapped in the tooth socket. The patient should contact his/her surgeon if they suspect that they have a case of dry socket; the surgeon may elect to clean the socket under local anesthetic so another blood clot forms or prescribe medication in topical form to apply to the affected site. A non-steroidal anti-inflammatory drug such as ibuprofen may be prescribed by the surgeon for pain relief. Generally dry sockets are self limiting and heal in a couple of weeks without treatment. Swelling should not be confused with dry socket, although painful swelling should be expected and is a sign that the healing process is progressing normally. There is no general duration for this problem; the severity and duration of the swelling vary from case to case. The instructions the surgeon gives the patient will tell the patient for how long they should expect swelling to last, including when to expect the swelling to peak and when the swelling will start to subside. If the swelling does not begin to subside when it is supposed to, the patient should contact his or her surgeon immediately. While the swelling will generally not disappear completely for several days after it peaks, swelling that does not begin to subside or gets worse may be an indication of infection. Swelling that re-appears after a few weeks is an indication of infection caused by a bone or tooth fragment still in the wound and should be treated immediately. This is primarily an issue with extraction of third molars, but can occur with the extraction of any tooth should the nerve be in close proximity to the surgical site. Two nerves are typically of concern and are found in duplicate (on the left and right side): Such injuries can occur while lifting teeth (typically the inferior alveolar) but are most commonly caused by inadvertent damage with a surgical drill. Such injuries are rare and are usually temporary. Depending on the type of injury (i.e. Seddon classification: neuropraxia, axonotmesis, and neurotmesis) they can be prolonged or permanent. Preventive removal of the third molars is a common practice in developed countries despite the lack of scientific data to support this practice. In 2006, the Cochrane Collaboration published a systematic review of randomized controlled trials in order to evaluate the effect of preventative removal of asymptomatic wisdom teeth . The authors found no evidence to either support or refute this practice. There was reliable evidence showing that preventative removal did not reduce or prevent late incisor crowding. The authors of the review suggested that the number of surgical procedures could be reduced by 60% or more. Likewise, ClinicalEvidence published a summary , largely based on the Cochrane review, that concluded prophylactic extraction is "Likely to be ineffective or harmful". ClinicalEvidence offered the following details: Wisdom teeth are vestigial third molars. In earlier times, when tooth loss in early adulthood was common, an additional molar had the potential to fill in a gap left by the loss of another tooth. It has also been postulated that the skulls of human ancestors had larger jaws with more teeth, which were possibly used to help chew down foliage to compensate for a lack of ability to efficiently digest the cellulose that makes up a plant cell wall. As human diet changed, a smaller jaw was selected by evolution, yet the third molars, or "wisdom teeth", still commonly develop in human mouths. Other findings suggest that a given culture's diet is a larger factor than genetics in the development of jaw size during human development (and, consequently, the space available for wisdom teeth). Different human populations differ greatly in the percentage of the population which form wisdom teeth, ranging from 99.8% in Bantu speakers to nearly 0% in Mexican Indians. The difference is related to the PAX9 gene (and perhaps other genes).

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/index.php/Wiskott-Aldrich_syndrome

# Wiskott-Aldrich syndrome Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD ; Syed Hassan A. Kazmi BSc, MD ; Cafer Zorkun, M.D., Ph.D. Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet counts), immune deficiency, and bloody diarrhea (due to the low platelet counts). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954. The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present similar but less severe symptoms and are caused by mutations of the same gene. The syndrome is named after Dr Robert Anderson Aldrich, an American pediatrician who described the disease in a family of Dutch-Americans in 1954, and Dr Alfred Wiskott, a German pediatrician who first noticed the syndrome in 1937. Wiskott described three brothers with a similar disease, whose sisters were unaffected. In 2006 a German research group analysed family members of Wiskott's three cases, and surmised that they probably shared a novel frameshift mutation of the first exon of the WAS gene. In the Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts. Wiskott–Aldrich syndrome was linked in 1994 to mutations in a gene on the short arm of the X chromosome, which was termed Wiskott-Aldrich syndrome protein (WASp). It was later discovered that the disease X-linked thrombocytopenia (XLT) was also due to WASp mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked neutropenia has been linked to particular mutations of the WASp gene. The WASp gene codes for the protein by the same name, which is 502 amino acids long and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the Arp2/3 complex. In T-cell, WASp is important because it is known to be activated via T-cell receptor (TCR) signaling pathways to induce cortical actin cytoskeleton rearrangements that are responsible for forming the immunological synapse. The immune deficiency is caused by decreased antibody production, and an inability for T cells to become polarized (making it a combined immunodeficiency). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T cells are unable to reorganize their actin cytoskeleton. The type of mutation to the WASp gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a missense mutation but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk. The immune deficiency is caused by decreased antibody production, and an inability for T cells to become polarized (making it a combined immunodeficiency). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T-cells are unable to reorganize their actin cytoskeleton. The type of mutation to the WASp gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a missense mutation but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.

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/index.php/Withdrawal_reflex

# Withdrawal reflex The nociceptive withdrawal reflex (NWR) is a spinal reflex intended to protect the body from damaging stimuli. The classic example is when you touch something hot and withdraw your body part from the hot object. The heat stimulates temperature and pain receptors in the skin, triggering a sensory impulse that travels to the central nervous system. The sensory neuron then synapses with interneurons that connect to motor neurons. Some of these send motor impulses to the flexors to allow withdrawal; some motor neurons send inhibitory impulses to the extensors so flexion is not inhibited - this is referred to as reciprocal innervation. While all of this occurs, other interneurons relay the sensory information up to the brain so that the person becomes aware of the pain and what happened. The NWR is also known as the flexion reflex.

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/index.php/Wittenoom,_Western_Australia

# Wittenoom, Western Australia Wittenoom is an area in the Pilbara region of Western Australia about 1,106 km north north east of Perth. During the 1950s, Wittenoom was the Pilbara's biggest town, but was shut down in 1966 due to health concerns from asbestos mining at the nearby Wittenoom Gorge. Today it is a ghost town with approximately 8 residents , who receive no government services. In December 2006, the Government of Western Australia announced that the town would be degazetted, and in June 2007, Hon Jon Ford, as Minister for Regional Development, announced that the townsite status had officially been removed. The town's name will accordingly be removed from official maps and road signs and the Shire of Ashburton will be able to close roads that lead to contaminated areas The Minister also released the non-technical summary of a report done in 2006 by independent geotechnical consultants into the extent and management of asbestos contamination in Wittenoom. This report, reviewed independently by the Department of Health, found that levels of asbestos fibres in Wittenoom presented an unacceptable public health risk. Wittenoom was named by Lang Hancock after Frank Wittenoom (1855-1939) who was his partner in the nearby Mulga Downs Station. The land around Wittenoom was originally settled by Frank Wittenoom's brother, politician Sir Edward Horne Wittenoom. Hancock discovered Wittenoom Gorge in the early 1930s and in 1937 started mining blue asbestos (crocidolite) there. In 1943 the mine was sold to a CSR Limited subsidiary, Australian Blue Asbestos Pty Ltd. By the late 1940s there was a need for a nearby townsite to house the mine workers and their families, and this was gazetted in 1950. The following year CSR requested the town name be changed to Wittenoom Gorge, and in 1974 it was changed back to Wittenoom. From 1950 until the early 1960s Wittenoom was Australia's only supplier of asbestos with 161,000 tonnes being mined. During that time 20,000 men, women and children lived and worked in Wittenoom. Since then, over 1,000 people have died from asbestos-related diseases including asbestosis, lung cancer and mesothelioma. The National Health and Medical Research Council estimates that the final death toll will eventually rise to over 2,000. Despite ongoing risks associated with airborne asbestos fibres, a number of residents still remained in early 2006, defying the Government of Western Australia's removal of services and stated intention to demolish the town. On 30 June 2006, the Government turned off the power grid to Wittenoom. Between May 2006 and November 2006, three residents took up the government's offer to buy their houses for up to A$39,804, plus an additional solatium of 10% and $10,000 relocation costs. In December 2006, Minister for the Pilbara and Regional Development Jon Ford announced that Wittenoom's status as a town would be removed, and in June 2007, he announced that the townsite status was officially removed. He also encouraged the remaining residents to accept the Government's relocation offer, as a recent detailed report into asbestos contamination in Wittenoom clearly demonstrates that the risks for most categories of people who use the various sites in and around Wittenoom are classified as medium to high. The Western Australian Department of Health examined the report and indicated that the levels of risk of exposure to contamination in Wittenoom translate into what is, from a Public Health perspective, an unacceptable level of risk. The Midnight Oil song, Blue Sky Mine, was inspired by the town and its mining industry, as were He Fades Away and Blue Murder by Alistair Hulett.

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/index.php/Wittig_reaction

# Wittig reaction Recent research has shown that the reaction mechanism presented above does not account for all experimental results. Mechanistic studies have been done mostly on unstablilized ylides, because the intermediates can be followed by NMR spectroscopy. The existence and interconversion of the betaine (3a and 3b) is still under debate and a subject of ongoing research. There is evidence that phosphonium ylides 1 can react with carbonyl compounds 2 via a π²s/π²a [2+2] cycloaddition to directly form the oxaphosphatanes 4a and 4b. The stereochemistry of the product 5 is due to the addition of the ylide 1 to the carbonyl 2 and to the ability of the intermediates to equilibrate.[citation needed] There are distinct differences in the mechanisms of aliphatic and aromatic aldehydes and of aromatic and aliphatic phosphonium ylides. Vedejs et al. have provided evidence that the Wittig reaction of unbranched aldehydes under salt-free conditions do not equilibrate and are therefore under kinetic reaction control. Vedejs has put forth a theory to explain the stereoselectivity of stabilized and unstabilized Wittig reactions. The simplest ylide used is methylenetriphenylphosphorane (Ph3P=CH2), and this is also the basis of an alternative synthesis of Wittig reagents. Substituted ylides can be made by alkylation of Ph3P=CH2 with a primary alkyl halide R−CH2−X, to produce a substituted phosphonium salt: A large variety of ketones and aldehydes are effective in the reaction, though carboxylic acid derivatives such as esters fail to react usefully. Thus mono-, di- and trisubstituted alkenes can all be prepared in good yield in most cases. The carbonyl compound can tolerate several groups such as OH, OR, aromatic nitro and even ester groups. There can be a problem with sterically hindered ketones, where the reaction may be slow and give poor yields, particularly with stabilised ylides, and in such cases the Horner-Wadsworth-Emmons (HWE) reaction (using phosphonate esters) is preferred. As mentioned above, the Wittig reagent itself is usually derived from a primary alkyl halide, because with most secondary halides the phosphonium salt is formed in poor yield. This means that most tetrasubstituted alkenes are best made by other means. However the Wittig reagent can tolerate many other variants. It may contain alkenes and aromatic rings, and it is compatible with ethers and even ester groups. Even C=O and nitril groups can be present if conjugated with the ylide- these are the stabilised ylides mentioned above. Bis-ylides (containing two P=C bonds) have also been made and used successfully. One limitation relates to the stereochemistry of the product. With simple ylides, the product is usually mainly the Z-isomer, although a lesser amount of the E-isomer is often formed also- this is particularly true when ketones are used. If the reaction is performed in DMF in the presence of LiI or NaI, the product is almost exclusively the Z-isomer. If the E-isomer is the desired product, the Schlosser modification may be used. With stabilised ylides the product is mainly the E-isomer, and this same isomer is also usual with the HWE reaction. The major limitation of the traditional Wittig reaction is that the reaction goes mainly via the erythro betaine intermediate, which leads to the Z-alkene. However Schlosser & Christmann found that the erythro betaine can be converted to the threo betaine using phenyllithium at low temperature (forming a betaine ylide) followed by HCl. Upon workup this leads to the E-alkene product as shown. Corey and H. Yamamoto found that the utility can be extended to a stereoselective synthesis of allylic alcohols, by reaction of the betaine ylid with a second aldehyde. For example: The most popular use of the Wittig reaction is for the introduction of a methylene group using methylenetriphenylphosphorane (Ph3P=CH2). In the example shown, even a sterically hindered ketone such as camphor can be successfully converted to its methylene derivative by heating with methyltriphenylphosphonium bromide and potassium tert-butoxide, which generate the Wittig reagent in situ. In another example, the phosphorane is produced using sodium amide as a base, and this successfully converts the aldehyde shown into alkene I in 62% yield. The reaction is performed in cold THF, and the sensitive nitro, azo and phenoxide groups all survive intact. The product can be used to incorporate a photostabiliser into a polymer, to protect the polymer from damage by UV radiation. Another example of its use is in the synthesis of leukotriene A methyl ester. The first step uses a stabilised ylide, where the carbonyl group is conjugated with the ylid preventing self condensation, although unexpectedly this gives mainly the cis product. The second Wittig reaction uses a non-stabilised Wittig reagent, and as expected this gives mainly the cis product. Note that the epoxide and ester functional groups survive intact.

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/index.php/Wnt_signaling_pathway

# Wnt signaling pathway The wnt signaling pathway describes a complex network of proteins most well known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals. The name Wnt was coined as a combination of Wg (wingless) and Int. The wingless gene had originally been identified as a segment polarity gene in Drosophila melanogaster that functions during embryogenesis. and also during adult limb formation during metamorphosis. The INT genes were originally identified as vertebrate genes near several integration sites of mouse mammary tumor virus (MMTV). The Int-1 gene and the wingless gene were found to be homologous, with a common evolutionary origin evidenced by similar amino acid sequences of their encoded proteins. Mutations of the wingless gene in the fruit fly were found in wingless flies, while tumors caused by MMTV were found to have copies of the virus integrated into the genome forcing overproduction of one of several Wnt genes. The ensuing effort to understand how similar genes produce such different effects has revealed that Wnts are a major class of secreted morphogenic ligands of profound importance in establishing the pattern of development in the bodies of all multicellular organisms studied. The Wnt pathway involves a large number of proteins that can regulate the production of Wnt signaling molecules, their interactions with receptors on target cells and the physiological responses of target cells that result from the exposure of cells to the extracellular Wnt ligands. Although the presence and strength of any given effect depends on the Wnt ligand, cell type, and organism, some components of the signaling pathway are remarkably conserved in a wide variety of organisms, from Caenorhabditis elegans to humans. Protein homology suggests that several distinct Wnt ligands were present in the common ancestor of all bilaterian life, and certain aspects of Wnt signaling are present in sponges and even in slime molds. The canonical Wnt pathway describes a series of events that occur when Wnt proteins bind to cell-surface receptors of the Frizzled family, causing the receptors to activate Dishevelled family proteins and ultimately resulting in a change in the amount of β-catenin that reaches the nucleus (Figure 2). Dishevelled (DSH) is a key component of a membrane-associated Wnt receptor complex (Figure 2) which, when activated by Wnt binding, inhibits a second complex of proteins that includes axin, GSK-3, and the protein APC (Figure 1). The axin/GSK-3/APC complex normally promotes the proteolytic degradation of the β-catenin intracellular signaling molecule. After this "β-catenin destruction complex" is inhibited, a pool of cytoplasmic β-catenin stabilizes, and some β-catenin is able to enter the nucleus and interact with TCF/LEF family transcription factors to promote specific gene expression (interaction 2, Figure 2). Some additional details of the pathway are described below. Cell surface Frizzled (FRZ) proteins usually interact with a transmembrane protein called LRP (Figure 2). LRP binds Frizzled, Wnt and axin and may stabilize a Wnt/Frizzled/LRP/Discheveled/axin complex at the cell surface ("receptor complex" in Figure 2). In vertebrates, several secreted proteins have been described that can modulate Wnt signaling by either binding to Wnts or binding to a Wnt receptor protein. For example, Sclerostin (not shown in a figure) can bind to LRP and inhibit Wnt signaling. The part of the pathway linking the cell surface Wnt-activated Wnt receptor complex to the prevention of β-catenin degradation is still under investigation. There is evidence that trimeric G proteins (G in Figure 2) can function downstream from Frizzled. It has been suggested that Wnt-activated G proteins participate in the disassembly of the axin/GSK3 complex. Several protein kinases and protein phosphatases have been associated with the ability of the cell surface Wnt-activated Wnt receptor complex to bind axin and disassemble the axin/GSK3 complex. Phosphorylation of the cytoplasmic domain of LRP by CK1 and GSK3 can regulate axin binding to LRP (interaction 1 in Figure 2). The protein kinase activity of GSK3 appears to be important for both the formation of the mebrane-associated Wnt/FRZ/LRP/DSH/Axin complex and the function of the Axin/APC/GSK3/β-catenin complex. Phosphorylation of β-catenin by GSK3 leads to the destruction of β-catenin (Figure 1). Liu et al (2005) report on 2-amino-4-[3,4-(methylenedioxy)benzyl-amino]-6-(3-methoxyphenyl)pyrimidine as an agonist of Wnt signaling. An example of the control of planar cell polarity in insects like Drosophila is determining which direction the tiny hairs on the wings of a fly are aligned. Planar cell polarity is distinct from and perpendicular to apical/basal polarity. The signaling pathway that is involved in planar cell polarity includes frizzled and dishevelled but not the axin complex proteins. The non-classical cadherins Fat, Dachsous and Flamingo can apparently modulate frizzled function. Other proteins including prickle, strabismus, rhoA and rho-kinase act downstream of frizzled and dishevelled to regulate the cytoskeleton and planar cell polarity. Some of the proteins involved planar cell patterning of the Drosophila wing are used in vertebtates during regulation of cell movements during events such as gastrulation. A common feature of both hair patterning in Drosophila and cell movements such as vertebrate gastrulation is control of actin filaments by G proteins such as Rho and Rac. The Wnt Receptor Ryk is required for Wnt mediated axon guidance on the controlateral side of the corpus callosum (Journ. of Neuroscience, 2006; 26 : 5840-5848) Traditionally, it is assumed that Wnt proteins can act as Stem Cells Growth Factors, promoting the maintenance and proliferation of stem cells (Nature. 2003 May 22;423(6938):448-52). However, a recent study conducted by the Stanford University School of Medicine revealed that Wnt appears to block proper communication, with the Wnt signaling pathway having a negative effect on stem cell function. Thus, in the case of muscle tissue, the misdirected stem cells instead of generating new muscle cells (myoblasts), they differentiated into scar-tissue-producing cells called fibroblasts. The stem cells failed to respond to instructions, actually creating wrong cell types.

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/index.php/Wnt_signalling_pathway

# Wnt signalling pathway The Wnt signaling pathway describes a complex network of proteins most well known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals. Some of the proteins involved in planar cell patterning of the Drosophila wing are used in vertebtates during regulation of cell movements during events such as gastrulation. A common feature of both hair patterning in Drosophila and cell movements such as vertebrate gastrulation is control of actin filaments by G proteins such as Rho and Rac. However, a recent study conducted by the Stanford University School of Medicine revealed that Wnt appears to block proper communication, with the Wnt signaling pathway having a negative effect on stem cell function. Thus, in the case of muscle tissue, the misdirected stem cells instead of generating new muscle cells (myoblasts), they differentiated into scar-tissue-producing cells called fibroblasts. The stem cells failed to respond to instructions, actually creating wrong cell types.

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/index.php/Wobble_base_pair

# Wobble base pair A wobble base pair is a G-U and I-U / I-A / I-C pair fundamental in RNA secondary structure. Its thermodynamic stability is comparable to that of the Watson-Crick base pair. Wobble base pairs are critical for the proper translation of the genetic code. The genetic code makes up for disparities in the number of amino acids (20) for codons (64), by using modified base pairs in the first base of the anti-codon. One important modified base is inosine which can pair with three bases: uracil, adenine, and cytosine. The fact that there are 61 amino-acid-coding codons and roughly 40 tRNA molecules presented a problem; in 1966 Francis Crick proposed the Wobble hypothesis to account for this. He postulated that the 5' base on the anti-codon was not as spatially confined as the other two bases, and could thus have non-standard base pairing. This would account for 60 codons for 40 tRNA. As an example yeast tRNAPhe has the anticodon 5'-GmAA-3' and can recognize the codons 5'-UUC-3' and 5'-UUU-3'. It is, therefore, possible for non-Watson-Crick base pairing to occur at the third codon position, i.e. the 3' nucleotide of the mRNA codon and the 5' nucleotide of the tRNA anticodon.

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/index.php/Wohl-Ziegler_reaction

# Wohl-Ziegler reaction In a typical setup a a stoichiometric amount of N-bromosuccinimide solution and a small quantity of initiator are added to a solution of the substrate in CCl4, and the reaction mixture is stirred and heated to the boiling point. Initiation of the reaction is indicated by more vigorous boiling; sometimes the heat source may need to be removed. Once all N-bromosuccinimide (which is denser than the solvent) has been converted to succinimide (which floats on top) the reaction has finished.

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/index.php/Wolcott-Rallison_syndrome

# Wolcott-Rallison syndrome Wolcott-Rallison syndrome abbreviated as WRS is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Patients with WRS have mutations in the EIF2AK3 gene, which encodes the pancreatic eukaryotic translation initiation factor 2-alpha kinase 3.

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/index.php/Wolf%27s_Law

# Wolf's Law Wolff's law is a theory developed by the German Anatomist/Surgeon Julius Wolff (1836-1902) in the 19th century that states that bone in a healthy person or animal will adapt to the loads it is placed under. If loading on a particular bone increases, the bone will remodel itself over time to become stronger to resist that sort of loading.The external cortical portion of the bone becomes thicker as a result. The converse is true as well: if the loading on a bone decreases, the bone will become weaker due to turnover, it is less metabolically costly to maintain and there is no stimulus for continued remodeling that is required to maintain bone mass. Many fighters will do things like knuckle push-ups as a form of conditioning, for example, so the impacts of strikes are only supplementary conditioning, as ideally in both sparring and striking practise as well as competitive contest your body should not be experiencing adequate stress for microtrauma adaptation. This is so the body can solely focus on technique and nervous recruitment and not tissue adaptation which can be distracting. Not including supplementary exercise does however guarantee that the body will not over-adapt and develop toughness specifically in response to training demands, which can be a factor for those concerned with making weight, and not wanting to develop bone or muscle weight they may not need for contest.

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/index.php/Wolff-Chaikoff_effect

# Wolff-Chaikoff effect It is an autoregulatory phenomenon which inhibits formation of thyroid hormones inside of the thyroid follicle. This becomes evident secondary to elevated levels of circulating iodide. Wolff-Chaikoff effect lasts several days, after which it is followed by an "escape phenomenon", which is described by resumption of normal organification of iodine and normal thyroid peroxidased function. "Escape phenomenon" is believed to occur because of decreased inorganic iodine concentration secondary to down-regulation of sodium-iodide symporter on the basolateral membrane of the Thyroid Follicular cell. Wolff-Chaikoff effect can be used as a treatment principle against thyroid storm by infusion a large amount of iodine to shut down the hyperfunctioning thyroid gland, or an unpleasant iatrogenic effect of several iodine containing drugs, of which the most famous is amiodarone.

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/index.php/Wolff-Parkinson-White_syndrome_overview

# Wolff-Parkinson-White syndrome overview Wolff-Parkinson-White (WPW) syndrome is the most common cause of ventricular pre-excitation and the second common cause of supraventricular tachycardia. There is a muscle fiber that bridges the atrioventricular groove providing electrical continuity between the atrium and ventricle in parallel to the atrioventricular node-His-Purkinje axis. The atrial impulse activates the entire or part of the ventricle or the ventricular impulse activates the entire atrium or part of it, earlier than normally be expected. Patients with WPW syndrome may present with abrupt palpitation, presyncope, syncope, or sudden cardiac death (SCD). In some patients, SCD is the first presentation of WPW syndrome, especially in the setting of atrial fibrillation with a rapid ventricular response. Wolff-Parkinson-White syndrome is named after the cardiologists Louis Wolff, John Parkinson, and Paul Dudley White who gave a definitive description of the conduction disorder of the heart in 1930. The term Wolff-Parkinson-White syndrome was coined in 1940. Bundle of Kent was first discovered by Albert Frank Stanley Kent, a British physiologist following finding the lateral branch in the atrioventricular groove of the monkey heart. Wolff-Parkinson-White (WPW) syndrome is the occurrence of arrhythmia in the presence of an accessory pathway. WPW can be classified according to the site of origin, location in the mitral or tricuspid annulus, type of conduction (antegrade vs retrograde), and characteristics of the conduction (decremental vs nondecremental). In addition, WPW can be classified based on the type of atrioventricular reciprocating tachycardia (AVRT) it causes, which can be either orthodromic (~95% of the cases) or antidromic.In normal individuals, electrical activity in the heart is initiated in the sinoatrial (SA) node (located in the right atrium), propagates to the atrioventricular (AV) node, and then through the bundle of His to the ventricles of the heart. Individuals with Wolf-Parkinson-White syndrome (WPW) have an accessory pathway, known as the bundle of Kent, that communicates between the atria and the ventricles. The conduction through the accessory pathway can be bidirectional (most commonly), only retrogarde (less common), or only antegrade (least common). The most common type of tachycardia associated with WPW is atrioventricular reciprocating tachycardia (AVRT). The accessory pathway does not share the rate-slowing properties of the AV node; therefore, the combination of an accessory pathway and cardiac arrhythmia can trigger ventricular fibrillation, a leading cause of sudden cardiac death. The prevalence of WPW syndrome is approximately 100-300 per 100000 individuals worldwide. The incidence of tachyarrhythmia was estimated to be 1000 cases per 100000 individuals in the year in patients with WPW pattern. The incidence of sudden cardiac death in patients with Wolff-Parkinson-White syndrome was estimated to be 70-450 per 100000 patient-years. WPW syndrome is more commonly observed among young patients. In one study WPW syndrome was observed in 7% of individuals over 60-year-old. Men are more commonly affected with WPW syndrome than women. The men to women ratio is approximately 2 to 1. There is no racial predilection for WPW syndrome. High-risk criteria for sudden cardiac death in Wolff-Parkinson-White syndrome during electrophysiology study include the presence of multiple accessory pathways, R-R interval <250 milliseconds in antegrade conduction of accessory pathway during inducing atrial fibrillation, sustained atrial fibrillation induced by AV re-entry tachycardia, presence of Structural heart disease such as ebstein anomaly or hypertrophic cardiomyopathy. Patients with WPW pattern can remain asymptomatic throughout all their lives, nearly 65% of adolescents and 40% of adults present ECG changes but remain asymptomatic. Common complications of tachyarrhythmia associated WPW disease include reduced blood pressure and syncope, tachycaria induced cardiomyopathy, cardiac arrest, ventricular fibrillation, sudden cardiac death, complications of ablation, side effects of medications. SCD may occur in WPW syndrome due to rapid conduction of atrial fibrillation with heart rate >240/min to the ventricles via the accessory bypass tract leading ventricular fibrillation. Prognosis is generally excellent in asymptomatic WPW pattern. Catheter ablation (radiofrequency ablation) has a success rate between 95 - 98%, which varies depending on the location and number of accessory pathways. Successful ablation prevents future supraventricular tachyarrhythmia. The risk of lethal arrhythmia in asymptomatic children is higher than in adults. Long-term rates of atrial fibrillation in adult patients that present with WPW remains high despite ablation. Increased risk of atrial fibrillation in ablated WPW patients may be related to atrial fibrillation genesis. The diagnose of WPW pattern is commonly made by an incidental ECG finding in an asymptomatic individuals. The characteristic EKG finding is a delta wave, which represents the pre-excitation of the ventricles through the accessory pathway. This phenomenon presents because the AV node has the property of slowing the impulses, therefore the conduction through the accessory pathway is faster and the ventricles are excited through two different pathways. The delta wave is an upstroke in the R wave of the QRS complex that is associated with a short PR interval. Delta waves are only present when the patient is in sinus rhythm, whentachycardia starts the delta wave is no longer present. Patients with WPW syndrome and episodes of atrial fibrillation may present rapid irregular wide-complex tachycardia on EKG. The combination of atrial fibrillation and WPW may increase the risk of very rapid antidromic AVRT and occurrence of ventricular fibrillation. AV node blocking agents are contraindicated in these patients because of enhancement of the conduction through the accessory pathway. Patients with Ebstein anomaly and WPW may exhibit more than one accessory pathway. The most common combination of accessory pathways in Ebstein anomaly are the right posteroseptal and right free wall pathway. Wolff-Parkinson-White syndrome is sometimes associated with Leber's hereditary optic neuropathy (LHON), a form of mitochondrial disease. Symptoms of WPW syndrome may include Palpitation, chest pain or chest tightness, diziness, light-headedness, Brief loss of consciousness, shortness of breath, exercise intolerance, anxiety. WPW syndrome, uncommonly presents as cardiac arrest or sudden cardiac death.The accessory pathway of WPW syndrome is present since birth. The age of presentation of tachyarrhythmia varies from patient to patient. Infants may develop heart failure if the tachyarrhythmia keeps without treatment. Symptoms of tachycardia related WPW syndrome in infants may include lethargy, breathlessness, loss of appetite. Atrial fibrillation in a patient with WPW should be suspected when there is ECG findings of an irregularly irregular rhythm and absent P waves suggestive of atrial fibrillation in the context of a heart rate higher than 240 beats per minute. The electrophysiologic study is used for determining the location and number of accessory pathways, determining the mechanism of tachycardia, establishing the diagnosis in those patients with questionable resting EKG. Treatment is based on the risk stratification of the individual. Risk stratification is performed to determine which individuals with WPW syndrome are at risk for sudden cardiac death (SCD). Sudden cardiac death in these individuals is due to the propagation of an atrial arrhythmia to the ventricles at a very high rate. Noninvasive tests have a 70% positive predictive value and 30% negative predictive value for identifying pathways with life-threatening properties.Electrophysiologic studies are useful for evaluation of patients' symptoms. Wolff-Parkinson-White syndrome patients who are hemodynamically unstable, as reflected by the presence of hypotension, cold extremities, mottling or peripheral cyanosis, or those who present with ischemic chest pain or decompensated heart failure must undergo cardioversion urgently. The medical therapy of hemodynamically stable patients with WPW syndrome depends on the type of the tachycardia. When the ECG findings suggest orthodromic AVRT, the patient should be managed similar to AVNRT, and administration of adenosine, beta-blocker verapamil, and procainamide is recommended. Among patients with antidromic AVRT, AV nodal blocking agents should be avoided and patients should be treated with either procainamide, ibutilide. The long term treatment of patients with WPW syndrome depends on the presence or absence of symptoms and their severity. Patients who have poorly tolerated symptomatic WPW syndrome should undergo [[catheter ablation. Effective medication for prevention of tachyarrhythmia AVRT in patients without preexcitation in resting ECG include oral beta-blocker, diltiazem, and verapamil. Oral flecainide and propaphenone for prevention of tachyarrhythmia is recommended in patients with preexcitation in resting ECG that are not candidates for catheter ablation and do not have structural or ischemic heart disease. Wolff-Parkinson-White syndrome is named after the cardiologists Louis Wolff, John Parkinson, and Paul Dudley White who gave a definitive description of the conduction disorder of the heart in 1930. The term Wolff-Parkinson-White syndrome was coined in 1940. Bundle of Kent was first discovered by Albert Frank Stanley Kent, a British physiologist following finding the lateral branch in the atrioventricular groove of the monkey heart. Wolff-Parkinson-White (WPW) syndrome is the occurrence of arrhythmia in the presence of an accessory pathway. WPW can be classified according to the site of origin, location in the mitral or tricuspid annulus, type of conduction (antegrade vs retrograde), and characteristics of the conduction (decremental vs nondecremental). In addition, WPW can be classified based on the type of atrioventricular reciprocating tachycardia (AVRT) it causes, which can be either orthodromic (~95% of the cases) or antidromic. In normal individuals, electrical activity in the heart is initiated in the sinoatrial (SA) node (located in the right atrium), propagates to the atrioventricular (AV) node, and then through the bundle of His to the ventricles of the heart. Individuals with Wolf-parkinson-White (WPW) have an accessory pathway, known as the bundle of Kent, that communicates between the atria and the ventricles. The conduction through the accessory pathway can be bidirectional (most commonly), only retrogarde (less common), or only antegrade (least common). The most common type of tachycardia associated with WPW is atrioventricular reciprocating tachycardia (AVRT). The accessory pathway does not share the rate-slowing properties of the AV node; therefore, the combination of an accessory pathway and cardiac arrhythmia can trigger ventricular fibrillation, a leading cause of sudden cardiac death. The prevalence of WPW syndrome is approximately 100-300 per 100000 individuals worldwide. The incidence of tachyarrhythmia was estimated to be 1000 cases per 100000 individuals in the year in patients with WPW pattern. The incidence of sudden cardiac death in patients with Wolff-Parkinson-White syndrome was estimated to be 70-450 per 100000 patient-years. WPW syndrome is more commonly observed among young patients. In one study WPW syndrome was observed in 7% of individuals over 60-year-old. Men are more commonly affected with WPW syndrome than women. The men to women ratio is approximately 2 to 1. There is no racial predilection for WPW syndrome. High-risk criteria for sudden cardiac death in Wolff-Parkinson-White syndrome during electrophysiology study include the presence of multiple accessory pathways, R-R interval <250 milliseconds in antegrade conduction of accessory pathway during inducing atrial fibrillation, sustained atrial fibrillation induced by AV re-entry tachycardia, precence of Structural heart disease such as ebstein anomaly or hypertrophic cardiomyopathy. Patients with WPW pattern can remain asymptomatic through all their lives, nearly 65% of adolescents and 40% of adults present ECG changes but remain asymptomatic. Complications Wolff-Parkinson-White syndrome is a consequence of symptomatic tachycardias and can occur at any age. Common complications of tachyarrhythmia associated WPW disease include reduced blood pressure and syncope, tachycaria induced cardiomyopathy, cardiac arrest, ventricular fibrillation, usdden cardiac death, complications of ablation, side effects of medications. SCD may occur in WPW syndrome due to rapid conduction of atrial fibrillation with heart rate >240/min to the ventricles via the accessory bypass tract leading ventricular fibrillation. Prognosis is generally excellent in asymptomatic WPW pattern.Catheter ablation (radiofrequency ablation) has a success rate between 95 - 98%, which varies depending on the location and number of accessory pathways. Successful ablation prevents future supraventricular tachyarrhythmia. The risk of lethal arrhythmia in asymptomatic children is higher than in adults. Long-term rates of atrial fibrillation in adult patients that present with WPW remains high despite ablation. Increased risk of atrial fibrillation in ablated WPW patients may be related atrial fibrillation genesis. The diagnose of WPW pattern is commonly made by an incidental ECG finding in an asymptomatic individuals. The characteristic EKG finding is a delta wave, which represents the pre-excitation of the ventricles through the accessory pathway. This phenomenon presents because the AV node has the property of slowing the impulses, therefore the conduction through the accessory pathway is faster, therefore the ventricles are excited through two different pathways. The delta wave is an upstroke in the R wave of the QRS complex that is associated with a short PR interval. Delta waves are only present when the patient is in sinus rhythm, whentachycardia starts the delta wave is no longer present. Patients WPW syndrome with episodes of atrial fibrillation will present ECG with rapid irregular wide-complex tachycardia. The combination of atrial fibrillation and WPW may increase the risk of very rapid antidromic AVRT and occurrence of ventricular fibrillation. AV node blocking agents are contraindicated in these patients because it will enhance the conduction through the accessory pathway. Patients with WPW may exhibit more than one accessory pathway which is common in patients with Ebstein's anomaly. The most common combination of accessory pathways in Ebstein anomaly was the right posteroseptal and right free wall pathway. Wolff-Parkinson-White syndrome is sometimes associated with Leber's hereditary optic neuropathy (LHON), a form of mitochondrial disease. Symptoms of WPW syndrome may include Palpitation, Chest pain or chest tightness, Dizziness, Light-headedness, Brief loss of consciousness, Shortness of breath, Exercise intolerance, Anxiety. The most common arrhythmias associated with Wolff-Parkinson-White syndrome is AV reentry tachycardia. WPW syndrome, uncommonly presents as cardiac arrest or sudden cardiac death.The accessory pathway of WPW syndrome is present since birth. The age of presentation of tachyarrhythmia varies from patient to patient. Infants may develop heart failure if not treated immediately. Symptoms of tachycardia related WPW syndrome in infants may include Lethargy, Breathlessness, Loss of appetite. Wolff-Parkinson-White (WPW) pattern is characterized by ECG findings such as a short PR interval and a delta wave and wide QRS complex.WPW syndrome is the occurrence of tachycardia with or without associated symptoms in a subject with existing WPW pattern. WPW syndrome can present as an orthodromic or antidromic AVRT during which the delta wave no longer appears. Atrial fibrillation in a patient with WPW should be suspected when there is ECG findings of an irregularly irregular rhythm and absent P waves suggestive of atrial fibrillation in the context of a heart rate higher than 240 beats per minute. .The electrophysiologic study is used for determining the location and number of accessory pathways, determining the mechanism of tachycardia, establishing the diagnosis in those patients with questionable resting EKG. Treatment is based on the risk stratification of the individual. Risk stratification is performed to determine which individuals with WPW syndrome are at risk for sudden cardiac death (SCD). Sudden cardiac death in these individuals is due to the propagation of an atrial arrhythmia to the ventricles at a very high rate. Noninvasive tests have a 70% positive predictive value and 30% negative predictive value for identifying pathways with life-threatening properties.Electrophysiologic studies are useful for evaluation of patients' symptoms. Wolff-Parkinson-White syndrome patients who are hemodynamically unstable, as reflected by the presence of hypotension, cold extremities, mottling or peripheral cyanosis, or those who present with ischemic chest pain or decompensated heart failure must undergo cardioversion urgently. The medical therapy of hemodynamically stable patients with WPW syndrome depends on the type of the tachycardia. When the ECG findings suggest orthodromic AVRT, the patient should be managed similarly to patients with supreventricular tachycardia followed by the sequential administration of adenosine, verapamil and procainamide in case of failure to improve. Among patients with antidromic AVRT, AV nodal blocking agents should be avoided and patients should be treated with either procainamide, ibutilide or flecainide. The long term treatment of patients with WPW syndrome depends on the presence or absence of symptoms and their severity. Patients who have poorly tolerated symptomatic WPW syndrome should undergo catheter ablation. Oral beta-blocker, diltiazem, and verapamil for prevention of AVRT in patients without preexcitation in resting ECG. Oral flecainide and propaphenone in patients with preexcitation in resting ECG that are not candidates for catheter ablation and do not have structural or ischemic heart disease.

wikidoc

/index.php/Wolff-Parkinson-White_syndrome_resident_survival_guide

# Wolff-Parkinson-White syndrome resident survival guide Wolff-Parkinson-White (WPW) syndrome is a condition of pre-excitation of the ventricles of the heart due to the presence of an accessory pathway known as the Bundle of Kent through which the electrical impulses bypass the AV node. The difference between WPW pattern and WPW syndrome is that WPW pattern is characterized by the presence of characteristic ECG findings, such as a short PR interval and a delta wave, whereas WPW syndrome is the occurrence of tachycardia with or without associated symptoms in a subject with existing WPW pattern. The treatment of WPW syndrome is targeted towards the restoration of the sinus rhythm, usually by the administration of either ibutilide or procainamide. The most common type of arrhythmia in WPW syndrome is AV reentrant tachycardia. Atrial fibrillation in a patient with WPW is life threatening and should be managed urgently. Atrial fibrillation in a patient with WPW should be suspected when there is ECG findings suggestive of atrial fibrillation in the context of a heart rate higher than 220 beats per minute. A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention. Boxes in red signify that an urgent management is needed. Shown below is an algorithm summarizing the initial approach to Wolff-Parkinson-White syndrome according to the 2003 ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias.

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/index.php/Wolffenstein-B%C3%B6ters_reaction

# Wolffenstein-Böters reaction According to one series of studies the mercury nitrate first takes benzene to the corresponding nitroso compound and through the diazonium salt to the phenol. The presence of nitrite is essential for the reaction; picric acid formation is prevented when urea, a trap for nitrous acid, is added to the mixture. From then on the reaction proceeds as a regular aromatic nitration. A conceptually related reaction at one time of interest to the pigment industry is the Bohn-Schmidt reaction (1889) involving the hydroxylation of hydroxyantraquinone with sulfuric acid and lead or selenium to a polyhydroxylated anthraquinone.

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/index.php/Wolfram_syndrome

# Wolfram syndrome Wolfram syndrome, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare genetic disorder, causing diabetes mellitus, optic atrophy, and deafness as well as various other possible disorders. It was first described in four siblings in 1938 by Dr. Don J. Wolfram, M.D. The disease affects the central nervous system (especially the brainstem). Wolfram syndrome was initially thought to be caused by mitochondrial dysfunction due to its symptoms and several reports of mitochondrial mutations. However, it has now been established that Wolfram syndrome is caused by endoplasmic reticulum dysfunction. The WFS1 or wolframin gene provides instructions for making the wolframin protein. The WFS1 gene is active in cells throughout the body, with strong activity in the heart, brain, lungs, inner ear, and pancreas. The pancreas provides enzymes that help digest food, and it also produces the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Within cells, wolframin is located in a structure called the endoplasmic reticulum. Among its many activities, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape to function properly. The endoplasmic reticulum also helps transport proteins, fats, and other materials to specific sites within the cell or to the cell surface. The function of wolframin is unknown. Based on its location in the endoplasmic reticulum, however, it may play a role in protein folding or cellular transport. In the pancreas, wolframin may help fold a protein precursor of insulin (called proinsulin) into the mature hormone that controls blood glucose levels. Research findings also suggest that wolframin may help maintain the correct cellular level of charged calcium atoms (calcium ions) by controlling how much is stored in the endoplasmic reticulum. In the inner ear, wolframin may help maintain the proper levels of calcium ions or other charged particles that are essential for hearing. More than 30 WFS1 mutations have been identified in individuals with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNA6. Individuals with DFNA6 deafness cannot hear low tones (low-frequency sounds), such as a tuba or the "m" in moon. DFNA6 hearing loss is unlike most forms of nonsyndromic deafness that affect high tones (high-frequency sounds), such as birds chirping, or all frequencies of sound. Most WFS1 mutations replace one of the protein building blocks (amino acids) used to make wolframin with an incorrect amino acid. One mutation deletes an amino acid from wolframin. WFS1 mutations probably alter the 3-dimensional shape of wolframin, which could affect its function. Because the function of wolframin is unknown, however, it is unclear how WFS1 mutations cause hearing loss. Some researchers suggest that altered wolframin disturbs the balance of charged particles in the inner ear, which interferes with the hearing process. Mutations in the WFS1 gene cause Wolfram syndrome, which is also known by the acronym DIDMOAD. This syndrome is characterised by childhood-onset diabetes mellitus (DM), which results from the improper control of glucose due to the lack of insulin; a gradual loss of vision caused by optic atrophy (OA), in which the nerve that connects the eye to the brain wastes away; and deafness (D). This syndrome can sometimes cause diabetes insipidus (DI), a condition in which the kidneys cannot conserve water. Other complications that affect the bladder and nervous system may also occur. Researchers have identified more than 100 WFS1 mutations that cause Wolfram syndrome. Some mutations delete or insert DNA from the WFS1 gene. As a result, little or no wolframin is present in cells. Other mutations replace one of the protein building blocks (amino acids) used to make wolframin with an incorrect amino acid. These mutations appear to reduce wolframin activity dramatically. Researchers suggest that the loss of wolframin disrupts the production of insulin, which leads to poor glucose control and diabetes mellitus. It is unclear how WFS1 mutations lead to other features of Wolfram syndrome. Wolfram syndrome must be differentiated from other similar conditions which lead to multiple endocrine disorders such as autoimmune polyendocrine syndrome, POEMS syndrome, Hirata syndrome, Kearns–Sayre syndrome and Wolfram syndromes. The first symptom is typically diabetes mellitus, which is usually diagnosed around the age of 6. The next symptom to appear is often optic atrophy, the wasting of optic nerves, around the age of 11. The first signs of this are loss of colour vision and peripheral vision. The condition worsens over time, and people with optic atrophy are usually blind within 8 years of the first symptoms. Life expectancy of people suffering from this syndrome is about 30 years. Research for designing therapeutic trials is ongoing via the Washington University Wolfram Study Group, supported by The Jack and J.T. Snow Scientific Research Foundation for Wolfram research.

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/index.php/Wolfson_Centre_for_Age-Related_Diseases

# Wolfson Centre for Age-Related Diseases The Wolfson Centre for Age-Related Diseases (CARD) is based at the Guy's Hospital campus of King's College London. It is made up of three research groups including the Receptors and Signalling Group, the Neurorestoration Group and Neurodegeneration and Clinical Trials Group.

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/index.php/Women%27s_College_Hospital

# Women's College Hospital Women's College Hospital maintains a focus on women's health, research in women's health, and ambulatory care. It was given the distinction of being the only 'collaborating centre' in the Western Hemisphere designated by the World Health Organization. The hospital was founded on October 1, 1883 as Women's Medical College, and was the first medical school in Toronto to admit women as students. It currently functions as an independent ambulatory care hospital. It moved to its current location in Toronto in 1935, and became a teaching hospital affiliated with the University of Toronto in 1961. Women's College Hospital merged with Sunnybrook Hospital and the Orthopedic and Arthritic Hospital in 1998 under the provisions of Ontario Bill 51, and became Sunnybrook and Women's College Health Sciences Centre. Women's College Hospital de-amalgamated in 2006 to become The New Women's College Hospital. In 2003, while still part of the erstwhile "Sunnybrook and Women's College Health Sciences Centre", the Women's College site housed the first ambulatory SARS clinic in Canada, (while the Sunnybrook site housed both the first in-patient SARS unit and Intensive Care Unit for SARS in Canada).

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/index.php/Wonder_(emotion)

# Wonder (emotion) Wonder is an emotion comparable to surprise in that it is most commonly felt when perceiving something rare or unexpected. Unlike surprise however, it is more definitely positive in valence and can endure for longer periods. It has also been specifically linked with curiosity and the drive for scientific investigation. Haidt, J. & Keltner, D . (2004). Appreciation of beauty and excellence. In C. Peterson and M. E. P. Seligman (Eds.) Character strengths and virtues. Washington DC: American Psychological Association Press. pp. 537-551.

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/index.php/Wong_Jack_Man

# Wong Jack Man Template:Chinese name Wong Jack Man (Chinese:黃澤民, born c.1940 in Hong Kong ) is a Chinese martial artist and martial arts teacher, best known for fighting Bruce Lee in a real-life challenge match in Oakland in 1964. Wong taught classes in Tai Chi Chuan, Xingyiquan and Northern Shaolin at the Fort Mason Center in San Francisco. He retired in 2005 after teaching for 45 years. His classes continued under his student Rick Wing. According to Linda Lee Cadwell, Bruce Lee's wife, Lee's teaching of Chinese martial arts to Caucasians made him unpopular with Chinese martial artists in San Francisco. Dan Inosanto stated that Wong Jack Man did not teach Caucasians, and that he showed up at Lee's school on Broadway several months after Lee began teaching and issued an ornate scroll with a challenge to stop teaching Caucasians if he lost. Wong stated that he requested a public fight with Lee after Lee had issued an open challenge during a demonstration at a Chinatown theater where Lee claimed to be able to defeat any martial artist in San Francisco. There are no witnesses that corroborates Wong's story, however. Wong stated it was after a mutual acquaintance delivered a note from Lee inviting him to fight that he showed up at Lee's school to challenge him. This "mutual acquaintance" has never been named and has never stepped forward to corroborate Wong's story. Wong contested the notion that Lee was fighting for the right to teach caucasians as not all of Wong's students were Chinese, Wong won't elaborate on whether any of those non-Chinese students were Caucasian, however. As the fight date approached, Wong tried to delay the match and even asked for restrictions on techniques such as no hitting the face, no kicking the groin, no eye jabs, etc. Bruce refused "rules", and the two fought no holds bar. Individuals known to have witnessed the match included Cadwell, James Lee (an associate of Bruce Lee, no relation) and William Chen, a teacher of Tai Chi Chuan. The details of the fight vary depending on the account. According to Bruce, Linda, and James Lee, the fight lasted 3 minutes with a decisive victory for Bruce. Wong was unsatisfied with Lee's account of the match and published his own version in the Chinese Pacific Weekly, a Chinese language newspaper in San Francisco. The article, which was featured on the front page, included a detailed description of the fight from Wong's perspective and concluded with an invitation to Bruce Lee for a public match if Lee found his version to be unacceptable. Lee never made a public response to the article. Wong later expressed regret over fighting Lee, attributing it to arrogance, both on the part of Lee and himself.

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/index.php/Wood_Spurge

# Wood Spurge It reproduces both from seeds and root runners that spread underground then sprout new plants. It often grows to a height of 80 cm, and has dark green leaves about 6 cm long. The complex green-yellow inflorescence (cyathium) typical of Euphorbia appears between April and June. The milky latex of the plant is toxic and it can cause irritation on contact with the skin.

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/index.php/Woodward-Hoffmann_rules

# Woodward-Hoffmann rules The Woodward-Hoffmann rules devised by Robert Burns Woodward and Roald Hoffmann are a set of rules in organic chemistry predicting the stereochemistry of pericyclic reactions based on orbital symmetry. These include electrocyclic reactions, cycloadditions, and sigmatropic reactions. Hoffmann was awarded the 1981 Nobel Prize in Chemistry for this work, shared with Kenichi Fukui who developed a similar model, while Woodward had died two years before he could win a second Nobel Prize for Chemistry. The rules apply to the observed stereospecificity of electrocyclic ring-opening and ring closing reactions at the termini of open chain conjugated polyenes either by application of heat (thermal reactions) or application of light (photochemical reactions). In the original publication in 1965 three rules are stated as: Organic reactions that obey these rules are said to be symmetry allowed. Reactions that take the opposite course are symmetry forbidden and require a lot more energy to take place if they take place at all. The stated rules are supported by theoretical calculations using the extended Hückel theory. For example, the activation energy required for thermal ring closing reaction of butadiene can be calculated as a function of the C-C-C bond angles keeping the other variables constant. Angles larger than 117° show a slight preference for a disrotatory reaction but with smaller angles a conrotatory reaction mode is preferred. It has been stated that the chemist E.J. Corey feels he is responsible for the ideas that laid the foundation for this research, and that Woodward unfairly neglected to credit him in the discovery. In a 2004 memoir published in the Journal of Organic Chemistry Corey makes his claim to fame with the single sentence: On May 4, 1964, I suggested to my colleague R. B. Woodward a simple explanation involving the symmetry of the perturbed (HOMO) molecular orbitals for the stereoselective cyclobutene to 1,3-butadiene and 1,3,5-hexatriene to cyclohexadiene conversions that provided the basis for the further development of these ideas into what became known as the Woodward-Hoffmann rules. In a 2004 rebuttal published in the Angewandte Chemie Roald Hoffmann denied the claim: he quotes Woodward from a lecture given in 1966 saying: I REMEMBER very clearly—and it still surprises me somewhat—that the crucial flash of enlightenment came to me in algebraic, rather than in pictorial or geometric form. Out of the blue, it occurred to me that the coefficients of the terminal terms in the mathematical expression representing the highest occupied molecular orbital of butadiene were of opposite sign, while those of the corresponding expression for hexatriene possessed the same sign. From here it was but a short step to the geometric, and more obviously chemically relevant, view that in the internal cyclisation of a diene, the top face of one terminal atom should attack the bottom face of the other, while in the triene case, the formation of a new bond should involve the top (or pari passu, the bottom) faces of both terminal atoms. In addition, Hoffmann points out that in 2 publications from 1963 and 1965 Corey described a total synthesis of the compound dihydrocostunolide and although in it an electrocyclic reaction is described Corey has nothing to offer with respect to explaining its stereospecifity.

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/index.php/Worcester_Wolves

# Worcester Wolves The Worcester Wolves is a basketball team from the city of Worcester, which plays in the British Basketball League. The Wolves play at in the 550-seat capacity Sports Hall of the University of Worcester, from whom they receive considerable financial backing and with whom they operate a basketball scholarship programme. The historic city of Worcester has, until recent years, not had much of a basketball history. Worcester City Chiefs were an active lower league club during the mid-1990s before moving to Solihull in 1996, leaving the city without a major basketball club. This changed in May, 2000 when Roger Clarke and Mick Donovan announced the formation of the Wolves franchise to play at the University of Worcester's brand new £2.5 million 'state of the art' Sports Hall. In their first season of action (2000-01) in National Basketball League Division 3 the wolves finished second in the 12 team league with a 18-3 record. Local rivals Bristol Bombers pipped them for the title, however luck would soon swing their way the following season. Initially placed in the regionalised NBL Division 2 in the "clean sheet reorganisation" of 2001, the Wolves played only the first game of the season in that division before being elevated (ahead of Bristol) into NBL Division 1 when Doncaster withdrew at the start of the season. University College Worcester Basketball Scholarships became available in September 2002 for talented players to study and play at the same time, and the club attracted a wealth of new talent including Ty Shaw (Idaho), Keith Jarrett and Rikki Prince (Both from Birmingham Bullets) that became the foundations of a strong first team. The excellent facilities and organisation which earned them the promotion continue to stand them in good stead, and over the years they became firmly established in what has now been renamed EBL Division 2, and won promotion to EBL Division 1 following an excellent campaign in 2003-04. Despite finishing in second place, behind the London Capitals, they managed to straighten the record by beating them in the Playoff final at the National Indoor Arena, winning 95-87. The victory capped off an excellent season that saw the Wolves also lift the Patron's Cup, following a 111-100 win against Hackney White Heat in the final, which was also played on their home court at the University of Worcester. Worcester had a reasonably successful debut season (2004-05) in EBL Division 1, finishing above fellow promotion winners London Capitals in 5th place with 13-9 record, which earned them a place in the post season playoffs. They built on their successes for the second season and finished 2005-06 in 4th place with a 17-9 record in the expanded Division 1. That season also saw the Wolves claim their biggest success to date, winning the National Trophy at the SkyDome Arena in Coventry, beating holders Sheffield Arrows 97-82 in the final. At the end of the 2005-06 season, the British Basketball League, the country's elite league was, not for the first time, suffering a membership crisis with three franchises, Birmingham Bullets, Brighton Bears and London Towers withdrawing from the league set-up. Although the Wolves management have claimed it was always their intention to move into the BBL, the possibility of it happening so quickly seemed near impossible. However with the lack of a West Midlands based franchise in the league, the BBL approached the Wolves and elected them into the elite league , along with London United. With an influx of new players, including former Plymouth Raider Solomon Sheard, Caja Rioja's Sergio Rodriguez and James Noel of the Masters College all signing up for the new-look team, expectations of upsetting the big boys was high, but the fairy tale beginning never materialized. The Wolves opened the season with a 77-82 loss at home to the Plymouth Raiders on September 30, 2006, and followed that with 21-point loss away to Milton Keynes Lions (74-96). It was a case of third time lucky as, on October 7, 2006, in front of a packed crowd at the "Wolves' Lair", Worcester edged past the Chester Jets with an 82-79 victory and Andy Harper posting 28 points for the home side. However the Wolves struggled and soon fell behind the pack, spending most of the season at the foot f the table. The highlight of the season for the Midlands club came on January 20, 2007, when second-place Sheffield Sharks were the visitors to the Wolves' Lair. The home side caused, without doubt, the biggest shock of the season by defeating the title-challengers 70-65, a result that would ultimately hand the Championship to Guildford. Despite this moral boosting win, Worcester continued to flounder and ended the season in tenth and last place with just four league wins to their name, eventually forcing head coach Josh Cooprider to resign. On July 15, 2007, Wolves announced that former Birmingham Bullets player/coach Skouson Harker would lead the team into the 2007-08 season. The Canadian would occupy a player/coach role for the first team as well as the University team and head the Academy.

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/index.php/Work_aversion

# Work aversion Work aversion, Workplace aversion, or Employment aversion is a psychological behavior, often part of an anxiety disorder, in which the subject intentionally refuses to be gainfully employed at all, or works far less than is necessary in order to meet ones needs . It has not been officially recognized as a disorder, and is not a disease, but rather a symptom of one or more psychiatric disorders. It is estimated that about four to five million people in the United States may be suffering from some form of work aversion, though the exact number is not known . The term work aversion does not refer to immature teens or young adults who "slack off" and fail to seek their first job or perform seriously at a job they obtain. Not all unemployed persons have work aversion. The subject of work aversion is typically an adult who has been previously employed, or who recently graduated from college or trade school, and for some psychological reason, feels turned off by employment. The subject who receives such a label generally has expenses, hence the need for steady employment. But due to medical issues, such as a phobia, s/he does not attempt to work or seek employment, and makes excuses to others for not doing so. The typical view of the subject by others is often laziness. But most persons suffering from work aversion are not lazy in the sense of lacking energy. The reason for failing to work is purely due to a psychological disorder. Since the term work aversion only applies to one with the need to earn income, complications will inevitably arise from lacking the money the subject needs from employment. These may include: Persons suffering from work aversion in need of money will often resort to extreme measures in order to obtain the funding needed to support themselves. These include: Treating work aversion involves treating the underlying psychological cause of the disorder, which often requires diagnostic testing. Often, this cause cannot be easily identified because the subject frequently has little or no self-recognition of the problem, lacks funding needed for diagnosis, and has little or no willpower to seek treatment. Methods of treatment for the underlying disorder include psychotherapy, counseling, medication, or some more unusual forms of treatment. Depending on the cause, lengths of treatment and success rates may vary. While some mild cases of work aversion may subside naturally over time without any treatment, other more severe cases may be incurable. These subjects are often considered candidates for Social Security Disability. Sometimes, environmental changes may help cure the disorder. These may include a career change or overhaul, a move to a new city or region, or self-employment. Sometimes, a subject may be able to find partial relief from a certain type of job or job environment where s/he feels comfortable. But, if the subject loses such a job, finding a replacement could be increasingly troublesome, and symptoms may reappear and worsen. If a subject is receiving funding for his/her expenses from a relative, friend, or other source, cutting off the funding does not motivate the subject to obtain employment, and will not improve this condition. A relative or friend who wants to help a subject should encourage him/her to seek treatment for the underlying cause. Many career couselors have turned to a therapy they identify as work-hardening. This means they put the person to work for a brief period of time in the first week, such as two hours per day. In the following week, they increase it to four hours per day. The amount of work increases each week until it becomes full-time, with the client being willing. This sometimes has proven to be successful.

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/index.php/Workplace_stress

# Workplace stress Workplace stress is the harmful physical and emotional response that occurs when there is a poor match between job demands and the capabilities, resources, or needs of the worker. Stress-related disorders encompass a broad array of conditions, including psychological disorders (e.g., depression, anxiety, post-traumatic stress disorder) and other types of emotional strain (e.g., dissatisfaction, fatigue, tension, etc.), maladaptive behaviors (e.g., aggression, substance abuse), and cognitive impairment (e.g., concentration and memory problems). In turn, these conditions may lead to poor work performance or even injury. Job stress is also associated with various biological reactions that may lead ultimately to compromised health, such as cardiovascular disease. Stress is a prevalent and costly problem in today's workplace. About one-third of workers report high levels of stress. One-fourth of employees view their jobs as the number one stressor in their lives. Three-fourths of employees believe the worker has more on-the-job stress than a generation ago. Evidence also suggests that stress is the major cause of turnover in organizations. Problems at work are more strongly associated with health complaints than are any other life stressor-more so than even financial problems or family problems. Many studies suggest that psychologically demanding jobs that allow employees little control over the work process increase the risk of cardiovascular disease. On the basis of research by the National Institute for Occupational Safety and Health and many other organizations, it is widely believed that job stress increases the risk for development of back and upper-extremity musculoskeletal disorders. High levels of stress are associated with substantial increases in health service utilization. Workers who report experiencing stress at work also show excessive health care utilization. In a 1998 study of 46,000 workers, health care costs were nearly 50% greater for workers reporting high levels of stress in comparison to "low risk" workers. The increment rose to nearly 150%, an increase of more than $1,700 per person annually, for workers reporting high levels of both stress and depression. Additionally, periods of disability due to job stress tend to be much longer than disability periods for other occupational injuries and illnesses. Job stress results from the interaction of the worker and the conditions of work. Views differ on the importance of worker characteristics versus working conditions as the primary cause of job stress. The differing viewpoints suggest different ways to prevent stress at work. According to one school of thought, differences in individual characteristics such as personality and coping style are most important in predicting whether certain job conditions will result in stress-in other words, what is stressful for one person may not be a problem for someone else. This viewpoint leads to prevention strategies that focus on workers and ways to help them cope with demanding job conditions. Although the importance of individual differences cannot be ignored, scientific evidence suggests that certain working conditions are stressful to most people. Such evidence argues for a greater emphasis on working conditions as the key source of job stress, and for job redesign as a primary prevention strategy. Personal interview surveys of working conditions, including conditions recognized as risk factors for job stress, were conducted in Member States of the European Union in 1990, 1995, and 2000. Results showed a trend across these periods suggestive of increasing work intensity. In 1990, the percentage of workers reporting that they worked at high speeds at least one-fourth of their working time was 48%, increasing to 54% in 1995 and to 56% in 2000. Similarly, 50% of workers reported they work against tight deadlines at least one-fourth of their working time in 1990, increasing to 56% in 1995 and 60 % in 2000. However, no change was noted in the period 1995–2000 (data not collected in 1990) in the percentage of workers reporting sufficient time to complete tasks. A substantial percentage of Americans work very long hours. By one estimate, more than 26% of men and more than 11% of women worked 50 hours per week or more in 2000. These figures represent a considerable increase over the previous three decades, especially for women. According to the Department of Labor, there has been an upward trend in hours worked among employed women, an increase in extended work weeks (>40 hours) by men, and a considerable increase in combined working hours among working couples, particularly couples with young children. Mood and sleep disturbances, upset stomach and headache, and disturbed relationships with family and friends are examples of stress-related problems. The effects of job stress on chronic diseases are more difficult to see because chronic diseases take a long time to develop and can be influenced by many factors other than stress. Nonetheless, evidence is rapidly accumulating to suggest that stress plays an important role in several types of chronic health problems-especially cardiovascular disease, musculoskeletal disorders, and psychological disorders. St. Paul Fire and Marine Insurance Company conducted several studies on the effects of stress prevention programs in hospital settings. Program activities included (1) employee and management education on job stress, (2) changes in hospital policies and procedures to reduce organizational sources of stress, and (3) establishment of employee assistance programs. In one study, the frequency of medication errors declined by 50% after prevention activities were implemented in a 700-bed hospital. In a second study, there was a 70% reduction in malpractice claims in 22 hospitals that implemented stress prevention activities. In contrast, there was no reduction in claims in a matched group of 22 hospitals that did not implement stress prevention activities.

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/index.php/World_AIDS_Day

# World AIDS Day World AIDS Day, observed December 1 each year, is dedicated to raising awareness of the AIDS pandemic caused by the spread of HIV infection. AIDS has killed more than 25 million people, with an estimated 38.6 million people living with HIV, making it one of the most destructive epidemics in recorded history. Despite recent, improved access to antiretroviral treatment and care in many regions of the world, the AIDS epidemic claimed an estimated 3.1 million (between 2.8 and 3.6 million) lives in 2005 of which, more than half a million (570,000) were children. The concept of a World AIDS Day originated at the 1988 World Summit of Ministers of Health on Programmes for AIDS Prevention. Since then, it has been taken up by governments, international organizations and charities around the world. From its inception until 2004, UNAIDS spearheaded the World AIDS Day campaign, choosing annual themes in consultation with other global health organizations. In 2005 this responsibility was turned over to World AIDS Campaign (WAC), who chose Stop AIDS: Keep the Promise as the main theme for World AIDS Day observences through 2010, with more specific sub-taglines chosen annually. This theme is not specific to World AIDS Day, but is used year-round in WAC's efforts to highlight HIV/AIDS awareness within the context of other major global events including the G8 Summit. World AIDS Campaign also conducts "in-country" campaigns throughout the world, like the Student Stop AIDS Campaign, an infection-awareness campaign targeting young people throughout the UK. It is common to hold memorials to honor persons who have died from HIV/AIDS on this day. Government and health officials also observe, often with speeches or forums on the AIDS topics. Since 1995 the President of the United States has made an official proclamation on World AIDS Day. Governments of other nations have followed suit and issued similar annoucements.

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/index.php/World_Cancer_Day

# World Cancer Day World Cancer Day is marked on the February 4th to raise awareness of the global impact of cancer and increase understanding of prevention, detection, treatment and care. Led by the International Union Against Cancer (UICC) — a global consortium of more than 280 cancer-fighting organizations in over 90 countries — World Cancer Day 2007 marked the first truly global recognition of this awareness day with the launch of the World Cancer Campaign called "Today's Children, Tomorrow's World." The five-year initiative underscores habits that parents can share with children to prevent cancer later in life. It's a striking statistic: 43% of cancers can be prevented through these healthy behaviours: • Provide a smoke-free environment for children • Be physically active, eat a balanced, healthy diet, and avoid obesity • Learn about vaccines for virus-related liver and cervical cancers • Avoid over-exposure to the sun Media in more than 50 countries spanning two dozen languages carried these key cancer-prevention messages in 2007 pegged to February 4. In addition to targeting the public through global communications marking World Cancer Day, the UICC encourages policy makers and member organizations to put cancer on the political agenda to drive home the regional relevance of cancer prevention. As a result, cancer-fighting organizations in 35 countries led prevention advocacy events on World Cancer Day 2007. . World Cancer Day 2006 was dedicated to raising awareness about childhood cancer. Under the slogan "My Child Matters" — the UICC announced a programme to promote early detection and access to treatment for children with cancer in limited-resources settings. [ ] World Cancer Day is a principal component of the UICC member-driven World Cancer Campaign. The World Cancer Campaign is a response to the Charter of Paris adopted on 4 February 2000 at the World Summit Against Cancer for the Millenium. This called for "an invincible alliance - between researchers, health-care professionals, patients, governments, industry and media - to fight cancer and its greatest allies, which are fear, ignorance and complacency."

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/index.php/World_Community_Autism_Program

# World Community Autism Program ## See also World Community Autism Program is a not-for-profit organisation founded in 2001 by autism researchers Sandra and Max Desorgher who have been advocates of a holistic nutritional approach to autism since 1994. They developed a lutein-free diet program, known as Sara's Diet, , also known as the Lutein-free diet, which has led to recoveries and significant improvements for people diagnosed with autism spectrum disorders and has been described as beneficial by the National Autistic Society, UK. ## Notes In 2000, Positive Health magazine published an article by the Desorghers called "Autism: Dietary Treatment Options", which explains the theory on which the lutein-free approach is based. In this theory, autism is seen as a neuro-gastro-immunological disorder resulting from an immunogenetic error during fetal development rather than as a psychological condition. According to this theory, the developing immune system selects lutein as a non-self pathogen. Autistic behaviors begin to emerge during early childhood as lutein-containing foods increasingly enter the infant's diet, triggering immune system responses as well as neurological and metabolic changes. This theory was further explained in "Autism, Pigments and the Immune System", published in 1999.

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/index.php/World_Health_Assembly

# World Health Assembly The World Health Assembly is the forum through which the World Health Organization (WHO) is governed by its 193 member states. It is the world's highest health policy setting body and is composed of health ministers from member states. The main tasks of the World Health Assembly are to approve the WHO programme and the budget for the following biennium and to decide major policy questions.

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/index.php/World_Health_Organization_Framework_Convention_on_Tobacco_Control

# World Health Organization Framework Convention on Tobacco Control The World Health Organization Framework Convention on Tobacco Control (abbreviated WHO FCTC) is a treaty adopted unanimously by the 56th World Health Assembly on May 21, 2003. It became the first World Health Organization treaty adopted under article 19 of the WHO constitution. The treaty came into force on February 27, 2005. It had been signed by 168 countries and is legally binding in 154 ratifying countries representing over 3 billion people. Notable non-parties are Russia (which has not signed the treaty) and the United States (which have signed but not ratified the treaty). The objective of the treaty is "to protect present and future generations from the devastating health, social, environmental and economic consequences of tobacco consumption and exposure to tobacco smoke." To this end, the treaty provides a framework of national, regional and international tobacco control measures, including the setting of broad limits on the production, sale, distribution, advertisement, taxation, and government policies towards tobacco. The United States has sought to change certain provisions of this treaty, but with limited success. Among the provisions opposed successfully were a mandatory ban on the distribution of free tobacco samples (which is now optional), a narrow definition of the term "minor" regarding the sale of tobacco (which now refers to domestic or national law) and broad limitations concerning the tobacco advertising, promotion and sponsorship (which were seen as violating free speech, and are now subject to constitutional limitations). Among the provisions unsuccessfully opposed by the U.S. were the requirement for warning labels to be written in the language of the country where the tobacco products are being sold, and the ban on deceptive and misleading descriptions such as "low tar" or "ultra-light", which might infringe on trademark protections.

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/index.php/World_Medical_Association

# World Medical Association ## Contents The World Medical Association (WMA), an international organization of physicians, was formally established on September 17, 1947, pursuant to the resolutions of the First General Assembly of WMA held in Paris, France. In 2007, the WMA had a membership of 84 national medical associations and represents some 9 million physicians. ## Mission The goal of the World Medical Association is to serve humanity by endeavoring to achieve the highest international standards in medical education, science, ethics, and health care for all peoples of the world. ## Presidency Yoram Blachar, an Israeli physician, was elected president of the World Health Association in October 2007. Blachar, 67, has been the chairman of the Israel Medical Association since 1995. Blachar said he would work to bring in African and Arab countries that were not yet members of the organization.

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/index.php/World_No_Tobacco_Day

# World No Tobacco Day World No Tobacco Day is observed around the world every year on May 31. The member states of the World Health Organization created World No Tobacco Day in 1987. It draws global attention to the tobacco epidemic and to the preventable death and disease it causes. It aims to reduce the 3.5 million yearly deaths from tobacco related health problems.

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/index.php/World_Organization_of_Family_Doctors

# World Organization of Family Doctors ## WONCA International Classification Committee The World Organization of National Colleges, Academies (Wonca) and Academic Associations of General Practitioners/Family Physicians or in short World Organization of Family Doctors is an international organization of national colleges, academies or organizations concerned with the academic aspects of general family practice. Wonca was founded in 1972.

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/index.php/World_Tuberculosis_Day

# World Tuberculosis Day World Tuberculosis Day, falling on 24 March each year, is designed to build public awareness that tuberculosis today remains an epidemic in much of the world, causing the deaths of about 1.6 million people each year, mostly in the third world. 24 March commemorates the day in 1882 when Dr Robert Koch astounded the scientific community by announcing that he had discovered the cause of tuberculosis, the TB bacillus. At the time of Koch's announcement in Berlin, TB was raging through Europe and the Americas, causing the death of one out of every seven people. Koch's discovery opened the way toward diagnosing and curing tuberculosis. In 1982, on the one-hundredth anniversary of Dr Koch's presentation, the International Union Against Tuberculosis and Lung Disease (IUATLD) proposed that 24 March be proclaimed an official World TB Day. In 1996, the World Health Organization (WHO) joined with the IUATLD and a wide range of other concerned organizations to increase the impact of World TB Day. The occurrence of TB in South Africa has tripled in recent years. The high HIV infection rate in South Africa has made the treatment of TB more difficult. South Africans receive a grant during the six months required for treatment, however treatment is purposefully disrupted to continue receiving the grant.

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/index.php/World_Vision

# World Vision World Vision, founded in the United States in 1950, is an international Christian relief and development organization whose stated goal is "working for the well being of all people, especially children." Working on six continents, World Vision is one of the largest Christian relief and development organisations in the world with a $2.6 billion budget (2007). World Vision was founded in 1950 by Dr. Bob Pierce, a young pastor and missionary, who had first been sent to China and South Korea in 1947 by the Youth for Christ missionary organization. Pierce remained at the head of World Vision for nearly two decades, but resigned from the organization in 1967. Pierce also founded the evangelical organization Samaritan's Purse. World Vision began caring for orphans and other children in need first in South Korea, then expanding throughout Asia and, eventually, in more than 90 countries, embracing larger issues of community development and advocacy for the poor as part of its basic mission to help children and their families build a sustainable future. World Vision International operates as a federation of interdependent national offices, each overseen by their own boards or advisory councils. A common mission statement and shared core values bind the partnership offices and members together. Each national partner abides by common policies and standards and holds each other accountable through an ongoing system of peer review. The partnership offices – located in Geneva, Bangkok, Nairobi, Cyprus, Los Angeles, and San José, Costa Rica – coordinate strategic operations of the organization and represent World Vision in the international arena. Each national office, whether in the developed or developing world, enjoys an equal voice in the organization's governance of world vision. An international board of directors oversees the World Vision partnership. The full board meets twice a year to appoint senior officers, approve strategic plans and budgets, and determine international policy. The current chairperson of the international board is Denis St. Armour of Canada. The international president is Dr. Dean R Hirsch According to World Vision's 2006 Consolidated Financial Statements, around 40% of their revenue comes from private sources, including individuals, World Vision clubs in schools, corporations and foundations. 27% comes from governments and multilateral aid agencies such as USAID. 30% comes from other World Vision programs and nonprofit organizaion as Gift in Kind. Aside from cash contributions, World Vision accepts gifts in kind, typically food commodities, medicine, and clothing donated through corporations and government agencies. Approximately half of World Vision's programs are funded through child sponsorship. Individuals, families, churches, schools, and other groups sponsor specific children or specific community projects in their own country or abroad. Sponsors send funds each month to provide support for the sponsored children or projects. World Vision Famine events like the 30 Hour Famine and 40 Hour Famine also help to raise money for impoverished countries. Typically, a group signs up to organize such an event, and then spends the next 30 or 40 hours abstaining from food, technology or other things that are taken for granted and increasing awareness about world hunger. Many schools and individuals are annually successful with this fundraising activity. According to World Vision's annual report, in 2005, 87% of its funding was spent on programs, 8% on fundraising and 5% on management and general overhead. World Vision has announced a goal of reducing the fundraising and overhead costs from the current 13% to 10%. World Vision aims to contribute to people's needs in five major areas; emergency relief, education, health care, economic development, and promotion of justice. World Vision activities include transformational development, emergency relief, strategic initiatives, public awareness campaigns and promoting Christianity. Transformational development occurs through focusing on improvement of children's lives. This process first helps people and their communities recognize the resources that lie within themselves to make change possible. With support from World Vision, communities transform themselves by carrying out their own development projects in health care, agriculture production, water projects, education, micro-enterprise development, advocacy and other community programs. World Vision provides emergency relief to people whose lives are endangered by disasters or conflict and who need immediate, skilled assistance. World Vision attempts to respond to all major emergencies around the world themselves or in cooperation with their partner agencies. For example, World Vision has responded to famine in Ethiopia and North Korea, hurricanes in Central America, the tsunami in the Indian Ocean nations, earthquakes in El Salvador, India, Taiwan and Turkey, and war refugees in Kosovo, Chechnya, Sierra Leone, Angola, and East Timor. World Vision also addresses the complex, systematic factors that perpetuate poverty by promoting justice. World Vision supports community awareness of the collective ability to address unjust practices and begin working for change. World Vision speaks out on issues such as child labor, debt relief for poor nations, and the use of children as combatants in armed conflict. World Vision International has endorsed the Universal Declaration of Human Rights and the United Nations Convention on the Rights of the Child as fundamental expressions of the freedoms and responsibilities that should exist in every country. World Vision fosters opportunities to help reduce conflict levels and to contribute to the peaceful resolution of hostilities and reconciliation of disputes. As a Christian organization, World Vision participates in strategic initiatives with Christian leaders and lay people of all denominations through conferences, consultations, training programmes and various educational opportunities. World Vision is an ecumenical organization willing to partner with all Christian churches. Yet, World Vision is respectful of other faiths. World Vision encourages public awareness about the needs of others, the causes of poverty, and the nature of compassionate response. These efforts include collaboration with media and community participation in fundraising. In all its communications, World Vision upholds the dignity of suffering children and families in presenting explanations of the causes and consequences of poverty, war, neglect, and abuse. World Vision believes witnessing from Christ is a fundamental part of their relief work. The organization believes that God, in the person of Jesus, offers hope of renewal, restoration, and reconciliation. World Vision seeks to express this message through "life, deed, word, and sign". World Vision's programs and services are provided without regard to race, ethnic origin, gender, or religion. World Vision offices often hire non-Christian staff, and in some countries the majority of staff may be people of other faiths who are sympathetic to World Vision's ethos and objectives. However, in the US all staff are required to sign a statement affirming their belief in Jesus Christ and background checks are often made with a candidate's pastor or priest.

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/index.php/Wound

# Wound In medicine, a wound is a type of physical trauma where in the skin is torn, cut or punctured (an open wound), or where blunt force trauma causes a contusion (a closed wound). In pathology, it specifically refers to a sharp injury which damages the dermis of the skin. Any other wound should be considered as severe. If there is any doubt, a wound should be considered as severe. "Severe" does not necessarily mean that it endangers life, but it must at least be seen by a physician. In the case of severe open wounds, there is a risk of blood loss (which could lead to shock), and an increased chance of infection due to bacteria entering a wound that is exposed to air. Due to the risk of infection, wounds should be kept clean, and closed if possible until professional help is available. Depending on their severity, closed wounds can be just as dangerous as open wounds. An injury to the brain such as a contusion is an extremely dire closed wound, and requires emergency medical attention. Open wounds can be classified into a number of different types, according to the object that caused the wound. The types of open wound are: Bacterial infection of wound can impede the healing process and lead to life threatening complications. Scientists at Sheffield University have identified a way of using light to rapidly detect the presence of bacteria. They are developing a portable kit in which specially designed molecules emit a light signal when bound to bacteria. Current laboratory-based detection of bacteria can take hours or even days.

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/index.php/Wound_healing

# Wound healing Wound healing, or wound repair, is the body's natural process of regenerating dermal and epidermal tissue. When an individual is wounded, a set of events takes place in a predictable fashion to repair the damage. These events overlap in time and must be artificially categorized into separate steps: the inflammatory, proliferative, and remodeling phases (Some authors consider healing to take place in four stages, by splitting different parts inflammation or proliferation into separate steps.). In the inflammatory phase, bacteria and debris are phagocytized and removed and factors are released that cause the migration and division of cells involved in the proliferative phase. The proliferative phase is characterized by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction. In angiogenesis, new blood vessels grow from endothelial cells. In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin. In epithelialization, epithelial cells crawl across the wound bed to cover it. In contraction, the wound is made smaller by the action of myofibroblasts, which establish a grip on the wound edges and contract themselves using a mechanism similar to that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis. In the maturation and remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis. In the inflammatory phase (lag phase/resting phase), clotting takes place in order to obtain hemostasis, or stop blood loss, and various factors are released to attract cells that phagocytise debris, bacteria, and damaged tissue and release factors that initiate the proliferative phase of wound healing. When tissue is first wounded, blood comes in contact with collagen, triggering blood platelets to begin secreting inflammatory factors. Platelets also express glycoproteins on their cell membranes that allow them to stick to one another and to aggregate, forming a mass. Fibrin and fibronectin cross-link together and form a plug that traps proteins and particles and prevents further blood loss. This fibrin-fibronectin plug is also the main structural support for the wound until collagen is deposited. Migratory cells use this plug as a matrix to crawl across, and platelets adhere to it and secrete factors. The clot is eventually lysed and replaced with granulation tissue and then later with collagen. Platelets, the cells present in the highest numbers shortly after a wound occurs, release a number of things into the blood, including ECM proteins and cytokines, including growth factors. Growth factors stimulate cells to speed their rate of division. Platelets also release other proinflammatory factors like serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, and histamine , which serve a number of purposes, including to increase cell proliferation and migration to the area and to cause blood vessels to become dilated and porous. Immediately after a blood vessel is breached, ruptured cell membranes release inflammatory factors like thromboxanes and prostaglandins that cause the vessel to spasm to prevent blood loss and to collect inflammatory cells and factors in the area. This vasoconstriction lasts five to ten minutes and is followed by vasodilation, a widening of blood vessels, which peaks at about 20 minutes post-wounding. Vasodilation is the result of factors released by platelets and other cells. The main factor involved in causing vasodilation is histamine. Histamine also causes blood vessels to become porous, allowing the tissue to become edematous because proteins from the bloodstream leak into the extravascular space, which increases its osmolar load and draws water into the area. Increased porousness of blood vessels also facilitates the entry of inflammatory cells like leukocytes into the wound site from the bloodstream. Within an hour of wounding, polymorphonuclear neutrophils (PMNs) arrive at the wound site and become the predominant cells in the wound for the first three days after the injury occurs, with especially high numbers on the second day. They are attracted to the site by fibronectin, growth factors, and substances such as neuropeptides and kinins. Neutrophils phagocytise debris and bacteria and also kill bacteria by releasing free radicals in what is called a 'respiratory burst'. They also cleanse the wound by secreting proteases that break down damaged tissue. Neutrophils usually undergo apoptosis once they have completed their tasks and are engulfed and degraded by macrophages. Other leukocytes to enter the area include helper T cells, which secrete cytokines to cause more T cells to divide and to increase inflammation and enhance vasodilation and vessel permeability. T cells also increase the activity of macrophages. Macrophages are essential to wound healing. They replace PMNs as the predominant cells in the wound by two days after injury. Attracted to the wound site by growth factors released by platelets and other cells, monocytes from the bloodstream enter the area through blood vessel walls. Numbers of monocytes in the wound peak one to one and a half days after the injury occurs. Once they are in the wound site, monocytes mature into macrophages, the main cell type that clears the wound area of bacteria and debris. The macrophage's main role is to phagocytise bacteria and damaged tissue, and it also debrides damaged tissue by releasing proteases. Macrophages also secrete a number of factors such as growth factors and other cytokines, especially during the third and fourth post-wounding days. These factors attract cells involved in the proliferation stage of healing to the area. Macrophages are stimulated by the low oxygen content of their surroundings to produce factors that induce and speed angiogenesis. and they also stimulate cells that reepithelialize the wound, create granulation tissue, and lay down a new extracellular matrix. Because they secrete these factors, macrophages are vital for pushing the wound healing process into the next phase. Because inflammation plays roles in fighting infection and inducing the proliferation phase, it is a necessary part of healing. However, inflammation can lead to tissue damage if it lasts too long. Thus the reduction of inflammation is frequently a goal in therapeutic settings. Inflammation lasts as long as there is debris in the wound. Thus the presence of dirt or other objects can extend the inflammatory phase for too long, leading to a chronic wound. As inflammation dies down, fewer inflammatory factors are secreted, existing ones are broken down, and numbers of neutrophils and macrophages are reduced at the wound site. These changes indicate that the inflammatory phase is ending and the proliferative phase is underway. About two or three days after the wound occurs, fibroblasts begin to enter the wound site, marking the onset of the proliferative phase even before the inflammatory phase has ended. As in the other phases of wound healing, steps in the proliferative phase do not occur in a series but rather partially overlap in time. Also called neovascularization, the process of angiogenesis occurs concurrently with fibroblast proliferation when endothelial cells migrate to the area of the wound. Because the activity of fibroblasts and epithelial cells requires oxygen, angiogenesis is imperative for other stages in wound healing, like epidermal and fibroblast migration. The tissue in which angiogenesis has occurred typically looks red (is erythematous) due to the presence of capillaries. In order to form new blood vessels and provide oxygen and nutrients to the healing tissue. stem cells called endothelial cells originating from parts of uninjured blood vessels develop pseudopodia and push through the ECM into the wound site. Through this activity, they establish new blood vessels. To migrate, endothelial cells need collagenases and plasminogen activator to degrade the clot and part of the ECM. Zinc-dependent metalloproteinases digest basement membrane and ECM to allow cell proliferation and angiogenesis. Endothelial cells are also attracted to the wound area by fibronectin found on the fibrin scab and by growth factors released by other cells. Endothelial growth and proliferation is also stimulated by hypoxia and presence of lactic acid in the wound. In a low-oxygen environment, macrophages and platelets produce angiogenic factors which attract endothelial cells chemotactically. When macrophages and other growth factor-producing cells are no longer in a hypoxic, lactic acid-filled environment, they stop producing angiogenic factors. Thus, when tissue is adequately perfused, migration and proliferation of endothelial cells is reduced. Eventually blood vessels that are no longer needed die by apoptosis. Simultaneously with angiogenesis, fibroblasts begin accumulating in the wound site. Fibroblasts begin entering the wound site two to five days after wounding as the inflammatory phase is ending, and their numbers peak at one to two weeks post-wounding. By the end of the first week, fibroblasts are the main cells in the wound Fibroplasia ends two to four weeks after wounding. In the first two or three days after injury, fibroblasts mainly proliferate and migrate, while later, they are the main cells that lay down the collagen matrix in the wound site. Fibroblasts from normal tissue migrate into the wound area from its margins. Initially fibroblasts use the fibrin scab formed in the inflammatory phase to migrate across, adhering to fibronectin. Fibroblasts then deposit ground substance into the wound bed, and later collagen, which they can adhere to for migration. Granulation tissue is needed to fill the void that has been left by a large, open wound that crosses the basement membrane. It begins to appear in the wound even during the inflammatory phase, two to five days post wounding, and continues growing until the wound bed is covered. Granulation tissue consists of new blood vessels, fibroblasts, inflammatory cells, endothelial cells, myofibroblasts, and the components of a new, provisional ECM. The provisional ECM is different in composition from the ECM in normal tissue and includes fibronectin, collagen, glycosaminoglycans, and proteoglycans. Its main components are fibronectin and hyaluronan, which create a very hydrated matrix and facilitate cell migration. Later this provisional matrix is replaced with an ECM that more closely resembles that found in non-injured tissue. Growth factors (PDGF, TGF-β) and fibronectin encourage proliferation, migration to the wound bed, and production of ECM molecules by fibroblasts. Fibroblasts also secrete growth factors that attract epithelial cells to the wound site. Hypoxia also contributes to fibroblast proliferation and excretion of growth factors, though too little oxygen will inhibit their growth and deposition of ECM components, and can lead to excessive, fibrotic scarring. One of fibroblasts' most important duties is the production of collagen. Fibroblasts begin secreting appreciable collagen by the second or third post-wounding day, and its deposition peaks at one to three weeks. Collagen production continues rapidly for two to four weeks, after which its destruction matches its production and so its growth levels off. Collagen deposition is important because it increases the strength of the wound; before it is laid down, the only thing holding the wound closed is the fibrin-fibronectin clot, which does not provide much resistance to traumatic injury. Also, cells involved in inflammation, angiogenesis, and connective tissue construction attach to, grow and differentiate on the collagen matrix laid down by fibroblasts. Even as fibroblasts are producing new collagen, collagenases and other factors degrade it. Shortly after wounding, synthesis exceeds degradation so collagen levels in the wound rise, but later production and degradation become equal so there is no net collagen gain. This homeostasis signals the onset of the maturation phase. Granulation gradually ceases and fibroblasts decrease in number in the wound once their work is done. At the end of the granulation phase, fibroblasts begin to commit apoptosis, converting granulation tissue from an environment rich in cells to one that consists mainly of collagen. The formation of granulation tissue in an open wound allows the reepithelialization phase to take place, as epithelial cells migrate across the new tissue to form a barrier between the wound and the environment. Basal keratinocytes from the wound edges and dermal appendages such as hair follicles, sweat glands and sebacious (oil) glands are the main cells responsible for the epithelialization phase of wound healing. They advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the middle. Keratinocytes migrate without first proliferating. . Migration can begin as early as a few hours after wounding. However, epithelial cells require viable tissue to migrate across, so if the wound is deep it must first be filled with granulation tissue. Thus the time of onset of migration is variable and may occur about one day after wounding. Cells on the wound margins proliferate on the second and third day post-wounding in order to provide more cells for migration. If the basement membrane is not breached, epithelial cells are replaced within three days by division and upward migration of cells in the stratum basale in the same fashion that occurs in uninjured skin. However, if the basement membrane is ruined at the wound site, reepithelization must occur from the wound margins and from skin appendages such as hair follicles and sweat and oil glands that enter the dermis that are lined with viable keratinocytes. If the wound is very deep, skin appendages may also be ruined and migration can only occur from wound edges. Migration of keratinocytes over the wound site is stimulated by lack of contact inhibition and by chemicals such as nitric oxide. Before they begin to migrate, cells must dissolve their desmosomes and hemidesmosomes, which normally anchor the cells by intermediate filaments in their cytoskeleton to other cells and to the ECM. Transmembrane receptor proteins called integrins, which are made of glycoproteins and normally anchor the cell to the basement membrane by its cytoskeleton, are released from the cell's intermediate filaments and relocate to actin filaments to serve as attachments to the ECM for pseudopodia during migration. Thus keratinocytes detach from the basement membrane and are able to enter the wound bed. Before they begin migrating, keratinocytes change shape, becoming longer and flatter and extending cellular processes like lamellipodia and wide processes that look like ruffles. Actin filaments and pseudopodia form. During migration, integrins on the pseudopod attach to the ECM, and the actin filaments in the projection pull the cell along. The interaction with molecules in the ECM through integrins further promotes the formation of actin filaments, lamellipodia, and filopodia. Epithelial cells climb over one another in order to migrate. This growing sheet of epithelial cells is often called the epithelial tongue. The first cells to attach to the basement membrane form the stratum basale. These basal cells continue to migrate across the wound bed, and epithelial cells above them slide along as well. The more quickly this migration occurs, the less of a scar there will be. Fibrin, collagen, and fibronectin in the ECM may further signal cells to divide and migrate Like fibroblasts, migrating keratinocytes use the fibronectin cross-linked with fibrin that was deposited in inflammation as an attachment site to crawl across. As keratinocytes migrate, they move over granulation tissue but underneath the scab (if one was formed), separating it from the underlying tissue. Epithelial cells have the ability to phagocytize debris such as dead tissue and bacterial matter that would otherwise obstruct their path. Because they must dissolve any scab that forms, keratinocyte migration is best enhanced by a moist environment, since a dry one leads to formation of a bigger, tougher scab. To make their way along the tissue, keratinocytes must dissolve the clot, debris, and parts of the ECM in order to get through. They secrete plasminogen activator, which activates plasmin to dissolve the scab. Cells can only migrate over living tissue, so they must excrete collagenases and proteases like matrix metalloproteinases (MMPs) to dissolve damaged parts of the ECM in their way, particularly at the front of the migrating sheet. Keratinocytes also dissolve the basement membrane, using instead the new ECM laid down by fibroblasts to crawl across. As keratinocytes continue migrating, new epithelial cells must be formed at the wound edges to replace them and to provide more cells for the advancing sheet. Proliferation behind migrating keratinocytes normally begins a few days after wounding and occurs at a rate that is 17 times higher in this stage of epithelialization than in normal tissues. Until the entire wound area is resurfaced, the only epithelial cells to proliferate are at the wound edges. Growth factors, stimulated by integrins and MMPs, cause cells to proliferate at the wound edges. Keratinocytes themselves also produce and secrete factors, including growth factors and basement membrane proteins, which aid both in epithelialization and in other phases of healing. Keratinocytes continue migrating across the wound bed until cells from either side meet in the middle, at which point contact inhibition causes them to stop migrating. When they have finished migrating, the keratinocytes secrete the proteins that form the new basement membrane. Cells reverse the morphological changes they underwent in order to begin migrating; they reestablish desmosomes and hemidesmosomes and become anchored once again to the basement membrane. Basal cells begin to divide and differentiate in the same manner as they do in normal skin to reestablish the strata found in reepithelialized skin. Around a week after the wounding takes place, fibroblasts have differentiated into myofibroblasts and the wound begins to contract In full thickness wounds, contraction peaks at 5 to 15 days post wounding. Contraction can last for several weeks and continues even after the wound is completely reepithelialized. If contraction continues for too long, it can lead to disfigurement and loss of function. Contraction occurs in order to reduce the size of the wound. A large wound can become 40 to 80% smaller after contraction. . Wounds can contract at a speed of up to 0.75 mm per day, depending on how loose the tissue in the wounded area is. Contraction usually does not occur symmetrically; rather most wounds have an 'axis of contraction' which allows for greater organization and alignment of cells with collagen. At first, contraction occurs without myofibroblast involvement. Later, fibroblasts, stimulated by growth factors, differentiate into myofibroblasts. Myofibroblasts, which are similar to smooth muscle cells, are responsible for contraction. Myofibroblasts contain the same kind of actin as that found in smooth muscle cells. Myofibroblasts are attracted by fibronectin and growth factors and they move along fibronectin linked to fibrin in the provisional ECM in order to reach the wound edges. They form connections to the ECM at the wound edges, and they attach to each other and to the wound edges by desmosomes. Also, at an adhesion called the fibronexus, actin in the myofibroblast is linked across the cell membrane to molecules in the extracellular matrix like fibronectin and collagen. Myofibroblasts have many such adhesions, which allow them to pull the ECM when they contract, reducing the wound size. In this part of contraction, closure occurs more quickly than in the first, myofibroblast-independent part. As the actin in myofibroblasts contracts, the wound edges are pulled together. Fibroblasts lay down collagen to reinforce the wound as myofibroblasts contract The contraction stage in proliferation ends as myofibroblasts stop contracting and commit apoptosis. The breakdown of the provisional matrix leads to a decrease in hyaluronic acid and an increase in chondroitin sulfate, which gradually triggers fibroblasts to stop migrating and proliferating. These events signal the onset of the maturation stage of wound healing. When the levels of collagen production and degradation equalize, the maturation phase of tissue repair is said to have begun. The maturation phase can last for a year or longer, depending on the size of the wound and whether it was initially closed or left open. During Maturation, type III collagen, which is prevalent during proliferation, is gradually degraded and the stronger type I collagen is laid down in its place. Originally disorganized collagen fibers are rearranged, cross-linked, and aligned along tension lines. As the phase progresses, the tensile strength of the wound increases, with the strength approaching 50% that of normal tissue by three months after injury and ultimately becoming as much as 80% as strong as normal tissue. Since activity at the wound site is reduced, the scar loses its erythematous appearance as blood vessels that are no longer needed are removed by apoptosis. The phases of wound healing normally progress in a predictable, timely manner; if they do not, healing may progress inappropriately to either a chronic wound such as a venous ulcer or pathological scarring such as a keloid scar.

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/index.php/Wouter_Basson

# Wouter Basson Wouter Basson (b. July 6, 1950) is a South African cardiologist and former head of the country's secret chemical and biological warfare project, Project Coast, during the Apartheid era. Much of what Basson was working on is still secret. It is known that in 1981, when he was working as a personal physician to prime minister Pieter Willem Botha, the country's Surgeon General hired Basson to work for the 7th SAMHS Medical Battalion, the medical military unit of the South African Defence Force. His job was to collect information about other countries' chemical and biological warfare capabilities under the name Project Coast. After his preliminary report, Basson became the head project officer and began to work on the country's chemical and biological weapons capability. He recruited about 200 researchers from around the world and received annual funds equivalent to $10 million. Project Coast secretly researched chemical and biological warfare in violation of the international BTWC agreement. Basson created four front companies; Delta G Scientific Company; Roodeplaat Research Laboratories (RRL), Protechnik and Infadel, which in 1989 was split into two companies - D. John Truter Financial Consultants and Sefmed Information Services. The companies were used to officially distance the military from the project, to procure necessary chemicals and channel funds for the research. According to later investigation, Basson had a free rein to do what he wanted. Delta G did most of the research, production and development of the chemical agents, while RRL developed chemical and biological pathogens and allegedly was involved with genetic engineering. Protechnik was a large nuclear, biological and chemical warfare plant developing defences against chemical weapons. Infadel dealt with those on a smaller scale and concentrated on financing and administration of other units and possibly channelling funds between military and research facilities. Many of the employees were not aware of what they were involved with. In the 1980s Basson and the project were allegedly involved with attacks and assassinations against the members of anti-apartheid movements. African leaders in South Africa, Angola and Namibia also claimed that the more dangerous chemicals were used for crowd control in the country, although the government claimed otherwise and claimed that chemical weapons were used against South African troops. Basson provided the Civil Cooperation Bureau (CCB) with lethal chemicals to be used against prominent anti-apartheid activists. Basson continued to travel all over world to gather information about chemical and biological warfare programs and set up other shell and paper companies as additional front companies, possibly for money laundering. When F. W. de Klerk became president in 1990, he ordered the production of the chemicals to be stopped and the lethal agents destroyed. Basson concentrated on non-lethal chemical agents and chemicals the government had not banned. That included a large amount of ecstasy and Mandrax that were apparently exported or allegedly sold to the drug dealers in communities active in the anti-apartheid movement (see Basson brownies). Most of the stockpile disappeared afterwards. Scientists working on the project later stated that they believed it was to be used to create drug-laced tear gas. In January 1992, Mozambique reported that a South African helicopter had attacked their soldiers by releasing an unknown lethal substance that led to four fatalities. Investigation by the United Nations, U.S. and the United Kingdom identified it as BZ nerve agent. USA and Britain began to pressure the South African government and in January 1993 Project Coast was decelerated. Basson was officially retired and hired to dismantle the project, and allegedly profited when some of the South African front companies were privatised. Later government investigation found that there were large amounts of chemicals and agents missing. In 1995 the South African government hired Basson to work for Transnet, a transportation and infrastructure company and possibly for other more secretive jobs. The USA and UK governments suspected that during his visits to Libya between 1993-1995, Basson might have sold chemical and biological weapons secrets. In 1995, the government of Nelson Mandela rehired Basson as an army surgeon, allegedly due to USA and UK pressure and possibly because the government wanted to keep eye on him. In 1996, South Africa's Truth and Reconciliation Commission (TRC) began to investigate the SADF and determined that the army had probably used lethal toxins against ANC activists. Basson was connected to many of these attacks. In 1997, the CIA told the South African government that Basson intended to leave the country. When Basson was arrested in a sting operation in Pretoria, he had a large quantity of ecstasy pills and various documents with him. TRC began to investigate Project Coast. Investigation led to suspicion that Basson had sold his secrets to governments of countries like Libya and Iraq. In 1997 they asked the help of the Netherlands Institute for Southern Africa (NIZA). NIZA's investigation report was included in the Truth Commission Files. At the same time, the Office for Serious Economic Offences, The National Intelligence Agency (NIA) and the Gauteng Attorney-General's Special Investigation Team investigated Basson's affairs. Conflict of interest slowed down the Commission investigation but the TRC gained more information from OSEO. Basson appeared before the Commission on July 31 1998 and gave evidence for 12 hours. Basson's lawyers constantly interrupted the questioning with legal technicalities. The Commission was, however, able to determine that Basson had been the primary decision maker in the Project Coast. Basson's trial began on October 4 1999 in Pretoria. At the time, the South African media had dubbed him "Doctor Death". Basson faced 67 charges, including drug possession, drug trafficking, fraud and embezzlement of a total of R36,000,000, 229 murders and conspiracy to murder and theft. Basson refused to seek amnesty from the Truth Commission. The prosecution presented 153 witnesses, but the case soon began to turn against them. On October 11, 1999 Judge Willie Hartzenberg dismissed 6 important charges, including four charges of murder and possible involvement in 200 deaths in Namibia, because he stated that the South African court could not prosecute crimes committed in other countries. Basson was also included in the Namibian amnesty of 1989. Hartzenberg then adjourned the trial for two weeks. After 18 months of trial, he reduced the number of charges to 46. In July 2001 Basson began to present his own evidence, being the only witness in his own behalf, speaking for 40 days. He stated that he had learned about the weapons of mass destruction from Saddam Hussein, that he had indeed had free rein in the project and that he had exchanged information with foreign governments. However, technically all that was legal. The defence argued that Basson should have immunity for anything that had happened in Namibia. On April 22 2002 Judge Hartzenberg dismissed all the remaining charges against Basson and granted him amnesty. The trial had lasted 30 months. The state threatened to appeal the judgment due to legal inaccuracies, but the Supreme Court of Appeal refused to order a retrial in 2003. After his release, Basson has continued to travel all over the world as a guest speaker, and has founded his own private medical practice. In June 2005, a group of Swiss investigators questioned him about illegal trade in weapons and nuclear material and asked the South African government to stop cooperating with them. Later that year the Constitutional Court, South Africa's highest court, overturned the judgement of the Supreme Court of Appeal. It ruled that crimes allegedly committed outside the country could be prosecuted in South Africa . Since then the National Prosecuting Authority has not instituted proceedings against Basson for crimes against humanity.

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/index.php/Wright%27s_stain

# Wright's stain Wright's stain is a technique in histology that is used to make the differences between cells visible under light microscopy. It is used in the examination of peripheral blood smears and bone marrow aspirates. Wright's stain is also used in cytogenetics to stain chromosomes on slides for visualization and diagnosis of sydromes and disease. It is named for James Homer Wright, who devised the stain, a modification of the Romanowsky stain, in 1902. Because it distinguishes easily between blood cells, it became widely used for performing differential white blood cell counts, which are routinely ordered when infections are expected, and as part of an assessment of overall health. There are related stains known as the buffered Wright stain, the Wright-Giemsa stain, and the buffered Wright-Giemsa stain, and specific instructions depend on the solutions being used, which may include Eosin Y, Azure B, and Methylene Blue (some commercial preparations combine solutions to simplify staining). The May-Grünwald stain, which produces a more intense coloration, also takes a longer time to perform.

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/index.php/Wrinkle

# Wrinkle A wrinkle is a ridge or crease of a surface. It usually refers to folds on fabric or clothes, or on the skin of an organism; the folds are generally random and do not exhibit any repeating pattern. In skin or other foldable material a wrinkle or fold may be permanent if the material is folded the same way each time. Skin wrinkles typically appear as a result of aging processes such as glycation or, temporarily, as the result of prolonged (more than a few minutes) immersion in water. Wrinkling in skin is caused by habitual facial expressions, aging, sun damage, smoking, poor hydration, and various other factors. Treatments and products (including anti-aging creams) promising to reduce, remove, or prevent age-related wrinkles are big business in many industrialized countries. Despite great demand, most such products and treatments have not been proven to give lasting or major positive effects. Stretching the skin via a face lift will remove some wrinkles. The wrinkles that occur in skin after prolonged exposure to water are sometimes referred to as prune fingers or water aging. This is a temporary skin condition where the skin on the palms of the hand or feet becomes wrinkly. It is caused when the keratin-laden epithelial skin is immersed in water . The skin expands and the resultant larger surface area forces it to wrinkle. Usually the tips of the fingers and toes are the first to wrinkle because of a thicker layer of keratin and an absence of hairs which secrete the protective oil called sebum. Wrinkled fingers often occur after taking a shower or bath and last up to fifteen minutes afterwards, until the water has evaporated or is absorbed into the body. Examples of wrinkles can be found in various animal species that grow loose, excess skin, particularly when they are young. Several breeds of dog, such as the Pug and the Shar Pei, have been bred to exaggerate this trait. In dogs bred for fighting, this is the result of selection for loose skin, which confers a protective advantage. Wrinkles are also associated with neoteny (cuteness), as they are a trait associated with juvenile animals. Fabric wrinkles occur as a result of cloth being bunched or folded unevenly. Wrinkled clothing is often undesirable in situations such as job interviews, or formal social events. There are products such as irons and fabric sprays to remove wrinkles from cloth. Some more modern fabrics have been engineered to be wrinkle-free or wrinkle-resistant by incorporating water-resistant polymers.

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/index.php/Wrist_and_hand_pain

# Wrist and hand pain ## Treatment The wrist contains eight carpal bones. These bones are aligned by a sequence of ligaments and cartilaginous connective tissue. Though pain and numbness is a frequent presentation, carpal tunnel syndrome is the most common diagnosis.

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/index.php/Wristop

# Wristop Wristop is a small wrist-mounted computer, which has an in-built processor for data processing. It can collect information from internal or external sensors. It can wirelessly control or collect data from other instruments. A wristop is designed to be a tool for a healthcare consumer who manages his/her own medical treatment. The small computer continuously collects information on a patient's wellbeing and sends this data wirelessly to an active wearable medical instrument (e.g. an insulin pump). The term "Wristop" especially refers to a device designed to co-operate with an insulin pump and to control it in the treatment of Type 1 diabetes. The wrist-wearable insulin pump controller gives the diabetic the possibility to monitor their energy consumption and control the insulin flow directly from a small watch-like device. Wristop was introduced at the Medica 2006 trade fair in Düsseldorf 16.11.2006 and was patented in May, 2006.

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/index.php/Writer%27s_cramp

# Writer's cramp Writer's cramp, also called mogigraphia and scrivener's palsy, causes a cramp or spasm affecting certain muscles of the hand and/or fingers . Writer's cramp is a task-specific focal dystonia of the hand . 'Focal' refers to the symptoms being limited to one location (the hand in this case), and 'task-specific' means that symptoms first occur only when the individual engages in a particular activity. Writer's cramp first affects an individual by inhibiting their ability to write. Although the etiology of writer's cramp is not well known, it was historically believed to be the result of excessive fine motor activity, possibly complicated by a tense or otherwise inappropriate writing technique. More recently, Rosenkranz et al. have suggested that this is not necessarily the case. Musician's cramp (a similar focal dystonia which affects some 1% of instrumentalists ) has historically been grouped together with writer's cramp because of this and their common task-specificity. Rosenkranz et al. have more recently identified significant differences between the two populations, however. No matter exactly how it arises, researchers generally agree that these types of focal dystonia are the result of a basal ganglia and/or sensorimotor cortex malfunction in the brain. Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, dropped items and a noticeable increase in dropped or chipped dishes), cramping pain with sustained use and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to restless leg syndrome. Affected persons may notice trembling in the diaphragm while breathing, or the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and the constant movement to avoid pain may result in the grinding and wearing down of teeth, or symptoms similar to TMD. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping. Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide a definitive diagnosis by showing pulsating nerve signals being transmitted to the muscles even when they are at rest. The brain appears to signal portions of fibers within the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate, tremble and contort. When called upon to perform an intentional activity, the muscles fatigue very quickly and some portions of the muscle groups do not respond (causing weakness) while other portions over-respond or become rigid (causing micro-tears under load). The symptoms worsen significantly with use, especially in the case of focal dystonia, and a "mirror effect" is often observed in other body parts: use of the right hand may cause pain and cramping in that hand as well as in the other hand and legs that were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures can worsen symptoms. Direct symptoms may be accompanied by secondary effects of the continuous muscle and brain activity, including disturbed sleep patterns, exhaustion, mood swings, mental stress, difficulty concentrating, blurred vision, digestive problems and short temper. People with dystonia may also become depressed and find great difficulty adapting their activities and livelihood to a progressing disability. Side effects from treatment and medications can also present challenges in normal activities. In some cases, symptoms may progress and then plateau for years, or stop progressing entirely. The progression may be delayed by treatment or adaptive lifestyle changes, while forced continued use may make symptoms progress more rapidly. In others, the symptoms may progress to total disability, making some of the more risky forms of treatment worth considering Although dystonias may be induced by chemical exposure/ingestion, brain injury, or hereditary/genetic predisposition, the task-specific focal dystonias such as writer's cramp are a unique challenge to diagnose and treat. Some cases may respond to chemical injections - botulinum toxin (botox) is often cited, though it is not helpful in all cases. Behavioral retraining attempts may include changing technique, switching hands, physical therapy, biofeedback, constraint-induced motion therapy, and others. None of these are effective in all cases, however.

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/index.php/Writing_therapy

# Writing therapy Writing therapy is a form of expressive therapy that uses the act of writing and processing the written word as therapy. Writing therapy posits that writing one's feelings gradually eases pain and strengthens the immune system. Writing therapeutically can take place individually or in a group and it can be administered in person with a therapist or remotely through mailing or the Internet. The field of writing therapy includes many practitioners in a variety of settings. The therapy is usually administered by a therapist or counsellor. Several interventions exist on-line, writing group leaders work in hospitals with patients dealing with their mental and physical illnesses and in university departments aiding student self-awareness and self-development. When administered at a distance it is useful for those who prefer to remain personally anonymous and are not ready to disclose their most private thoughts and anxieties in a face to face situation. As with most forms of therapy, writing therapy is adapted and used to work with a wide range of psychoneurotic illnesses including bereavement, desertion and abuse. Many of these interventions take the form of classes where clients write on specific themes chosen by their therapist or counsellor. Assignments may include writing unsent letters to selected individuals, alive or dead, followed by imagined replies from the recipient or parts of the patient's body, or a dialogue with the recovering alcoholic's bottle of alcohol. By far the greater part of the research into writing therapy has been conducted in the US, especially in recent years. The earliest and most important work was directed by James Pennebaker , a psychology professor who became deeply interested in the physical and mental benefits of self disclosure. In Pennebaker's original experiments one group of his students was directed to write for 20 minutes on three consecutive days on the worst traumas of their lives, while an equal number was asked to write of trivial matters. Firstly, the amount of undisclosed trauma in the life of the average American student was surprisingly high. And secondly, there was a marked difference between these two groups of students. In those who had written of trivial matters there was no change either in their physical or mental health whereas those who had done these brief trauma-recall exercises showed a marked strengthening of their immune system, decreased visits to the doctor and significant increases in pychological well-being. These findings were measured using physiological markers (long term serum measures, antibody levels, cell activity, enzyme levels, muscular activity, etc.) behavioural markers and self-report (distress, depression, etc). Following on from Pennebaker's original work, there has been a renewed interest in the therapeutic value of abreaction. This was first discussed by Josef Breuer and Freud in Studies on Hysteria but not much explored since. An additional line of enquiry that has particular bearing on the difference between talking and writing derives from Robert Ornstein's studies (The Right Mind:1997) into the bicameral structure of the brain. L'Abate postulates that: 'One could argue, for instance, that talk and writing differ in relative cerebral dominance. … if language is more related to the right hemisphere, then writing may be more related to the left hemisphere. If this is the case, then writing might use or even stimulate parts of the brain that are not stimulated by talking.' (L'Abate: 2004) With the accessibility provided by the Internet the reach of the writing therapies has grown beyond all recognition. It has become possible for a client and therapist anywhere in the world to work together, provided they can write the same language. They simply 'enter' into a private 'chat room' and engage in an ongoing text dialogue in 'real time'. This requires the services of a counsellor or therapist, albeit sitting at a computer. Given the huge disjunction between the amount of mental illness compared with the paucity of skilled resources, new ways have been sought to provide therapy other than drugs. In the more advanced societies pressure for cost-effective treatments, supported by evidence-based results, has come from both insurance companies and government agencies. Hence the decline in long term intensive psychoanalysis and the rise of much briefer forms, such as cognitive therapy. Currently the most widely used mode of Internet Writing Therapy is via e-mail; see analytic psychotherapist Nathan Field's paper The Therapeutic Action of Writing in Self-Disclosure and Self-Expression . It is asynchronous; that is, messages are passed between therapist and client within an agreed time frame, say one week, but at any time within that week. Where both parties remain anonymous the client benefits from the 'disinhibition' effect; that is to say, feels freer to disclose memories, thoughts and feelings that they might withhold in a face-to-face situation. Both client and therapist have time for reflecting on the past and recapturing forgotten memories, time for privately processing their reactions and giving thought to their own responses. With etherapy space is eliminated and time expanded. Overall it considerably reduces the amount of therapeutic input, as well as the speed and pressure that therapists habitually have to work under. Ironically, the anonymity and invisibility provides a therapeutic environment that comes much closer than classical analysis to Freud's ideal of the 'analytic blank screen'. Sitting behind the patient on the couch still leaves room for a multitude of clues to the analyst's individuality; e-therapy provides almost none. Whether distance and reciprocal anonymity reduces or increases the level of transference has yet to be investigated. The oldest and most widely practised form of self-help through writing is that of keeping a personal journal (as distinct from a diary of weekly appointments) in which the writer records their most meaningful thoughts and feelings. One individual benefit is that the act of writing puts a powerful brake on the torment of endlessly repeating troubled thoughts to which everyone is prone. Quite what happens when near-obsessive ruminations, which frequently take place in the small hours of the night, are committed to paper is difficult to describe. It does feel as if the trap door of a mental treadmill has been opened to allow persecutory thoughts to escape. Though the accompanying feelings may persist for a time, the thoughts begin to integrate or dissipate or reach some constructive resolution.

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/index.php/Wrong_Planet

# Wrong Planet Wrong Planet (sometimes referred to by its URL, WrongPlanet.net) is an online forum for individuals with Asperger syndrome. The site was started in 2004 by Dan Grover and Alex Plank and includes a chatroom, a large forum, a dating section, and articles describing how to deal with daily issues. After a post to Slashdot describing an interview with Bram Cohen, Wrong Planet grew; the success of the Cohen interview spurred the site to produce a series of interviews with other figures in the Autism community such as author Temple Grandin and movie producer Joey Travolta. The site conducted an interview with America's Next Top Model contestant Heather Kuzmich who frequently talked about her Asperger's during Cycle 9 of the show. In 2005, a 19-year-old member of the site, William Freund, gave Wrong Planet national mainstream publicity in the United States after being mentioned on Fox News and programs such as Good Morning America after he donned a cape and paintball mask and went on a shooting rampage in Aliso Viejo, California. He shot and killed two people before going home and killing himself with a shot to the torso.

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/index.php/Wuchereria_bancrofti

# Wuchereria bancrofti Wuchereria bancrofti is a parasitic filarial nematode worm spread by a mosquito vector. It is one of the three parasites that cause lymphatic filariasis. Named for Otto Wucherer and Joseph Bancroft, it affects over 120 million people, primarily in Africa, South America, and other tropical and sub-tropical countries. Elephantiasis can result if the infection is left untreated. Limited treatment modalities exist and no vaccines have been developed. W. bancrofti carry out their life cycle in two hosts. Human beings serve as the definitive host and mosquitoes as their intermediate hosts. The adult parasites reside in the lymphatics. They are viviparous. The first stage larvae are known as microfilariae. The microfilaria are present in the circulation. The microfilaria migrate between the deep and the peripheral circulation. During the day they are present in the deep veins and during the night the migrate to the peripheral circulation. Next, the worm is transferred into a vector; the most common vectors are the mosquito species: Culex, Anopheles, Aedes, and Mansonia. Inside their second host, it matures into motile larvae. When its current host feeds, and it is egested into the blood stream of its new human host. The larvae moves to the lymph nodes, predominantly in the legs and genital area, and develops into adult worm over the course of a year. By this time, an adult female can produce microfilariae itself. W. bancrofti displays a large size gap between the male and female—a difference known as sexual dimorphism. The adult male worm is long and slender, between four and five centimeters in length, a tenth of a centimeter in diameter, and features a curved tail. The female, in contrast, is six to ten centimeters long, and three times larger in diameter than the male. This size deviation can be attributed to the vast numbers of microfilariae that the female produces each day. The onset of symptoms is slow, but the effects are very apparent after several years. During the initial inflammatory stage, a host can exhibit swelling, granulation lesions, and impaired circulation. Following, the lymph nodes are enlarged and dilated. They become hardened and clogged with fibrous tissue, and this prevents the lymphatic system from operating correctly. The microfilariae also cause swelling, thickening, and discolouration of the skin. Without the proper drainage of fluids, the affected tissue will expand and elephantiasis, a gross expansion of body, will result, followed sometimes by death. The parasite's severe symptoms can be avoided by the use of therapeutic drugs. Both diethylcarbamazine and sodium caparsolate are used to kill the worms and their microfilariae. Diethylcarbamazine is most commonly used and is administered orally. Protection is similar to that of other mosquito spread illnesses; one can use barriers both physical (a mosquito net) and chemical (insect repellent).

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/index.php/Wyeth_Pharmaceuticals

# Wyeth Pharmaceuticals Wyeth, formerly known as American Home Products (AHP), is one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey. They are known for manufacturing the over-the-counter (OTC) drugs Robitussin and the analgesic Advil (ibuprofen), as well as the prescription drugs Premarin and Effexor, which both boast over $3 billion in sales annually. In 1860, pharmacists John and Frank Wyeth opened a drugstore with a small research lab. In 1862, on the suggestion of doctors, they began to manufacture large quantities of commonly ordered medicines. They were successful, and in 1864 they began supplying medicines and beef extract to the Union army during the Civil War. In 1872, Henry Bower, an employee of Wyeth, developed one of the first rotary compressed tablet machines in the United States. This enabled the mass production of medicines with unprecedented precision and speed. It was massively successful, and the Wyeth brothers won multiple awards at the Centennial Exhibition. In 1883, Wyeth opened its first foreign facility in Montreal, Canada and began vaccine production. Six years later, a fire destroyed the brothers' original Walnut Street store; the brothers sold the retail business and began focusing on mass-production. John Wyeth died in 1907 and his only son, Stuart, became the company's president. American Home Products, the holding company now known as Wyeth, was incorporated on February 4th, 1926. The Whitehall building in downtown Manhattan became the corporation's first headquarters. Global sales became stronger due to the sales of Wyeth's Kolynos brand of toothpaste. In 1929, Stuart Wyeth died and left controlling interest to Harvard University. In 1930, Wyeth purchased Anacin, a product for tension headaches which quickly became the company's flagship product. One year later, Harvard sold Wyeth to American Home Products for $2.9 million. In 1935, Alvin G. Brush, a Certified Public Accountant, became CEO of the entire organization and would serve for thirty years. Under Brush's leadership, 34 new companies were acquired in the next fifteen years, including Chef Boyardee and the S.M.A. Corporation, a pharmaceutical firm specializing in innovative infant formulas. Wyeth also made its first licensing deal, acquiring an antibiotic for arthritis vaccine research. In 1941, the United States entered World War II, and Wyeth shipped typical wartime drugs such as sulfa bacteriostatics, blood plasma, typhus vaccine, quinine, and atabrine tablets. Wyeth was later rewarded for its contribution to the war effort. During this time, Wyeth launched its penicillin research facility with G. Raymond Rettew. In 1943, Wyeth merged with Ayerst, McKenna and Harrison, Ltd. of Canada. With this merger came Premarin, the world's first conjugated estrogen medicine, which to this day is one of Wyeth's flagship products. Wyeth was one of 22 companies selected by the government in 1944 to manufacture penicillin for the military, and later for the general public. In 1951, Wyeth launched Antabuse, a drug for the treatment of alcoholism, as well as the antihistamine Phenergan. Ansolyen was launched the next year as a high blood pressure medication. The anticonvulsant Mysoline was introduced in 1954. Other drugs introduced during this time include Isordil, a vasodilator for treatment of angina, Dryvax, a freeze-dried smallpox vaccine, and Ovral, a combined oral contraceptive pill. Pharmaceuticals were generating an ever-increasing percentage of Wyeth's sales. Wyeth became a leading US vaccine producer after supplying polio vaccine for Salk trials. The corporate headquarters were moved to Radnor, Pennsylvania, where they remained until 2003. William F. Laporte became the Chairman and President of AHP in 1965, and served until 1981. The World Health Organization initiated the Global Smallpox Eradication Program in 1967, and approached Wyeth to develop a better injection system for smallpox vaccines which could be used in the field. Wyeth waived patent royalties on its innovative bifurcated needle, aiding in the delivery of over 200 million smallpox vaccines per year. Wyeth's oral contraceptives became extremely popular in the US. John W. Culligan, after becoming Chairman and CEO in 1981, spun off less profitable lines and focused resources on consumer and prescription drugs. Wyeth made history in 1984 with the introduction of Advil, the first nonprescription ibuprofen in America, as well as the most famous prescription-to-OTC switch in history. John R. Stafford became CEO and Chairman in 1986. He completed the divestiture of non-core businesses such as household products, foods, and candy. Wyeth and Ayerst merged to form Wyeth-Ayerst Laboratories, thus strengthening and consolidating Wyeth's pharmaceutical operations. In the late 1980s, Wyeth acquired the animal health businesses of Bristol-Myers and Parke-Davis. David J. Richards, M.D. was appointed to the Vice President position. Wyeth also acquired A.H. Robins, makers of Robitussin, ChapStick, Dimetapp, and the Dalkon Shield. Premarin becomes the #1 prescribed drug in the US in 1993. Effexor (venlafaxine HCl), the first serotonin-norepinephrine reuptake inhibitor (SNRI), is introduced for the treatment of clinical depression and is later indicated for generalized anxiety disorder and social anxiety disorder. In 1993, Wyeth founded the Women's Health Research Institute, the only institute in the pharmaceutical industry entirely dedicated to reasearch in women's health. The Institute conducts trials in menopausal issues, endometriosis, contraception, and more. In 1994, Wyeth acquired American Cyanamid and its subsidiary Lederle Laboratories. This acquisition brought the Lederle Praxis vaccines, new research and development capacity, and Centrum, the leading US multivitamin. Wyeth's sales topped $13 billion in 1995; two years later, Premarin became the company's first brand to reach $1 billion in sales. In 1995, Wyeth acquired the animal health division of Solvay, which was folded into Fort Dodge Animal Health. The acquisition gave Fort Dodge Animal Health strong market presence in Europe and Asia as well as expanding its product portfolio to include swine and poultry vaccines. In 1997, Wyeth's controversial diet drug fenfluramine was taken off the market by the US Food and Drug Administration (FDA) after several reports of deaths and other health problems associated with the drug combination known as fen-phen occurred. In 1998, American Home Products was left at the altar by British pharma powerhouse SmithKline Beecham, who pulled the plug on the estimated $70 billion merger. The deal was reportedly killed in response to British regulators who feared losing jobs to a proposed US headquarters location. (SmithKline Beecham merged with fellow Brit Glaxo Wellcome in 1999 to form the world's leading drug company.) This was the start of a three-year losing streak in the mergers and acquisitions game for AHP. In 1999, another American Home Products merger fell through, this time a proposed $34 billion merger-of-equals with chemical and biotech manufacturer Monsanto. Though the companies issued a combined statement saying the breakup was mutual "because (the deal) was not in the best interests of shareholders," rumors circulated that AHP had canceled the deal due to issues in the soon-to-be-combined boardroom. (Monsanto announced in December of 1999 that it would merge with Pharmacia & Upjohn instead; the new conglomerate eventually unloaded Monsanto again, before being bought themselves by Pfizer in 2003.) Wyeth Consumer Healthcare (formerly Whitehall-Robins Consumer Healthcare) operates in over 65 countries. The division had sales of $2.5 billion in 2004 and is the fifth largest over-the-counter health products company in the world. Wyeth Pharmaceuticals, formerly Wyeth-Ayerst Laboratories, is the original company founded by the Wyeth brothers, originally known as John Wyeth and Brother. They focus on the research, develop, and marketing of prescription drugs. The pharmaceuticals division is further subdivided into five subdivisions: Wyeth Research, Prescription Products, Biotech, Vaccines, and Nutritionals. Fort Dodge Animal Health was founded in 1912 as "Fort Dodge Serum Company". The company was established in Fort Dodge, Iowa, to manufacture hog cholera serum. It became a division of American Home Products (now Wyeth) in 1945. They are a leading manufacturer of prescription and over-the-counter vaccines and pharmaceuticals for veterinary medicine as well as livestock. Its global headquarters are located in Overland Park, Kansas. On 1 July, 2006, Wyeth launched Prevnar — its international vaccine for Invasive Pneumococcal Disease (IPD) — in India. Prevnar is the first and only pneumococcal conjugate vaccine for infants and children which protects against pneumococcal disease like meningitis, bacterial pneumonia, septicaemia and bacteraemia (bacteria in the blood.)

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/index.php/X-inactivation

# X-inactivation X-inactivation (also called lyonization) is a process by which one of the two copies of the X chromosome present in female mammals is inactivated. The inactive X chromosome is silenced by packaging in repressive heterochromatin. X-inactivation occurs so that the female, with two X chromosomes, does not have twice as many X chromosome gene products as the male, which only possess a single copy of the X chromosome (see dosage compensation). The choice of which X chromosome will be inactivated is random in placental mammals such as mice and humans, but once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell. Unlike the random X-inactivation in placental mammals, inactivation in marsupials applies exclusively to the paternally derived X chromosome. In 1959 Susumu Ohno showed that the two X-chromosomes of mammals were different: one appeared like the autosomes; the other was condensed and heterochromatic (Ohno S, Kaplan WD, Kinosita R: Formation of the sex chromatin by a single X-chromosome in liver cells of rattus norvegicus. Exp Cell Res 18: 415-418, 1959). This finding suggested that one of the X-chromosomes underwent inactivation independently to two groups of investigators. Mary Lyon proposed the random inactivation of one female X chromosome in 1961 to explain the mottled phenotype of female mice heterozygous for coat color genes. The Lyon hypothesis also accounted for the findings that one copy of the X chromosome in female cells was highly condensed, and that mice with only one copy of the X chromosome developed as fertile females. Ernest Beutler, studying heterozygous women for G6PD deficiency independently proposed that there were two red cell populations of erythrocytes in such heterozygotes, deficient cells and normal cells (Beutler E, Yeh M, Fairbanks VF: The normal human female as a mosaic of X-chromosome activity: Studies using the gene for G-6-PD deficiency as a marker. Proc Natl Acad Sci USA 48: 9-16, 1962). All mouse cells undergo an early, imprinted inactivation of the paternally-derived X chromosome in two-cell or four-cell stage embryos. The extraembryonic tissues (which give rise to the placenta and other tissues supporting the embryo) retain this early imprinted inactivation, and thus only the maternal X chromosome is active in these tissues. In the early blastocyst, this initial, imprinted X-inactivation is reversed in the cells of the inner cell mass (which give rise to the embryo), and in these cells both X chromosomes become active again. Each of these cells then independently and randomly inactivates one copy of the X chromosome. This inactivation event is irreversible during the lifetime of the cell, so all the descendants of a cell which inactivated a particular X chromosome will also inactivate that same chromosome. This leads to mosaicism if a female is heterozygous for a X-linked gene, which can be observed in the coloration of calico cats. Normal females possess two X chromosomes, and in any given cell one chromosome will be active (designated as Xa) and one will be inactive (Xi). However, studies of individuals with extra copies of the X chromosome show that in cells with more than two X chromosomes there is still only one Xa, and all the remaining X chromosomes are inactivated. This indicates that the default state of the X chromosome in females is inactivation, but one X chromosome is always selected to remain active. It is hypothesized that there is an autosomally-encoded 'blocking factor' which binds to the X chromosome and prevents its inactivation. The model postulates that there is limiting blocking factor, so once the available blocking factor molecule binds to one X chromosome the remaining X chromosome(s) are not protected from inactivation. This model is supported by the existence of a single Xa in cells with many X chromosomes and by the existence of two active X chromosomes in cell lines with twice the normal number of autosomes. Sequences at the X inactivation center (XIC), present on the X chromosome, control the silencing of the X chromosome. The hypothetical blocking factor is predicted to bind to sequences within the XIC. The X-inactivation center (XIC) on the X chromosome is necessary and sufficient to cause X-inactivation. Chromosomal translocations which place the XIC on an autosome lead to inactivation of the autosome, and X chromosomes lacking the XIC are not inactivated. The XIC contains two non-translated RNA genes, Xist and Tsix, which are involved in X-inactivation. The XIC also contains binding sites for both known and unknown regulatory proteins. The Xist gene encodes a large RNA which is not believed to encode a protein. The Xist RNA is the major effector of X-inactivation. The inactive X chromosome is coated by Xist RNA, whereas the Xa is not. The Xist gene is the only gene which is expressed from the Xi but not from the Xa. X chromosomes which lack the Xist gene cannot be inactivated. Artificially placing and expressing the Xist gene on another chromosome leads to silencing of that chromosome. Prior to inactivation, both X chromosomes weakly express Xist RNA from the Xist gene. During the inactivation process, the future Xa ceases to express Xist, whereas the future Xi dramatically increases Xist RNA production. On the future Xi, the Xist RNA progressively coats the chromosome, spreading out from the XIC; the Xist RNA does not localize to the Xa. The silencing of genes along the Xi occurs soon after coating by Xist RNA. Like Xist, the Tsix gene encodes a large RNA which is not believed to encode a protein. The Tsix RNA is transcribed antisense to Xist, meaning that the Tsix gene overlaps the Xist gene and is transcribed on the opposite strand of DNA from the Xist gene. Tsix is a negative regulator of Xist; X chromosomes lacking Tsix expression (and thus having high levels of Xist transcription) are inactivated much more frequently than normal chromosomes. Like Xist, prior to inactivation, both X chromosomes weakly express Tsix RNA from the Tsix gene. Upon the onset of X-inactivation, the future Xi ceases to express Tsix RNA (and increases Xist expression), whereas Xa continues to express Tsix for several days. The inactive X chromosome does not express the majority of its genes, unlike the active X chromosome. This is due to the silencing of the Xi by repressive heterochromatin, which coats the Xi DNA and prevents the expression of most genes. Compared to the Xa, the Xi has high levels of DNA methylation, low levels of histone acetylation, low levels of histone H3 lysine-4 methylation, and high levels of histone H3 lysine-9 methylation, all of which are associated with gene silencing. Additionally, a histone variant called macroH2A is exclusively found on nucleosomes along the Xi. DNA packaged in heterochromatin, such as the Xi, is more condensed than DNA packaged in euchromatin, such as the Xa. The inactive X forms a discrete body within the nucleus called a Barr body. The Barr body is generally located on the periphery of the nucleus, is late replicating within the cell cycle, and, as it contains the Xi, contains heterochromatin modifications and the Xist RNA. A fraction of the genes along the X chromosome escape inactivation on the Xi. The Xist gene is expressed at high levels on the Xi and is not expressed on the Xa. Other genes are expressed equally from the Xa and Xi; mice contain few genes which escape silencing whereas up to a quarter of human X chromosome genes are expressed from the Xi. Many of these genes occur in clusters. Many of the genes which escape inactivation are present along regions of the X chromosome which, unlike the majority of the X chromosome, contain genes also present on the Y chromosome. These regions are termed pseudoautosomal regions, as individuals of either sex will receive two copies of every gene in these regions (like an autosome), unlike the majority of genes along the sex chromosomes. Since individuals of either sex will receive two copies of every gene in a pseudoautosomal region, no dosage compensation is needed for females, so it is postulated that these regions of DNA have evolved mechanisms to escape X-inactivation. The genes of pseudoautosomal regions of the Xi do not have the typical modifications of the Xi and have little Xist RNA bound. The existence of genes along the inactive X which are not silenced explains the defects in humans with abnormal numbers of the X chromosome, such as Turner syndrome (X0) or Klinefelter syndrome (XXY). Theoretically, X-inactivation should eliminate the differences in gene dosage between affected individuals and individuals with a normal chromosome complement, but in affected individuals the dosage of these non-silenced genes will differ as they escape X-inactivation.

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/index.php/X-linked_congenital_stationary_night_blindness

# X-linked congenital stationary night blindness ## Contents X-linked congenital stationary night blindness (CSNB) is a rare X-linked non-progressive retinal disorder. It has two forms, complete, also known as type-1 (CSNB1), and incomplete, also known as type-2 (CSNB2), depending on severity. In the complete form (CSNB1), there is no measurable rod cell response to light, whereas this response is measurable in the incomplete form. Patients with this disorder have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients also often have reduced visual acuity, myopia, nystagmus, and strabismus. CSNB1 is caused by mutations in the gene NYX, which encodes a protein involved in retinal synapse formation or synaptic transmission. CSNB2 is caused by mutations in the gene CACNA1F, which encodes a voltage-gated calcium channel CaV1.4. ## Overview The X-linked varieties of congenital stationary night blindness (CSNB) can be differentiated from the autosomal forms by the presence of myopia, which is typically absent in the autosomal forms. Patients with CSNB often have impaired night vision, myopia, reduced visual acuity, strabismus, and nystagmus. Individuals with the complete form of CSNB (CSNB1) have highly impaired rod sensitivity (reduced ~300x) as well as cone dysfunction. Patients with the incomplete form can present with either myopia or hyperopia. ## Symptoms CSNB was originally believed to be caused by malfunction in neurotransmission from rods to bipolar cells in the retina. This is due to electroretinogram (ERG) measurements on CSNB patients which show a drastic decrease in the size of the scotopic b-wave in comparison to the a-wave, in CSNB2, or a complete loss of both in CSNB1. The a-wave is believed to represent the response of rods to visual input and remains largely unchanged in CSNB2 patients. The b-wave, however, is believed to result from electrical activity of bipolar cells and is decreased or non-existent in both CSNB1 and 2. CSNB1 patients also show mildly altered cone activity. Further study has demonstrated that the defects found in CSNB patients are better explained by more general defects in both the rod and cone ON-signaling pathways. ## Cause The complete form of X-linked congenital stationary night blindness, also known as nyctalopia, is caused by mutations in the NYX (Nyctalopin on X-chromosome), which encodes a small leucine-rich repeat (LRR) family protein of unknown function. This protein consists of an N-terminal signal peptide and 11 LRRs (LRR1-11) flanked by cysteine-rich LRRs (LRRNT and LRRCT). At the C-terminus of the protein there is a putative GPI anchor site. Although the function of NYX is yet to be fully understood, it is believed to be located extracellularly. A naturally occurring deletion of 85 bases in NYX in some mice leads to the "nob" (no b-wave) phenotype, which is highly similar to that seen in CSNB1 patients. NYX is expressed primarily in the rod and cone cells of the retina. There are currently almost 40 known mutations in NYX associated with CSNB1, Table 1., located throughout the protein. As the function of the nyctalopin protein is unknown, these mutations have not been further characterized. However, many of them are predicted to lead to truncated proteins that, presumably, are non-functional. ## Pathophysiology The incomplete form of X-linked congenital stationary night blindness (CSNB2) is caused by mutations in the CACNA1F gene, which encodes the voltage-gated calcium channel CaV1.4 expressed heavily in retina. One of the important properties of this channel is that it inactivates at an extremely low rate. This allows it to produce sustained Ca2+ entry upon depolarization. As photoreceptors depolarize in the absence of light, CaV1.4 channels operate to provide sustained neurotransmitter release upon depolarization. This has been demonstrated in CACNA1F mutant mice that have markedly reduced photoreceptor calcium signals. There are currently 55 mutations in CACNA1F located throughout the channel, Table 2 and Figure 1. While most of these mutations result in truncated and, likely, non-functional channels, it is expected that they prevent the ability of light to hyperpolarize photoreceptors. Of the mutations with known functional consequences, 4 produce channels that are either completely non-functional, and two that result in channels which open at far more hyperpolarized potentials than wild-type. This will result in photoreceptors that continue to release neurotransmitter even after light-induced hyperpolarization.

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/index.php/X-linked_severe_combined_immunodeficiency

# X-linked severe combined immunodeficiency X-linked Severe Combined Immunodeficiency (X-SCID) is an immunodeficiency disease which causes deficiency of lymphocytes, cells that help protect our bodies. This mutation occurs in the gene responsible for the functionality of the interleukin 2 receptor, also known as or IL2RG. Also, X-SCID is an X-linked recessive trait. Persons afflicted with X-SCID often have infections very early in life, before three months of age. This is followed by pneumonitis, an inflammation of the lung which produces common symptoms such as cough, fever, chills, and shortness of breath. In addition, moniliasis, a type of fungal infection, is a telltale sign of X-SCID. Moniliasis involves moist areas of the body such as skin, the mouth, respiratory tract, and vagina. Symptoms of moniliasis include difficulty in swallowing, pain on swallowing and oral lesions. Recurrent eczema-like rashes are also a common symptom. X-SCID is usually fatal in the first years of life. X-SCID is X-linked mutation, which means males born from a female carrier (either heterozygous or homozygous), will inherit X-SCID, and thus, express it. Many times, X-linked mutations can be passed by a healthy, unaffected mother. A heterozygous woman carrier will have a 50% chance of transmitting the disease-causing mutation. Females who are heterozygous are carriers, but will not be affected. Interleukins are produced by lymphocytes, among other cell types, and are released in response to antigenic and non-antigenic stimuli. The gene IL2RG codes for the common gamma chain protein, which is a common subunit of the induvidual receptors for Interleukin 2, Interleukin 4, Interleukin 7, Interleukin 9, Interleukin 15 and Interleukin 21. Signalling from these receptors normally promotes growth and differentiation of T-cells, B cells, natural killer cells, glial cells, and cells of the monocyte lineage, depending on the cell type and receptor activated. This gene is mutated in X-SCID. Its mutation is caused by large deletions in the IL2RG gene, that disable the common gamma chain so that it is unable to bind with other receptor subunits and signal cytokine activation. The gene is located on Xq13, with a DNA length of 4.2 kb. Analysis has shown that the mRNA length is 3.6 kb long. IL2RG has 369 amino acids, and contains eight exons and seven introns. Diagnosis of X-SCID is possible through observation and investigation of the immune system. A healthy immune system should contain large amounts of lymphocytes, but individuals with X-SCID will contain unusually small amounts of T-cells, non-functional B-cells, and no natural killer cells. There are also tests of lymphocyte function. These tests introduce agents to the immune system and observation, one can see how the lymphocytes react. Antibody responses to introduced vaccines and infections are absent, and T-cell responses to mitogens, substances that stimulate lymphocyte transformation, are deficient. Immunoglobulins, substances that aid in fighting off infections, are very low. Also, the thymic shadow is absent on chest X-rays. Since the mutation in X-SCID is X-linked, there are genetic tests for detecting carriers in XSCID pedigrees. One method is to look for family-specific IL2RG mutations. Finally, if none of those options are available, there is an unusual pattern of nonrandom X-chromosome inactivation on lymphocytes in carriers, thus looking for such inactivation would prove useful. X-SCID is characterized by an abnormally low number of lymphocytes and susceptibility to various infections. Susceptibility is in part due to the atrophy of the thymus, an organ in which lymphocytes thrive and later become T-cells. There is a lack of delayed hypersensitivity, sensitivity regulated by T-lymphocytes. In particular, IL2 promotes lymphocyte growth and differentiation. This process happens after interaction with its receptors (IL2R) which has three subunits, to which only its third, the gamma chain, is of importance. The gamma chain subunit is known as IL2RG, and is necessary of the function of IL2 receptors. Thus, a mutation in IL2RG results in a synergistic effect: a lack in the growth and differentiation in lymphocytes. Bone marrow transplantation is standard procedure for immune reconstitution. Though the BMT process is 'common', it requires immunodeficiency specialists for maximum potential. Infants, in which there is no donor, can undergo BMT, only if the marrow is first depleted of its mature T-cells. The T-cells must be depleted in order to remove mismatched T-cells which would cause a reaction in the infant. Gene therapy is also available to replace the mutant allele. Though, this process can be achieved through various processes, it has been successful in treating X-SCID by insertion of functional, healthy genes with a retrovirus. This, coupled with the bone marrow stem cells, has been successful in treating individuals with X-SCID. (ref: http://www.nature.com/nature/journal/v443/n7109/full/nature05220.html ) Although over 10 children have now been cured almost completly of X-SCID, at least three of the children have gone on to develop leukimia probably as a direct result of the therapy (ref: http://www.medicalnewstoday.com/articles/42339.php ) There is no information on birth ratios/rates, but "X-Linked SCID is the most common form of SCID and it has been estimated to account for 46% to 70% of all SCID cases."

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/index.php/X-ray

# X-rays X-radiation (composed of X-rays, or Röntgen rays) is a form of electromagnetic radiation with a wavelength in the range of 10 to 0.01 nanometers, corresponding to frequencies in the range 30 petahertz (PHz) to 30 exahertz (EHz) (3 × 1016 Hz to 3 × 1019 Hz) and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays. In many languages it is called Röntgen radiation after one of the first investigators of the X-rays, Wilhelm Conrad Röntgen. Röntgen had called them X-rays to signify an unknown type of radiation. X-rays are primarily used for diagnostic radiography and crystallography. As a result, the term X-ray is metonymically used to refer to a radiographic image produced using this method, in addition to the method itself. X-rays are a form of ionizing radiation and as such can be dangerous. From about 0.12 to 12 keV they are classified as soft X-rays, and from about 12 to 120 keV as hard X-rays, due to their penetrating abilities. The distinction between X-rays and gamma rays has changed in recent decades. Originally, the electromagnetic radiation emitted by X-ray tubes had a longer wavelength than the radiation emitted by radioactive nuclei (gamma rays). So older literature distinguished between X- and gamma radiation on the basis of wavelength, with radiation shorter than some arbitrary wavelength, such as 10−11 m, defined as gamma rays. However, as shorter wavelength continuous spectrum "X-ray" sources such as linear accelerators and longer wavelength "gamma ray" emitters were discovered, the wavelength bands largely overlapped. The two types of radiation are now usually defined by their origin: X-rays are emitted by electrons outside the nucleus, while gamma rays are emitted by the nucleus. However, the effect of ionizing radiation on matter (especially living tissue) is more closely related to the amount of energy deposited rather than the charge. This is called the absorbed dose: The equivalent dose is the measure of the biological effect of radiation on human tissue. For X-rays it is equal to the absorbed dose. The rem is the traditional unit of dose equivalent. This describes the Energy delivered by <math>\gamma</math> or X-radiation (indirectly ionizing radiation) for humans. The SI counterpart is the Sievert (Sv). One Sievert is equal to 100 rem. Because the rem is a relatively large unit, typical equivalent dose is measured in millirem (mrem), or one thousandth of a rem. In microsievert (μSv) - 1/1000000 Sv -, 1 mrem equals 10 μSv. Medical X-rays are a major source of manmade radiation exposure, accounting for 58% in the USA in 1987, but since most radiation exposure is natural (82%) it only accounts for 10% of total USA radiation exposure. The average person living in the United States is exposed to approximately 150 mrem annually from background sources alone. Reported dosage due to dental X-rays seems to vary significantly. Depending on the source, a typical dental X-ray of a human results in an exposure of perhaps, 3 , 40 , 300 , or as many as 900 mrems (30 to 9,000 μSv). X-rays are a type of electromagnetic radiation with wavelengths of around 10-10 meters. When medical X-rays are being produced, a thin metallic sheet is placed between the emitter and the target, effectively filtering out the lower energy (soft) X-rays. This is often placed close to the window of the X-ray tube. The resultant X-ray is said to be hard. Soft X-rays overlap the range of extreme ultraviolet. The frequency of hard X-rays is higher than that of soft X-rays, and the wavelength is shorter. Hard X-rays overlap the range of "long"-wavelength (lower energy) gamma rays, however the distinction between the two terms depends on the source of the radiation, not its wavelength; X-ray photons are generated by energetic electron processes, gamma rays by transitions within atomic nuclei. The basic production of X-rays is by accelerating electrons in order to collide with a metal target. In medical applications, this is usually tungsten or a more crack resistant alloy of rhenium (5%) and tungsten (95%), but sometimes molybdenum for more specialised applications, such as when soft X-rays are needed as in mammography. In crystallography, a copper target is most common, with cobalt often being used when fluorescence from iron content in the sample might otherwise present a problem. Here the electrons suddenly decelerate upon colliding with the metal target and if enough energy is contained within the electron it is able to knock out an electron from the inner shell of the metal atom and as a result electrons from higher energy levels then fill up the vacancy and X-ray photons are emitted. This process is extremely inefficient (~0.1%) and thus to produce reasonable flux of X-rays plenty of energy has to be wasted into heat which has to be removed. The maximum energy of the produced X-ray photon in keV is limited by the energy of the incident electron, which is equal to the voltage on the tube, so an 80 kV tube can't create higher than 80 keV X-rays. The voltages used in diagnostic X-ray tubes, and thus the highest energies of the X-rays, range from roughly 20 to 150 kV. The spectral lines generated depends on the target (anode) element used and thus are called characteristic lines. Usually these are transitions from upper shells into K shell (called K lines), into L shell (called L lines) and so on. There is also a continuum Bremsstrahlung radiation given off by the electrons as they are scattered by the strong electric field near the high-Z (proton number) nuclei. In medical diagnostic applications, the low energy (soft) X-rays are unwanted, since they are totally absorbed by the body, increasing the dose. A thin metal (often aluminum, but can be one of many X-Ray filters) sheet is placed over the window of the X-ray tube, filtering out the low energy end of the spectrum. X-rays can detect cancer, cysts, and tumors. Due to their short wavelength, in medical applications X-rays act more like a particle than a wave. This is in contrast to their application in crystallography, where their wave-like nature is most important. Nowadays, for many (non-medical) applications, X-ray production is achieved by synchrotrons (see synchrotron light). Its unique features are brightness many orders of magnitude greater than X-ray tubes, wide spectrum, high collimation, and linear polarization. To create a blood or artery X-ray, also called digital angiography, iodine is injected into the veins and a digitized image is created. Then, a second image is established of only the parts of the X-rayed section without iodine. The first image is subtracted then a final image is produced containing both the first and second images together. Lastly, the results are printed. The doctor or surgeon then compares the results of the angiography to a perfect angiography structure to see if there are any malfunctions. To take an X-ray of the bones, no iodization is required. Short X-ray pulses are shot through a body at first. Next, the bones absorb the most waves because they are more dense and contain Ca which absorbs stronger than the carbon, oxygen, and nitrogen atoms of soft tissue (due to more electrons in Ca atom). The X-rays that do not get absorbed turn the photographic film from white to black, leaving a white shadow of bones on the film. The detection of X-rays is based on various methods. The most commonly known methods, "Image Receptors" (IR), are a photographic plate, X-ray film in a cassette, and rare earth screens. A photographic plate or film is used in hospitals to produce images of the internal organs and bones of a patient. They are also used in industrial radiography processes, for example, to inspect welded seams. Since photographic plates are sensitive to X-rays, they provide a convenient and easy means of recording the image. X-ray film is usually provided as pre-loaded paper cartridges with the film inside a light proof paper envelope. An additional paper coated in a thin layer of lead is often included in contact with the photographic film. The lead reflects the x-rays back through the photo film to more or less double the sensitivity of the assembly. Thus, photographic film has to be used the right way round, and is marked as such. The emulsion is frequently coated on both sides of the film or plate in order to increase the sensitivity further. The part of the patient to be X-rayed is placed between the X-ray source and the photographic receptor to produce what is a shadow of all the internal structure of that particular part of the body being X-rayed. The X-rays are blocked by dense tissues such as bone and pass through soft tissues. Those areas where the X-rays strike the photographic receptor turn black when it is developed. So where the X-rays pass through "soft" parts of the body such as organs, muscle, and skin, the plate or film turns black. Contrast compounds, containing high atomic numbered elements such as barium or iodine, which are radiopaque, can be injected in the artery of a particular organ, or given intravenously. The contrast compounds essentially block the X-rays and hence the circulation of the organ can be more readily seen. Many years ago thorium was used as a contrast medium (Thorotrast) — this caused many people to be injured or even die from the effects of the radiation from the thorium. Photographic plates are losing favour in many X-ray facilities because of the necessity to have processing facilities readily at hand, and because the photographic plates themselves, plus the processing chemicals are relatively expensive consumables. Silver (necessary to the radiographic and photographic industry) is a non-renewable resource. Computed (CR) and digital radiography (DR) has started to replace film. Archiving of these new technologies is also space saving for facilities. Each IR technology required a lot of exposure (to the patient). This has been reduced by the use of intensifying screens. An increasingly common method of detecting X-rays is the use of Photostimulable Luminescence (PSL), pioneered by Fuji in the 1980s. In modern hospitals a PSP plate is used in place of the photographic plate. After the plate is X-rayed, excited electrons in the phosphor material remain 'trapped' in 'colour centres' in the crystal lattice until stimulated by a laser beam passed over the plate surface. The light given off during laser stimulation is collected by a photomultiplier tube and the resulting signal is converted into a digital image by computer technology, which gives this process its common name, computed radiography (also referred to as digital radiography). The PSP plate can be used over and over again, and existing x-ray equipment requires no modification to use them. Initially, most common detection methods were based on the ionization of gases, as in the Geiger-Müller counter: a sealed volume, usually a cylinder, with a polymer or thin metal window contains a gas, and a wire, and a high voltage is applied between the cylinder (cathode) and the wire (anode). When an X-ray photon enters the cylinder, it ionizes the gas and forms ions and electrons. Electrons accelerate toward the anode, in the process causing further ionization along their trajectory. This process, known as an avalanche, is detected as a sudden flow of current, called a "count" or "event". Ultimately, the electrons form a virtual cathode around the anode wire drastically reducing the electric field in the outer portions of the tube. This halts the collisional ionizations and limits further growth of avalanches. As a result, all "counts" on a Geiger counter are the same size and it can give no indication as to the particle energy of the radiation, unlike the proportional counter. The intensity of the radiation is measurable by the Geiger counter as the counting-rate of the system. In order to gain energy spectrum information a diffracting crystal may be used to first separate the different photons, the method is called wavelength dispersive X-ray spectroscopy (WDX or WDS). Position-sensitive detectors are often used in conjunction with dispersive elements. Other detection equipment may be used which are inherently energy-resolving, such as the aforementioned proportional counters. In either case, use of suitable pulse-processing (MCA) equipment allows digital spectra to be created for later analysis. For many applications, counters are not sealed but are constantly fed with purified gas (thus reducing problems of contamination or gas aging). These are called "flow counter". Some materials such as sodium iodide (NaI) can "convert" an X-ray photon to a visible photon; an electronic detector can be built by adding a photomultiplier. These detectors are called "scintillators", filmscreens or "scintillation counters". The main advantage of using these is that an adequate image can be obtained while subjecting the patient to a much lower dose of X-rays. X-rays are also used in "real-time" procedures such as angiography or contrast studies of the hollow organs (e.g. barium enema of the small or large intestine) using fluoroscopy acquired using an X-ray image intensifier. Angioplasty, medical interventions of the arterial system, rely heavily on X-ray-sensitive contrast to identify potentially treatable lesions. Since the 1970s, new semiconductor detectors have been developed (silicon or germanium doped with lithium, Si(Li) or Ge(Li)). X-ray photons are converted to electron-hole pairs in the semiconductor and are collected to detect the X-rays. When the temperature is low enough (the detector is cooled by Peltier effect or even cooler liquid nitrogen), it is possible to directly determine the X-ray energy spectrum; this method is called energy dispersive X-ray spectroscopy (EDX or EDS); it is often used in small X-ray fluorescence spectrometers. These detectors are sometimes called "solid state detectors". Cadmium telluride (CdTe) and its alloy with zinc, cadmium zinc telluride detectors have an increased sensitivity, which allows lower doses of X-rays to be used. Practical application in medical imaging didn't start taking place until the 1990s. Currently amorphous selenium is used in commercial large area flat panel X-ray detectors for mammography and chest radiography. Current research and development is focussed around pixel detectors, such as CERN's energy resolving Medipix detector. Note: A standard semiconductor diode, such as a 1N4007, will produce a small amount of current when placed in an X-ray beam. A test device once used by Medical Imaging Service personnel was a small project box that contained several diodes of this type in series, which could be connected to an oscilloscope as a quick diagnostic. Silicon drift detectors (SDDs), produced by conventional semiconductor fabrication, now provide a cost-effective and high resolving power radiation measurement. Unlike conventional X-ray detectors, such as Si(Li)s, they do not need to be cooled with liquid nitrogen. With the advent of large semiconductor array detectors it has become possible to design detector systems using a scintillator screen to convert from X-rays to visible light which is then converted to electrical signals in an array detector. Indirect Flat Panel Detectors (FPDs) are in widespread use today in medical, dental, veterinary and industrial applications. A common form of these detectors is based on amorphous silicon thin film transistor (TFT)/photodiode arrays. The array technology is a variant on the amorphous silicon TFT arrays used in many flat panel displays, like the ones in computer laptops. The array consists of a sheet of glass covered with a thin layer of silicon that is in an amorphous or disordered state. At a microscopic scale, the silicon has been imprinted with millions of transistors arranged in a highly ordered array, like the grid on a sheet of graph paper. Each of these TFTs is attached to a light-absorbing photodiode making up an individual pixel (picture element). Photons striking the photodiode are converted into two carriers of electrical charge, called electron-hole pairs. Since the number of charge carriers produced will vary with the intensity of incoming light photons, an electrical pattern is created that can be swiftly converted to a voltage and then a digital signal, which is interpreted by a computer to produce a digital image. Although silicon has outstanding electronic properties, it is not a particularly good absorber of X-ray photons. For this reason, X-rays first impinge upon scintillators made from eg. gadolinium oxysulfide or cesium iodide. The scintillator absorbs the X-rays and converts them into visible light photons that then pass onto the photodiode array. While generally considered invisible to the human eye, in special circumstances X-rays can be visible. Brandes, in an experiment a short time after Röntgen's landmark 1895 paper, reported after dark adaptation and placing his eye close to an X-ray tube, seeing a faint "blue-gray" glow which seemed to originate within the eye itself. Upon hearing this, Röntgen reviewed his record books and found he too had seen the effect. When placing an X-ray tube on the opposite side of a wooden door Röntgen had noted the same blue glow, seeming to emanate from the eye itself, but thought his observations to be spurious because he only saw the effect when he used one type of tube. Later he realized that the tube which had created the effect was the only one powerful enough to make the glow plainly visible and the experiment was thereafter readily repeatable. The knowledge that X-rays are actually faintly visible to the dark-adapted naked eye has largely been forgotten today; this is probably due to the desire not to repeat what would now be seen as a recklessly dangerous and harmful experiment with ionizing radiation. It is not known what exact mechanism in the eye produces the visibility: it could be due to conventional detection (excitation of rhodopsin molecules in the retina), direct excitation of retinal nerve cells, or secondary detection via, for instance, X-ray induction of phosphorescence in the eyeball with conventional retinal detection of the secondarily produced visible light. If the intensity of an X-ray beam is high enough, the ionization of the air will make the beam visible with a white glow. The beamline from the wiggler at the ID11 at ESRF is one example of such high intensity. Since Röntgen's discovery that X-rays can identify bony structures, X-rays have been developed for their use in medical imaging. Radiology is a specialized field of medicine. Radiographers employ radiography and other techniques for diagnostic imaging. Indeed, this is probably the most common use of X-ray technology. X-rays are especially useful in the detection of pathology of the skeletal system, but are also useful for detecting some disease processes in soft tissue. Some notable examples are the very common chest X-ray, which can be used to identify lung diseases such as pneumonia, lung cancer or pulmonary edema, and the abdominal X-ray, which can detect ileus (blockage of the intestine), free air (from visceral perforations) and free fluid (in ascites). In some cases, the use of X-rays is debatable, such as gallstones (which are rarely radiopaque) or kidney stones (which are often visible, but not always). Also, traditional plain X-rays pose very little use in the imaging of soft tissues such as the brain or muscle. Imaging alternatives for soft tissues are computed axial tomography (CAT or CT scanning), magnetic resonance imaging (MRI) or ultrasound. Since 2005, X-rays are listed as a carcinogen by the U.S. government. The benefits of the X-ray investigation should be balanced with the potential hazards to the unborn fetus. Lead is the most common shield against X-Rays because of its high density (11340 kg/m3), ease of installation and low cost. The maximum range of a high-energy photon such as an X-ray in matter is infinite - at every point in the matter traversed by the photon, there is a probability of interaction. Thus there is a very small probability of no interaction over very large distances. The shielding of photons is therefore exponential - doubling the thickness of shielding will square the shielding effect. The following table shows the recommended thickness of lead shielding in function of X-Ray energy, from the Recommendations by the Second International Congress of Radiology. Among the important early researchers in X-rays were Professor Ivan Pulyui, Sir William Crookes, Johann Wilhelm Hittorf, Eugen Goldstein, Heinrich Hertz, Philipp Lenard, Hermann von Helmholtz, Nikola Tesla, Thomas Edison, Charles Glover Barkla, Max von Laue, and Wilhelm Conrad Röntgen. Physicist Johann Hittorf (1824 - 1914) observed tubes with energy rays extending from a negative electrode. These rays produced a fluorescence when they hit the glass walls of the tubes. In 1876 the effect was named "cathode rays" by Eugen Goldstein, and today are known to be streams of electrons. Later, English physicist William Crookes investigated the effects of electric currents in gases at low pressure, and constructed what is called the Crookes tube. It is a glass cylinder mostly (but not completely) evacuated, containing electrodes for discharges of a high voltage electric current. He found, when he placed unexposed photographic plates near the tube, that some of them were flawed by shadows, though he did not investigate this effect. Crookes also noted that his cathode rays caused the glass walls of his tube to glow a dull blue colour. Crookes failed to realise that it wasn't actually the cathode rays that caused the blue glow, but the low level x-rays produced when the cathode rays struck the glass. Crookes tubes created electrons by ionization of the residual air in the tube by a high DC voltage of anywhere between a few kilovolts and 100 kV. This voltage accelerated the electrons coming from the cathode to a high enough velocity that they created X-rays when they struck the anode or the glass wall of the tube. Many of the early Crookes tubes undoubtedly radiated X-rays, because early researchers noticed effects that were attributable to them. In 1877 Ukranian-born Ivan Pulyui, a lecturer in experimental physics at the University of Vienna, constructed various designs of Geissler vacuum discharge tube to investigate their properties. He continued his investigations when appointed professor at the Czech Technical University in Prague (Prague Polytechnic). In 1886 he found that sealed photographic plates became dark when exposed to the emanations from the tubes. Early in 1896, just a few weeks after Röntgen published his first X-ray photograph, Pulyui published high-quality x-ray images in journals in Paris and London. Although Pulyui had studied with Röntgen at the University of Strasbourg in the years 1873-75, his biographer Gaida (1997) asserts that his subsequent research was conducted independently. As a result of experiments into what he called cold light Ivan Pulyui is reputed to have developed an X-ray emitting device as early as 1881. He reputedly first demonstrated an X-ray photograph of a 13-year-old boy's broken arm and an X-ray photograph of his daughter's hand with a pin lying under it. The device became known as the Pulyui lamp and was mass-produced for a period. Reputedly, Pulyui personally presented one to Wilhelm Conrad Röntgen who went on to be credited as the major developer of the technology. Pulyui published his results in a scientific paper, Luminous Electrical Matter and the Fourth State of Matter in the Notes of the Austrian Imperial Academy of Sciences (1880-1883), but expressed his ideas in an obscure manner using obsolete terminology. Pulyui did gain some recognition when the work was translated and published as a book by the Royal Society in the UK. Pulyui made many other discoveries as well. He is particularly noted for inventing a device for determining the mechanical equivalent of heat that was exhibited at the Exposition Universelle, Paris, 1878. Pulyui also participated in opening of several power plants in Austria-Hungary. The first medical X-ray made in the United States was obtained using a discharge tube of Pulyui's design. In January 1896, on reading of Röntgen's discovery, Frank Austin of Dartmouth College tested all of the discharge tubes in the physics laboratory and found that only the Pulyui tube produced X-rays. This was a result of Pulyui's inclusion of an oblique "target" of mica, used for holding samples of fluorescent material, within the tube. On 3 February 3, 1896 Gilman Frost, professor of medicine at the college, and his brother Edwin Frost, professor of physics, exposed the wrist of Eddie McCarthy, whom Edwin had treated some weeks earlier for a fracture, to the x-rays and collected the resulting image of the broken bone on gelatin photographic plates obtained from Howard Langill, a local photographer also interested in Röntgen's work. In April 1887, Nikola Tesla began to investigate X-rays using high voltages and tubes of his own design, as well as Crookes tubes. From his technical publications, it is indicated that he invented and developed a special single-electrode X-ray tube , which differed from other X-ray tubes in having no target electrode. The principle behind Tesla's device is nowadays called the Bremsstrahlung process, in which a high-energy secondary X-ray emission is produced when charged particles (such as electrons) pass through matter. By 1892, Tesla performed several such experiments, but he did not categorize the emissions as what were later called X-rays. Tesla generalized the phenomenon as radiant energy of "invisible" kinds. Tesla stated the facts of his methods concerning various experiments in his 1897 X-ray lecture before the New York Academy of Sciences. Also in this lecture, Tesla stated the method of construction and safe operation of X-ray equipment. His X-ray experimentation by vacuum high field emissions also led him to alert the scientific community to the biological hazards associated with X-ray exposure. X-rays were first generated and detected by Fernando Sanford (1854-1948), the foundation Professor of Physics at Stanford University, in 1891. From 1886 to 1888 he had studied in the Hermann Helmholtz laboratory in Berlin, where he became familiar with the cathode rays generated in vacuum tubes when a voltage was applied across separate electrodes, as previously studied by Heinrich Hertz and Philipp Lenard. His letter of January 6, 1893 (describing his discovery as "electric photography") to The Physical Review was duly published and an article entitled Without Lens or Light, Photographs Taken With Plate and Object in Darkness appeared in the San Francisco Examiner. In 1892, Heinrich Hertz began experimenting and demonstrated that cathode rays could penetrate very thin metal foil (such as aluminium). Philipp Lenard, a student of Heinrich Hertz, further researched this effect. He developed a version of the cathode tube and studied the penetration by X-rays of various materials. Philipp Lenard, though, did not realize that he was producing X-rays. Hermann von Helmholtz formulated mathematical equations for X-rays. He postulated a dispersion theory before Röntgen made his discovery and announcement. It was formed on the basis of the electromagnetic theory of light (Wiedmann's Annalen, Vol. XLVIII). However, he did not work with actual X-rays. On November 8, 1895, Wilhelm Conrad Röntgen, a German physics professor, began observing and further documenting X-rays while experimenting with vacuum tubes. Röntgen, on December 28, 1895, wrote a preliminary report "On a new kind of ray: A preliminary communication". He submitted it to the Würzburg's Physical-Medical Society journal. This was the first formal and public recognition of the categorization of X-rays. Röntgen referred to the radiation as "X", to indicate that it was an unknown type of radiation. The name stuck, although (over Röntgen's great objections), many of his colleagues suggested calling them Röntgen rays. They are still referred to as such in many languages. Röntgen received the first Nobel Prize in Physics for his discovery. Röntgen was working on a primitive cathode ray generator that was projected through a glass partially evacuated tube. Suddenly he noticed a faint green light against the wall. The odd thing he had noticed, was that the light from the cathode ray generator was traveling through a bunch of the materials in its way (paper, wood, and books). He then started to put various objects in front of the generator, and as he was doing this, he noticed that the outline of the bones from his hand were displayed on the wall. Röntgen said he did not know what to think and kept experimenting. Two months after his initial discovery, he published his paper translated "On a New Kind of Radiation" and gave a demonstration in 1896. Röntgen had his lab notes burned after his death, but this is a likely reconstruction by his biographers. Rontgen discovered the medical use of X radiation when he saw a picture of his wife's hand on a photographic plate formed due to X-rays. The photograph was apparently the first ever of a human body part using X-rays. In 1895, Thomas Edison investigated materials' ability to fluoresce when exposed to X-rays, and found that calcium tungstate was the most effective substance. Around March 1896, the fluoroscope he developed became the standard for medical X-ray examinations. Nevertheless, Edison dropped X-ray research around 1903 after the death of Clarence Madison Dally, one of his glassblowers. Dally had a habit of testing X-ray tubes on his hands, and acquired a cancer in them so tenacious that both arms were amputated in a futile attempt to save his life. Someone shot President William McKinley, while he was attending the 1901 Pan-American Exposition in Buffalo, New York. The individual fired twice at close range with a .32 caliber revolver. The first bullet was removed but the second remained somewhere in McKinley's stomach. McKinley survived for some time and requested that Thomas Edison rush an X-ray machine to Buffalo to find the stray bullet. McKinley died of septic shock due to bacterial infection. The X-ray machine wasn't used. Prior to the 20th century and for a short while after, x-rays were generated in cold cathode tubes. These tubes had to contain a small quantity of gas (invariably air) as a current will not flow in such a tube if they are fully evacuated. One of the problems with early x-ray tubes is that the generated x-rays caused the glass to absorb the gas and consequently the efficiency quickly falls off. Larger and more frequently used tubes were provided with a means of restoring the air. This often took the form of small side tube which contained a small piece of mica - a substance that traps comparatively large quantities of air within its structure. A small electrical heater heats the mica and causes it to release a small amount of air restoring the tube's efficiency. However the mica itself has a limited life and the restore process was consequently difficult to control. In 1904, Sir John Ambrose Flemming invented the thermionic diode valve (tube). This used a heated cathode which permitted current to flow in a vacuum. The principle was quickly applied to x-ray tubes, and hard vacuum heated cathode x-ray tubes completely solved the problem of efficiency reduction. Two years later, physicist Charles Barkla discovered that X-rays could be scattered by gases, and that each element had a characteristic X-ray. He won the 1917 Nobel Prize in Physics for this discovery. Max von Laue, Paul Knipping and Walter Friedrich observed for the first time the diffraction of X-rays by crystals in 1912. This discovery, along with the early works of Paul Peter Ewald, William Henry Bragg and William Lawrence Bragg gave birth to the field of X-ray crystallography. The Coolidge tube was invented the following year by William D. Coolidge which permitted continuous production of X-rays; this type of tube is still in use today. The use of X-rays for medical purposes (to develop into the field of radiation therapy) was pioneered by Major John Hall-Edwards in Birmingham, England. In 1908, he had to have his left arm amputated owing to the spread of X-ray dermatitis . The X-ray microscope were invented in the 1950s. The Chandra X-ray Observatory launched on July 23, 1999, has been allowing the exploration of the very violent processes in the universe which produce X-rays. Unlike visible light, which is a relatively stable view of the universe, the X-ray universe is unstable, it features stars being torn apart by black holes, galactic collisions, and novas, neutron stars that build up layers of plasma that then explode into space. An X-ray laser device was proposed as part of the Reagan administration's Strategic Defense Initiative (SDI) in the 1980s, but the first and only test of the device (a sort of laser "blaster", or death ray, powered by a thermonuclear explosion) gave inconclusive results. For technical and political reasons, the overall project (including the X-ray laser) was de-funded (though was later revived by the second Bush administration as the National Missile Defense using different technologies).

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# X-ray crystallography X-ray crystallography is the science of determining the arrangement of atoms within a crystal from the manner in which a beam of X-rays is scattered from the electrons within the crystal. The method produces a three-dimensional picture of the density of electrons within the crystal, from which the mean atomic positions, their chemical bonds, their disorder and sundry other information can be derived. By definition, a crystal is a solid in which a particular arrangement of atoms (its unit cell) is repeated indefinitely along three principal directions known as the basis (or lattice) vectors, which are not necessarily perpendicular. A wide variety of materials can form crystals — such as salts, metals, minerals, semiconductors, as well as various inorganic, organic and biological molecules — which has made X-ray crystallography fundamental to many scientific fields. The oldest and most precise method of X-ray crystallography is single-crystal X-ray diffraction, in which a beam of X-rays is reflected from evenly spaced planes of a single crystal, producing a diffraction pattern of spots called reflections. Each reflection corresponds to one set of evenly spaced planes within the crystal. The density of electrons within the crystal is determined from the position and brightness of the various reflections observed as the crystal is gradually rotated in the X-ray beam; this density, together with supplementary data, allows the atomic positions to be inferred. For single crystals of sufficient purity and regularity, X-ray diffraction data can determine the mean chemical bond lengths and angles to within a few thousandths of an ngström and to within a few tenths of a degree, respectively. The data also allow the static and dynamic disorder in the atomic positions to be estimated, which is usually less than a few tenths of an ngström. At its most basic level, X-ray crystallography is useful in identifying known materials, characterizing new materials and in discerning materials that appear similar by other experiments. However, X-ray crystal structures have many other applications; for example, they can account for unusual electronic or elastic properties of a material, shed light on chemical interactions and processes, or serve as the basis for understanding enzymatic mechanisms and designing pharmaceuticals against diseases. The term "X-ray crystallography" is also sometimes applied to methods that involve X-ray diffraction from polycrystalline materials, such as powders of small crystals studied by X-ray powder diffraction. The technique of single-crystal X-ray crystallography has three basic steps. The first — and often most difficult — step is to obtain an adequate crystal of the material under study. The crystal should be sufficiently large, pure in composition and regular in structure, with no large internal imperfections such as cracks or twinning. In the second step, the crystal is placed in an intense beam of X-rays, usually of a single wavelength (monochromatic X-rays), producing the regular pattern of reflections. As the crystal is gradually rotated, previous reflections disappear and new ones appear; the intensity of every spot is recorded meticulously at every orientation of the crystal. Multiple data sets may have to be collected, with each set covering slightly more than half a full rotation of the crystal and containing tens of thousands of reflection intensities. In the third step, these data are combined computationally with complementary chemical information to produce and refine a model of the arrangement of atoms within the crystal. The final, refined model — now called a crystal structure — is usually stored in a public database. As the crystal's unit cell becomes larger, the atomic-level picture provided by X-ray crystallography becomes less well-resolved (more "fuzzy") for a given number of observed reflections. Two limiting cases of X-ray crystallography are often discerned, "small-molecule" and "macromolecular" crystallography. Small-molecule crystallography typically involves crystals with fewer than 100 atoms in their asymmetric unit; such crystal structures are usually so well resolved that its atoms can be discerned as isolated "blobs" of electron density. By contrast, macromolecular crystallography often involves tens of thousands of atoms in the unit cell. Such crystal structures are generally less well-resolved (more "smeared out"); the atoms and chemical bonds appear as tubes of electron density, rather than as isolated atoms. In general, small molecules are also easier to crystallize than macromolecules; however, X-ray crystallography has proven possible even for viruses with hundreds of thousands of atoms. Crystals have long been admired for their regularity and symmetry, but they were not investigated scientifically until the 17th century, when Johannes Kepler hypothesized (1611) that the hexagonal symmmetry of snowflake crystals was due to a regular packing of spherical water particles. Crystal symmetry was investigated experimentally by Nicolas Steno (1669), who showed that the angles between the faces are the same in every exemplar of a single type of crystal, and by René Just Haüy (1784), who discovered that every face of a crystal can be described by three small integers, the so-called Miller indices. These studies led Haüy to the correct idea that crystals are a regular three-dimensional array (a Bravais lattice) of atoms and molecules; a single unit cell is repeated indefinitely along three principal directions that are not necessarily perpendicular. In the 19th century, a complete catalog of the possible symmetries of a crystal was worked out by Johann Hessel, Auguste Bravais, Yevgraf Fyodorov, , Arthur Schönflies and (belatedly) William Barlow. On the basis of the available data and physical reasoning, Barlow proposed several crystal structures in the 1880s that were ultimately proven correct by X-ray crystallography; however, the available data were too few in the 1880s to accept his models as conclusive. X-rays were discovered by Wilhelm Conrad Röntgen in 1895, just as the studies of crystal symmetry were being concluded. Physicists were initially uncertain of the nature of X-rays, although it was soon suspected (correctly) that they were waves of electromagnetic radiation, in other words, another form of light. At that time, the wave model of light — specifically, the Maxwell theory of electromagnetic radiation — was well accepted among scientists, and experiments by Charles Glover Barkla showed that X-rays exhibited phenomena associated with electromagnetic waves, including transverse polarization and spectral lines akin to those observed in the visible wavelengths. Single-slit experiments in the laboratory of Arnold Sommerfeld suggested the wavelength of X-rays was roughly 1 Angström, one ten millionth of a millimetre. Being composed of photons, X-rays also exhibit particle-like properties, e.g., in the ionization of gases; these properties led William Henry Bragg to suggest in 1907 that X-rays were not electromagnetic radiation, since the concept of the photon was relatively new (1905) and not generally accepted. However, Bragg's view was itself not broadly accepted and the observation of X-ray diffraction in 1912 confirmed for most scientists that X-rays were a form of electromagnetic radiation. Any remaining doubt was resolved in 1922, when Arthur Compton confirmed the photon model by studying the scattering of X-rays from electrons. To summarize, crystals are regular arrays of atoms and X-rays can be considered waves of electromagnetic radiation. Atoms scatter X-rays, primarily through their electrons; just as an ocean wave striking a lighthouse produces secondary circular waves emanating from the lighthouse, so an X-ray striking an electron produces secondary spherical waves emanating from the electron. This phenomenon is known as scattering, and the electron (or lighthouse) is known as the scatterer. As described in the Mathematical derivation below, the X-ray scattering is determined by the density of electrons within the crystal. Since the energy of an X-ray is much greater than that of an atomic electron, the scattering may be modeled as Thomson scattering, the interaction of an electromagnetic ray with a free electron; this model is generally adopted to describe the polarization of the scattered radiation. The intensity of Thomson scattering declines as 1/m² with the mass m of the charged particle that is scattering the radiation; hence, the atomic nuclei, which are thousands of times heavier than an electron, contribute negligibly to the scattered X-rays. Any wave impinging on a regular array of scatterers produces diffraction, as predicted first by Francesco Maria Grimaldi in 1665. To produce significant diffraction, the spacing between the scatterers and the wavelength of the impinging wave should be roughly similar in size. James Gregory observed the optical diffraction of sunlight through a bird's feather in the later 17th century. The first man-made diffraction grating was constructed by David Rittenhouse in 1787, and improved by Joseph von Fraunhofer in 1821. Similarly, X-ray diffraction results from an electromagnetic wave (the X-ray) impinging on a regular array of scatterers (the crystal). By good fortune, the wavelength of X-rays and the spacing between unit cells in crystals are typically of the same order of magnitude (1-100 ngströms); prior to X-ray diffraction, however, the spacings between unit cells in a crystal were not known with certainty. The idea that crystals could be used as a diffraction grating for X-rays arose in 1912 in a conversation between Paul Peter Ewald and Max von Laue in the English Garden in Munich. Ewald had proposed a resonator model of crystals for his thesis, but this model could not be validated using visible light, since the wavelength was much larger than the spacing between the resonators. Von Laue realized that electromagetic radiation of a shorter wavelength was needed to observe such small spacings, and suggested that X-rays might have a wavelength comparable to the unit-cell spacing in crystals. Von Laue worked with two technicians, Walter Friedrich and his assistant Paul Knipping, to shine a beam of X-rays through a sphalerite crystal and record its diffraction on a photographic plate. After being developed, the plate showed a large number of well-defined spots arranged in a pattern of intersecting circles around the spot produced by the central beam. Von Laue developed a law that connects the scattering angles and the size and orientation of the unit-cell spacings in the crystal, for which he was awarded the Nobel Prize in Physics in 1914. After von Laue's pioneering research, the field developed rapidly, most notably by physicists William Lawrence Bragg and his father William Henry Bragg. In 1912-1913, the younger Bragg developed Bragg's law, which connects the observed scattering with reflections from evenly spaced planes within the crystal. The earliest structures were generally simple and marked by one-dimensional symmetry; as the field progressed over the next decades, the structures of two- and three-dimensional arrangements of atoms in the unit-cell became feasible. The potential of X-ray crystallography for determining the structure of molecules and minerals — then only known vaguely from chemical and hydrodynamic experiments — was realized immediately. The earliest structures were generally simple inorganic crystals and minerals. The first atomic-resolution structure to be solved (in 1914) was that of table salt, which proved the existence of ionic compounds and that crystals are not necessarily comprised of molecules. The structure of diamond was solved in the same year, proving the tetrahedral arrangement of its chemical bonds and showing that the C-C single bond was 1.52 ngströms. Other early structures included copper, calcium fluoride (CaF2, also known as fluorite), calcite (CaCO3) and pyrite (FeS2) in 1914; spinel (MgAl2O4) in 1915; the rutile and anatase forms of titanium dioxide (TiO2) in 1916; pyrochroite and, by extension, brucite [Mn(OH)2 and Mg(OH)2, respectively] in 1919; and wurtzite (hexagonal ZnS) in 1920. The structure of graphite was solved in 1916 by the related method of powder diffraction, which was developed by Peter Debye and Paul Scherrer and, independently, by Albert Hull in 1917. The structure of graphite was determined from single-crystal diffraction in 1924 by two groups independently. Hull also used the powder method to determine the structures of various metals, such as iron and magnesium. X-ray crystallography has led to a better understanding of chemical bonds and non-covalent interactions. The initial studies revealed the typical radii of atoms, and confirmed many theoretical models of chemical bonding, such as the tetrahedral bonding of carbon in the diamond structure, the octahedral bonding of metals observed in ammonium hexachloroplatinate (IV), and the resonance observed in the planar carbonate group and in aromatic molecules. Kathleen Lonsdale's 1928 structure of hexamethylbenzene established the hexagonal symmetry of benzene and showed a clear difference in bond length between the aliphatic C-C bonds and aromatic C-C bonds; this finding led to the idea of resonance between chemical bonds, which had profound consequences for the development of chemistry. Her conclusions were anticipated by William Henry Bragg, who published models of naphthalene and anthracene in 1921 based on other molecules, an early form of molecular replacement. Also in the 1920s, Victor Moritz Goldschmidt and later Linus Pauling developed rules for eliminating chemically unlikely structures and for determining the relative sizes of atoms. These rules led to the structure of brookite (1928) and an understanding of the relative stability of the rutile, brookite and anatase forms of titanium oxide. The distance between two covalently bonded atoms is a sensitive measure of the bond strength and its bond order; thus, X-ray crystallographic studies have led to the discovery of even more exotic types of bonding in inorganic chemistry, such as metal-metal double bonds, metal-metal quadruple bonds, and three-center, two-electron bonds. X-ray crystallography — or, strictly speaking, an inelastic Compton scattering experiment — has also provided evidence for the partially covalent character of hydrogen bonds. In the field of organometallic chemistry, the X-ray structure of ferrocene initiated scientific studies of sandwich compounds, while that of Zeise's salt stimulated research into "back bonding" and metal-pi complexes in general. Finally, X-ray crystallography had a pioneering role in the development of supramolecular chemistry, particularly in clarifying the structures of the crown ethers and the principles of host-guest chemistry. In material sciences, many complicated inorganic and organometallic systems have been analyzed using single-crystal methods, such as fullerenes, metalloporphyrins, and other complicated compounds. Single-crystal diffraction is also used in the pharmaceutical industry, due to recent problems with polymorphs. The major factors affecting the quality of single-crystal structures is crystal's size and regularity; recrystallization is a commonly used technique to improve these factors in small-molecule crystals. The Cambridge Structural Database contains over 400,000 structures; over 99% of these structures were determined by X-ray diffraction. In mineralogy, a systematic X-ray crystallographic study of the silicates was undertaken in the 1920s, beginning with the structure of garnet in 1924 by Menzer. As the Si/O ratio is altered, the resulting crystals exhibited significant changes in their internal arrangements. Machatschki extended these insights to minerals in which aluminum substitutes for silicon in the silicates. In metallurgy, the first alloy crystal structures began to be determined in the mid-1920s. Linus Pauling's structure of the alloy Mg2Sn led to his theory governing the stability and structure of complex ionic crystals. The first structure of an organic compound, hexamethylenetetramine, was solved in 1923. This was followed by several studies of long-chain fatty acids, which are an important component of biological membranes. In the 1930s, the structures of much larger molecules with two-dimensional complexity began to be solved. A significant advance was the structure of phthalocyanine, a large planar molecule that has an approximate four-fold symmetry and resembles porphyrins found in nature, such as heme, corrin and chlorophyll. X-ray crystallography of biological molecules took off with Dorothy Crowfoot Hodgkin, who solved the structures of cholesterol (1937), vitamin B12 (1945) and penicillin (1954), for which she was awarded the Nobel Prize in Chemistry in 1964. In 1969, she succeeded in solving the structure of insulin, on which she worked for over thirty years. Crystal structures of proteins (which are irregular and hundreds of times larger than cholesterol) began to be solved in the late 1950's, beginning with the structure of sperm whale myoglobin by Max Perutz and Sir John Cowdery Kendrew, for which they were awarded the Nobel Prize in Chemistry in 1962. Since that success, over 39000 X-ray crystal structures of proteins, nucleic acids and other biological molecules have been determined. For comparison, the nearest competing method, NMR spectroscopy has produced roughly 6000 structures. Moreover, crystallography can solve structures of arbitrarily large molecules, whereas solution-state NMR is restricted to relatively small molecules (less than 70 kDa). X-ray crystallography is now used routinely by scientists to determine how a pharmaceutical interacts with its protein target and what changes might be advisable to improve it. However, intrinsic membrane proteins remain challenging to crystallize because they require detergents or other means to solubilize them in isolation, and such detergents often interfere with crystallization. Such membrane proteins are a large component of the genome and include many proteins of great physiological importance, such as ion channels and receptors. X-ray crystallography is a form of elastic scattering; the outgoing X-rays have the same energy as the incoming X-rays, only with altered direction. Since the energy of a photon is inversely proportional to its wavelength, elastic scattering means that the outgoing photons have the same wavelength as the incoming photons. By contrast, inelastic scattering occurs when energy is transferred from the incoming X-ray to the crystal, e.g., by exciting an inner-shell electron to a higher energy level. Such inelastic scattering changes the wavelength of the outgoing beam, making it longer and less energetic. Inelastic scattering is useful for probing such excitations of matter, but are not as useful in determining the distribution of scatterers within the matter, which is the goal of X-ray crystallography. X-rays range in wavelength from 10 to 0.01 nanometers (one billionth of a meter); a typical wavelength used for crystallography is roughly 1  (0.1 nm), which is on the scale of covalent chemical bonds and the radius of a single atom. Longer-wavelength photons (such as ultraviolet radiation) would not have sufficient resolution to determine the atomic positions. At the other extreme, shorter-wavelength photons such as gamma rays are difficult to produce in large numbers, difficult to focus, and interact too strongly with matter, producing particle-antiparticle pairs. Therefore, X-rays are the "sweetspot" for wavelength when determining atomic-resolution structures from the scattering of electromagnetic radiation. X-ray diffraction involves the scattering of X-rays from a single crystal. Other forms of elastic X-ray scattering include powder diffraction, SAXS and several types of X-ray fiber diffraction, which was used by Rosalind Franklin in determining the double-helix structure of DNA. In general, X-ray diffraction produces isolated spots ("reflections"), while the other methods produce smooth, continuous scattering. In general, X-ray diffraction offers more structural information than these other techniques; however, it requires a sufficiently large and regular crystal, which is not always possible to obtain. All of these scattering methods generally use monochromatic X-rays, X-rays that are restricted to a single wavelength with minor deviations. A broad spectrum of X-rays (that is, a blend of X-rays with different wavelengths) can also be used to carry out X-ray diffraction, a technique known as the Laue method. This is the method used in the original discovery of X-ray diffraction. Laue scattering provides much structural information with only a short exposure to the X-ray beam, and is therefore used in structural studies of very rapid events (time-resolved X-ray crystallography). However, it is not as well-suited as monochromatic scattering for determining the full atomic structure of a crystal. It is better suited to crystals with relatively simple atomic arrangements, such as minerals. The Laue back reflection mode records X-rays scattered backwards also from a broad spectrum source. This is useful if the sample is too thick or bulky for X-rays to transmit through it. The diffracting planes in the crystal are determined by knowing that the normal to the diffracting plane bisects the angle between the incident beam and the diffracted beam. A Greninger chart can be used to interpret the back reflection Laue photograph. The X-calibre RTXDB and MWL 110 are commercial systems for Laue back reflection pattern recording. This technique can be used in materials analysis or non destructive inspection. As derived below, elastic scattering can be represented as a Fourier transform of the density of the scatterers, as long as the scattering is weak; the scattered beams should be much less intense than the incoming beam. When the scattering is weak, the scattered beams pass through the remainder of the crystal without undergoing a second scattering event. (Such re-scattered waves are called "secondary scattering".) Since X-rays interact relatively weakly with the electrons, this is generally not a significant consideration; however, any sufficiently thick crystal will produce secondary scattering. By contrast, electron beams may produce strong secondary scattering even for small crystals (e.g., 100 μm) used in X-ray crystallography. In such cases, extremely thin samples, roughly 100 nanometers or less, must be used to avoid secondary scattering; the primary scattered electron beams leave the sample before they have a chance to undergo secondary scattering. Since this thickness corresponds roughly to the diameter of many viruses, a promising direction is the electron diffraction of isolated macromolecular assemblies, such as viral capsids and molecular machines, which may be carried out with a cryo-electron microscope. Neutron diffraction is an excellent method for structure determination, although it has been difficult to obtain intense, monochromatic beams of neutrons in sufficient quantities. Traditionally, nuclear reactors have been used, although the new Spallation Neutron Source holds much promise in the near future. Being uncharged, neutrons scatter much more readily from the atomic nuclei rather than from the electrons. Therefore, neutron scattering is very useful for observing the positions of light atoms with few electrons, especially hydrogen, which is essentially invisible in the X-ray diffraction of larger molecules. Neutron scattering also has the remarkable property that the solvent can be made invisible by adjusting the ratio of normal water, H2O, and heavy water, D2O. A crystalline sample is by definition periodic; a crystal is composed of many unit cells repeated indefinitely in three independent directions. Such periodic systems have a Fourier transform that is concentrated at periodically repeating points in reciprocal space known as Bragg peaks; the Bragg peaks correspond to the reflection spots observed in the diffraction image. Since the amplitude at these reflections grows linearly with the number N of scatterers, the observed intensity of these spots should grow quadratically, like N². In other words, using a crystal concentrates the weak scattering of the individual unit cells into a much more powerful, coherent reflection that can be observed above the noise. This is an example of constructive interference. In a non-crystalline sample, molecules within that sample would be in random orientations and therefore would have a continuous Fourier spectrum that spreads its amplitude more uniformly and with a much reduced intensity, as is observed in SAXS. More importantly, the orientational information is lost. In the crystal, the molecules adopt the same orientation within the crystal, whereas in a liquid, powder or amorphous state, the observed signal is averaged over the possible orientations of the molecules. Although theoretically possible with sufficiently low-noise data, it is generally difficult to obtain atomic-resolution structures of complicated, asymmetric molecules from such rotationally averaged scattering data. An intermediate case is fiber diffraction in which the subunits are arranged periodically in at least one dimension. Crystallography requires a pure crystal of high regularity. In some cases, such crystals can be obtained readily, such as samples of metals, minerals or other macroscopic materials. The regularity of such crystals can sometimes be improved with annealing and other methods. However, in many cases, obtaining a diffraction-quality crystal is the chief barrier to solving its atomic-resolution structure. Small-molecule and macromolecular crystallography differ in the range of possible techniques used to produce diffraction-quality crystals. Small molecules generally have few degrees of conformational freedom, and may be crystallized by a wide range of methods, such as chemical vapor deposition and recrystallisation. By contrast, macromolecules generally have many degrees of freedom and their crystallization must be carried out to maintain a stable structure. For example, proteins and larger RNA molecules cannot be crystallized if their tertiary structure has been unfolded; therefore, the range of crystallization conditions is restricted to solution conditions in which such molecules remain folded. Protein crystals are almost always grown in solution. The most common approach is to lower the solubility of its component molecules very gradually; however, if this is done too quickly, the molecules will precipitate from solution, forming a useless dust or amorphous gel on the bottom of the container. Crystal growth in solution is characterized by two steps: nucleation of a microscopic crystallite (possibly having only 100 molecules), followed by growth of that crystallite, ideally to a diffraction-quality crystal. The solution conditions that favor the first step (nucleation) are not always the same conditions that favor the second step (its subsequent growth). The crystallographer's goal is to identify solution conditions that favor the development of a single, large crystal, since larger crystals offer improved resolution of the molecule. Consequently, the solution conditions should disfavor the first step (nucleation) but favor the second (growth), so that only one large crystal forms per droplet. If nucleation is favored too much, a shower of small crystallites will form in the droplet, rather than one large crystal; if favored too little, no crystal will form whatsoever. In some cases, the crystallographer can identify good solution conditions for growing very small crystals that do not continue to grow and which are too small for crystallography. In such cases, the tiny crystals can be transferred to new solution conditions that favor growth more strongly; the small crystals act as pre-nucleated seeds for subsequent growth. In an alternative approach, a larger but poor-quality crystal may be crushed, and the pieces used as seed crystals to obtain higher quality crystals. It is extremely difficult to predict good conditions for nucleation or growth of well-ordered crystals. In practice, favorable conditions are identified by screening; a very large batch of the molecules is prepared, and a wide variety of crystallization solutions are tested. Hundreds, even thousands, of solution conditions are generally tried before finding one that succeeds in crystallizing the molecules. The various conditions can use one or more physical mechanisms to lower the solubility of the molecule; for example, some may change the pH, some contain salts of the Hofmeister series or chemicals that lower the dielectric constant of the solution, and still others contain large polymers such as polyethylene glycol that drive the molecule out of solution by entropic effects. It is also common to try several temperatures for encouraging crystallization, or to gradually lower the temperature so that the solution becomes supersaturated. These methods require large amounts of the target molecule, as they use high concentration of the molecule(s) to be crystallized. Due to the difficult in obtaining such large quantities (milligrams) of crystallisation grade protein, dispensing robots have been developed that are capable of accurately dispensing crystallisation trial drops that are of the order on 100 nanoliters in volume. This means that roughly 10-fold less protein is used per-experiment when compared to crystallisation trials setup by hand (on the order on 1 microliters) . Several factors are known to inhibit or mar crystallization. The growing crystals are generally held at a constant temperature and protected from shocks or vibrations that might disturb their crystallization. Impurities in the molecules or in the crystallization solutions are often inimical to crystallization. Conformational flexibility in the molecule also tends to make crystallization less likely, due to entropy. Ironically, molecules that tend to self-assemble into regular helices are often unwilling to assemble into crystals. Crystals can be marred by twinning, which can occur when a unit cell can pack equally favorably in multiple orientations; although recent advances in computational methods have begun to allow the structures of twinned crystals to be solved, it is still very difficult. Having failed to crystallize a target molecule, a crystallographer may try again with a slightly modified version of the molecule; even small changes in molecular properties can lead to large differences in crystallization behavior. Once they are full-grown, the crystals are mounted so that they may be held in the X-ray beam and rotated. There are several methods of mounting. Although crystals were once loaded into glass capillaries with the crystallization solution (the mother liquor), a more modern approach is to scoop the crystal up in a tiny loop, made of nylon or plastic and attached to a solid rod, that is then flash-frozen with liquid nitrogen. This freezing reduces the radiation damage of the X-rays, as well as the noise in the Bragg peaks due to thermal motion (the Debye-Waller effect). However, untreated crystals often crack if flash-frozen; therefore, they are generally pre-soaked in a cryoprotectant solution before freezing. Unfortunately, this pre-soak may itself cause the crystal to crack, ruining it for crystallography. Generally, successful cryo-conditions are identified by trial and error. The capillary or loop is mounted on a goniometer, which allows it to be positioned accurately within the X-ray beam and rotated. Since both the crystal and the beam are often very small, the crystal must be centered within the beam to within roughly 25 microns accuracy, which is aided by a camera focused on the crystal. The most common type of goniometer is the "kappa goniometer", which offers three angles of rotation: the ω angle, which rotates about an axis roughly perpendicular to the beam; the κ angle, about an axis at roughly 50° to the ω axis; and, finally, the φ angle about the loop/capillary axis. When the κ angle is zero, the ω and φ axes are aligned. The κ rotation allows for convenient mounting of the crystal, since the arm in which the crystal is mounted may be swung out towards the crystallographer. The oscillations carried out during data collection (mentioned below) involve the ω axis only. An older type of goniometer is the four-circle goniometer, and its relatives such as the six-circle goniometer. The mounted crystal is then irradiated with a beam of monochromatic X-rays. The brightest and most useful X-ray sources are synchrotrons; their much higher luminosity allows for better resolution. They also make it convenient to tune the wavelength of the radiation, which is useful for multi-wavelength anomalous dispersion (MAD) phasing, described below. Synchrotrons are generally national facilities, each with several dedicated beamlines where data is collected around the clock, seven days a week. Crystallographers apply for a slot of time, which they must use whenever it is granted, even at 3am on a national holiday. Crystallographers will sometimes stay awake for days, collecting data continuously until their allotted time runs out. Smaller, weaker X-ray sources are often used in laboratories to check the quality of crystals before bringing them to a synchrotron and sometimes to solve a crystal structure. In such systems, electrons are boiled off of a cathode and accelerated through a strong electric potential of roughly 50 kV; having reached a high speed, the electrons collide with a metal plate, emitting bremsstrahlung and some strong spectral lines corresponding to the excitation of inner-shell electrons of the metal. The most common metal used is copper, which can be kept cool easily, due to its high thermal conductivity, and which produces strong Kα and Kβ lines. The Kβ line is sometimes suppressed with a thin layer (0.0005 in. thick) of nickel foil. The simplest and cheapest variety of sealed X-ray tube has a stationary anode and produces circa 2 kW of X-ray radiation. The more expensive variety has a rotating-anode type source that produces circa 14 kW of X-ray radiation. X-rays are generally filtered to a single wavelength (made monochromatic) and collimated to a single direction before they are allowed to strike the crystal. The filtering not only simplifies the data analysis, but also removes radiation that degrades the crystal without contributing useful information. Collimation is done either with a collimator (basically, a long tube) or with a clever arrangement of gently curved mirrors. Mirror systems are preferred for small crystals (under 0.3 mm) or with large unit cells (over 150 ). When a crystal is mounted and exposed to an intense beam of X-rays, it scatters the X-rays into a pattern of spots or reflections that can be observed on a screen behind the crystal. A similar pattern may be seen by shining a laser pointer at a compact disc. The relative intensities of these spots provide the information to determine the arrangement of molecules within the crystal in atomic detail. The intensities of these reflections may be recorded with photographic film, an area detector or with a charge-coupled device (CCD) image sensor. The peaks at small angles correspond to low-resolution data, whereas those at high angles represent high-resolution data; thus, an upper limit on the eventual resolution of the structure can be determined from the first few images. Some measures of diffraction quality can be determined at this point, such as the mosaicity of the crystal and its overall disorder, as observed in the peak widths. Some pathologies can be quickly diagnosed as well, such as twinning or a prominent ice ring. One image of spots is insufficient to reconstruct the whole crystal; it represents only a small slice of the full Fourier transform. To collect all the necessary information, the crystal must be rotated step-by-step through 180°, with an image recorded at every step; actually, slightly more than 180° is required to cover reciprocal space, due to the curvature of the Ewald sphere. However, if the crystal has a higher symmetry, a smaller angle such as 90° or 45° may be recorded. The axis of the rotation should generally be changed at least once, to avoid developing a "blind spot" in reciprocal space close to the rotation axis. It is customary to rock the crystal slightly (by 0.5-2°) to catch a broader region of reciprocal space. Multiple data sets may be necessary for certain phasing methods. For example, MAD phasing requires that the scattering be recorded at at least three (and usually four, for redundancy) wavelengths of the incoming X-ray radiation. A single crystal may degrade too much during the collection of one data set, owing to radiation damage; in such cases, data sets on multiple crystals must be taken. In order to process the data, a crystallographer must first index the reflections within the multiple images recorded. This means identifying the dimensions of the unit cell and which image peak corresponds to which position in reciprocal space. A byproduct of indexing is to determine the symmetry of the crystal, i.e., its space group. Some space groups can be eliminated from the beginning, since they require symmetries known to be absent in the molecule itself. For example, symmetries with reflection symmetries cannot be observed in chiral molecules; thus, only 65 space groups of 243 possible are allowed for protein molecules which are almost always chiral. Indexing is generally accomplished using an autoindexing routine . Having assigned symmetry, the data is then integrated. This converts the hundreds of images containing the thousands of reflections into a single file, consisting of (at the very least) records of the Miller index of each reflection, and an intensity for each reflection (at this state the file often also includes error estimates and measures of partiality (what part of a given reflection was recorded on that image). A full data set may consist of hundreds of separate images taken at different orientations of the crystal. The first step is to merge and scale these various images, that is, to identify which peaks appear in two or more images (merging) and to scale the relative images so that they have a consistent intensity scale. This is important, since the relative intensities of the peaks is the key information from which the structure is determined. The technique of crystallographic data collection and the often high symmetry of crystalline materials, means that many symmetry-equivalent reflections are recorded multiple times - this allows a merging or symmetry related R-factor to be calculated, based upon how similar the measured intensities of symmetry equivalent reflections are, thus giving a score to assess the quality of the data. The data collected from a diffraction experiment is a reciprocal space representation of the crystal lattice. The position of each diffraction 'spot' is governed by the size and shape of the unit cell, and the inherent symmetry within the crystal. The intensity of each diffraction 'spot' is recorded, and is proportional to the square root of the structure factor amplitude. The structure factor is a complex number containing information relating to both the amplitude and phase of a wave. In order to obtain an interpretable electron density map, both amplitude and phase must be known (an electron density map allows a crystallographer to build a starting model of the molecule). The phase cannot be directly recorded during a diffraction experiment: this is known as the phase problem. Initial phase estimates can be obtained be in a variety of ways: While all four of the above methods are used to solve the phase problem for protein crystallography, small molecule crystallography generally yields data suitable for structure solution using Direct methods/ab initio phasing. Having obtained initial phases, an initial model can be built. This model can be used to refine the phases, leading to an improved model, and so on. Given a model of some atomic positions, these positions and their respective Debye-Waller factors (accounting for the thermal motion of the atom - aka B-factors) can be refined to fit the observed diffraction data, ideally yielding a better set of phases. A new model can then be fit to the new electron density map and a further round of refinement is carried out. This continues until the correlation between the diffraction data and the model is maximized. The agreement is measured by an R-factor defined as A similar quality criterion is Rfree, which is calculated from a subset (~10%) of reflections that were not included in the structure refinement. Both R factors depend on the resolution of the data. As a rule of thumb, Rfree should be approximately the resolution in ngströms divided by 10; thus, a data-set with 2  resolution should yield a final Rfree of roughly 0.2. Chemical bonding features such as stereochemistry, hydrogen bonding and distribution of bond lengths and angles are complementary measures of the model quality. Phase bias is a serious problem in such iterative model building. Omit maps are a common technique used to check for this. It may not be possible to observe every atom of the crystallized molecule - it must be remembered that the resulting electron density is an average of all the molecules within the crystal. In some cases, there is too much residual disorder in those atoms, and the resulting electron density for atoms existing in many conformations is smeared to such an extent that it is no longer detectable in the electron density map.. Weakly scattering atoms such as hydrogen are routinely invisible. It is also possible for a single atom to appear multiple times in an electron density map, e.g., if a protein sidechain has multiple (<4) allowed conformations. In still other cases, the crystallographer may detect that the covalent structure deduced for the molecule was incorrect, or changed. For example, proteins may be cleaved or undergo posttranslational modifications that were not detected prior to the crystallization. Once the model of a molecule's structure has been finalized, it is often deposited in a crystallographic database such as the Protein Data Bank (for protein structures) or the Cambridge Structural Database (for small molecules). Many structures obtained in private commercial ventures to crystallize medicinally relevant proteins, are not deposited in public crystallographic databases. The main goal of X-ray crystallography is to determine the density of electrons f(r) throughout the crystal. To do this, X-ray scattering is used to collect data about its Fourier transform F(q), which is then inverted mathematically to obtain the density defined in real space, using the formula which will be used below. The vector q corresponds to a point in reciprocal space, that is, to a particular oscillation in the electron density as one moves in the direction in which q points. The length of q corresponds to 2π divided by the wavelength of the oscillation. The intensities of the reflections observed in X-ray diffraction give us the magnitudes |F(q)| but not the phases φ(q). To obtain the phases, full sets of reflections are collected with known alterations to the scattering, either by modulating the wavelength past a certain absorption edge or by adding strongly scattering (i.e., electron-dense) metal atoms such as mercury. Combining the magnitudes and phases yields the full Fourier transform F(q), which may be inverted to obtain the electron density f(r). Crystals are often idealized as being perfectly periodic. In that ideal case, the atoms are positioned on a perfect lattice, the electron density is perfectly periodic, and the Fourier transform F(q) is zero except when q belongs to the reciprocal lattice (the so-called Bragg peaks). In reality, however, crystals are not perfectly periodic; atoms vibrate about their mean position, and there may be disorder of various types, such as mosaicity, dislocations, various point defects, and heterogeneity in the conformation of crystallized molecules. Therefore, the Bragg peaks have a finite width and there may be significant diffuse scattering, a continuum of scattered X-rays that fall between the Bragg peaks. An intuitive understanding of X-ray diffraction can be obtained from the Bragg model of diffraction. In this model, a given reflection is associated with a set of evenly spaced sheets running through the crystal, usually passing through the centers of the atoms of the crystal lattice. The orientation of a particular set of sheets is identified by its three Miller indices (h, k, l), and let their spacing be noted by d. William Lawrence Bragg proposed a model in which the incoming X-rays are scattered specularly (mirror-like) from each plane; from that assumption, X-rays scattered from adjacent planes will combine constructively (constructive interference) when the angle θ between the plane and the X-ray results in a path-length difference that is an integer multiple n of the X-ray wavelength λ A reflection is said to be indexed when its Miller indices (or, more correctly, its reciprocal lattice vector components) have been identified from the known wavelength and the scattering angle 2θ. Such indexing gives the unit-cell parameters, the lengths and angles of the unit-cell, as well as its space group. Since Bragg's law does not interpret the relative intensities of the reflections, however, it is generally inadequate to solve for the arrangement of atoms within the unit-cell; for that, a Fourier transform method must be carried out. The incoming X-ray beam has a polarization and should be represented as a vector wave; however, for simplicity, let it be represented here as a scalar wave. We also ignore the complication of the time dependence of the wave and just focus on the wave's spatial dependence. Plane waves can be represented by a wave vector kin, and so the strength of the incoming wave at time t=0 is given by At position r within the sample, let there be a density of scatterers f(r); these scatterers should produce a scattered spherical wave of amplitude proportional to the local amplitude of the incoming wave times the number of scatterers in a small volume dV about r Let's consider the fraction of scattered waves that leave with an outgoing wave-vector of kout and strike the screen at rscreen. Since no energy is lost (elastic, not inelastic scattering), the wavelengths are the same as are the magnitudes of the wave-vectors |kin| = |kout|. From the time that the photon is scattered at r until it is absorbed at rscreen, the photon undergoes a change in phase A S \int d\mathbf{r} f(\mathbf{r}) e^{i \mathbf{k}_{in} \cdot \mathbf{r}} e^{i \mathbf{k}_{out} \cdot \left( \mathbf{r}_{\mathrm{screen}} - \mathbf{r} ight)} = A S e^{i \mathbf{k}_{out} \cdot \mathbf{r}_{\mathrm{screen}}} \int d\mathbf{r} f(\mathbf{r}) e^{i \left( \mathbf{k}_{in} - \mathbf{k}_{out} ight) \cdot \mathbf{r}} </math> The electron density f(r) is a real function, which imposes a constraint on its Fourier transform. Specifically, the Fourier transform of a negative frequency must have the same magnitude as the corresponding positive frequency, but opposite phase In other words, the Fourier transforms of the negative and positive frequency vectors are complex conjugates of one another; in X-ray crystallography, these corresponding reflections are called Friedel mates. This allows one to measure the full Fourier transform from only half the reciprocal space, e.g., by slightly more than a 180° rotation (see next section). In symmetric crystals, other reflections may have the same intensity (Bijvoet mates); in such cases, one can measure even less of the reciprocal space, e.g., slightly more than 90°. Each X-ray diffraction image represents only a slice, a spherical slice of reciprocal space, as may be seen by the Ewald sphere construction. Both kout and kin have the same length, due to the elastic scattering, since the wavelength has not changed. Therefore, they may be represented as two radial vectors in a sphere in reciprocal space, which shows the values of q that are sampled in a given diffraction image. Since there is a slight spread in the incoming wavelengths of the incoming X-ray beam, the values of |F(q)| can be measured only for q vectors located between the two spheres corresponding to those radii. Therefore, to obtain a full set of Fourier transform data, it is necessary to rotate the crystal through slightly more than 180°, or sometimes less if sufficient symmetry is present. A full 360° rotation is not needed because of a symmetry intrinsic to the Fourier transforms of real functions (such as the electron density), but "slightly more" than 180° is needed to cover all of reciprocal space within a given resolution because of the curvature of the Ewald sphere (add Figure to illustrate this). In practice, the crystal is rocked by a small amount (0.25-1°) to incorporate reflections near the boundaries of the spherical Ewald shells. Therefore, the autocorrelation function c(r) of the electron density (also known as the Patterson function ) can be computed directly from the reflection intensities, without computing the phases. In principle, this could be used to determined the crystal structure directly; however, it is difficult to realize in practice. The autocorrelation function corresponds to the distribution of vectors between atoms in the crystal; thus, a crystal of N atoms in its unit cell may have N(N-1) peaks in its Patterson function. Given the inevitable errors in measuring the intensities, and the mathematical difficulties of reconstructing atomic positions from the interatomic vectors, this technique is rarely used to solve structures, except for the simplest crystals.

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# X-ray image intensifier An X-ray image intensifier (XRII), sometimes called a C-Arm, refers to a special image intensifier device used in medical imaging involving x rays. It consists of an input window, input phosphor, photocathode, vacuum and electron optics, output phosphor and output window. It allows for lower x-ray doses to be used on patients by magnifying the intensity produced in the output image, enabling the viewer to easily see the structure of the object being imaged. They were introduced by Philips in 1955. These are used in most xray departments as 'screening rooms'. The types of investigations for which this machine can be used for is vast. Examples include: Smaller in design than a fixed image intensifier, mobile screening units are becomming more and more powerful. This has enabled more advanced and technical procedures to be carried out in confined locations. MII's are routinely used in most hospitals for: Image intensifiers are usually set up for two purposes. For either plain fluoroscopy or digital subtraction angiography (DSA). All image intensifiers are set up with software capable of adjusting settings to suit different user requirements, depending on the procedure and body area being imaged. In simple flouroscopy for example, imaging of the throat would not require the same amount of exposure as that of the abdomen. And on DSA capable models, preset programs are available which enables the user to decide a rate of how many images or frames per second are acquired.

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# XCL1 Chemokine (C motif) ligand (XCL1) is a small cytokine belonging to the C chemokine family that is also known as lymphotactin. Chemokines are known for their function in inflammatory and immunological responses. This family C chemokines differs in structure and function from most chemokines. There are only two chemokines in this family and what separated them from other chemokines is that they only have two cysteines; one N-terminal cysteine and one cysteine downstream. These both are called Lymphotactin, alpha and beta form, and claim special characteristics only found between the two. Lymphotactins can go through a reversible conformational change which changes its binding shifts. In normal tissues, XCL1 is found in high levels in spleen, thymus, small intestine and peripheral blood leukocytes, and at lower levels in lung, prostate gland and ovary. Secretion of XCL1 is responsible for the increase of intracellular calcium in peripheral blood lymphocytes. Cellular sources for XCL1 include activated thymic and peripheral blood CD8+ T cells. XCL1 is also expressed by dendritic cells (DC). NK cells also secrete XCL1 along with other chemokines early in infections. In humans, XCL1 is closely related to another chemokine called XCL2, whose gene is found at the same locus on chromosome 1. Both of these chemokines share many genetic and functional similarities; however XCL2 has only been known to be observed in humans and not in mice. XCL1 induces it chemotactic function by binding to a chemokine receptor called XCR1. XCL1 is expressed on macrophages, fibroblasts, and specific lymphocytes. XCL1's gene is found on the long arm of chromosome 1, located on cytogenetic band q24.2 as seen in the infobox. The encoding gene is made of 6,017 DNA bases to encode for the protein XCL1. This gene contains three exons and two introns as well as several transcription initiation sites. This gene encodes for the 114-amino acid protein called XCL1 which is similar to other chemokines except that it lacks the first and third cysteine characteristics. This means that XCL1 only contains one cysteine creating a disulfide bond instead of two or three like the other chemokines. The genetic differences between XCL1 and XCL2 are very small. Both proteins are from the same family containing the C motif structure containing one disulfide bond and have almost identical tertiary structures. These C chemokines also have the same flanking regions, meaning regions of the gene including the promoter and other places of protein binging that do not contribute to the RNA transcribed gene. Gene mapping of this chemokine family shows similarities in their intron and exon locations with only one distinct difference. XCL1 has only one difference in its first intron that encodes for a large ribosomal subunit called L7a. In XCL2 have of the region encoding for L7a is cut off. The only other genetic difference between the two mature proteins is the different amino acid in positions 7 and 8. This amino acid difference may account for some biological differences. Some difficulties with comparing these two chemokines is that XCL2 has never been observed in a mouse. One thing that sets XCL1 apart from other cytokines is its structure. While most chemokines have two disulfide bonds that connect the N-terminus to the core of the structure, XCL1 only has one. This simple difference in disulfide bonds changes the overall tertiary structure of XCL1 from other chemokines. There are two parts of the lymphotactin protein, structures Ltn10 and Ltn40, that folds into each other, which make it biologically active. This conformational change alters the binding structures on the chemokine. This understanding of the interfolding provides more of a basis to understanding to the lymphotactin kinetics. Most of the secreted XCL1 comes from a specific kind of dendritic cell that is involved in antigen cross-presentation. This means that XCL1 is involved in the activation of cytotoxic T cells by a dendritic cell. XCL1 can also be secreted by NK cells along with other chemokines in the beginning of infection. This has been associated with the T helper cell type 1 defense. This secretion has also been observed to facilitate the NK cells to communicate with DC containing XCR1 on their surface. In the same way, secretion of XCL1 encourages Cytotoxic T cells to also communicate with DC containing SCR1. The pair of XCL1 and XCR1 are known to be involved in cross-presentation, antigen uptake, and induction of innate as well as adaptive cytotoxic immunity.

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# XCL2 Chemokine (C motif) ligand 2 (XCL2) is a small cytokine belonging to the XC chemokine family that is highly related to another chemokine called XCL1. It is predominantly expressed in activated T cells, but can also be found at low levels in unstimulated cells. XCL2 induces chemotaxis of cells expressing the chemokine receptor XCR1. Its gene is located on chromosome 1 in humans.

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# XCR1 The protein encoded by this gene is a chemokine receptor belonging to the G protein-coupled receptor superfamily. The family members are characterized by the presence of 7 transmembrane domains and numerous conserved amino acids. This receptor is most closely related to RBS11 and the MIP1-alpha/RANTES receptor. It transduces a signal by increasing the intracellular calcium ions level. The viral macrophage inflammatory protein-II is an antagonist of this receptor and blocks signaling. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. Cross-presenting dendritic cells (DCs) in the spleen develop into XCR1+ DCs in the small intestine, T cell zones of Peyer's patches, and T cell zones and sinuses of mesenteric lymph nodes. XCR1+ DCs specialize in cross-presentations of orally applied antigens. The integrin SIRPα is also a differentiating factor for the XCR1+ DCs. The development transcription factor Batf3 helps develop the differences between XCR1+ DCs and CD103+ CD11b- DCs. XCL1 contributes to chemotaxis only in CD8+ murine cells, but not other DC types, B cells, T cells, or NK cells. Only some of these CD8+ murine cells expressed XCR1 receptors. NK cells release XCL1 along with IFN-γ and some other chemokines upon encountering certain bacteria such as Listeria or MCMV. XCR1+ and CD8+cells work together to cross-present antigen and communicate CD8+ activation. Cross presentation of XCR1+ CD8+ and XCR1+ CD8- cells was strongest, as is expected since they have XCR1 receptors. CD4+ and CD8+ may become outdated terms, since the activity of the cell appears to be primarily dependent upon the expression of XCR1, which will make a population far more similar than the expression of CD4 or CD8. XCR1+ cells are dependent on the growth factor Ftl3 ligand and are nonexistent in Batf3- deficient mice. Also, XCR1+ DCs are related to CD103+CD11b- DCs. XCL1 is expressed by medullary thymic epithelial T cells (mTECs) while XCR1 is expressed by thymic dendritic cells (tDCs). This communication helps with the destruction of cells that are not self-tolerant. When mice lose the ability to express XCL1, they are deficient in accumulation of tDCs and producing naturally occurring regulatory T cells (nT reg cells). The displaying of XCL1 by mTECs, tDC chemotaxis, and nT reg cell production are all decreased in mice that lack Aire, demonstrating it as a important regulator of XCL1 production. Naive CD8+ T cells are prepared when tumors form by cross-presentation via XCR1+ DCs and as a result will require a lower threshold to respond to antigen. Memory CD8+ T lymphocytes (mCTLs) are activated first after infection and then are signaled by CXCR3, IL-12, and CXCL9 by other XCR1+ DCs. In order to make a powerful secondary infection response, cytokine and chemokine signaling between XCR1+ DCs and NK cells must occur.

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# XDH (gene) Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The enzyme is a homodimer. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism.

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xDNA is a modified form of DNA with 8 nucleobases: the four natural bases A, C, G, and T, and four artificial modifications of these made longer by the addition of an extra benzene ring: xA, xC, xG, and xT. A pairs with xT, C pairs with xG, G pairs with xC, and T pairs with xA, so the distance between the two halves of the double helix is consistently greater. The double helix is thus wider and has a longer pitch. Experiments with xDNA are expected to provide new insight into the behavior of natural DNA. Also, the extended bases xA, xC, xG, and xT are fluorescent, and single strands composed of only extended bases can recognize and bind to single strands of natural DNA, which could make them useful tools for studying biological systems. The same research group also constructed whidened DNA, called yDNA.

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