All people with ALPS have signs of lymphoproliferation, which makes it the most common clinical manifestation of the disease. The increased proliferation of lymphoid cells can cause the size of lymphoid organs such as the lymph nodes and spleen to increase (lymphadenopathy and splenomegaly, present in respectively over 90% and over 80% of patients). The liver is enlarged (hepatomegaly in 30 - 40% of patients).

Autoimmune disease is the second most common clinical manifestation and one that most often requires treatment. Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic. These include: Autoimmune hemolytic anemia, Autoimmune neutropenia, Autoimmune thrombocytopenia.

Other signs can affect organ systems similar to systemic lupus erythematosus (least common, affecting <5% of patients) Symptoms of the nervous system include: Autoimmune cerebellar ataxia; Guillain–Barré syndrome; transverse myelitis. Gastrointestinal signs like Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis can be found or (Dermatologic) Urticaria, (Pulmonary) bronchiolitis obliterans, (Renal) Autoimmune glomerulonephritis, nephrotic syndrome.

Another sign are cancers such as Hodgkin and non-Hodgkin lymphomas which appear to be increased, possibly due to Epstein–Barr virus-encoded RNA-positivity. Some carcinomas may occur. Unaffected family members with genetic mutations are also at an increased risk of developing cancer.

Clinically, RALD is characterized by splenomegaly, a relatively mild degree of peripheral lymphadenopathy, and autoimmunity. The autoimmune phenotype can present in childhood or adulthood and primarily includes autoimmune hemolytic anemia, ITP, and neutropenia. Some patients have a history of recurrent respiratory tract infections. It is unclear if increased risk for malignancy is part of RALD.

Importantly, however, the clinical and laboratory phenotype resembles juvenile myelomonocytic leukemia. The high fatality rate of this childhood blood cancer puts it in sharp contrast when compared to the relatively benign and chronic course of RALD. Approximately 15-30% of patients diagnosed with JMML have somatic, activating RAS mutations. However, due to the difficulty in distinguishing JMML from RALD, it is possible a subset of patients treated for JMML actually have RALD and could therefore avoid the aggressive JMML treatment. This distinction is under investigation.

RAS-associated autoimmune leukoproliferative disorder (RALD) is a rare genetic disorder of the immune system. RALD is characterized by lymphadenopathy, splenomegaly, autoimmunity, and elevation in granulocytes and monocytes. It shares many features with autoimmune lymphoproliferative syndrome and is caused by somatic mutations in NRAS or KRAS. This was first described by investigators João Oliveira and Michael Lenardo from the National Institutes of Health.

2003 nomenclature

- IA - Fas

- IB - Fas ligand

- IIA - Caspase 10

- IIB - Caspase 8

- III - unknown

- IV - Neuroblastoma RAS viral oncogene homolog

Revised nomenclature (2010)

- ALPS-FAS: Fas. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described.

- ALPS-sFAS: Fas. Somatic FAS mutations in DNT compartment. 10% of patients

- ALPS-FASL: Fas ligand. Germline FASL mutations. 3 reported cases

- ALPS-CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients

- ALPS-U: Undefined. 20% of patients

- CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder

- RALD: NRAS, KRAS. Somatic mutations in NRAS and KRAS in lympocyte compartment. No longer considered a subtype of ALPS but distinct disesase

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.

An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:

- By the component(s) of the immune system affected

- By whether the immune system is overactive or underactive

- By whether the condition is congenital or acquired

According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immunodeficiencies exceeds the number of PIDs.

It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.

Iodine deficiency is one of the leading causes of preventable mental handicaps worldwide, producing typical reductions in IQ of 10 to 15 IQ points. It has been speculated that deficiency of iodine and other micronutrients may be a possible factor in observed differences in IQ between ethnic groups: see race and intelligence for a further discussion of this controversial issue.

Cretinism is a condition associated with iodine deficiency and goiter, commonly characterised by mental deficiency, deafness, squint, disorders of stance and gait and stunted growth due to hypothyroidism. Paracelsus was the first to point out the relation between goitrous parents and their mentally disabled children.

As a result of restricted diet, isolation, intermarriage, etc., as well as low iodine content in their food, children often had peculiar stunted bodies and retarded mental faculties, a condition later known to be associated with thyroid hormone deficiency. Diderot, in his 1754 "Encyclopédie", described these patients as "crétins". In French, the term "crétin des Alpes" also became current, since the condition was observed in remote valleys of the Alps in particular. The word "cretin" appeared in English in 1779.

While reporting recent progress towards overcoming iodine-deficiency disorders worldwide, "The Lancet" noted: "According to World Health Organization, in 2007, nearly 2 billion individuals had insufficient iodine intake, a third being of school age." A conclusion was made that the single most preventable cause of intellectual disability is that of iodine deficiency.

Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in a goiter, sometimes as an endemic goiter as well as cretinism due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important public health issue as it is a preventable cause of intellectual disability.

Iodine is an essential dietary mineral; the thyroid hormones thyroxine and triiodothyronine contain iodine. In areas where there is little iodine in the diet, typically remote inland

areas where no marine foods are eaten, iodine deficiency is common. It is also common in mountainous regions of the world where food is grown in iodine-poor soil.

Prevention includes adding small amounts of iodine to table salt, a product known as "iodized salt". Iodine compounds have also been added to other foodstuffs, such as flour, water and milk, in areas of deficiency. Seafood is also a well known source of iodine.

Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). It resulted in 2700 deaths in 2013 up from 2100 deaths in 1990.

The period between infection and the first symptoms (incubation period) is typically 1–3 months in humans. Incubation periods as short as four days and longer than six years have been documented, depending on the location and severity of the contaminated wound and the amount of virus introduced. Initial signs and symptoms of rabies are often nonspecific such as fever and headache. As rabies progresses and causes inflammation of the brain and/or meninges, signs and symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations, progressing to delirium, and coma. The person may also have hydrophobia.

Death usually occurs 2 to 10 days after first symptoms. Survival is rare once symptoms have presented, even with the administration of proper and intensive care. Jeanna Giese, who in 2004 was the first patient treated with the Milwaukee protocol, became the first person ever recorded to have survived rabies without receiving successful post-exposure prophylaxis. An intention-to-treat analysis has since found this protocol has a survival rate of about 8%.

Rabies is a viral disease that causes inflammation of the brain in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, the result is nearly always death. The time period between contracting the disease and the start of symptoms is usually one to three months; however, this time period can vary from less than one week to more than one year. The time is dependent on the distance the virus must travel along nerves to reach the central nervous system.

Rabies is caused by "lyssaviruses", including the rabies virus and Australian bat lyssavirus. Rabies is spread when an infected animal scratches or bites another animal or human. Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose. Globally, dogs are the most common animal involved. More than 99% of rabies cases in countries where dogs commonly have the disease are caused by dog bites. In the Americas, bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs. Rodents are very rarely infected with rabies. The rabies virus travels to the brain by following the peripheral nerves. The disease can only be diagnosed after the start of symptoms.

Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world. Immunizing people before they are exposed is recommended for those who are at high risk. The high-risk group includes people who work with bats or who spend prolonged periods in areas of the world where rabies is common. In people who have been exposed to rabies, the rabies vaccine and sometimes rabies immunoglobulin are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms. Washing bites and scratches for 15 minutes with soap and water, povidone iodine, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. Only six people have survived a rabies infection after showing symptoms, and this was with extensive treatment known as the Milwaukee protocol.

Rabies caused about 17,400 deaths worldwide in 2015. More than 95% of human deaths caused by rabies occur in Africa and Asia. About 40% of deaths occur in children under the age of 15. Rabies is present in more than 150 countries and on all continents but Antarctica. More than 3 billion people live in regions of the world where rabies occurs. A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs. Many small island nations do not have rabies at all. It is classified as a neglected tropical disease.

Radon () is a radioactive, colorless, odorless, tasteless noble gas, occurring naturally as the decay product of radium. It is one of the densest substances that remains a gas under normal conditions, and is considered to be a health hazard due to its radioactivity. Its most stable isotope, Rn, has a half-life of 3.8 days. Due to its high radioactivity, it has been less well-studied by chemists, but a few compounds are known.

Radon is formed as part of the normal radioactive decay chain of uranium into Pb. Uranium has been present since the earth was formed and its most common isotope has a very long half-life (4.5 billion years), which is the time required for one-half of uranium to break down. Thus, uranium and radon, will continue to occur for millions of years at about the same concentrations as they do now.

Radon is responsible for the majority of the mean public exposure to ionizing radiation. It is often the single largest contributor to an individual's background radiation dose, and is the most variable from location to location. Radon gas from natural sources can accumulate in buildings, especially in confined areas such as attics, and basements. It can also be found in some spring waters and hot springs.

According to a 2003 report "EPA's Assessment of Risks from Radon in Homes" from the United States Environmental Protection Agency, epidemiological evidence shows a clear link between lung cancer and high concentrations of radon, with 21,000 radon-induced U.S. lung cancer deaths per year—second only to cigarette smoking. Thus in geographic areas where radon is present in heightened concentrations, radon is considered a significant indoor air contaminant.

For much of the second phase of his career, Cyclist Lance Armstrong faced constant allegations of doping. Armstrong consistently denied allegations of doping until a partial confession during a broadcast interview with Oprah Winfrey in January 2013.

The 2007 Tour de France was affected by a series of scandals and speculations related to doping. By the end of the Tour, two cyclists were dismissed for failing tests and the wearer of the yellow jersey was voluntarily retired by his team for lying about his whereabouts and missing doping tests. A fourth rider was confirmed to having used doping while in a training session prior to the 2007 Tour and a fifth rider failed tests late in the race, with his result being officially announced just after the end of the Tour. During the competition, two teams were asked to withdraw after at least one member was found to have doped.

The events generated criticism and a general distrustful attitude toward the sport of professional cycling from media and public opinion. The doping allegations also resulted in several team sponsors threatening to retire their support if events advanced further. Some media such as German TV channels ARD and ZDF left the Tour once the first scandals broke. Following the Tour's conclusion, the sport's governing bodies spoke out about ways to combat the prevalence of doping in cycling and key team sponsors elected to withdraw their support due to the reputational damage caused by the scandals. The 2007 Tour de France has been referred to as one of the most controversial Tours. After the end of the Tour, "The Times" of London ranked it 4th in its list of the top 50 sporting scandals.

Coenurosis (a.k.a. Caenurosis and Coenuriasis, gid or sturdy in the vernacular) is a parasitic infection that develops in the intermediate hosts of some tapeworm species ("Taenia multiceps", "T. serialis, T. brauni," or "T. glomerata") and are caused by the coenurus, the larval stage of these worms. This disease occurs mainly in sheep and other ungulates, but occasionally can occur in humans too by accidental ingestion of worms' eggs.

Adult worms of these species develop in the small intesine of the definitive hosts (dogs, foxes, and other canids), causing a disease from the group of taeniasis. Humans cannot be definitive hosts for these species of tapeworms.

Radon concentration is usually measured in the atmosphere in becquerels per cubic meter (Bq/m), which is an SI derived unit. As a frame of reference, typical domestic exposures are about 100 Bq/m indoors and 10-20 Bq/m outdoors. In the US, radon concentrations are often measured in picocuries per liter (pCi/l), with 1 pCi/l = 37 Bq/m.

The mining industry traditionally measures exposure using the "working level" (WL) index, and the cumulative exposure in "working level months" (WLM): 1 WL equals any combination of short-lived Rn progeny (Po, Pb, Bi, and Po) in 1 liter of air that releases 1.3 × 10 MeV of potential alpha energy; one WL is equivalent to 2.08 × 10 joules per cubic meter of air (J/m). The SI unit of cumulative exposure is expressed in joule-hours per cubic meter (J·h/m). One WLM is equivalent to 3.6 × 10 J·h/m. An exposure to 1 WL for 1 working month (170 hours) equals 1 WLM cumulative exposure.

A cumulative exposure of 1 WLM is roughly equivalent to living one year in an atmosphere with a radon concentration of 230 Bq/m.

The radon (Rn) released into the air decays to Pb and other radioisotopes. The levels of Pb can be measured. The rate of deposition of this radioisotope is dependent on the weather.

Although coenurosis is more commonly associated with domestic animals, it has also been documented in wildlife. It has been found in mountain ungulates in the French Alps. It is believed that the ungulates are being contaminated by infected sheepdogs. Understanding how this disease is transmitted from sheepdogs to wild animals is important in managing the spread of this potentially dangerous zoonotic disease. A potential management strategy would be for farmers to properly dispose of carcasses that they find on their land. In wild gelada monkeys in Ethiopia, coenurosis was found to affect the fitness of these primates. Mortality increased and fertility was inhibited. The disease has also been documented in wild sheep and other ruminants and rarely documented in rodents, horses, and cats. Very few cases have been identified but this could be due to limited research on wild coenurosis. Animals infected with this disease tend to hide or take cover from predators and therefore may not be seen by humans. However, coenurosis has been known to increase mortality and decrease fertility in wild animal populations.

Since the introduction of doping tests in 1964, many cyclists were caught in the Tour de France. In recent years, 1996 Tour de France winner Bjarne Riis and points classification winner Erik Zabel, along with most of their Team Telekom team-mates, confessed to using erythropoietin (EPO). In 1997, former points classification winner Djamolidine Abdoujaparov was disqualified from the Tour de France for doping use. In 1998, the Festina affair had several main contenders removed from the race. In the next years, several riders were removed from the Tour de France for doping (see List of doping cases in cycling).

In addition, several riders were not allowed to start the previous Tour, including Jan Ullrich and Ivan Basso because of their involvement in the Operación Puerto doping case, a Spanish investigation against doctor Eufemiano Fuentes and a number of accomplices accused of administering prohibited doping products to approximately two hundred professional athletes, to enhance their performance.

After the completion of the 2006 Tour, winner Floyd Landis was found to have an elevated testosterone to epitestosterone ratio on a sample taken following Stage 17 of the race, and at the time of the 2007 Tour prologue. Since the results of an independent arbitration hearing were still pending Landis was prevented from defending his title. He was stripped of his 2006 Tour title in September 2007.

Armstrong has been criticized for his disagreements with outspoken opponents of doping such as Paul Kimmage and Christophe Bassons. Bassons wrote a number of articles for a French newspaper during the 1999 Tour de France which made references to doping in the peloton. Subsequently, Armstrong had an altercation with Bassons during the 1999 Tour de France where Bassons said Armstrong rode up alongside on the Alpe d'Huez stage to tell him "it was a mistake to speak out the way I (Bassons) do and he (Armstrong) asked why I was doing it. I told him that I'm thinking of the next generation of riders. Then he said 'Why don't you leave, then?'"

Armstrong later confirmed Bassons's story. On the main evening news on TF1, a French television station, Armstrong said: "His accusations aren't good for cycling, for his team, for me, for anybody. If he thinks cycling works like that, he's wrong and he would be better off going home". Kimmage, a professional cyclist in the 1980s who later became a sports journalist, referred to Armstrong as a "cancer in cycling". He also asked Armstrong questions in relation to his "admiration for dopers" at a press conference at the Tour of California in 2009, provoking a scathing reaction from Armstrong. This spat continued and is exemplified by Kimmage's articles in "The Sunday Times".

Another notable critic of Armstrong was David Walsh, also a reporter for "The Sunday Times". Referred to as a "little troll" by Armstrong, Walsh revealed in a 2001 "Sunday Times" story that he had ties to controversial Italian doctor Michele Ferrari. Two years later, Walsh's book "L.A. Confidentiel" alleged, based on testimony by Armstrong's former masseuse Emma O'Reilly, that clandestine trips were made to pick up and deliver doping products to Armstrong's team.

Until his 2013 admission, Armstrong continually denied using illegal performance-enhancing drugs and described himself as the most tested athlete in the world. However, a 1999 urine sample showed traces of corticosteroid; a medical certificate showed he used an approved cream for saddle sores which contained the substance. O'Reilly claimed that team officials conspired with a compliant doctor to falsify Armstrong's prescription, and that Armstrong never had the condition. She also claimed that, on other occasions, she was asked to dispose of used syringes for Armstrong and pick up strange parcels for the team.

From his return to cycling in the fall of 2008 through March 2009, Armstrong submitted to twenty-four unannounced drug tests by various anti-doping authorities. All of the tests were negative for performance-enhancing drugs.

U.S. federal prosecutors pursued allegations of doping by Armstrong from 2010–2012. The effort convened a grand jury to investigate doping charges, including taking statements under oath from Armstrong's former team members and other associates; met with officials from France, Belgium, Spain, and Italy; and requested samples from the French anti-doping agency. The investigation was led by federal agent Jeff Novitzky, who also investigated suspicions of steroid use by baseball players Barry Bonds and Roger Clemens. The probe was terminated on February 3, 2012 with no charges filed.

Tyler Hamilton, a professional cyclist who rode as Lance Armstrong's principal Domestique on the U.S. Postal Cycling team from 1999 through 2001, has extensively documented the history and methods of doping by Armstrong, himself, and others in "The Secret Race", a book co-authored with Daniel Coyle and published in 2012. The book also describes the investigation by Jeff Novitzky and the Food and Drug Administration and Hamilton's befuddlement that the investigation was dropped.