<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Diabetes and explain in detail? [/INST] Diabetes mellitus, commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appetite. If left untreated, diabetes can cause many health complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes and cognitive impairment.Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus:
Type 1 diabetes results from failure of the pancreas to produce enough insulin due to loss of beta cells. This form was previously referred to as "insulin-dependent diabetes mellitus" or "juvenile diabetes". The loss of beta cells is caused by an autoimmune response. The cause of this autoimmune response is unknown. Although Type 1 diabetes usually appears during childhood or adolescence, it can also develop in adults.
Type 2 diabetes begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses, a lack of insulin may also develop. This form was previously referred to as "non insulin-dependent diabetes mellitus" or "adult-onset diabetes". Type 2 diabetes is more common in older adults, but a significant increase in the prevalence of obesity among children has led to more cases of type 2 diabetes in younger people. The most common cause is a combination of excessive body weight and insufficient exercise.
Gestational diabetes is the third main form, and occurs when pregnant women without a previous history of diabetes develop high blood sugar levels. In women with gestational diabetes, blood sugar usually returns to normal soon after delivery. However, women who had gestational diabetes during pregnancy have a higher risk of developing type 2 diabetes later in life.Type 1 diabetes must be managed with insulin injections. Prevention and treatment of type 2 diabetes involves maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Type 2 diabetes may be treated with oral antidiabetic medications, with or without insulin. Control of blood pressure and maintaining proper foot and eye care are important for people with the disease. Insulin and some oral medications can cause low blood sugar (hypoglycemia). Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes. Gestational diabetes usually resolves after the birth of the baby.As of 2019, an estimated 463 million people had diabetes worldwide (8.8% of the adult population), with type 2 diabetes making up about 90% of the cases. Rates are similar in women and men. Trends suggest that rates will continue to rise. Diabetes at least doubles a persons risk of early death. In 2019, diabetes resulted in approximately 4.2 million deaths. It is the 7th leading cause of death globally. The global economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion. In the United States, diabetes cost nearly US$327 billion in 2017. Average medical expenditures among people with diabetes are about 2.3 times higher.

Signs and symptoms
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Diabetic emergencies
People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital. A rarer but more dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars.Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2 diabetes depending on the medication being used. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and rarely permanent brain damage or death in severe cases. Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive. Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.

Complications
All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20) but may be the first symptom in those who have otherwise not received a diagnosis before that time.The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease and about 75% of deaths in people with diabetes are due to coronary artery disease. Other macrovascular diseases include stroke, and peripheral artery disease. These complications are also a strong risk factor for severe COVID-19 illness.The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves. Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness. Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that people with diabetes visit an eye doctor once a year. Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation. Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes. The symptoms can include numbness, tingling, sudomotor dysfunction, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.
There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function. Having diabetes, especially when on insulin, increases the risk of falls in older people.

Causes
Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types". "Hybrid forms of diabetes" include slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. "Hyperglycemia first detected during pregnancy" includes gestational diabetes mellitus and diabetes mellitus in pregnancy (type 1 or type 2 diabetes first diagnosed during pregnancy). The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.

Type 1
Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults."Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used. Still, type 1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addisons disease). These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.

Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans. Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.

Type 2
Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus. Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the livers glucose production.Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Even those who are not obese may have a high waist–hip ratio.Dietary factors such as sugar-sweetened drinks are associated with an increased risk. The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people. Lack of physical activity may increase the risk of diabetes in some people.Adverse childhood experiences, including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.Antipsychotic medication side effects (specifically metabolic abnormalities, dyslipidemia and weight gain) and unhealthy lifestyles (including poor diet and decreased physical activity), are potential risk factors.

Gestational diabetes
Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery. It is recommended that all pregnant women get tested starting around 24–28 weeks gestation. It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time. However, after pregnancy approximately 5–10% of women with gestational diabetes are found to have another form of diabetes, most commonly type 2. Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetuss blood may inhibit fetal surfactant production and cause infant respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.

Other types
Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting 1–2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus, there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.Some cases of diabetes are caused by the bodys tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke "steroid diabetes"). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.
Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes. It was first discovered in 1990 or 1991.
The following is a list of disorders that may increase the risk of diabetes:

Pathophysiology
Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the bodys cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.When glucose concentration in the blood remains high over time, the kidneys reach a threshold of reabsorption, and the body excretes glucose in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia). In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).

Diagnosis
Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following:
Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight.
Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as in a glucose tolerance test (OGTT)
Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while fasting or not fasting
Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 7.0 mmol/L (126 mg/dL) is considered diagnostic for diabetes mellitus.
Per the WHO, people with fasting glucose levels from 6.1 to 6.9 mmol/L (110 to 125 mg/dL) are considered to have impaired fasting glucose. People with plasma glucose at or above 7.8 mmol/L (140 mg/dL), but not over 11.1 mmol/L (200 mg/dL), two hours after a 75 gram oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease. The American Diabetes Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9 mmol/L (100 to 125 mg/dL).Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.

Prevention
There is no known preventive measure for type 1 diabetes. Type 2 diabetes—which accounts for 85–90% of all cases worldwide—can often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet. Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.

Management
Diabetes management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of appropriate medications (insulin, oral medications).
Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels. Per the American College of Physicians, the goal of treatment is an HbA1C level of 7-8%. Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, high blood pressure, metabolic syndrome obesity, and lack of regular exercise. Specialized footwear is widely used to reduce the risk of diabetic foot ulcers by relieving the pressure on the foot.The principles of managing diabetes may be similar across the general population with diabetes, however some considerations may need to be addressed when tailoring intervention, mainly in special populations.
Considering those with severe mental illness, the efficacy of type 2 diabetes self-management interventions is still poorly explored, with insufficient scientific evidence to show whether these interventions have similar results to those observed in general population.

Lifestyle
People with diabetes can benefit from education about the disease and treatment, dietary changes, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes. No single dietary pattern is best for all people with diabetes. Healthy dietary patterns, such as the Mediterranean diet, low-carbohydrate diet, or DASH diet, are often recommended, although evidence does not support one over the others. According to the ADA, "reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia", and for individuals with type 2 diabetes who cannot meet the glycemic targets or where reducing anti-glycemic medications is a priority, low or very-low carbohydrate diets are a viable approach. For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.

Medications
Glucose control
Most medications used to treat diabetes act by lowering blood sugar levels through different mechanisms. There is broad consensus that when people with diabetes maintain tight glucose control – keeping the glucose levels in their blood within normal ranges – they experience fewer complications, such as kidney problems or eye problems. There is however debate as to whether this is appropriate and cost effective for people later in life in whom the risk of hypoglycemia may be more significant.There are a number of different classes of anti-diabetic medications. Type 1 diabetes requires treatment with insulin, ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the basal rate and short-acting insulin with meals. Type 2 diabetes is generally treated with medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment with insulin or GLP-1 agonists.Metformin is generally recommended as a first-line treatment for type 2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the livers production of glucose. Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type 2 diabetes. These include agents that increase insulin release (sulfonylureas), agents that decrease absorption of sugar from the intestines (acarbose), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP (sitagliptin), agents that make the body more sensitive to insulin (thiazolidinedione) and agents that increase the excretion of glucose in the urine (SGLT2 inhibitors). When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are then increased until glucose targets are reached.

Blood pressure lowering
Cardiovascular disease is a serious complication associated with diabetes, and many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes. However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg, and a subsequent systematic review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 – 140mmHg, although there was an increased risk of adverse events.2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death. There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs), or aliskiren in preventing cardiovascular disease. Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits.

Aspirin
The use of aspirin to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended by some in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%). National guidelines for England and Wales by the National Institute for Health and Care Excellence (NICE) recommend against the use of aspirin in people with type 1 or type 2 diabetes who do not have confirmed cardiovascular disease.

Surgery
Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long-term mortality is decreased. There is, however, a short-term mortality risk of less than 1% from the surgery. The body mass index cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.A pancreas transplant is occasionally considered for people with type 1 diabetes who have severe complications of their disease, including end stage kidney disease requiring kidney transplantation.

Self-management and support
In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care in a team approach. Home telehealth support can be an effective management technique.The use of technology to deliver educational programs for adults with type 2 diabetes includes computer-based self-management interventions to collect for tailored responses to facilitate self-management. There is no adequate evidence to support effects on cholesterol, blood pressure, behavioral change (such as physical activity levels and dietary), depression, weight and health-related quality of life, nor in other biological, cognitive or emotional outcomes.

Epidemiology
In 2017, 425 million people had diabetes worldwide, up from an estimated 382 million people in 2013 and from 108 million in 1980. Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980. Type 2 makes up about 90% of the cases. Some data indicate rates are roughly equal in women and men, but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.The WHO estimates that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death. However another 2.2 million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes. For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0 million deaths worldwide, using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries, where more than 80% of diabetic deaths occur. The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030. The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet). The global number of diabetes cases might increase by 48% between 2017 and 2045.

History
Diabetes was one of the first diseases described, with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine." The Ebers papyrus includes a recommendation for a drink to take in such cases. The first described cases are believed to have been type 1 diabetes. Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis. The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career. This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.Two types of diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500 CE with one type being associated with youth and another type with being overweight. Effective treatment was not developed until the early part of the 20th century when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922. This was followed by the development of the long-acting insulin NPH in the 1940s.

Etymology
The word diabetes ( or ) comes from Latin diabētēs, which in turn comes from Ancient Greek διαβήτης (diabētēs), which literally means "a passer through; a siphon". Ancient Greek physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease. Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through", which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go". The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.
The word mellitus ( or ) comes from the classical Latin word mellītus, meaning "mellite" (i.e. sweetened with honey; honey-sweet). The Latin word comes from mell-, which comes from mel, meaning "honey"; sweetness; pleasant thing, and the suffix -ītus, whose meaning is the same as that of the English suffix "-ite". It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a person with diabetes had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.

Society and culture
The 1989 "St. Vincent Declaration" was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economically – expenses due to diabetes have been shown to be a major drain on health – and productivity-related resources for healthcare systems and governments.
Several countries established more and less successful national diabetes programmes to improve treatment of the disease.People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.

Naming
The term "type 1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus. Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus. Beyond these two types, there is no agreed-upon standard nomenclature.Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.

Other animals
In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Coagulation factor VII and explain in detail? [/INST] Coagulation factor VII (EC 3.4.21.21, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene F7.  It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or blood-coagulation factor VIIa, activated blood coagulation factor VII), which in turn activates factor IX and factor X.
Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by the FDA for the control of bleeding in hemophilia. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market.
In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) approved in more than 2 decades. As an rFVIIa product, eptacog beta works in a complex with tissue factor to activate factor X to Xa, thereby bypassing FVIII and FIX. The activation of Factor X to Xa initiates the coagulation cascade’s common pathway, leading to clot formation at the site of hemorrhage. Activated FVII binds to endothelial protein C receptor (EPCR), which enhances hemostasis.14 One study showed that eptacog beta binds to EPCR with 25% to 30% more affinity than eptacog alfa, displacing protein C from EPCR binding sites and downregulating activated protein C generation, contributing to its hemostatic effect.

Physiology
The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with tissue factor (TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin (factor IIa), factor Xa, IXa, XIIa, and the FVIIa-TF complex itself </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Auditory processing disorder and explain in detail? [/INST] Auditory processing disorder (APD), rarely known as King-Kopetzky syndrome or auditory disability with normal hearing (ADN), is a neurodevelopmental disorder affecting the way the brain processes auditory information. Individuals with APD usually have normal structure and function of the outer, middle, and inner ear (peripheral hearing). However, they cannot process the information they hear in the same way as others do, which leads to difficulties in recognizing and interpreting sounds, especially the sounds composing speech. It is thought that these difficulties arise from dysfunction in the central nervous system. It is highly prevalent in individuals with other neurodevelopmental disorders, such as Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorders, Dyslexia, and Sensory Processing Disorder.
The American Academy of Audiology notes that APD is diagnosed by difficulties in one or more auditory processes known to reflect the function of the central auditory nervous system. It can affect both children and adults. Although the actual prevalence is currently unknown, it has been estimated to be 2–7% in children in US and UK populations. APD can continue into adulthood. Cooper and Gates (1991) estimated the prevalence of adult APD to be 10 to 20%. It has been reported that males are twice as likely to be affected by the disorder as females, and that prevalence is higher in the elderly and increases with age.Neurodevelopmental forms of APD are differentiable from aphasia in that aphasia is by definition caused by acquired brain injury, but acquired epileptic aphasia has been viewed as a form of APD.

Signs and symptoms
Many people experience problems with learning and day-to-day tasks with difficulties over time. Adults with this disorder can experience the signs and symptoms below:
talk louder than necessary
talk softer than necessary
have trouble remembering a list or sequence
often need words or sentences repeated
have poor ability to memorize information learned by listening
interpret words too literally
need assistance hearing clearly in noisy environments
rely on accommodation and modification strategies
find or request a quiet work space away from others
request written material when attending oral presentations
ask for directions to be given one step at a time

Relation to attention deficit hyperactivity disorder
It has been discovered that APD and ADHD present overlapping symptoms. Below is a ranked order of behavioral symptoms that are most frequently observed in each disorder. Professionals evaluated the overlap of symptoms between the two disorders. The order below is of symptoms that are almost always observed. This chart shows that although the symptoms listed are different, it is easy to get confused between many of them.
There is a co-occurrence between ADHD and APD. A systematic review published in 2018 detailed one study that showed 10% of children with APD have confirmed or suspected ADHD. It also stated that it is sometimes difficult to distinguish the two, since characteristics and symptoms between APD and ADHD tend to overlap. The systematic review mentioned here described this overlap between APD and other behavioral disorders and whether or not it was easy to distinguish those children that solely had auditory processing disorder.

Relation to specific language impairment and developmental dyslexia
There has been considerable debate over the relationship between APD and Specific language impairment (SLI).
SLI is diagnosed when a child has difficulties with understanding or producing spoken language for no obvious cause. The problems cannot be explained in terms of peripheral hearing loss. The child is typically late in starting to talk, and may have problems in producing speech sounds clearly, and in producing or understanding complex sentences. Some theoretical accounts of SLI regard it as the result of auditory processing problems. However, this view of SLI is not universally accepted, and others regard the main difficulties in SLI as stemming from problems with higher-level aspects of language processing. Where a child has both auditory and language problems, it can be difficult to sort out the causality at play.Similarly with developmental dyslexia, researchers continue to explore the hypothesis that reading problems emerge as a downstream consequence of difficulties in rapid auditory processing. Again, cause and effect can be hard to unravel. This is one reason why some experts have recommended using non-verbal auditory tests to diagnose APD. Specifically regarding neurological factors, dyslexia has been linked to polymicrogyria which causes cell migrational problems. Children that have polymicrogyri almost always present with deficits on APD testing. It has also been suggested that APD may be related to cluttering, a fluency disorder marked by word and phrase repetitions.
It has been found that a higher than expected proportion of individuals diagnosed with SLI and dyslexia on the basis of language and reading tests also perform poorly on tests in which auditory processing skills are tested. APD can be assessed using tests that involve identifying, repeating or discriminating speech, and a child may do poorly because of primary language problems. In a study comparing children with a diagnosis of dyslexia and those with a diagnosis of APD, they found the two groups could not be distinguished. Analogous results were observed in studies comparing children diagnosed with SLI or APD, the two groups presenting with similar diagnostic criteria. As such, the diagnosis a child receives may depend on which specialist they consult: the same child who might be diagnosed with APD by an audiologist may instead be diagnosed with SLI by a speech-language therapist or with dyslexia by a psychologist.

Causes
Acquired
Acquired APD can be caused by any damage to or dysfunction of the central auditory nervous system and can cause auditory processing problems. For an overview of neurological aspects of APD, see T. D. Griffiths 2002 article "Central Auditory Pathologies".

Genetics
Some studies have indicated an increased prevalence of a family history of hearing impairment in these patients. The pattern of results is suggestive that auditory processing disorder may be related to conditions of autosomal dominant inheritance. The ability to listen to and comprehend multiple messages at the same time is a trait that is heavily influenced by our genes, say federal researchers. These "short circuits in the wiring" sometimes run in families or result from a difficult birth, just like any learning disability. Auditory processing disorder can be associated with conditions affected by genetic traits, such as various developmental disorders. Inheritance of auditory processing disorder refers to whether the condition is inherited from your parents or "runs" in families.  Central auditory processing disorder may be hereditary neurological traits from the mother or the father.

Developmental
In the majority of cases of developmental APD, the cause is unknown. An exception is acquired epileptic aphasia or Landau-Kleffner syndrome, where a childs development regresses, with language comprehension severely affected. The child is often thought to be deaf, but normal peripheral hearing is found. In other cases, suspected or known causes of APD in children include delay in myelin maturation, ectopic (misplaced) cells in the auditory cortical areas, or genetic predisposition. In a family with autosomal dominant epilepsy, seizures which affected the left temporal lobe seemed to cause problems with auditory processing. In another extended family with a high rate of APD, genetic analysis showed a haplotype in chromosome 12 that fully co-segregated with language impairment.Hearing begins in utero, but the central auditory system continues to develop for at least the first decade. There is considerable interest in the idea that disruption to hearing during a sensitive period may have long-term consequences for auditory development. One study showed thalamocortical connectivity in vitro was associated with a time sensitive developmental window and required a specific cell adhesion molecule (lcam5) for proper brain plasticity to occur. This points to connectivity between the thalamus and cortex shortly after being able to hear (in vitro) as at least one critical period for auditory processing. Another study showed that rats reared in a single tone environment during critical periods of development had permanently impaired auditory processing. Bad auditory experiences, such as temporary deafness by cochlear removal in rats leads to neuron shrinkage. In a study looking at attention in APD patients, children with one ear blocked developed a strong right-ear advantage but were not able to modulate that advantage during directed-attention tasks.In the 1980s and 1990s, there was considerable interest in the role of chronic Otitis media (middle ear disease or glue ear) in causing APD and related language and literacy problems. Otitis media with effusion is a very common childhood disease that causes a fluctuating conductive hearing loss, and there was concern this may disrupt auditory development if it occurred during a sensitive period. Consistent with this, in a sample of young children with chronic ear infections recruited from a hospital otolargyngology department, increased rates of auditory difficulties were found later in childhood. However, this kind of study will have sampling bias because children with otitis media will be more likely to be referred to hospital departments if they are experiencing developmental difficulties. Compared with hospital studies, epidemiological studies, which assesses a whole population for otitis media and then evaluate outcomes, have found much weaker evidence for long-term impacts of otitis media on language outcomes.

Somatic
It seems that somatic anxiety (that is, physical symptoms of anxiety such as butterflies in the stomach or cotton mouth) and situations of stress may be determinants of speech-hearing disability.

Diagnosis
Questionnaires can be used for the identification of persons with possible auditory processing disorders, as these address common problems of listening. They can help in the decision for pursuing clinical evaluation. One of the most common listening problems is speech recognition in the presence of background noise. According to the respondents who participated in a study by Neijenhuis, de Wit, and Luinge (2017), the following symptoms are characteristic in children with listening difficulties, and they are typically problematic with adolescents and adults. They include:
Difficulty hearing in noise
Auditory attention problems
Better understanding in one on one situations
Difficulties in noise localization
Difficulties in remembering oral informationAccording to the New Zealand Guidelines on Auditory Processing Disorders (2017) a checklist of key symptoms of APD or comorbidities that can be used to identify individuals who should be referred for audiological and APD assessment includes, among others:

Difficulty following spoken directions unless they are brief and simple
Difficulty attending to and remembering spoken information
Slowness in processing spoken information
Difficulty understanding in the presence of other sounds
Overwhelmed by complex or "busy" auditory environments e.g. classrooms, shopping malls
Poor listening skills
Insensitivity to tone of voice or other nuances of speech
Acquired brain injury
History of frequent or persistent middle ear disease (otitis media, glue ear).
Difficulty with language, reading or spelling
Suspicion or diagnosis of dyslexia
Suspicion or diagnosis of language disorder or delayFinally, the New Zealand guidelines state that behavioral checklists and questionnaires should only be used to provide guidance for referrals, for information gathering (for example, prior to assessment or as outcome measures for interventions), and as measures to describe the functional impact of auditory processing disorder.  They are not designed for the purpose of diagnosing auditory processing disorders. The New Zealand guidelines indicate that a number of questionnaires have been developed to identify children who might benefit from evaluation of their problems in listening.  Examples of available questionnaires include the Fishers Auditory Problems Checklist, the Childrens Auditory Performance Scale, the Screening Instrument for Targeting Educational Risk, and the Auditory Processing Domains Questionnaire among others. All of the previous questionnaires were designed for children and none are useful for adolescents and adults.The University of Cincinnati Auditory Processing Inventory (UCAPI) was designed for use with adolescents and adults seeking  testing for evaluation of problems with listening and/or to be used following diagnosis of an auditory processing disorder to determine the subjects status.  Following a model described by Zoppo et al. (2015) a 34-item questionnaire was developed that investigates auditory processing abilities in each of the six common areas of complaint in APD (listening and concentration, understanding speech, following spoken instructions, attention, and other.)  The final questionnaire was standardized on normally-achieving young adults ranging from 18 to 27 years of age.  Validation data was acquired from subjects with language-learning or auditory processing disorders who were either self-reported or confirmed by diagnostic testing.  A UCAPI  total score is calculated by combining the totals from the six listening conditions and provides an overall value to categorize listening abilities. Additionally, analysis of the scores from the six listening conditions provides an auditory profile for the subject. Each listening condition can then be utilized by the professional in making recommendation for diagnosing problem of learning through listening and treatment decisions.  The UCAPI provides information on listening problems in various populations that can aid examiners in making recommendations for assessment and management.APD has been defined anatomically in terms of the integrity of the auditory areas of the nervous system. However, children with symptoms of APD typically have no evidence of neurological disease and the diagnosis is made on the basis of performance on behavioral auditory tests. Auditory processing is "what we do with what we hear", and in APD there is a mismatch between peripheral hearing ability (which is typically normal) and ability to interpret or discriminate sounds. Thus in those with no signs of neurological impairment, APD is diagnosed on the basis of auditory tests. There is, however, no consensus as to which tests should be used for diagnosis, as evidenced by the succession of task force reports that have appeared in recent years. The first of these occurred in 1996. This was followed by a conference organized by the American Academy of Audiology.Experts attempting to define diagnostic criteria have to grapple with the problem that a child may do poorly on an auditory test for reasons other than poor auditory perception: for instance, failure could be due to inattention, difficulty in coping with task demands, or limited language ability. In an attempt to rule out at least some of these factors, the American Academy of Audiology conference explicitly advocated that for APD to be diagnosed, the child must have a modality-specific problem, i.e. affecting auditory but not visual processing. However, a committee of the American Speech-Language-Hearing Association subsequently rejected modality-specificity as a defining characteristic of auditory processing disorders.

Definitions
in 2005 The American Speech-Language-Hearing Association (ASHA) published "Central Auditory Processing Disorders" as an update to the 1996 "Central Auditory Processing: Current Status of Research and Implications for Clinical Practice". The American Academy of Audiology has released more current practice guidelines related to the disorder. ASHA formally defines APA as "a difficulty in the efficiency and effectiveness by which the central nervous system (CNS) utilizes auditory information."In 2018, the British Society of Audiology published a position statement and practice guidance on auditory processing disorder (APD) updated its definition of APD. According to the Society, APD refers to the inability to process speech and on-speech sounds.Auditory processing disorder can be developmental or acquired. It may result from ear infections, head injuries or neurodevelopmental delays that affect processing of auditory information. This can include problems with: "...sound localization and lateralization (see also binaural fusion); auditory discrimination; auditory pattern recognition; temporal aspects of audition, including temporal integration, temporal discrimination (e.g., temporal gap detection), temporal ordering, and temporal masking; auditory performance in competing acoustic signals (including dichotic listening); and auditory performance with degraded acoustic signals".The Committee of UK Medical Professionals Steering the UK Auditory Processing Disorder Research Program have developed the following working definition of auditory processing disorder: "APD results from impaired neural function and is characterized by poor recognition, discrimination, separation, grouping, localization, or ordering of speech sounds. It does not solely result from a deficit in general attention, language or other cognitive processes."

Types of testing
The SCAN-C for children and SCAN-A for adolescents and adults are the most common tools for screening and diagnosing APD in the USA.   Both tests are standardized on a large number of subjects and include validation data on subjects with auditory processing disorders.   The SCAN test batteries include screening tests: norm-based criterion-referenced scores; diagnostic tests: scaled scores, percentile ranks and ear advantage scores for all tests except the Gap Detection test.  The four tests include four subsets on which the subject scores are derived include: discrimination of monaurally presented single words against background noise (speech in noise), acoustically degraded single words (filtered words), dichotically presented single words and sentences.
Random Gap Detection Test (RGDT) is also a standardized test. It assesses an individuals gap detection threshold of tones and white noise. The exam includes stimuli at four different frequencies (500, 1000, 2000, and 4000 Hz) and white noise clicks of 50 ms duration. It is a useful test because it provides an index of auditory temporal resolution. In children, an overall gap detection threshold greater than 20 ms means they have failed and may have an auditory processing disorder based on abnormal perception of sound in the time domain.
Gaps in Noise Test (GIN) also measures temporal resolution by testing the patients gap detection threshold in white noise.
Pitch Patterns Sequence Test (PPT) and Duration Patterns Sequence Test (DPT) measure auditory pattern identification. The PPS has s series of three tones presented at either of two pitches (high or low). Meanwhile, the DPS has a series of three tones that vary in duration rather than pitch (long or short). Patients are then asked to describe the pattern of pitches presented.
Masking Level Difference (MLD) at 500 Hz measures overlapping temporal processing, binaural processing, and low-redundancy by measuring the difference in threshold of an auditory stimulus when a masking noise is presented in and out of phase.
The Staggered Spondaic Word Test (SSW) is one of the oldest tests for APD developed by Jack Katz. Although it has fallen into some disuse by audiologists as it is complicated to score, it is one of the quickest and most sensitive tests to determine APD.

Modality-specificity and controversies
The issue of modality-specificity has led to considerable debate among experts in this field.  Cacace and McFarland have argued that APD should be defined as a modality-specific perceptual dysfunction that is not due to peripheral hearing loss. They criticise more inclusive conceptualizations of APD as lacking diagnostic specificity. A requirement for modality-specificity could potentially avoid including children whose poor auditory performance is due to general factors such as poor attention or memory. Others, however, have argued that a modality-specific approach is too narrow, and that it would miss children who had genuine perceptual problems affecting both visual and auditory processing. It is also impractical, as audiologists do not have access to standardized tests that are visual analogs of auditory tests. The debate over this issue remains unresolved between modality-specific researchers such as Cacace, and associations such as the American Speech-Language-Hearing Association (among others). It is clear, however, that a modality-specific approach will diagnose fewer children with APD than a modality-general one, and that the latter approach runs a risk of including children who fail auditory tests for reasons other than poor auditory processing. Although modality-specific testing has been advocated for well over a decade, the visual analog of APD testing has met with sustained resistance from the fields of optometry and ophthalmology.Another controversy concerns the fact that most traditional tests of APD use verbal materials. The British Society of Audiology has embraced Moores (2006) recommendation that tests for APD should assess processing of non-speech sounds. The concern is that if verbal materials are used to test for APD, then children may fail because of limited language ability. An analogy may be drawn with trying to listen to sounds in a foreign language. It is much harder to distinguish between sounds or to remember a sequence of words in a language you do not know well: the problem is not an auditory one, but rather due to lack of expertise in the language.In recent years there have been additional criticisms of some popular tests for diagnosis of APD. Tests that use tape-recorded American English have been shown to over-identify APD in speakers of other forms of English. Performance on a battery of non-verbal auditory tests devised by the Medical Research Councils Institute of Hearing Research was found to be heavily influenced by non-sensory task demands, and indices of APD had low reliability when this was controlled for. This research undermines the validity of APD as a distinct entity in its own right and suggests that the use of the term "disorder" itself is unwarranted. In a recent review of such diagnostic issues, it was recommended that children with suspected auditory processing impairments receive a holistic psychometric assessment including general intellectual ability, auditory memory, and attention, phonological processing, language, and literacy. The authors state that "a clearer understanding of the relative contributions of perceptual and non-sensory, unimodal and supramodal factors to performance on psychoacoustic tests may well be the key to unravelling the clinical presentation of these individuals."Depending on how it is defined, APD may share common symptoms with ADD/ADHD, specific language impairment, and autism spectrum disorders. A review showed substantial evidence for atypical processing of auditory information in children with autism. Dawes and Bishop noted how specialists in audiology and speech-language pathology often adopted different approaches to child assessment, and they concluded their review as follows: "We regard it as crucial that these different professional groups work together in carrying out assessment, treatment and management of children and undertaking cross-disciplinary research."  In practice, this seems rare.To ensure that APD is correctly diagnosed, the examiners must differentiate APD from other disorders with similar symptoms. Factors that should be taken into account during the diagnosis are: attention, auditory neuropathy, fatigue, hearing and sensitivity, intellectual and developmental age, medications, motivation, motor skills, native language and language experience, response strategies and decision-making style, and visual acuity.It should also be noted that children under the age of seven cannot be evaluated correctly because their language and auditory processes are still developing. In addition, the presence of APD cannot be evaluated when a childs primary language is not English.

Characteristics
The American Speech-Language-Hearing Association state that children with (central) auditory processing disorder often:

have trouble paying attention to and remembering information presented orally, and may cope better with visually acquired information
have problems carrying out multi-step directions given orally; need to hear only one direction at a time
have poor listening skills
need more time to process information
have difficulty learning a new language
have difficulty understanding jokes, sarcasm, and learning songs or nursery rhymes
have language difficulties (e.g., they confuse syllable sequences and have problems developing vocabulary and understanding language)
have difficulty with reading, comprehension, spelling, and vocabularyAPD can manifest as problems determining the direction of sounds, difficulty perceiving differences between speech sounds and the sequencing of these sounds into meaningful words, confusing similar sounds such as "hat" with "bat", "there" with "where", etc.  Fewer words may be perceived than were actually said, as there can be problems detecting the gaps between words, creating the sense that someone is speaking unfamiliar or nonsense words. In addition, it is common for APD to cause speech errors involving the distortion and substitution of consonant sounds. Those with APD may have problems relating what has been said with its meaning, despite obvious recognition that a word has been said, as well as repetition of the word.  Background noise, such as the sound of a radio, television or a noisy bar can make it difficult to impossible to understand speech, since spoken words may sound distorted either into irrelevant words or words that dont exist, depending on the severity of the auditory processing disorder. Using a telephone can be problematic for someone with auditory processing disorder, in comparison with someone with normal auditory processing, due to low quality audio, poor signal, intermittent sounds and the chopping of words. Many who have auditory processing disorder subconsciously develop visual coping strategies, such as lip reading, reading body language, and eye contact, to compensate for their auditory deficit, and these coping strategies are not available when using a telephone.As noted above, the status of APD as a distinct disorder has been queried, especially by speech-language pathologists and psychologists, who note the overlap between clinical profiles of children diagnosed with APD and those with other forms of specific learning disability. Many audiologists, however, would dispute that APD is just an alternative label for dyslexia, SLI, or ADHD, noting that although it often co-occurs with these conditions, it can be found in isolation.

Subcategories
Based on sensitized measures of auditory dysfunction and on psychological assessment, patients can be subdivided into seven subcategories:
middle ear dysfunction
mild cochlear pathology
central/medial olivocochlear efferent system (MOCS) auditory dysfunction
purely psychological problems
multiple auditory pathologies
combined auditory dysfunction and psychological problems
unknownDifferent subgroups may represent different pathogenic and aetiological factors. Thus, subcategorization provides further understanding of the basis of auditory processing disorder, and hence may guide the rehabilitative management of these patients. This was suggested  by Professor Dafydd Stephens and F Zhao at the Welsh Hearing Institute, Cardiff University.

Treatment
Treatment of APD typically focuses on three primary areas: changing learning environment, developing higher-order skills to compensate for the disorder, and remediation of the auditory deficit itself. However, there is a lack of well-conducted evaluations of intervention using randomized controlled trial methodology. Most evidence for effectiveness adopts weaker standards of evidence, such as showing that performance improves after training. This does not control for possible influences of practice, maturation, or placebo effects. Recent research has shown that practice with basic auditory processing tasks (i.e. auditory training) may improve performance on auditory processing measures and phonemic awareness measures.  Changes after auditory training have also been recorded at the physiological level. Many of these tasks are incorporated into computer-based auditory training programs such as Earobics and Fast ForWord, an adaptive software available at home and in clinics worldwide,  but overall, evidence for effectiveness of these computerised interventions in improving language and literacy is not impressive. One small-scale uncontrolled study reported successful outcomes for children with APD using auditory training software.Treating additional issues related to APD can result in success. For example, treatment for phonological disorders (difficulty in speech) can result in success in terms of both the phonological disorder as well as APD. In one study, speech therapy improved auditory evoked potentials (a measure of brain activity in the auditory portions of the brain).While there is evidence that language training is effective for improving APD, there is no current research supporting the following APD treatments:

Auditory Integration Training typically involves a child attending two 30-minute sessions per day for ten days.
Lindamood-Bell Learning Processes (particularly, the Visualizing and Verbalizing program)
Physical activities that require frequent crossing of the midline (e.g., occupational therapy)
Sound Field Amplification
Neuro-Sensory Educational Therapy
NeurofeedbackHowever, use of an individual FM transmitter/receiver system by teachers and students has been shown to produce significant improvements with children over time.

History
Samuel J. Kopetzky first described the condition in 1948. P. F. King, first discussed the etiological factors behind it in 1954. Helmer Rudolph Myklebusts 1954 study, "Auditory Disorders in Children". suggested auditory processing disorder was separate from language learning difficulties </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Williams syndrome and explain in detail? [/INST] Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people with WS, with particular challenges with visual spatial tasks such as drawing. Verbal skills are relatively unaffected. Many people with WS have an outgoing personality, an openness to engaging with other people, and a happy disposition. Medical issues with teeth, heart problems (especially supravalvular aortic stenosis), and periods of high blood calcium are common.Williams syndrome is caused by a genetic abnormality, specifically a deletion of about 27 genes from the long arm of one of the two chromosome 7s. Typically, this occurs as a random event during the formation of the egg or sperm from which a person develops. In a small number of cases, it is inherited from an affected parent in an autosomal dominant manner. The different characteristic features have been linked to the loss of specific genes. The diagnosis is typically suspected based on symptoms and confirmed by genetic testing.Treatment of WS includes special education programs and various types of therapy. Surgery may be done to correct heart problems. Dietary changes or medications may be required for high blood calcium. The syndrome was first described in 1961 by New Zealander John C. P. Williams. Williams syndrome affects between one in 20,000 and one in 7,500 people at birth. Life expectancy is less than that of the general population, mostly due to the increased rates of heart disease.

Signs and symptoms
The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. People with WS tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.Most people with WS are highly verbal relative to their intelligence, and are often very sociable, having what has been described as a "cocktail party"-type personality.  People with Williams syndrome hyperfocus on the eyes of others in social engagements.

Physical
People with WS experience many cardiac problems, commonly heart murmurs and the narrowing of major blood vessels, as well as supravalvular aortic stenosis. Other symptoms may include gastrointestinal problems, such as severe or prolonged colic, abdominal pain and diverticulitis, nocturnal enuresis (bed wetting) and urinary difficulties, dental irregularities and defective tooth enamel, and hormone problems, the most common being hypercalcemia. Hypothyroidism has been reported to occur in children, although no proof has been found of it occurring in adults; adults with WS have a higher risk of developing type-2 diabetes, with some cases apparent as young as 21 years old.People with WS often have hyperacusia and phonophobia, which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve.  People with WS can also tend to demonstrate a love of music, and they appear significantly more likely to possess absolute pitch. Also, higher prevalences of left-handedness and left-eye dominance seem to occur.Ophthalmologic issues are common in WS.  Up to 75% of subjects in some studies have strabismus (ocular misalignment), particularly esotropia, due to inherent subnormal binocular visual function
and cognitive deficits in visuospatial construction. People with WS have problems with visual processing, but this is related to difficulty in dealing with complex spatial relationships rather than depth perception per se.

Nervous system
Because of missing multiple genes, many effects on the brain are seen, including abnormalities in the cerebellum, right parietal lobe, and left frontal cortical regions.  This pattern is consistent with the visual-spatial disabilities and problems with behavioral timing often seen in WS.Frontal-cerebellar pathways, involved in behavioral timing, are often abnormally developed in people with WS, which may be related to their deficits in coordination and execution of fine motor tasks such as drawing and writing. In addition, people with WS often exhibit gross motor difficulties, including trouble walking downstairs,  overactive motor reflexes (hyperreflexia), and hyperactive, involuntary movement of the eyes (nystagmus).Williams syndrome is also noteworthy for exhibiting abnormalities in the parietal-dorsal areas of the neocortex, but not the ventral areas. The parietal-dorsal area handles visual processing that supports visual-spatial analysis of the environment, while the ventral is related to semantic recognition of visual stimuli, and the recognition of faces. Thus, people with WS are often able to visually identify and recognize whole objects, and refer to them by name, but struggle with visuospatial construction (seeing an object as being composed of many smaller parts, and recreating it) and orienting themselves in space.People with WS are often affable and hyperverbal, demonstrating the decreased inhibition ability that stems from dorsal-frontal deficits. Some studies suggest that the amygdala of a person with Williams syndrome has greater volume than the average persons (though it is smaller than average in childhood).
In general, neuroimaging studies demonstrate that people with WS have diminished amygdala reactivity in response to socially frightening stimuli (such as disapproving faces), but demonstrate hyperreactivity in the amygdala when presented with nonsocial fear stimuli (such as frightening animals). This may partially account for the apparent absence of social inhibition observed in people with the syndrome, as well as the prevalence of anxious symptoms (but see fear for details on the relationship between the amygdala and fear response). Also, some evidence indicates that people with WS exhibit  amygdalal hyperactivity when viewing happy facial expressions. They are talkative and eager to please, indicating a cocktail party personality.Increased volume and activation of the left auditory cortex has been observed in people with WS, which has been interpreted as a neural correlation of patients rhythm propensity and fondness of music. Similar sizes of the auditory cortex have been previously reported only in professional musicians.

Development
The earliest observable symptoms of WS include low birth weight, failure to thrive, trouble breastfeeding, nocturnal irritability, and gastroesophageal reflux. Facial dysmorphies thought to be characteristic of the syndrome are also present early in development, as are heart murmurs. Research on the development of the syndrome suggests that congenital heart disease is typically present at an early age, often at the infants first pediatric appointment. Heart problems in infancy often lead to the initial diagnosis of WS.Developmental delays are present in most cases of WS, and include delay of language abilities and delayed motor-skill development. People with WS develop language abilities quite late relative to other children, with the childs first word often occurring as late as 3 years of age. Language abilities are often observed to be deficient until adolescence, in terms of semantics, morphology, and phonology, though not in vocabulary.Williams syndrome is also marked by a delay in the development of motor skills. Infants with WS develop the ability to lift their heads and sit without support months later than typically developing children. These delays continue into childhood, where patients with WS are delayed in learning to walk. In young children, the observed motor delay is around 5–6 months, though some research suggests that children with WS have a delay in development that becomes more extreme with age. Children with motor delays as a result of WS are particularly behind in the development of coordination, fine motor skills such as writing and drawing, response time, and strength and dexterity of the arms. Impaired motor ability persists (and possibly worsens) as children with WS reach adolescence.Adults and adolescents with Williams syndrome typically achieve a below-average height and weight, compared with unaffected populations. As people with WS age, they frequently develop joint limitations and hypertonia, or abnormally increased muscle tone. Hypertension, gastrointestinal problems, and genitourinary symptoms often persist into adulthood, as well as cardiovascular problems. Adults  are typically limited in their ability to live independently or work in competitive employment settings, but this developmental impairment is attributed more to psychological symptoms than physiological problems.

Social and psychological
People with Williams syndrome report higher anxiety levels as well as phobia development, which may be associated with hyperacusis (high sensitivity to certain frequencies of sound). Compared with other children with delays, those with Williams syndrome display a significantly greater number of fears. 35% of these children met the DSM definition of having a phobia as compared with 1–4.3% for those with other types of developmental delays. Williams syndrome is also strongly associated with attention deficit hyperactivity disorder and related psychological symptoms such as poor concentration, hyperactivity, and social disinhibition.Furthermore, cognitive abilities (IQs) of people with WMS typically range from mild to moderate levels of intellectual disability. One study of 306 children with Williams syndrome found IQ scores ranging from 40 to 112 with a mean of 69.32 (the mean IQ score of the general population is 100). IQ scores above this range have been reported in people with smaller genetic deletions. In particular, people with Williams syndrome experience challenges in visual-motor skills and visuospatial construction. Most affected people are unable to spatially orient themselves and many experience difficulty when given a task that requires even the most basic visual problem-solving. Many adults with Williams syndrome cannot complete a simple six-piece puzzle designed for young children, for example. These visuospatial deficits may be related to damage to the dorsal cortical pathway for visual processing.Despite their physical and cognitive deficits, people with Williams syndrome exhibit impressive social and verbal abilities.  Williams patients can be highly verbal relative to their IQ. When children with Williams syndrome are asked to name an array of animals, they may well list a wild assortment of creatures such as a koala, saber-toothed cat, vulture, unicorn, sea lion, yak, ibex and Brontosaurus, a far greater verbal array than would be expected of children with IQs in the 60s.  Some other strengths that have been associated with Williams syndrome are auditory short-term memory and facial recognition skills. The language used by people with Williams syndrome differs notably from unaffected populations, including people matched for IQ. People with Williams syndrome tend to use speech that is rich in emotional descriptors, high in prosody (exaggerated rhythm and emotional intensity), and features unusual terms and strange idioms.Among the hallmark traits of people with Williams syndrome is an apparent lack of social inhibition. Dykens and Rosner (1999) found that 100% of those with Williams syndrome were kind-spirited, 90% sought the company of others, 87% empathize with others pain, 84% are caring, 83% are unselfish/forgiving, 75% never go unnoticed in a group, and 75% are happy when others do well.  Infants with Williams syndrome make normal and frequent eye contact, and young children with Williams will often approach and hug strangers. People affected by Williams syndrome typically have high empathy, showing relative strength in reading peoples eyes to gauge intentions, emotions, and mental states. The level of friendliness observed in people with Williams is often inappropriate for the social setting, however,  and teens and adults with Williams syndrome often experience social isolation, frustration, and loneliness despite their clear desire to connect to other people.While these children often came off as happy due to their sociable nature, often there are internal drawbacks to the way they act. 76–86% of these children were reported as believing that they either had few friends or problems with their friends. This is possibly due to the fact that although they are very friendly to strangers and love meeting new people, they may have trouble interacting on a deeper level. 73–93% were reported as unreserved with strangers, 67% highly sensitive to rejection, 65% susceptible to teasing, and the statistic for exploitation and abuse was unavailable. There are external problems as well. 91–96% demonstrate inattention, 75% impulsivity, 59–71% hyperactivity 46–74% tantrums, 32–60% disobedience, and 25–37% fighting and aggressive behavior.In one experiment, a group of children with Williams syndrome showed no signs of racial bias, unlike children without the syndrome. They did show gender bias, however, to a similar degree to children without the syndrome, suggesting separate mechanisms for these biases.

Cause
Williams syndrome is a microdeletion syndrome caused by the spontaneous deletion of genetic material from the chromosomal region 7q11.23. This is a hemizygous deletion, which results in haploinsufficient expression of the 25–27 genes in this region. CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes typically deleted. Hemizygosity for the ELN gene, which codes for the extracellular matrix protein elastin, is associated with connective-tissue abnormalities and cardiovascular disease (specifically supravalvular aortic stenosis and supravalvular pulmonary stenosis). Elastin insufficiency may also contribute to distinct faces, harsh or hoarse voice, hernias, and bladder diverticula often found in those with Williams syndrome. Hemizygosity in LIMK1, GTF2I, GTF2IRD1, and perhaps other genes may help explain the characteristic difficulties with visual–spatial tasks. Additionally, some evidence shows that the hemizygosity in several of these genes, including CLIP2, may contribute to the unique behavioral characteristics, learning disabilities, and other cognitive difficulties seen in WS.

Diagnosis
According to the Williams Syndrome Association, its diagnosis begins with the recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of WS include puffiness around the eyes, a long philtrum, and a stellate pattern in the iris. Physiological symptoms that often contribute to a WS diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, and feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.If a physician suspects a case of WS, the diagnosis is confirmed using one of two possible genetic tests: Micro-array analysis or the fluorescent in situ hybridization test, which examines chromosome 7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with WS lack half of the 7q11.23 region of chromosome 7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of WS.  This confirmatory genetic test has been validated in epidemiological studies  and has been demonstrated to be a more effective method of identifying WS than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).Reliance on facial features to identify WS may cause a misdiagnosis of the condition. Among the more reliable features suggestive of WS are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long, smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Even with significant clinical experience,  reliably identifying Williams syndrome based on facial features alone is difficult.This is particularly the case in individuals of non-white backgrounds, where typical WS facial features (such as full lips) are more prevalent.

Treatment
No cure for Williams syndrome has been found. Suggested treatments include avoidance of extra calcium and vitamin D, and treating high levels of blood calcium. Blood-vessel narrowing can be a significant health problem and is treated on an individual basis.
Physical therapy is helpful to patients with joint stiffness and low muscle tone. Developmental and speech therapy can also help children and increase the success of their social interactions. Other treatments are based on a patients particular symptoms.The American Academy of Pediatrics recommends annual cardiology evaluations for individuals with WS. Other recommended assessments include ophthalmologic evaluations, an examination for inguinal hernia, objective hearing assessment, blood-pressure measurement, developmental and growth evaluation, orthopedic assessments on joints and muscle tone, and ongoing feeding and dietary assessments to manage constipation and urinary problems.Behavioral treatments have been shown to be effective. In regards to social skills, it may be effective to channel their nature by teaching basic skills. Some of these are the appropriate way to approach someone, how and when to socialize in settings such as school or the workplace, and warning of the signs and dangers of exploitation. For the fear that they demonstrate cognitive-behavioral approaches, such as therapy, they are the recommended treatments. One of the things to be careful of with this approach is to make sure that the patients charming nature does not mask any underlying feelings.Perhaps the most effective treatment for those with WS is music. Those affected have shown relative strength in regards to music, albeit only in pitch and rhythm tasks. Not only do they show strength in the field, but also a particular fondness for it. Music may help with the internal and external anxiety with which these people are more likely to be afflicted. Notably, the typical person processes music in the superior temporal and middle temporal gyri. Those with WS have reduced activation in these areas, but an increase in the right amygdala and cerebellum.People affected by WS are supported by multiple organizations, including the Canadian Association for Williams Syndrome and the Williams Syndrome Registry.

Epidemiology
Williams syndrome has historically been estimated to occur in roughly one in every 20,000 live births, but  more recent epidemiological studies have placed the occurrence rate at closer to one in every 7,500 live births, a significantly larger prevalence. As increasing evidence suggests WS is more common than originally noted (about 6% of all genetic cases of developmental disability), researchers have begun to theorize past underdiagnosis of the syndrome. One theorized reason for the increase in epidemiological estimates is that a substantial minority of individuals with the genetic markers of WS syndrome lack the characteristic facial features or the diminished intelligence  considered to be diagnostic of the syndrome, and often are not immediately recognized as having the syndrome.

History
Williams syndrome was first described by J. C. P. Williams and his colleagues, who wrote in 1961 of four patients with supravalvular aortic stenosis, mental disability, and facial features including a broad forehead, large chin, low-set, "drooping" cheeks, widely spaced eyes, and wide-set mouth. A year after this report, German physician A. J. Beuren described three new patients with the same presentation. This led to the syndromes full original name, Williams-Beuren syndrome, which is still used in some medical publications. From 1964 to 1975, small research reports broadened medical knowledge of this syndromes cardiovascular problems. Then in 1975, K. Jones and D. Smith conducted a large-scale report on numerous patients with WS, ranging in age from infancy to adulthood, and described the behavioral and observable physical symptoms in greater detail than previously recorded.

Society and culture
The adjective "elfin" may have originated to describe the facial features of people with WS; before its scientific cause was understood, people believed that individuals with the syndrome, who have exceptionally charming and kind personalities, had extraordinary, even magical, powers. This has been proposed to be the origin of the folklore of elves, fairies, and other forms of the good people or wee folk present in English folklore.In a review of the symptoms and features of the syndrome, Laskari, Smith, and Graham emphasized that many family members of individuals with WS reject use of terminology such as "elfin", as well as descriptions of social symptoms as "cocktail party syndrome". Physicians, family members of individuals with WS syndrome, and WS associations alike have called for the curtailment of such terms.One notable person with the syndrome is Gabrielle Marion-Rivard, a Canadian actress and singer who won the Canadian Screen Award for Best Actress in 2014 for her performance in the film Gabrielle. Another is Jeremy Vest, member of the Hows Your News? team, featured in the TV series and film of the same name.

Further reading
Articles
Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.; Reiss, Allan L. (2012). "Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome". Current Opinion in Neurology (Review). 25 (2): 112–24. doi:10.1097/WCO.0b013e328351823c. PMC 3680360. PMID 22395002.
Karmiloff-Smith, A.; dSouza, D.; Dekker, T. M.; Van Herwegen, J.; Xu, F.; Rodic, M.; Ansari, D. (2012). "Genetic and environmental vulnerabilities in children with neurodevelopmental disorders". Proceedings of the National Academy of Sciences (Review). 109: 17261–5. Bibcode:2012PNAS..109S7261K. doi:10.1073/pnas.1121087109. JSTOR 41763522. PMC 3477396. PMID 23045661.
Kitagawa, Hirochika; Fujiki, Ryoji; Yoshimura, Kimihiro; Oya, Hiroyuki; Kato, Shigeaki (2011). "Williams syndrome is an epigenome-regulator disease". Endocrine Journal (Review). 58 (2): 77–85. doi:10.1507/endocrj.k10e-393 </s>