title: P. V. Narasimha Rao

text: In the year 2019, an independent biographical documentary film named "P V: Change with Continuity" (2019) directed and produced by Sravani Kotha and Srikar Reddy Gopaladinne released on the streaming platform Vimeo. The documentary features rare archival footage and interviews of several distinguished people closely related to Rao's life and work.


title: P. V. Narasimha Rao

text: Suresh Kumar appeared as Rao in the 2019 film "" directed by Krish which chart the life of the Indian actor-politician N. T. Rama Rao. The same year, Ajit Satbhai portrayed Rao as the former Prime Minister of India in the film "The Accidental Prime Minister" by Vijay Gutte, about Manmohan Singh.


title: P. V. Narasimha Rao

text: "Pradhanmantri" (), a 2013 Indian docudrama television series which aired on ABP News and covers the various policies and political tenures of Indian PMs, based the twentieth episode - "P. V. Narasimha Rao and Corruption charges against him" - on his term as the country's leader; Ravi Jhankal portrayed the role of Rao.


title: P. V. Narasimha Rao

text: Rao was awarded the Pratibha Murthy Lifetime Achievement Award. Many people across the party line supported the name of P. V. Narasimha Rao for Bharat Ratna. Telangana Chief Minister K. Chandrashekhar Rao supported the move to give Bharat Ratna to Rao. BJP leader Subramanian Swamy supported the move to give Bharat Ratna to Rao. According to Sanjay Baru, PM Manmohan Singh wanted to give Bharat Ratna to Rao during his tenure but failed.


title: P. V. Narasimha Rao

text: In September 2020, Telangana Legislative Assembly adopted a resolution seeking to confer Bharat Ratna on Rao. The resolution also requested the Central Government to rename the University of Hyderabad after him.


title: Prader–Willi syndrome

text: Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become constantly hungry, which often leads to obesity and type 2 diabetes. Mild to moderate intellectual impairment and behavioral problems are also typical of the disorder. Often, affected individuals have a narrow forehead, small hands and feet, short height, and light skin and hair. Most are unable to have children.


title: Prader–Willi syndrome

text: About 74% of cases occur when part of the father's chromosome 15 is deleted. In another 25% of cases, the affected person has two copies of the maternal chromosome 15 from the mother and lacks the paternal copy. As parts of the chromosome from the mother are turned off through imprinting, they end up with no working copies of certain genes. PWS is not generally inherited, but rather the genetic changes happen during the formation of the egg, sperm, or in early development. No risk factors are known for the disorder. Those who have one child with PWS have less than a 1% chance of the next child being affected. A similar mechanism occurs in Angelman syndrome, except the defective chromosome 15 is from the mother, or two copies are from the father.


title: Prader–Willi syndrome

text: Prader–Willi syndrome has no cure. Treatment may improve outcomes, especially if carried out early. In newborns, feeding difficulties may be supported with feeding tubes. Strict food supervision is typically required, starting around the age of three, in combination with an exercise program. Growth hormone therapy also improves outcomes. Counseling and medications may help with some behavioral problems. Group homes are often necessary in adulthood.


title: Prader–Willi syndrome

text: PWS affects between 1 in 10,000 to 30,000 people worldwide. The condition is named after Swiss physicians Andrea Prader and Heinrich Willi who, together with Alexis Labhart, described it in detail in 1956. An earlier description was made in 1887 by British physician John Langdon Down.


title: Prader–Willi syndrome

text: PWS symptoms can range from poor muscle tone during infancy to behavioral problems in early childhood. Some symptoms usually found in infants, besides poor muscle tone, are a lack of eye coordination, some are born with almond-shaped eyes, and due to poor muscle tone, some may not have a strong sucking reflex. Their cries are weak, and they have difficulty waking up. Another sign of this condition is a thin upper lip.


title: Prader–Willi syndrome

text: More aspects seen in a clinical overview include hypotonia and abnormal neurologic function, hypogonadism, developmental and cognitive delays, hyperphagia and obesity, short stature, and behavioral and psychiatric disturbances.


title: Prader–Willi syndrome

text: Holm "et al." (1993) describe the following features and signs as indicators of PWS, although not all will be present:


title: Prader–Willi syndrome

text: Individuals with PWS are at risk of learning and attention difficulties. Curfs and Fryns (1992) conducted research into the varying degrees of learning disability found in PWS.


title: Prader–Willi syndrome

text: Cassidy found that 40% of individuals with PWS have borderline/low average intelligence, a figure higher than the 32% found in Curfs and Fryns' study. However, both studies suggest that most individuals (50–65%) fall within the mild/borderline/low average intelligence range.


title: Prader–Willi syndrome

text: Children with PWS show an unusual cognitive profile. They are often strong in visual organization and perception, including reading and vocabulary, but their spoken language (sometimes affected by hypernasality) is generally poorer than their comprehension. A marked skill in completing jigsaw puzzles has been noted, but this may be an effect of increased practice.


title: Prader–Willi syndrome

text: Auditory information processing and sequential processing are relatively poor, as are arithmetic and writing skills, visual and auditory short-term memory, and auditory attention span. These sometimes improve with age, but deficits in these areas remain throughout adulthood.


title: Prader–Willi syndrome

text: PWS is frequently associated with a constant insatiable appetite, which persists no matter how much the patient eats, often resulting in morbid obesity. Caregivers need to strictly limit the patients' access to food, usually by installing locks on refrigerators and on all closets and cabinets where food is stored. It is the most common genetic cause of morbid obesity in children. Currently, no consensus exists as to the cause for this symptom, although genetic abnormalities in chromosome 15 disrupt the normal functioning of the hypothalamus. Given that the hypothalamic arcuate nucleus regulates many basic processes, including appetite, a link may well exist. In the hypothalamus of people with PWS, nerve cells that produce oxytocin, a hormone thought to contribute to satiety, have been found to be abnormal.


title: Prader–Willi syndrome

text: People with PWS have high ghrelin levels, which are thought to directly contribute to the increased appetite, hyperphagia, and obesity seen in this syndrome. Cassidy states the need for a clear delineation of behavioral expectations, the reinforcement of behavioural limits, and the establishment of regular routines.


title: Prader–Willi syndrome

text: The main mental health difficulties experienced by people with PWS include compulsive behaviour (usually manifested in skin picking) and anxiety. Psychiatric symptoms, for example, hallucinations, paranoia and depression, have been described in some cases and affect about 5–10% of young adults. Patients are also often extremely stubborn and prone to anger. Psychiatric and behavioural problems are the most common cause of hospitalization.


title: Prader–Willi syndrome

text: Typically, 70–90% of affected individuals develop behavioral patterns in early childhood. Aspects of these patterns can include stubbornness, temper tantrums, controlling and manipulative behavior, difficulty with change in routine, and compulsive-like behaviors.


title: Prader–Willi syndrome

text: Several aspects of PWS support the concept of a growth hormone deficiency. Specifically, individuals with PWS have short stature, are obese with abnormal body composition, have reduced fat-free mass, have reduced lean body mass and total energy expenditure, and have decreased bone density. PWS is characterized by hypogonadism. This is manifested as undescended testes in males and benign premature adrenarche in females. Testes may descend with time or can be managed with surgery or testosterone replacement. Adrenarche may be treated with hormone replacement therapy.


title: Prader–Willi syndrome

text: PWS is commonly associated with development of strabismus. In one study, over 50% of patients had strabismus, mainly esotropia.


title: Prader–Willi syndrome

text: Some individuals (often those with deletions) may have hypopigmented fundi due to OCA2 haploinsufficiency.


title: Prader–Willi syndrome

text: PWS is related to an epigenetic phenomenon known as imprinting. Normally, a fetus inherits an imprinted maternal copy of PW genes and a functional paternal copy of PW genes. Due to imprinting, the maternally inherited copies of these genes are virtually silent, and the fetus therefore relies on the expression of the paternal copies of the genes. In PWS, however, there is mutation/deletion of the paternal copies of PW genes, leaving the fetus with no functioning PW genes. The PW genes are the "SNRPN" and "NDN" genes, along with clusters of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109, 29 copies of SNORD116 (HBII-85) and 48 copies of SNORD115 (HBII-52). These genes are located on chromosome 15 located in the region 15q11-13. This so-called PWS/AS region in the paternal chromosome 15 may be lost by one of several genetic mechanisms, which in the majority of instances occurs through chance mutation. Other, less common mechanisms include uniparental disomy, sporadic mutations, chromosome translocations, and gene deletions.


title: Prader–Willi syndrome

text: Region 15q11-13 is implicated in both PWS and Angelman syndrome (AS). While PWS results from the loss of PW genes within this region on the paternal chromosome, loss of a different gene (UBE3A) within the same region on the maternal chromosome causes AS. PWS and AS represent the first reported instances of disorders related to imprinting in humans.


title: Prader–Willi syndrome

text: The risk to the sibling of an affected child of having PWS depends upon the genetic mechanism which caused the disorder. The risk to siblings is <1% if the affected child has a gene deletion or uniparental disomy, up to 50% if the affected child has a mutation of the imprinting control region, and up to 25% if a parental chromosomal translocation is present. Prenatal testing is possible for any of the known genetic mechanisms.


title: Prader–Willi syndrome

text: A microdeletion in one family of the snoRNA HBII-52 has excluded it from playing a major role in the disease.


title: Prader–Willi syndrome

text: Studies of human and mouse model systems have shown deletion of the 29 copies of the C/D box snoRNA SNORD116 (HBII-85) to be the primary cause of PWS.


title: Prader–Willi syndrome

text: It is traditionally characterized by hypotonia, short stature, hyperphagia, obesity, behavioral issues (specifically obsessive–compulsive disorder-like behaviors), small hands and feet, hypogonadism, and mild intellectual disability. However, with early diagnosis and early treatment (such as with growth hormone therapy), the prognosis for persons with PWS is beginning to change. Like autism, PWS is a spectrum disorder and symptoms can range from mild to severe and may change throughout the person's lifetime. Various organ systems are affected.


title: Prader–Willi syndrome

text: Traditionally, PWS was diagnosed by clinical presentation. Currently, the syndrome is diagnosed through genetic testing; testing is recommended for newborns with pronounced hypotonia. Early diagnosis of PWS allows for early intervention and the early prescription of growth hormone. Daily recombinant growth hormone (GH) injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.


title: Prader–Willi syndrome

text: The mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternally contributed PWS/AS region on chromosome 15q11-q13. Such testing detects over 97% of cases. Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who are too young to manifest sufficient features to make the diagnosis on clinical grounds or in those individuals who have atypical findings.


title: Prader–Willi syndrome

text: PWS is often misdiagnosed as other syndromes due to many in the medical community's unfamiliarity with it. Sometimes it is misdiagnosed as Down syndrome, simply because of the relative frequency of Down syndrome compared to PWS.


title: Prader–Willi syndrome

text: While PWS has no cure, several treatments are available to lessen the condition's symptoms. During infancy, subjects should undergo therapies to improve muscle strength. Speech and occupational therapy are also indicated. During the school years, children benefit from a highly structured learning environment and extra help. The largest problem associated with the syndrome is severe obesity. Access to food must be strictly supervised and limited, usually by installing locks on all food-storage places including refrigerators. Physical activity in individuals with PWS for all ages is needed to optimize strength and promote a healthy lifestyle.


title: Prader–Willi syndrome

text: Prescription of daily recombinant GH injections are indicated for children with PWS. GH supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.


title: Prader–Willi syndrome

text: Because of severe obesity, obstructive sleep apnea is a common sequela, and a positive airway pressure machine is often needed. A person who has been diagnosed with PWS may have to undergo surgical procedures. One surgery that has proven to be unsuccessful for treating the obesity is gastric bypass.


title: Prader–Willi syndrome

text: Behavior and psychiatric problems should be detected early for the best results. These issues are best when treated with parental education and training. Sometimes medication is introduced, as well. Serotonin agonists have been most effective in lessening temper tantrums and improving compulsivity.


title: Prader–Willi syndrome

text: Despite its rarity, PWS has been often referenced in popular culture, partly due to curiosity surrounding the insatiable appetite and the obesity symptomatic of the syndrome.


title: Prader–Willi syndrome

text: The syndrome has been depicted and documented several times in television. A fictional individual with PWS featured in the episode "Dog Eat Dog" of the television series "", which aired in the US on 24 November 2005. In July 2007 Channel 4 aired a 2006 documentary called "Can't Stop Eating", surrounding the everyday lives of two people with PWS, Joe and Tamara. In a 2010 episode of "," Sheryl Crow helped Ty Pennington rebuild a home for a family whose youngest son, Ethan Starkweather, was living with the syndrome. In a 2012 episode of "Mystery Diagnosis" on the Discovery Health channel, Conor Heybach, who has Prader–Willi syndrome, shared how he was diagnosed with it.


title: Myelodysplastic syndrome

text: A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.


title: Myelodysplastic syndrome

text: Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cell, platelet, and white blood cell counts. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. The types of MDS are based on specific changes in the blood cells and bone marrow.


title: Myelodysplastic syndrome

text: Treatments may include supportive care, drug therapy, and hematopoietic stem cell transplantation. Supportive care may include blood transfusions, medications to increase the making of red blood cells, and antibiotics. Drug therapy may include the medications lenalidomide, antithymocyte globulin, and azacitidine. Certain people can be cured with chemotherapy followed by a stem-cell transplant from a donor.


title: Myelodysplastic syndrome

text: About seven per 100,000 people are affected, with about four per 100,000 people newly acquiring the condition each year. The typical age of onset is 70 years. The outlook depends on the type of cells affected, the number of blasts in the bone marrow or blood, and the changes present in the chromosomes of the affected cells. The typical survival time following diagnosis is 2.5 years. The conditions were first recognized in the early 1900s. The current name came into use in 1976.


title: Myelodysplastic syndrome

text: Many individuals are asymptomatic, and blood cytopenia or other problems are identified as a part of a routine blood count:


title: Myelodysplastic syndrome

text: Although some risk exists for developing acute myelogenous leukemia, about 50% of deaths occur as a result of bleeding or infection. However, leukemia that occurs as a result of myelodysplasia is notoriously resistant to treatment. Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness, dyspnea, and pallor, but at least half the patients are asymptomatic and their MDS is discovered only incidentally on routine blood counts. Previous chemotherapy or radiation exposure is an important factor in the person's medical history. Fever, weight loss and splenomegaly should point to a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) rather than pure myelodysplastic process.


title: Myelodysplastic syndrome

text: Some people have a history of exposure to chemotherapy (especially alkylating agents such as melphalan, cyclophosphamide, busulfan, and chlorambucil) or radiation (therapeutic or accidental), or both (e.g., at the time of stem cell transplantation for another disease). Workers in some industries with heavy exposure to hydrocarbons such as the petroleum industry have a slightly higher risk of contracting the disease than the general population. Xylene and benzene exposures have been associated with myelodysplasia. Vietnam veterans exposed to Agent Orange are at risk of developing MDS. A link may exist between the development of MDS "in atomic-bomb survivors 40 to 60 years after radiation exposure" (in this case, referring to people who were in close proximity to the dropping of the atomic bombs in Hiroshima and Nagasaki during World War II). Children with Down syndrome are susceptible to MDS, and a family history may indicate a hereditary form of sideroblastic anemia or Fanconi anemia.


title: Myelodysplastic syndrome

text: MDS most often develops without an identifiable cause. Risk factors include exposure to an agent known to cause DNA damage, such as radiation, benzene, and certain chemotherapies; other risk factors have been inconsistently reported. Proving a connection between a suspected exposure and the development of MDS can be difficult, but the presence of genetic abnormalities may provide some supportive information. Secondary MDS can occur as a late toxicity of cancer therapy (therapy associated MDS, t-MDS). MDS after exposure to radiation or alkylating agents such as busulfan, nitrosourea, or procarbazine, typically occurs 3–7 years after exposure and frequently demonstrates loss of chromosome 5 or 7. MDS after exposure to DNA topoisomerase II inhibitors occurs after a shorter latency of only 1–3 years and can have a 11q23 translocation. Other pre-existing bone-marrow disorders such as acquired aplastic anemia following immunosuppressive treatment and Fanconi anemia can evolve into MDS.


title: Myelodysplastic syndrome

text: MDS is thought to arise from mutations in the multipotent bone-marrow stem cell, but the specific defects responsible for these diseases remain poorly understood. Differentiation of blood precursor cells is impaired, and a significant increase in levels of apoptotic cell death occurs in bone-marrow cells. Clonal expansion of the abnormal cells results in the production of cells that have lost the ability to differentiate. If the overall percentage of bone-marrow myeloblasts rises over a particular cutoff (20% for WHO and 30% for FAB), then transformation to acute myelogenous leukemia (AML) is said to have occurred. The progression of MDS to AML is a good example of the multistep theory of carcinogenesis in which a series of mutations occurs in an initially normal cell and transforms it into a cancer cell.


title: Myelodysplastic syndrome

text: Although recognition of leukemic transformation was historically important (see History), a significant proportion of the morbidity and mortality attributable to MDS results not from transformation to AML, but rather from the cytopenias seen in all MDS patients. While anemia is the most common cytopenia in MDS patients, given the ready availability of blood transfusion, MDS patients rarely experience injury from severe anemia. The two most serious complications in MDS patients resulting from their cytopenias are bleeding (due to lack of platelets) or infection (due to lack of white blood cells). Long-term transfusion of packed red blood cells leads to iron overload.


title: Myelodysplastic syndrome

text: The recognition of epigenetic changes in DNA structure in MDS has explained the success of two (namely the hypomethylating agents 5-azacytidine and decitabine) of three (the third is lenalidomide) commercially available medications approved by the U.S. Food and Drug Administration to treat MDS. Proper DNA methylation is critical in the regulation of proliferation genes, and the loss of DNA methylation control can lead to uncontrolled cell growth and cytopenias. The recently approved DNA methyltransferase inhibitors take advantage of this mechanism by creating a more orderly DNA methylation profile in the hematopoietic stem cell nucleus, thereby restoring normal blood counts and retarding the progression of MDS to acute leukemia.


title: Myelodysplastic syndrome

text: Some authors have proposed that the loss of mitochondrial function over time leads to the accumulation of DNA mutations in hematopoietic stem cells, and this accounts for the increased incidence of MDS in older patients. Researchers point to the accumulation of mitochondrial iron deposits in the ringed sideroblast as evidence of mitochondrial dysfunction in MDS.


title: Myelodysplastic syndrome

text: Since at least 1974, the deletion in the long arm of chromosome 5 has been known to be associated with dysplastic abnormalities of hematopoietic stem cells. By 2005, lenalidomide, a chemotherapy drug, was recognized to be effective in MDS patients with the 5q- syndrome, and in December 2005, the US FDA approved the drug for this indication. Patients with isolated 5q-, low IPSS risk, and transfusion dependence respond best to lenalidomide. Typically, prognosis for these patients is favorable, with a 63-month median survival. Lenalidomide has dual action, by lowering the malignant clone number in patients with 5q-, and by inducing better differentiation of healthy erythroid cells, as seen in patients without 5q deletion.


title: Myelodysplastic syndrome

text: Mutations in splicing factors have been found in 40–80% of cases with myelodysplastic syndrome, particularly in those with ringed sideroblasts.


title: Myelodysplastic syndrome

text: Mutations in the genes encoding for isocitrate dehydrogenase 1 and 2 ("IDH1" and "IDH2") occur in 10–20% of patients with myelodysplastic syndrome, and confer a worsened prognosis in low-risk MDS. Because the incidence of "IDH1/2" mutations increases as the disease malignancy increases, these findings together suggest that "IDH1/2" mutations are important drivers of progression of MDS to a more malignant disease state.


title: Myelodysplastic syndrome

text: GATA2 deficiency is a group of disorders caused by a defect, familial, or sporadic inactivating mutations, in one of the two "GATA2" genes. These autosomal dominant mutations cause a reduction in the cellular levels of the gene's product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymph-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are low and individuals develop over time hematological, immunological, lymphatic, or other presentations. Prominent among these presentations is MDS that often progresses to acute myelocytic leukemia, or less commonly, chronic myelomonocytic leukemia.


title: Myelodysplastic syndrome

text: Transient myeloproliferative disease is the abnormal proliferation of a clone of noncancerous megakaryoblasts in the liver and bone marrow. The disease is restricted to individuals with Down syndrome or genetic changes similar to those in Down syndrome, develops during pregnancy or shortly after birth, and resolves within 3 months, or in about 10% of cases, progresses to acute megakaryoblastic leukemia.


title: Myelodysplastic syndrome

text: The elimination of other causes of cytopenias, along with a dysplastic bone marrow, is required to diagnose a myelodysplastic syndrome, so differentiating MDS from anemia, thrombocytopenia, and leukopenia is important.


title: Myelodysplastic syndrome

text: The features generally used to define an MDS are blood cytopenias, ineffective hematopoiesis, dyserythropoiesis, dysgranulopoiesis, dysmegakaropoiesis, and increased myeloblasts.


title: Myelodysplastic syndrome

text: Dysplasia can affect all three lineages seen in the bone marrow. The best way to diagnose dysplasia is by morphology and special stains


title: Myelodysplastic syndrome

text: (PAS) used on the bone marrow aspirate and peripheral blood smear. Dysplasia in the myeloid series is defined by:


title: Myelodysplastic syndrome

text: Other stains can help in special cases (PAS and naphthol ASD chloroacetate esterase positivity) in eosinophils is a marker of abnormality seen in chronic eosinophilic leukemia and is a sign of aberrancy.


title: Myelodysplastic syndrome

text: On the bone-marrow biopsy, high-grade dysplasia (RAEB-I and RAEB-II) may show atypical localization of immature precursors, which are islands of immature precursors cells (myeloblasts and promyelocytes) localized to the center of the intertrabecular space rather than adjacent to the trabeculae or surrounding arterioles. This morphology can be difficult to differentiate from treated leukemia and recovering immature normal marrow elements. Also, topographic alteration of the nucleated erythroid cells can be seen in early myelodysplasia (RA and RARS), where normoblasts are seen next to bony trabeculae instead of forming normal interstitially placed erythroid islands.


title: Myelodysplastic syndrome

text: Myelodysplasia is a diagnosis of exclusion and must be made after proper determination of iron stores, vitamin deficiencies, and nutrient deficiencies are ruled out. Also, congenital diseases such as congenital dyserythropoietic anemia (CDA I through IV) have been recognized, Pearson's syndrome (sideroblastic anemia), Jordans anomaly – vacuolization in all cell lines may be seen in Chanarin-Dorfman syndrome, aminolevulinic acid enzyme deficiency and other more esoteric enzyme deficiencies are known to give a pseudomyelodysplastic picture in one of the cell lines; however, all three cell lines are never morphologically dysplastic in these entities with the exception of chloramphenicol, arsenic toxicity, and other poisons.


title: Myelodysplastic syndrome

text: All of these conditions are characterized by abnormalities in the production of one or more of the cellular components of blood (red cells, white cells other than lymphocytes, and platelets or their progenitor cells, megakaryocytes).


title: Myelodysplastic syndrome

text: In the late 1990s, a group of pathologists and clinicians working under the World Health Organization (WHO) modified this classification, introducing several new disease categories and eliminating others. In 2008, the WHO developed a new classification scheme that is based more on genetic findings, but morphology of the cells in the peripheral blood, bone marrow aspirate, and bone marrow biopsy are still the screening tests used to decide which classification is best and which cytogenetic aberrations may be related.


title: Myelodysplastic syndrome

text: Note : not all physicians concur with this reclassification, because the underlying pathology of this disease is not well understood.


title: Myelodysplastic syndrome

text: The WHO has proposed a criterion for diagnosis and classification of MDS that may apply to most cases. However, occasional cases are difficult to classify into defined categories because of one or more unusual features:


title: Myelodysplastic syndrome

text: The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to AML.


title: Myelodysplastic syndrome

text: The IPSS scoring system can help triage patients for more aggressive treatment (i.e. bone marrow transplant) as well as help determine the best timing of this therapy. Supportive care with blood products and hematopoietic growth factors (e.g. erythropoietin) is the mainstay of therapy. The regulatory environment for the use of erythropoietins is evolving, according to a recent US Medicare National coverage determination. However, no comment on the use of hematopoietic growth factors for MDS was made in that document.


title: Myelodysplastic syndrome

text: Chemotherapy with the hypomethylating agents 5-azacytidine and decitabine has been shown to decrease blood transfusion requirements and to retard the progression of MDS to AML. Lenalidomide was approved by the FDA in December 2005 only for use in the 5q- syndrome. In the United States, treatment of MDS with lenalidomide costs about $9,200 per month. The chemotherapy may be supported by other drugs like all-trans retinoic acid (ATRA), however the evidence of benefit is not clear.


title: Myelodysplastic syndrome

text: HLA-matched allogeneic stem cell transplantation, particularly in younger (i.e. less than 40 years of age) and more severely affected patients, offers the potential for curative therapy. The success of bone marrow transplantation has been found to correlate with severity of MDS as determined by the IPSS score, with patients having a more favorable IPSS score tend to have a more favorable outcome with transplantation.


title: Myelodysplastic syndrome

text: Iron overload can develop in MDS as a result of the RBC transfusions, which are a major part of the supportive care for anemic MDS patients. Although the specific therapies patients receive may alleviate the RBC transfusion need in some cases, many MDS patients may not respond to these treatments, thus may develop secondary hemochromatosis due to iron overload from repeated RBC transfusions.


title: Myelodysplastic syndrome

text: Patients requiring relatively large numbers of RBC transfusions can experience the adverse effect of chronic iron overload on their liver, heart, and endocrine functions.


title: Myelodysplastic syndrome

text: For patients requiring many RBC transfusions, serum ferritin levels, number of RBC transfusions received, and associated organ dysfunction (heart, liver, and pancreas) should be monitored to determine iron levels. Monitoring serum ferritin may also be useful, aiming to decrease ferritin levels to .Currently, two iron chelators are available in the US, deferoxamine for intravenous use and deferasirox for oral use. These options now provide potentially useful drugs for treating the iron overload problem. A third chelating agent is available in Europe, deferiprone, for oral use, but is not available in the US.


title: Myelodysplastic syndrome

text: Clinical trials in MDS patients are ongoing, with iron chelating agents to address the question of whether iron chelation alters the natural history of patients with MDS who are transfusion dependent. Reversal of some of the consequences of iron overload in MDS by iron chelation therapy has been shown. Both the MDS Foundation and the National Comprehensive Cancer Network MDS Guidelines Panel have recommended that chelation therapy be considered to decrease iron overload in selected MDS patients. Evidence also suggests a potential value exists to iron chelation in patients who will undergo a stem-cell transplant. Although deferasirox is generally well tolerated (other than episodes of gastrointestinal distress and kidney dysfunction in some patients), recently a safety warning by the FDA and Novartis was added to deferasirox treatment guidelines. Following postmarketing use of deferasirox, rare cases of acute kidney failure or liver failure occurred, some resulting in death. Due to this, patients should be closely monitored on deferasirox therapy prior to the start of therapy and regularly thereafter.


title: Myelodysplastic syndrome

text: The outlook in MDS is variable, with about 30% of patients progressing to refractory AML. The median survival time varies from years to months, depending on type. Stem-cell transplantation offers possible cure, with survival rates of 50% at 3 years, although older patients do poorly.


title: Myelodysplastic syndrome

text: Younger age; normal or moderately reduced neutrophil or platelet counts; low blast counts in the bone marrow (< 20%) and no blasts in the blood; no Auer rods; ringed sideroblasts; normal or mixed karyotypes without complex chromosome abnormalities; and "in vitro" marrow culture with a nonleukemic growth pattern


title: Myelodysplastic syndrome

text: Advanced age; severe neutropenia or thrombocytopenia; high blast count in the bone marrow (20–29%) or blasts in the blood;


title: Myelodysplastic syndrome

text: Auer rods; absence of ringed sideroblasts; abnormal localization or immature granulocyte precursors in bone marrow section;


title: Myelodysplastic syndrome

text: completely or mostly abnormal karyotypes, or complex marrow chromosome abnormalities and "in vitro" bone marrow culture with a leukemic growth pattern


title: Myelodysplastic syndrome

text: Cytogenetic abnormalities can be detected by conventional cytogenetics, a FISH panel for MDS, or virtual karyotype.


title: Myelodysplastic syndrome

text: The best prognosis is seen with RA and RARS, where some nontransplant patients live more than a decade (typical is on the order of 3–5 years, although long-term remission is possible if a bone-marrow transplant is successful). The worst outlook is with RAEB-T, where the mean life expectancy is less than 1 year. About one-quarter of patients develop overt leukemia. The others die of complications of low blood count or unrelated diseases. The International Prognostic Scoring System is another tool for determining the prognosis of MDS, published in "Blood" in 1997. This system takes into account the percentage of blasts in the marrow, cytogenetics, and number of cytopenias.


title: Myelodysplastic syndrome

text: Although not yet formally incorporated in the generally accepted classification systems, molecular profiling of myelodysplastic syndrome genomes has increased the understanding of prognostic molecular factors for this disease. For example, in low-risk MDS, "IDH1" and "IDH2" mutations are associated with significantly worsened survival.


title: Myelodysplastic syndrome

text: The exact number of people with MDS is not known because it can go undiagnosed and no tracking of the syndrome is mandated. Some estimates are on the order of 10,000 to 20,000 new cases each year in the United States alone. The number of new cases each year is probably increasing as the average age of the population increases, and some authors propose that the number of new cases in those over 70 may be as high as 15 per 100,000 per year.


title: Myelodysplastic syndrome

text: The typical age at diagnosis of MDS is between 60 and 75 years; a few people are younger than 50, and diagnoses are rare in children. Males are slightly more commonly affected than females.


title: Myelodysplastic syndrome

text: Since the early 20th century, some people with acute myelogenous leukemia were begun to be recognized to have a preceding period of anemia and abnormal blood cell production. These conditions were lumped together with other diseases under the term "refractory anemia". The first description of "preleukemia" as a specific entity was published in 1953 by Block "et al." The early identification, characterization and classification of this disorder were problematical, and the syndrome went by many names until the 1976 FAB classification was published and popularized the term MDS.


title: Myelodysplastic syndrome

text: In 1974 and 1975, a group of pathologists from France, the US, and Britain produced the first widely used classification of these diseases. This French-American-British classification was published in 1976, and revised in 1982. It was used by pathologists and clinicians for almost 20 years. Cases were classified into five categories:


title: Bob Dole

text: Robert Joseph Dole (July 22, 1923 – December 5, 2021) was an American politician and attorney who represented Kansas in the United States Senate from 1969 to 1996. He was the Republican Leader of the Senate during the final 11 years of his tenure, including three non-consecutive years as Senate Majority Leader. Prior to his 27 years in the Senate, he served in the United States House of Representatives from 1961 to 1969. Dole was also the Republican presidential nominee in the 1996 election and the vice presidential nominee in the 1976 election.


title: Bob Dole

text: Dole was born and raised in Russell, Kansas, where he established a legal career after serving with distinction in the United States Army during World War II. Following a period as Russell County Attorney, he won election to the House of Representatives in 1960. In 1968, Dole was elected to the Senate, where he served as chairman of the Republican National Committee from 1971 to 1973 and chairman of the Senate Finance Committee from 1981 to 1985. He led the Senate Republicans from 1985 to his resignation in 1996, and served as Senate Majority Leader from 1985 to 1987 and from 1995 to 1996. In his role as Republican leader, he helped defeat Democratic President Bill Clinton's health care plan.


title: Bob Dole

text: President Gerald Ford chose Dole as his running mate in the 1976 election after Vice President Nelson Rockefeller withdrew from seeking a full term. Ford was defeated by Democrat Jimmy Carter in the general election. Dole sought the Republican presidential nomination in 1980, but quickly dropped out of the race. He experienced more success in the 1988 Republican primaries but was defeated by Vice President George H. W. Bush. Dole won the Republican presidential nomination in 1996 and selected Jack Kemp as his running mate. The Republican ticket lost in the general election to Clinton, making Dole the first unsuccessful major party nominee for both president and vice president. He resigned from the Senate during the 1996 campaign and did not seek public office again after the election.


title: Bob Dole

text: Dole remained active after retiring from public office. He appeared in numerous commercials and television programs and served on various councils. In 2012, Dole unsuccessfully advocated Senate ratification of the Convention on the Rights of Persons with Disabilities. He initially supported Jeb Bush in the 2016 Republican primaries, but later became the only former Republican presidential nominee to endorse Donald Trump in the general election. Dole was a member of the advisory council of the Victims of Communism Memorial Foundation and special counsel at the Washington, D.C., office of law firm Alston & Bird. Dole was awarded the Congressional Gold Medal on January 17, 2018. He was married to former U.S. Senator Elizabeth Dole of North Carolina.


title: Bob Dole

text: Dole was born on July 22, 1923, in Russell, Kansas, the son of Bina M. (née Talbott; 1904–1983) and Doran Ray Dole (1901–1975). His father, who had moved the family to Russell shortly before Robert was born, earned money by running a small creamery. One of Dole's father's customers was the father of his future Senate colleague Arlen Specter. The Doles lived in a house at 1035 North Maple in Russell and it remained his official residence throughout his political career.


title: Bob Dole

text: Dole graduated from Russell High School in the spring of 1941 and enrolled at the University of Kansas the following fall. Dole had been a star high school athlete in Russell, and Kansas basketball coach Phog Allen traveled to Russell to recruit him to play for the Jayhawks basketball team. While at KU, Dole was on the basketball team, the track team, and the football team. In football, Dole played at the end position. In 1942 he was a teammate of the founder and longtime owner of the Tennessee Titans Bud Adams, Adams's only season playing football at Kansas. While in college, Dole joined the Kappa Sigma fraternity, and in 1970 he was bestowed with the Fraternity's "Man of the Year" honor. Dole's collegiate studies were interrupted by World War II, when he enlisted in the United States Army.


title: Bob Dole

text: Dole attended the University of Arizona in Tucson from 1948 to 1949, before transferring to Washburn University in Topeka, where he graduated with both undergraduate and law degrees in 1952.


title: Bob Dole

text: Dole joined the United States Army's Enlisted Reserve Corps in 1942 to fight in World War II, becoming a second lieutenant in the Army's 10th Mountain Division.


title: Bob Dole

text: In April 1945, while engaged in combat near Castel d'Aiano in the Apennine mountains southwest of Bologna, Italy, Dole was seriously wounded by a German shell that struck his upper back and right arm, shattering his collarbone and part of his spine. "I lay face down in the dirt," Dole said. "I could not see or move my arms. I thought they were missing."


title: Bob Dole

text: As Lee Sandlin describes, when fellow soldiers saw the extent of his injuries, they believed all they could do was "give him the largest dose of morphine they dared and write an 'M' for 'morphine' on his forehead in his own blood, so that nobody else who found him would give him a second, fatal dose."


title: Bob Dole

text: Dole was paralyzed from the neck down and transported to a military hospital near Kansas. Having blood clots, a life-threatening infection, and a fever of almost , he was expected to die. After large doses of penicillin were not successful, he overcame the infection with the administration of streptomycin, which at the time was still an experimental drug. He remained despondent, "not ready to accept the fact that my life would be changed forever". He was encouraged to see Hampar Kelikian, an orthopedist in Chicago who had been working with veterans returning from war. Although during their first meeting Kelikian told Dole that he would never be able to recover fully, the encounter changed Dole's outlook on life, who years later wrote of Kelikian, a survivor of the Armenian genocide, "Kelikian inspired me to focus on what I had left and what I could do with it, rather than complaining what had been lost." Dr. K, as Dole later came to affectionately call him, operated on him seven times, free of charge, and had, in Dole's words, "an impact on my life second only to my family".


title: Bob Dole

text: Dole recovered from his wounds at the Percy Jones Army Hospital in Battle Creek, Michigan. This complex of federal buildings, no longer a hospital, is now named Hart–Dole–Inouye Federal Center in honor of three patients who became United States Senators: Dole, Philip Hart, and Daniel Inouye. Dole was decorated three times, receiving two Purple Hearts for his injuries, and the Bronze Star with "V" Device for valor for his attempt to assist a downed radioman. The injuries left him with limited mobility in his right arm and numbness in his left arm. He minimized the effect in public by keeping a pen in his right hand, and learned to write with his left hand. In 1947, he was medically discharged from the Army as a captain.


title: Bob Dole

text: Dole ran for office for the first time in 1950 and was elected to the Kansas House of Representatives, serving a two-year term. During his term he served on the following committees: Assessment and Taxation, Gas and Oil, and Military Affairs and Soldiers Compensation. He became the County Attorney of Russell County in 1952. Dole was elected to the United States House of Representatives from Kansas's 6th congressional district in 1960. After his first term, Kansas lost a congressional district, and most of Dole's district was merged with the neighboring 2nd district to form a new 1st district, encompassing much of central and western Kansas. Dole was elected from this merged district in 1962 and was re-elected two more times.


title: Bob Dole

text: During his tenure in the House, Dole voted in favor of the Civil Rights Acts of 1964 and 1968, and the Voting Rights Act of 1965.


title: Bob Dole

text: In 1968, Dole defeated former Kansas Governor William H. Avery for the Republican nomination for the United States Senate to succeed retiring Senator Frank Carlson. He subsequently won the seat in the general election. Dole was re-elected in 1974, 1980, 1986, and 1992, before resigning on June 11, 1996, to focus on his presidential campaign.


title: Bob Dole

text: While in the Senate, Dole served as chairman of the Republican National Committee from 1971 to 1973, the ranking Republican on the Agriculture Committee from 1975 to 1978, and the chairman of the Finance Committee from 1981 to 1985. In November 1984, Dole was elected Senate Majority Leader, defeating Ted Stevens 28–25, in the fourth round of balloting.


title: Bob Dole

text: The continuing war in Vietnam was the dominant source of political division on Capitol Hill in the early 1970s; in 1970 Democratic Senator George McGovern of South Dakota took the Senate floor and condemned the deliberative body's role in maintaining the US presence in Vietnam, saying the Senate chamber "reeks of blood", soon followed by freshman Republican senator Dole on the floor, who vociferously attacked McGovern. Dole was appointed chair of the Republican National Committee the next year. Over time in the Senate, Dole was seen by some as having a moderate voting record. During the following years of the 1970s, Dole and McGovern worked together on the Senate Hunger and Human Needs Committee. They partnered to help pass legislation making food stamps and school lunches more accessible, and fraud more difficult. They expanded the school lunch program and helped establish the Special Supplemental Food Program for Women, Infants and Children (WIC), a federal assistance program for low-income pregnant women, breast-feeding women and children under the age of five.


title: Bob Dole

text: Dole served on congressional agriculture committees throughout the course of his political career, and became the Republican Party's chief spokesman on farm policy and nutrition issues in the Senate. When Ronald Reagan was elected president in 1980, Dole held the chairmanship of the Senate Agriculture Committee's Nutrition Subcommittee and the Senate Finance Committee. Together with McGovern, Dole spearheaded the elimination of the purchase requirement to receive food stamp benefits and the simplification of eligibility requirements.


title: Bob Dole

text: Facing a reluctant President and Congress as chairman of the Senate Finance Committee in 1982, Dole was the driving force behind a large tax increase, promoting it as a reform measure to collect money owed by tax cheats and under-taxed businesses. In December of that year, "The New York Times" referred to Dole as changing from "hard-line conservative" to "mainstream Republicanism". He became Senate Majority leader in 1985 initially serving in that position for two years. Democrats took control of the Senate following the 1986 United States Senate elections, and Dole became Senate Minority Leader for the next eight years. Dole was a major supporter and advocate of the Americans with Disabilities Act of 1990.


title: Bob Dole

text: The Republicans took control of both the Senate and House of Representatives in the 1994 mid-term elections, due to the fallout from President Bill Clinton's policies including his health care plan, and Dole became Senate Majority Leader for the second time. In October 1995, a year before the presidential election, Dole and Speaker of the House Newt Gingrich led the Republican-controlled Congress to pass a spending bill that President Clinton vetoed, leading to the federal government shutdown from 1995 to 1996. On November 13, Republican and Democratic leaders, including Vice President Al Gore, Dick Armey, and Dole, met to try to resolve the budget and were unable to reach an agreement. By January 1996, Dole was more open to compromise to end the shutdown (as he was campaigning for the Republican presidential nomination), but he was opposed by other Republicans who wanted to continue until their demands were met. In particular, Gingrich and Dole had a tense working relationship as they were potential rivals for the 1996 Republican nomination. Clinton aide George Stephanopoulos cited the shutdown as having a role in Clinton's successful re-election campaign. In a January 3, 1996, Briefing Room address, amid the ongoing United States federal government shutdowns of 1995–1996, President Clinton noted Dole as a lawmaker that was "working together in good faith" to reopen the government.


title: Bob Dole

text: From 1992 to 1996, Dole played a major role in mobilizing support for Bosnia in the Senate, and pressuring the Clinton administration and NATO to resolve the war there.


title: Bob Dole

text: In 1996, Dole was the first sitting Senate Party Leader to receive his party's nomination for president. He hoped to use his long experience in Senate procedures to maximize publicity from his rare positioning as Senate Majority Leader against an incumbent president but was stymied by Senate Democrats. Dole resigned his seat on June 11, 1996, to focus on the campaign, saying he had "nowhere to go but the White House or home".


title: Bob Dole

text: Dole ran unsuccessfully for vice president on a ticket headed by President Gerald Ford in 1976. Incumbent Vice President Nelson Rockefeller had announced the previous November his retirement from politics, opting against a run for a full term as vice president, and Dole was chosen as Ford's running mate. Dole was known for his sarcastic one-liner comments, often directed against himself, and during the vice presidential debate replied to Walter Mondale concerning the issues of Watergate and the Nixon pardon, "It is an appropriate topic, I guess, but it's not a very good issue any more than the war in Vietnam would be or World War II or World War I or the war in Korea—all Democrat wars, all in this century. I figured up the other day, if we added up the killed and wounded in Democrat wars in this century, it would be about 1.6 million Americans, enough to fill the city of Detroit."


title: Bob Dole

text: Dole ran for the 1980 Republican presidential nomination, eventually won by Ronald Reagan. Despite Dole's national exposure from the '76 campaign, he finished behind Reagan, George H. W. Bush, and four others in Iowa and New Hampshire, receiving only 2.5% and 0.4% of votes cast in those contests, respectively. Dole ceased campaigning after the New Hampshire results and announced his formal withdrawal from the race on March 15, instead being re-elected to his third term as Senator that year.


title: Bob Dole

text: Dole made another attempt for the Republican presidential nomination in 1988, formally announcing his candidacy in his hometown of Russell, Kansas, on November 9, 1987. At the ceremony, Dole was presented by the VFW with a cigar box, similar to the one he had used to collect donations for his war-related medical expenses, containing more than $7,000 in campaign donations. Dole started out strongly by defeating Vice President George H. W. Bush in the Iowa caucus—Bush finished third, behind television evangelist Pat Robertson.


title: Bob Dole

text: Bush defeated Dole in the New Hampshire primary a week later. After the returns had come in on the night of that primary, Dole appeared to lose his temper in a television interview with Tom Brokaw, saying Bush should "stop lying about my record", in response to a Bush commercial which accused Dole of "straddling" on taxes.


title: Bob Dole

text: Despite a key endorsement by Senator Strom Thurmond, Dole was defeated by Bush again in South Carolina in early March. Several days later, every southern state voted for Bush in a Super Tuesday sweep. This was followed by another loss in Illinois, which persuaded Dole to withdraw from the race.


title: Bob Dole

text: Despite the 1994 elections, President Clinton's popularity soared due to a booming economy and public opinion polls supporting him in the 1995 budget shutdown. As a result, Clinton and Vice President Al Gore faced no serious opposition in the Democratic primaries. A few months before his death in April 1994, Richard Nixon warned Dole, "If the economy's good, you're not going to beat Clinton." Dole was the early front runner for the GOP nomination in the 1996 presidential race. At least eight candidates ran for the nomination. Dole was expected to win the nomination against underdog candidates such as the more conservative Senator Phil Gramm of Texas and more moderate Senator Arlen Specter of Pennsylvania. Pat Buchanan upset Dole in the early New Hampshire primary, however, with Dole finishing second and former Tennessee governor Lamar Alexander finishing third. Speechwriter Kerry Tymchuk observed, "Dole was on the ropes because he wasn't conservative enough."


title: Bob Dole

text: Dole eventually won the nomination, becoming the oldest first-time presidential nominee at the age of 73 years, 1 month (President Ronald Reagan was 73 years, 6 months in 1984, for his second presidential nomination). If elected, he would have become the oldest president to take office and the first Kansas native to become president (as Dwight Eisenhower was born in Texas). Dole found the initial draft of the nomination acceptance speech written by Mark Helprin too hardline, so Kerry Tymchuk, who was part of the "'Let Dole be Dole' crowd", revised the speech to cover the themes of honor, decency, and straight talk. It included the following line, a gibe at the all-or-nothing rookie Republicans who had ridden the 1994 midterm GOP wave into Congress: "In politics honorable compromise is no sin. It is what protects us from absolutism and intolerance"'.


title: Bob Dole

text: In his acceptance speech, Dole stated, "Let me be the bridge to an America that only the unknowing call myth. Let me be the bridge to a time of tranquility, faith, and confidence in action," to which incumbent president Bill Clinton responded, "We do not need to build a bridge to the past, we need to build a bridge to the future."


title: Bob Dole

text: As told in the Doles' joint biography, "Unlimited Partners", speechwriter and biographer Kerry Tymchuk wrote "that he was going to make a statement. He was going to risk it all for the White House. He knew his time as leader was over. It would have been tough to come back [to the Senate as leader] if he lost in November. He knew it was time to move up or move out."


title: Bob Dole

text: Dole promised a 15% across-the-board reduction in income tax rates and made former Representative and supply side advocate Jack Kemp his running mate for vice president. Dole found himself criticized from both the left and the right within the Republican Party over the convention platform, one of the major issues being the inclusion of the Human Life Amendment. Clinton framed the narrative against Dole early, painting him as a mere clone of unpopular then-House Speaker Newt Gingrich, warning America that Dole would work in concert with the Republican Congress to slash popular social programs, like Medicare and Social Security, dubbed by Clinton as "Dole-Gingrich". Dole's tax-cut plan found itself under attack from the White House, who said it would "blow a hole in the deficit".


title: Bob Dole

text: During the infancy of the Internet, Dole-Kemp was the first presidential campaign to have a website, which was set up by Arizona State college students Rob Kubasko and Vince Salvato, and edged out Clinton-Gore. The Dole-Kemp presidential campaign page is still live as of 2021.


title: Bob Dole

text: Concerns over Dole's age and lagging campaign were exemplified by an incident on September 18, 1996. At a rally in Chico, California, he was reaching down to shake the hand of a supporter, when the railing on the stage gave way and he tumbled four feet. While only slightly injured in the fall, "the televised image of his painful grimace underscored the age difference between him and Clinton" and proved an ominous sign for Republican hopes of retaking the White House.


title: Bob Dole

text: During the latter half of October 1996, Dole made a campaign appearance with Heather Whitestone, the first deaf Miss America, where both of them signed "I love you" to the crowd. Around that time, Dole and his advisers knew that they would lose the election, but in the last four days of the campaign they went on the "96-hour victory tour" to help Republican House candidates.


title: Bob Dole

text: Dole lost, as pundits had long expected, to incumbent President Bill Clinton in the 1996 election. Clinton won in a 379–159 Electoral College landslide, capturing 49.2% of the vote against Dole's 40.7% and Ross Perot's 8.4%. As Nixon had predicted, Clinton was able to ride a booming economy to a second term in the White House.


title: Bob Dole

text: Dole is the last World War II veteran to have been the presidential nominee of a major party. During the campaign, Dole's advanced age was brought up, with critics stating that he was too old to be president.


title: Bob Dole

text: In his election night concession speech, Dole remarked "I was thinking on the way down in the elevator – tomorrow will be the first time in my life I don't have anything to do." Dole later wrote "I was wrong. Seventy-two hours after conceding the election, I was swapping wisecracks with David Letterman on his late-night show." During the immediate aftermath of his 1996 loss to Clinton, Dole recalled that his critics thought that "I didn't loosen up enough, I didn't show enough leg. They said I was too serious . . . It takes several months to stop fretting about it and move on. But I did." Dole remarked that his decisive defeat to Clinton made it easier for him to be "magnanimous". On his decision to leave politics for good after the 1996 presidential election campaign, despite his guaranteed stature as a former Senate leader, Dole stated, "People were urging [me] to be a hatchet man against Clinton for the next four years. I couldn't see the point. Maybe after all those partisan fights, you look for more friendships. One of the nice things I've discovered is that when you're out of politics, you have more credibility with the other side . . . And you're out among all kinds of people, and that just doesn't happen often for an ex-president; he doesn't have the same freedom. So it hasn't been all bad."


title: Bob Dole

text: The 1996 presidential election, despite ending in a loss, opened up numerous opportunities for Dole owing in part to his sense of humor. He engaged in a career of writing, consulting, public speaking, and television appearances. Dole was the first defeated presidential nominee to become a political celebrity.


title: Bob Dole

text: In November 1996, Dole appeared on "Late Show with David Letterman" and also made a cameo appearance on "Saturday Night Live", parodying himself (shortly after losing the presidential election). He guest-starred as himself on NBC's Brooke Shields sitcom "Suddenly Susan" in January 1997.


title: Bob Dole

text: Dole became a television commercial spokesman for such products as Viagra, Visa, Dunkin' Donuts, and Pepsi-Cola (with Britney Spears). He was an occasional political commentator on the interview program "Larry King Live", and was a guest a number of times on Comedy Central's satirical news program, "The Daily Show with Jon Stewart". Dole was, for a short time in 2003, a commentator opposite Bill Clinton on CBS's "60 Minutes".


title: Bob Dole

text: After leaving office, Dole joined the Washington, D.C. firm Verner, Liipfert, Bernhard, McPherson and Hand, where he was a registered lobbyist on behalf of foreign governments (including those of Kosovo, Taiwan, and Slovenia); the American Society of Anesthesiologists; Tyco; and the Chocolate Industry Coalition. In 2003, after Verner, Liipfert was acquired by Piper Rudnick, Dole joined the Washington, D.C. law and lobbying firm Alston & Bird LLP, where he continued his lobbying career. While working for Alston & Bird, Dole was registered as a foreign agent in order to represent the government of Taiwan in Washington.


title: Bob Dole

text: Dole was head of the Federal City Council, a group of business, civic, education, and other leaders interested in economic development in Washington, D.C., from 1998 to 2002.


title: Bob Dole

text: Dole was also involved in many volunteer activities. He served as national chairman of the World War II Memorial Campaign, which raised funds for the building of the National World War II Memorial. After being built, he visited the memorial on a weekly basis for many years to greet visitors and remember those who served.


title: Bob Dole

text: Dole also teamed up with his former political rival, Bill Clinton, in 2001 on the Families of Freedom Foundation, a scholarship fund campaign to pay for the college educations for the families of 9/11 victims. It helped raise more than $100 million.


title: Bob Dole

text: The Robert J. Dole Institute of Politics, housed on the University of Kansas campus in Lawrence, Kansas, was established to bring bipartisanship back to politics. The institute, which opened in July 2003 to coincide with Dole's 80th birthday, has featured such notable speakers as former President Bill Clinton, and awarded the inaugural Dole Leadership Prize to Rudy Giuliani for his leadership as the Mayor of New York City during the September 11 attacks in 2001.


title: Bob Dole

text: Dole's legacy also includes a commitment to combating hunger, both in the United States and around the globe. In addition to numerous domestic programs, and along with former Senator George McGovern (D-South Dakota), Dole created an international school lunch program through the George McGovern-Robert Dole International Food for Education and Child Nutrition Program, which, funded largely through the Congress, helps fight child hunger and poverty by providing nutritious meals to children in schools in developing countries. This internationally popular program would go on to provide more than 22 million meals to children in 41 countries in its first eight years. It has since led to greatly increased global interest in and support for school-feeding programs—which benefit girls and young women, in particular—and won McGovern and Dole the 2008 World Food Prize.


title: Bob Dole

text: Dole offered the inaugural lecture to dedicate the University of Arkansas Clinton School of Public Service on September 18, 2004. During the lecture, he chronicled his life as a public servant and discussed the importance of public service related to defense, civil rights, the economy and daily life. Dole also gave the 2008 Vance Distinguished Lecture at Central Connecticut State University.


title: Bob Dole

text: Dole wrote several books, including one on jokes told by the presidents of the United States, in which he ranks the presidents according to their level of humor. Dole released his autobiography, "One Soldier's Story: A Memoir", on April 12, 2005. The book chronicles his World War II experiences and his battle to survive his war injuries.


title: Bob Dole

text: After the Clinton–Lewinsky scandal broke in 1998, Dole urged his party to practice "restraint" in their reaction to the scandal. After the resulting late-1998 impeachment of President Clinton, Dole proposed that, instead of holding an impeachment trial, the Senate instead censure Clinton and then have Clinton sign the censure himself in the presence of congressional leaders, the Vice President, Cabinet members, and the justices of the Supreme Court. Some Democratic Senate came to support the notion of having a censure motion instead of holding an impeachment trial. However, the Senate instead held an impeachment trial in which Clinton was acquitted.


title: Bob Dole

text: President George W. Bush appointed Dole and Donna Shalala, former Secretary of Health and Human Services, as co-chairs of the commission to investigate problems at Walter Reed Army Medical Center in 2007. That same year, Dole joined fellow former Senate majority leaders Howard Baker, Tom Daschle, and George Mitchell to found the Bipartisan Policy Center, a non-profit think-tank that works to develop policies suitable for bipartisan support. Dole also served as a director for the Asia Universal Bank, a bank domiciled in Kyrgyzstan during the discredited Kurmanbek Bakiyev presidential regime which was subsequently shut down owing to its involvement in money laundering.


title: Bob Dole

text: Dole issued a letter critical of Newt Gingrich, focusing on Dole and Gingrich's time working together on Capitol Hill, on January 26, 2012. The letter was issued immediately before the Florida primary. Dole endorsed Mitt Romney for the Republican nomination. Dole cited the association made between himself and Gingrich as fellow Congressional leaders in Democratic advertisements as a key factor for his 1996 presidential defeat.


title: Bob Dole

text: Dole appeared on the Senate floor to advocate ratification of the Convention on the Rights of Persons with Disabilities on December 4, 2012. Democratic Senator John Kerry explained: "Bob Dole is here because he wants to know that other countries will come to treat the disabled as we do." The Senate rejected the treaty by a vote of 61–38, less than the 66 required for ratification. Many Republican senators voted against the bill, fearing it would interfere with American sovereignty. Dole began a reunion tour of his home state of Kansas in early 2014, seeking to visit each of the state's 105 counties. At each stop he spent approximately an hour speaking with old friends and well-wishers. Dole endorsed and campaigned for incumbent Kansas Senator Pat Roberts during the latter's 2014 re-election bid.


title: Bob Dole

text: In 2015, Dole endorsed former Florida governor Jeb Bush in his presidential campaign. After Bush ended his campaign following the South Carolina primary, Dole endorsed Florida senator Marco Rubio's campaign. During the campaign, Dole criticized Texas senator Ted Cruz, stating that he "question[ed] his allegiance to the party" and that there would be "wholesale losses" if he were to win the Republican nomination. Dole endorsed Donald Trump after the latter clinched the Republican nomination, while all other then-living Republican presidential nominees, George H. W. Bush, George W. Bush, John McCain, and Mitt Romney refused to do so, and became the lone former nominee to attend the 2016 Republican National Convention. Dole had attended every GOP convention since 1964, and did not consider skipping the 2016 edition even though Trump's politics were closer to that of Dole's 1996 primary rival Pat Buchanan.


title: Bob Dole

text: Former Dole advisers, including Paul Manafort, played a major role in Trump's presidential campaign. Following Trump's electoral victory, Dole coordinated with the Trump campaign and presidential transition team to set up a series of meetings between Trump's staff and Taiwanese officials as well as assisting in successful efforts to include favorable language towards Taiwan in the 2016 Republican Party platform. In February 2016 Dole donated $20,000 to help pay for a camp for children with cancer in central Kansas.


title: Bob Dole

text: Dole was awarded the Congressional Gold Medal for his service to the nation as a "soldier, legislator and statesman" in January 2018. Despite being immobile, Dole signaled to an aide to assist him in standing for the U.S. national anthem prior to the ceremony.


title: Bob Dole

text: Dole, at age 95 and in a wheelchair, stood up with the help of an aide at the funeral of George H. W. Bush in the United States Capitol rotunda on December 4, 2018, and saluted to pay his respects to the late president and fellow World War II veteran.


title: Bob Dole

text: Dole expressed concern the Commission on Presidential Debates were biased against President Trump and his reelection campaign in a public statement on October 9, 2020, saying how he knew all the Republicans on the commission and feared that "none of them support[ed]" the president.


title: Bob Dole

text: While he endorsed Trump in both 2016 and 2020, in an interview with "USA Today" conducted for his 98th birthday, Dole said he was "Trumped out", and that Trump had lost the 2020 election despite his attempts to overturn the 2020 U.S. presidential election. He further stated, "He lost the election, and I regret that he did, but they did", adding that Trump "had Rudy Giuliani running all over the country, claiming fraud. He never had one bit of fraud in all those lawsuits he filed and statements he made." At one point during the conversation Dole said, "I'm a Trumper", and added at another, "I'm sort of Trumped out, though."


title: Bob Dole

text: Dole was presented with the Presidential Citizens Medal by President Ronald Reagan on January 18, 1989.


title: Bob Dole

text: Senator Dole was presented the Presidential Medal of Freedom by President Bill Clinton on January 17, 1997, for service to his country in the military and in his political career. In his acceptance remarks in the East Room of the White House, Dole remarked "I had a dream that I would be here this historic week receiving something from the president — but I thought it would be the front-door key".


title: Bob Dole

text: Dole received the U.S. Senator John Heinz Award for Greatest Public Service by an Elected or Appointed Official, an award given out annually by Jefferson Awards, in 1997.


title: Bob Dole

text: Dole received the American Patriot Award from the National Defense University in 2004 for his lifelong dedication to the United States and his service in World War II.


title: Bob Dole

text: On September 30, 2015, the National Commemoration of the Armenian Genocide Centennial (NCAGC) honored Senator Dole with the organization's Survivor's Gratitude Award in the category of "Hero of Responsibility and Principle" for his tireless efforts in raising attention to the Armenian Genocide and its victims.


title: Bob Dole

text: For his lobbying efforts on behalf of Kosovo Albanians before, during, and after the Kosovo War, Albanian President Bujar Nishani awarded Dole Albania's highest civilian honor, the National Flag Order medal, at a May 2017 ceremony in Washington, D.C.


title: Bob Dole

text: Dole was awarded the Congressional Gold Medal for his service to the nation as a "soldier, legislator and statesman" on January 17, 2018.


title: Bob Dole

text: The U.S. Congress unanimously passed a bill promoting the 95-year-old Dole from captain to colonel for his service during World War II in 2019. "I've had a great life and this is sort of icing on the cake. It's not that I have to be a colonel; I was happy being a captain and it pays the same," Dole said, jokingly.


title: Bob Dole

text: Dole married Phyllis Holden, an occupational therapist at a veterans hospital, in Battle Creek, Michigan, in 1948, three months after they met. Their daughter, Robin, was born on October 15, 1954. Dole and Holden divorced January 11, 1972. Holden died on April 22, 2008.


title: Bob Dole

text: Dole met his second wife, Elizabeth Halford, in 1972. The couple was married on December 6, 1975. They had no children.


title: Bob Dole

text: Dole was a Freemason and a member of Russell Lodge No. 177, Russell, Kansas. In 1975, Dole was elevated to the 33rd degree of the Scottish Rite.


title: Bob Dole

text: Dole often referred to himself in the third person in conversation. In a 1996 appearance on "Saturday Night Live", he jokingly refuted the habit to Norm Macdonald, saying: "That's not something Bob Dole does. That's not something Bob Dole has ever done, or that Bob Dole will ever do." He had no relation to the Dole Food Company or its namesake James Dole, although confusion between the two did lead Burhanettin Ozfatura, the mayor of İzmir, Turkey, to ban the sale of Dole bananas in the city in February 1995.


title: Bob Dole

text: Dole had surgery for prostate cancer in 1991. He later spoke before Congress and on public service announcements about early detection of the disease and the erectile dysfunction that resulted from his surgery. He then became a paid spokesman for Viagra. He also starred in a parody of his Viagra commercials for "the little blue can" of Pepsi.


title: Bob Dole

text: In 2001, Dole, at age 77, was treated successfully for an abdominal aortic aneurysm by vascular surgeon Kenneth Ouriel, who said Dole "maintained his sense of humor throughout his care".


title: Bob Dole

text: Dole underwent a hip replacement operation that required him to receive blood thinners in December 2004. One month after the surgery, doctors determined that he was bleeding inside his head. He spent 40 days at Walter Reed Army Medical Center; upon his release, his stronger left arm was of limited use. Dole told a reporter that he needed help to handle the simplest of tasks, since both of his arms were of limited use. He continued to go to Walter Reed several times a week for occupational therapy for his left shoulder.


title: Bob Dole

text: In 2009, Dole was hospitalized for an elevated heart rate and sore legs for which he underwent a successful skin graft procedure. He was hospitalized with pneumonia in February 2010 after undergoing knee surgery. Dole spent ten months at Walter Reed Army Medical Center recovering from the surgery and experienced three bouts with pneumonia. He was released from the hospital in November 2010. Dole was readmitted to Walter Reed Army Medical Center in January 2011 and spent about six days there being treated for a fever and a minor infection.


title: Bob Dole

text: Dole was hospitalized in November 2012 at Walter Reed National Military Medical Center, according to then-Senate Majority Leader Harry Reid.


title: Bob Dole

text: Dole was hospitalized at Walter Reed National Military Medical Center for low blood pressure on September 13, 2017. He stayed for 24 hours before returning home.


title: Bob Dole

text: In February 2021, Dole announced that he had been diagnosed with stage four lung cancer, and subsequently underwent immunotherapy, forgoing chemotherapy due to its negative effect on his body. He died of complications from the disease in his sleep at his home in Washington, D.C., on the morning of December 5, 2021, at the age of 98.


title: Bob Dole

text: Numerous politicians paid tribute to Dole after his death, including, President Joe Biden and former presidents Jimmy Carter, Bill Clinton, George W. Bush, Barack Obama and Donald Trump. President Biden issued an order for flags to be flown at half-staff through December 11, 2021, with House Speaker Nancy Pelosi and Senate Majority Leader Chuck Schumer announcing that Dole would lay in state at the U.S. Capitol on December 9.


title: Bob Dole

text: A funeral service was held at Washington National Cathedral on December 10 and was attended by President Biden with first lady Jill Biden, Vice President Kamala Harris with her husband, second gentleman Doug Emhoff, former president Bill Clinton, former vice presidents Mike Pence, Dick Cheney and Dan Quayle, Senate Minority Leader Mitch McConnell, and former senators Pat Roberts and Tom Daschle, among others. Later that same day, a memorial ceremony was held at the National World War II Memorial where Chairman of the Joint Chiefs of Staff General Mark A. Milley, actor Tom Hanks and Today Show co-anchor Savannah Guthrie were among those who spoke.


title: Bob Dole

text: Dole's casket then returned to Kansas where a memorial service was held at the Catholic Church in his boyhood home of Russell, Kansas, on December 11. The service was open to the public. Speakers included Kansas Governor Laura Kelly, Senators Jerry Moran and Roger Marshall and former Senator Pat Roberts. His casket then went to lie in repose at the Kansas Statehouse. Following that, the casket returned to Washington and he was interred at Arlington National Cemetery.


title: Clementine Churchill

text: Clementine Ogilvy Spencer Churchill, Baroness Spencer-Churchill, (; 1 April 1885 – 12 December 1977) was the wife of Winston Churchill, Prime Minister of the United Kingdom, and a life peer in her own right. While legally the daughter of Sir Henry Hozier, her mother Lady Blanche's known infidelity and his suspected infertility make her paternal parentage uncertain.


title: Clementine Churchill

text: Clementine (pronounced Clemen-teen) met Churchill in 1904 and they began their marriage of 56 years in 1908. They had five children together, one of whom (named Marigold) died at the age of two from sepsis. During the First World War, Clementine organised canteens for munitions workers and during the Second World War, she acted as Chairman of the Red Cross Aid to Russia Fund, President of the Young Women's Christian Association War Time Appeal and Chairman of Maternity Hospital for the Wives of Officers, Fulmer Chase, South Bucks.


title: Clementine Churchill

text: Throughout her life she was granted many titles, the final being a life peerage following the death of her husband in 1965. In her later years, she sold several of her husband's portraits to help support herself financially. She died in her London home at the age of 92.


title: Clementine Churchill

text: Although legally the daughter of Sir Henry Hozier and Lady Blanche Hozier (a daughter of David Ogilvy, 10th Earl of Airlie), her paternity is a subject of much debate, as Lady Blanche was well known for infidelity. After Sir Henry found Lady Blanche with a lover in 1891, she managed to avert her husband's suit for divorce because of his own infidelities, and thereafter the couple separated.


title: Clementine Churchill

text: Lady Blanche maintained that Clementine's biological father was Capt. William George "Bay" Middleton, a noted horseman; Mary Soames, Clementine's youngest child, believed this. However, Clementine's biographer, Joan Hardwick, has surmised (due in part to Sir Henry Hozier's reputed sterility) that all Lady Blanche's "Hozier" children were actually fathered by her sister's husband, Algernon Bertram Freeman-Mitford, 1st Baron Redesdale (1837–1916), better known as a grandfather of the famous Mitford sisters of the 1920s. Whatever her true paternity, Clementine is recorded as being the daughter of Lady Blanche and Sir Henry.


title: Clementine Churchill

text: In the summer of 1899, when Clementine was 14, her mother moved the family to Dieppe, a coastal community in the north of France. There the family spent an idyllic summer, bathing, canoeing, picnicking, and blackberrying. While in Dieppe, the family became well acquainted with 'La Colonie', or the other English inhabitants living by the sea. This group consisted of military men, writers and painters, such as Aubrey Beardsley and Walter Sickert. The latter came to be a great friend of the family.


title: Clementine Churchill

text: According to Clementine's daughter, Mary Soames, Clementine was deeply struck by Sickert and thought he was the most handsome and compelling man she had ever seen. The Hoziers' happy life in France ended when Kitty, the eldest daughter, was struck with typhoid fever. Blanche Hozier sent Clementine and her sister Nellie to Scotland so she could devote her time completely to Kitty. Kitty died on 5 March 1900.


title: Clementine Churchill

text: Clementine was educated first at home, then briefly at the Edinburgh school run by Karl Fröbel, the nephew of the German educationist, Friedrich Fröbel, and his wife Johanna and later at Berkhamsted School for Girls (now Berkhamsted School) and at the Sorbonne in Paris. She was twice secretly engaged to Sir Sidney Peel, who had fallen in love with her when she was 18.


title: Clementine Churchill

text: Clementine first met Winston Churchill in 1904 at a ball in Crewe Hall, the home of the Earl and Countess of Crewe. In March 1908, they met again when seated side by side at a dinner party hosted by Lady St Helier, a distant relative of Clementine. On their first brief encounter, Winston had recognised Clementine's beauty and distinction; now, after an evening spent in her company, he realised she was a girl of lively intelligence and great character. After five months of meeting each other at social events, as well as frequent correspondence, Winston proposed to Clementine during a house party at Blenheim Palace on 11 August 1908, in a small summer house known as the Temple of Diana.


title: Clementine Churchill

text: Winston and Clementine were married on 12 September 1908 in St. Margaret's, Westminster. They honeymooned in Baveno, Venice and Veveří Castle in Moravia before settling into a London home at 33 Eccleston Square. They had five children: Diana (1909–1963), Randolph (1911–1968), Sarah (1914–1982), Marigold (1918–1921) and Mary (1922–2014). Only Mary, the youngest, shared their parents' longevity (Marigold died at the age of two and Diana, Sarah, and Randolph died in their 50s or 60s). The Churchills' marriage was close and affectionate despite the stresses of public life.


title: Clementine Churchill

text: During the First World War, Clementine Churchill organised canteens for munitions workers on behalf of YMCA in the North East Metropolitan Area of London, for which she was appointed a Commander of the Order of the British Empire (CBE) in 1918.


title: Clementine Churchill

text: Clementine travelled to Dundee in 1922, campaigning on behalf of her husband in the 1922 general election while he was incapacitated after having his appendix removed.


title: Clementine Churchill

text: In the 1930s, Clementine travelled without Winston aboard Lord Moyne's yacht, the "Rosaura", to exotic islands: Borneo, Celebes, the Moluccas, New Caledonia, and the New Hebrides. During this trip, many believe that she had an affair with Terence Philip, a wealthy art dealer seven years her junior. However, no conclusive evidence of this has been produced: indeed, Philip was believed by many to have been homosexual. She brought back from this trip a Bali dove. When it died, she buried it in the garden at Chartwell beneath a sundial. On the sundial's base, she had inscribed:


title: Clementine Churchill

text: As the wife of a politician who often took controversial stands, Clementine was used to being snubbed and treated rudely by the wives of other politicians. However, she could take only so much. Once, traveling with Lord Moyne and his guests, the party was listening to a BBC broadcast in which the speaker, a vehemently pro-appeasement politician, criticised Winston by name. Vera, Lady Broughton, a guest of Moyne, said "hear, hear" at the criticism of Churchill. Clementine waited for her host to offer a conciliatory word but, when none came, she stormed back to her cabin, wrote a note to Moyne, and packed her bags. Lady Broughton came and begged Clementine to stay, but she would accept no apologies for the insult to her husband. She went ashore and sailed for home the next morning.


title: Clementine Churchill

text: During the Second World War, she was Chairman of the Red Cross Aid to Russia Fund, the president of the Young Women's Christian Association War Time Appeal and the Chairman of Maternity Hospital for the Wives of Officers, Fulmer Chase. While touring Russia near the end of the war, she was awarded the Order of the Red Banner of Labour.


title: Clementine Churchill

text: In 1946, she was appointed Dame Grand Cross of the Order of the British Empire, becoming Dame Clementine Churchill .


title: Clementine Churchill

text: She was awarded honorary degrees by the University of Glasgow, University of Oxford and University of Bristol.


title: Clementine Churchill

text: After more than 56 years of marriage, Clementine was widowed on 24 January 1965 when Winston died at the age of 90.


title: Clementine Churchill

text: After Sir Winston's death, on 17 May 1965 she was created a life peer as Baroness Spencer-Churchill, of Chartwell in the County of Kent. She sat as a cross-bencher, but her growing deafness precluded her taking a regular part in parliamentary life.


title: Clementine Churchill

text: In her final few years, inflation and rising expenses left Lady Spencer-Churchill in financial difficulties and in early 1977 she sold at auction five paintings by her late husband. After her death, it was discovered that she had destroyed the Graham Sutherland portrait of her husband because Sir Winston had disliked it.


title: Clementine Churchill

text: Lady Spencer-Churchill died at her London home, at 7 Princes Gate, Knightsbridge, of a heart attack on 12 December 1977. She was 92 years old and had outlived her husband by almost 13 years, as well as three of her five children.


title: Clementine Churchill

text: She is buried with her husband and children at St Martin's Church, Bladon, near Woodstock in Oxfordshire.


title: Clementine Churchill

text: A plaque on the Berkhamsted house where the young Clementine Hozier had lived during her education at Berkhamsted Girls' School was unveiled in 1979 by her youngest daughter, Baroness Soames. A blue plaque also commemorates her residence there.


title: Fourier series

text: A Fourier series () is a summation of harmonically related sinusoidal functions, also known as components or harmonics. The result of the summation is a periodic function whose functional form is determined by the choices of cycle length (or "period"), the number of components, and their amplitudes and phase parameters. With appropriate choices, one cycle (or "period") of the summation can be made to approximate an arbitrary function in that interval (or the entire function if it too is periodic). The number of components is theoretically infinite, in which case the other parameters can be chosen to cause the series to converge to almost any "well behaved" periodic function (see Pathological and Dirichlet–Jordan test). The components of a particular function are determined by "analysis" techniques described in this article. Sometimes the components are known first, and the unknown function is "synthesized"


title: Fourier series

text: Convergence of Fourier series means that as more and more components from the series are summed, each successive "partial Fourier series" sum will better approximate the function, and will equal the function with a potentially infinite number of components. The mathematical proofs for this may be collectively referred to as the "Fourier Theorem" (see ). The figures below illustrate some partial Fourier series results for the components of a square wave.


title: Fourier series

text: Another analysis technique (not covered here), suitable for both periodic and non-periodic functions, is the Fourier transform, which provides a frequency-continuum of component information. But when applied to a periodic function all components have zero amplitude, except at the harmonic frequencies. The inverse Fourier transform is a synthesis process (like the Fourier series), which converts the component information (often known as the frequency domain representation) back into its time domain representation.


title: Fourier series

text: Since Fourier's time, many different approaches to defining and understanding the concept of Fourier series have been discovered, all of which are consistent with one another, but each of which emphasizes different aspects of the topic. Some of the more powerful and elegant approaches are based on mathematical ideas and tools that were not available in Fourier's time. Fourier originally defined the Fourier series for real-valued functions of real arguments, and used the sine and cosine functions as the basis set for the decomposition. Many other Fourier-related transforms have since been defined, extending his initial idea to many applications and birthing an area of mathematics called Fourier analysis.


title: Fourier series

text: This section describes the analysis process that derives the parameters of a Fourier series that approximates a known function, formula_1  An example of synthesizing an unknown function from known parameters is discrete-time Fourier transform.


title: Fourier series

text: The Fourier series can be represented in different forms. The "amplitude-phase" form, "sine-cosine" form, and "exponential" form are commonly used and are expressed here for a real-valued function formula_2. (See and for alternative forms).


title: Fourier series

text: The number of terms summed, formula_3, is a potentially infinite integer. Even so, the series might not converge or exactly equate to formula_2 at all values of formula_5 (such as a single-point discontinuity) in the analysis interval. For the well-behaved functions typical of physical processes, equality is customarily assumed, and the Dirichlet conditions provide sufficient conditions.


title: Fourier series

text: The integer index, formula_6, is also the number of cycles the formula_7 harmonic makes in the function's period formula_8. Therefore:


title: Fourier series

text: Clearly can represent functions that are just a sum of one or more of the harmonic frequencies. The remarkable thing, for those not yet familiar with this concept, is that it can also represent the intermediate frequencies and/or non-sinusoidal functions because of the potentially infinite number of terms (formula_3).


title: Fourier series

text: The coefficients formula_17 and formula_19 can be understood and derived in terms of the cross-correlation between formula_2 and a sinusoid at frequency formula_13. For a general frequency formula_31 and an analysis interval formula_32 the cross-correlation function:


title: Fourier series

text: is essentially a matched filter, with "template" formula_33. The maximum of formula_34 is a measure of the amplitude formula_35 of frequency formula_36 in the function formula_2, and the value of formula_38 at the maximum determines the phase formula_39 of that frequency. Figure 2 is an example, where formula_2 is a square wave (not shown), and frequency formula_36 is the formula_42 harmonic. It is also an example of deriving the maximum from just two samples, instead of searching the entire function. That is made possible by a trigonometric identity:


title: Fourier series

text: which introduces the definitions of formula_44 and formula_45.  And we note for later reference that formula_46 and formula_47 can be simplified:


title: Fourier series

text: formula_48The derivative of formula_49 is zero at the phase of maximum correlation.formula_50And the correlation peak value is:


title: Fourier series

text: Therefore formula_44 and formula_45 are the Cartesian coordinates of a vector with polar coordinates formula_17 and formula_55


title: Fourier series

text: Therefore an alternative form of the Fourier series, using the Cartesian coordinates, is the sine-cosine form:


title: Fourier series

text: This is the customary form for generalizing to . Negative values of formula_6 correspond to negative frequency (explained in ).


title: Fourier series

text: It can be shown that the Fourier series converges to formula_2 at every point formula_5 where formula_70 is differentiable, and therefore:


title: Fourier series

text: When formula_71, the Fourier series converges to 0, which is the half-sum of the left- and right-limit of "s" at formula_71. This is a particular instance of the Dirichlet theorem for Fourier series.


title: Fourier series

text: A proof that a Fourier series is a valid representation of any periodic function (that satisfies the Dirichlet conditions) is overviewed in .


title: Fourier series

text: In engineering applications, the Fourier series is generally presumed to converge almost everywhere (the exceptions being at discrete discontinuities) since the functions encountered in engineering are better-behaved than the functions that mathematicians can provide as counter-examples to this presumption. In particular, if formula_70 is continuous and the derivative of formula_2 (which may not exist everywhere) is square integrable, then the Fourier series of formula_70 converges absolutely and uniformly to formula_2. If a function is square-integrable on the interval formula_77, then the Fourier series converges to the function at almost every point. It is possible to define Fourier coefficients for more general functions or distributions, in such cases convergence in norm or weak convergence is usually of interest.


title: Fourier series

text: If formula_2 is a complex-valued function of a real variable formula_79 both components (real and imaginary part) are real-valued functions that can be represented by a Fourier series. The two sets of coefficients and the partial sum are given by:


title: Fourier series

text: This is identical to except formula_84 and formula_85 are no longer complex conjugates. The formula for formula_84 is also unchanged:


title: Fourier series

text: The notation formula_84 is inadequate for discussing the Fourier coefficients of several different functions. Therefore, it is customarily replaced by a modified form of the function (formula_70, in this case), such as formula_90 or formula_91, and functional notation often replaces subscripting:


title: Fourier series

text: In engineering, particularly when the variable formula_5 represents time, the coefficient sequence is called a frequency domain representation. Square brackets are often used to emphasize that the domain of this function is a discrete set of frequencies.


title: Fourier series

text: Another commonly used frequency domain representation uses the Fourier series coefficients to modulate a Dirac comb:


title: Fourier series

text: where formula_36 represents a continuous frequency domain. When variable formula_5 has units of seconds, formula_36 has units of hertz. The "teeth" of the comb are spaced at multiples (i.e. harmonics) of formula_98, which is called the fundamental frequency. formula_99 can be recovered from this representation by an inverse Fourier transform:


title: Fourier series

text: The constructed function formula_101 is therefore commonly referred to as a Fourier transform, even though the Fourier integral of a periodic function is not convergent at the harmonic frequencies.


title: Fourier series

text: The Fourier series is named in honor of Jean-Baptiste Joseph Fourier (1768–1830), who made important contributions to the study of trigonometric series, after preliminary investigations by Leonhard Euler, Jean le Rond d'Alembert, and Daniel Bernoulli. Fourier introduced the series for the purpose of solving the heat equation in a metal plate, publishing his initial results in his 1807 "Mémoire sur la propagation de la chaleur dans les corps solides" ("Treatise on the propagation of heat in solid bodies"), and publishing his "Théorie analytique de la chaleur" ("Analytical theory of heat") in 1822. The "Mémoire" introduced Fourier analysis, specifically Fourier series. Through Fourier's research the fact was established that an arbitrary (at first, continuous and later generalized to any piecewise-smooth) function can be represented by a trigonometric series. The first announcement of this great discovery was made by Fourier in 1807, before the French Academy. Early ideas of decomposing a periodic function into the sum of simple oscillating functions date back to the 3rd century BC, when ancient astronomers proposed an empiric model of planetary motions, based on deferents and epicycles.


title: Fourier series

text: The heat equation is a partial differential equation. Prior to Fourier's work, no solution to the heat equation was known in the general case, although particular solutions were known if the heat source behaved in a simple way, in particular, if the heat source was a sine or cosine wave. These simple solutions are now sometimes called eigensolutions. Fourier's idea was to model a complicated heat source as a superposition (or linear combination) of simple sine and cosine waves, and to write the solution as a superposition of the corresponding eigensolutions. This superposition or linear combination is called the Fourier series.


title: Fourier series

text: From a modern point of view, Fourier's results are somewhat informal, due to the lack of a precise notion of function and integral in the early nineteenth century. Later, Peter Gustav Lejeune Dirichlet and Bernhard Riemann expressed Fourier's results with greater precision and formality.


title: Fourier series

text: Although the original motivation was to solve the heat equation, it later became obvious that the same techniques could be applied to a wide array of mathematical and physical problems, and especially those involving linear differential equations with constant coefficients, for which the eigensolutions are sinusoids. The Fourier series has many such applications in electrical engineering, vibration analysis, acoustics, optics, signal processing, image processing, quantum mechanics, econometrics, shell theory, etc.