Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation. While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.

EATL had been defined as a single type of small intestine lymphoma, but in 2008, the World Health Organization (WHO) divided the disease into two subtypes: 1) EATL type I, which occurs in individuals with coeliac disease, a chronic immune disorder causing inflammatory responses to dietary gluten primarily in the upper reaches (i.e. jejunum and duodenum) of the small intestine; and 2) EATL type II, a disorder similar to EATL type I that occurs without coeliac disease. While type I and II EATL share many similar features, post-2008 studies found some significant differences between the two types. In 2016, the WHO redefined the two diseases as separate entities, keeping the term enteropathy-associated T-cell lymphoma for the coeliac disease-associated lymphoma and terming type 2 disease as monomorphic epitheliotropic intestinal T cell lymphoma (MEITL). EATL is five to ten times more common than is MEITL. The WHO also defined a third type of intestinal T-cell lymphoma that cannot not be classified as EATL or MEITL as peripheral T-cell lymphoma not otherwise specified (ITCL-NOS).

EATL arises from the malignant transformation of small-intestinal intraepithelial lymphocytes (IEL). IEL are a heterogeneous group of principally T-cell lymphocytes residing in epithelial tissues that interface the environment, such as the mucosa of the bronchi, reproductive tract and gastrointestinal tract. At these sites, IEL are exposed and regulate immune responses to non-dietary and dietary antigens, pathogenic and non-pathogenic organisms and injured self tissues. Gastrointestinal tract IEL appear in the epithelium of the small intestine, colon, stomach and esophagus, residing between the epithelial cells that line these organs' lumens. These IEL often exhibit natural killer and cytotoxic T-cell cell activation markers, contain various toxic agents (e.g. perforin, granzyme) and therefore are capable, if activated, of causing severe tissue injuries. With coeliac disease, the IEL react to the glutelins in dietary gluten by increasing their numbers, becoming pathologically active, producing chronic inflammation that injures intestinal cells, interfering with nutrient absorption and creating an environment conducive to their malignant transformation into EATL.

Optimal treatment of EATL has used regimens consisting of intensive chemotherapy, hematopoietic stem cell transplantation and, in cases with bulky, obstructive and/or perforated bowel disease, surgical intervention. The disease has a five-year overall survival rate of only ~20%. However, recent studies focusing on the malignant IEL in EATL have increased understanding of the disease and suggested newer chemotherapy-based strategies and novel molecular targets that might be attacked therapeutically to improve the disease's prognosis.

Presentation
EATL typically occurs in patients with a history of coeliac disease and who may have been previously diagnosed with Type I or II refractory disease, but in any case, affected individuals present with worsening coeliac disease symptoms of abdominal pain, malabsorption, diarrhea, weight loss, fever or night sweats. EATL diagnosis is more likely if symptoms develop suddenly, or if the serious symptoms of bowel obstruction and/or bowel perforation caused by bulky EATL masses develop. Patients with ulcerative jejunitis usually present with more severe symptoms, including more frequent bowel perforations and obstructions. Some patients with no history of coeliac disease present with symptoms or signs of a small-intestinal lymphoma but on diagnostic workup are found to have coeliac disease.

Pathophysiology

Genetics
The cause of EATL, while not fully understood, is by definition related to celiac disease. Individuals are genetically predisposed to develop celiac disease because of the specific types of HLA-DQ proteins expressed by their antigen-presenting cells (APC). HLA-DQ proteins are on the surface of APC and function to present foreign or self antigens to the T cell receptors (TCR) expressed on the surface of T-cells and thereby to stimulate these cells either to initiate or suppress immune responses to the presented antigens. HLA-DQ proteins are composed of α and β polypeptide chains encoded by the HLA-DQA1 and HLA-DQB1 genes, respectively. Since there are several different alleles (i.e. gene variants) at these two genetic loci, individuals are usually heterozygous, i.e. have inherited different alleles from each parent at each locus; uncommonly, however, individuals are homozygous at one or both loci because their parents have the same alleles at one or both loci. The HLA-DQ proteins that predispose individuals to coeliac disease bind and respond specifically to gluten-related antigens presented to them by APC. The genetic predisposition to develop coeliac disease is clinically determined by identifying the serotypes of an individual's APC's HLA-DQ proteins using serotype-specific antibody preparations and/or by identifying the alleles at an individual's HLA-DQA1 and HLA-DQB1 genetic loci. Studies show that:
 Celiac disease affects ~1% of the population in most parts of the world.
 Ninety to one hundred percent of patients with coeliac disease have inherited genes at the HLA-DQ locus that encode HLA-DQ2 and/or HLA-DQ8 serotype proteins.
 About 2-3% of individuals who inherit these HLA-DQ2 and/or HLA-DQ8 serotypes develop coeliac disease.
 About 90% of coeliac disease patients are homozygous for (i.e. inherited from both parents) either the HLADQA1*0501 or HLADQA1*0505 alleles at the HLA-DQA1 locus plus either the HLADQB1*0201 or HLA-DQB1*0202 alleles at the HLA-DQB1 locus; <5% of coeliac disease patients are heterozygous (i.e. inherited from just one parent) for these alleles; and 5-10% of coeliac disease patients have inherited HLA-DQA1*03 plus HLA-DQB1*0302 alleles at the respective HLA-DQA1 and DAQB1 loci.
 Less than 1% of all individuals with coeliac disease develop EATL.
 Individuals homozygous for the HLADQB1*0201 allele at the HLA-DQB1 locus develop a particularly severe and tissue-damaging form of coeliac disease and have a greatly increased rate of developing EATL.
 The vast majority of patients with coeliac disease who develop EATL have either the HLADQA1*0501 or HLADQB1*0201 allele (see previous paragraphs) at the HLA-DQB1 locus.

Intraepithelial lymphocytes
IEL are a diverse population of lymphocytes, which unlike most peripheral lymphocytes, do not recirculate through the blood and/or lymphatic system but rather reside permanently in the epithelium of various organs. In the GI tract, IEL localize between the epithelial cells lining the colon, small intestine, stomach, and esophagus where they serve to maintain the mucosal barrier, combat infection by pathogens, and regulate immune responses to antigens originating from the diet, pathogens, and damaged tissues. Human IEL are classified into those which express the TCR (i.e. TCL+IEL) and those which do not (i.e. TCR-IEL). TCL+IEL are further divided into 4 subtypes, TCRαβ+CD4+ IEL, TCRαβ+CD4+CD8αα+ IEL, TCRαβ+CD8αβ+ IEL, and TCRλδ+CD8αα+. These subtypes are based on the expression of alpha (α) and beta (β) chain-containing TCR (i.e. αβTCR); gamma (γ) and delta (δ) chain-containing TCR (i.e. γδTCR); CD4; CD8αβ; and/or CD8αα by individual IEL.. A fifth TCL+IEL subtype, TCRαβ+CD8αα+, occurs in mice but its presence in the human intestine is disputed. Human TCR-IEL are also divided into 4 sub-types: their: ILC1-like IEL have morphological and functional similarities to normal intestinal epithelial cells and express NKp46; ICL3-like IEL have morphological similarities to normal epithelial cells and, similar to Th1 cells, make Interleukin 17 (IL-17) and Interleukin 22 (IL-22) cytokines and express the RORγt transcription factor and NKp44; iCD3-IEL express iCD3; and iCD8α-IEL express iCD3 and CD8α. CD3 designates a protein complex that is attached to the cell surface membrane whereas iCD3 refers to a CD3 protein complex in which one or more of its proteins resides abnormally in the cell's cytosol Studies suggest that iCD3+IEL are the principal cell type that becomes malignant in EATL cases that are not classified as de novo (see next section). These cells also express CD103 and, frequently, CD30.

Acquisition of malignancy
Coeliac disease patients may be asymptomatic, minimally symptomatic, and/or well-controlled on a gluten-free diet (i.e. a diet free of cereal, rye, wheat, and barley) but nonetheless develop EATL. About 46% of all AETL cases occur in this setting and have had their malignancy described as de novo EATL. The remaining ~54% of EATL cases develop in coeliac disease patients whose disease becomes refractory to dietary control, exhibits increasing symptoms, and  progress over ~4–10 years through Type I refractor coeliac disease (Type 1 RCD) and Type II refractory coeliac disease (Type II RCD) to become EATL. The rates at which non-refractory celiac disease, Type I RCD, and Type II RCD progress to de novo or EATL are <1%, 3-14%, and 33-52%, respectively.

De novo EATL
De novo EATL can occur in individuals whose coeliac disease was undiagnosed until EATL was found or who have mild/well-controlled coeliac disease. The findings in these patients usually differ little from those found in mild/well-controlled cases that do not progress to EATL; their small intestinal mucosa is populated by increased number of IEL and exhibits tissue destruction (e.g. small intestinal villus atrophy), Nonetheless, their IEL are normal-appearing, small cells that on examination are polyclonal (i.e. genetically diverse), express CD3 and CD8, and do not have genetic abnormalities. The mechanism behind the development of EATL in these individuals is not understood.

Type I refractory coeliac disease
Type I RCD patients, who constitute 15-23% of all patients with RCD, are refractory to the gluten diet as evidenced by their worsening symptoms, increased tissue destruction, and rising numbers of TCRαβ+CD*αβ+IEL in tissue lesions. Some Type I RCD  patients may have failed to respond to the diet from the onset of their disease. If either cases, these patients show no change in the normal appearance and polyclonal nature of their small intestinal IEL and these IEL show no genetic abnormalities. The cause for these coeliac disease patients progressing to Type I RCD, after excluding the very common problem of failure to fully exclude gluten from their diets, is either due to their genetic makeup (see above section on genetics) or is unknown.

Type II refractory coeliac disease
Type I RCD patients may progress to Type II RCD as evidenced by their more severe symptoms, increased intestinal tissue destruction, and expanding numbers of intestinal IEL, particularly iCD3+IEL. Their IEL typically consist of genetically different subpopulations of cells that have a monoclonal rearrangement of their TCR and therefore are descendant from a single ancestral cell. Subpopulations of these IEL also have one or more of the following genetic abnormalities: trisomy of chromosome 1's long (or "q") arm at position 22-44 (abbreviated 1-q22-24); genomic alterations around the TP53 tumor suppressor gene at position 13.1 on the short or "p" arm of chromosome 17; genomic alterations around the CDKN2A tumor suppressor and CDKN2B cell proliferation regulator at position p21.3 on chromosome 9 that result in loss of heterozygosity for both genes; and/or activating mutations in JAK1 (75% of cases) and STAT3 (25% of cases). In Type II RCD, the same types of abnormal ILE found in the small intestine may be detected in the colon, stomach, mesenteric lymph nodes, blood, bone marrow, and epithelium of the airways and skin. Finally, the small intestinal lesions in Type II RCD contain IL-2 and IL-21 as well as increased levels of IL-15. Laboratory studies indicate that these 3 cytokines acting individually or in synergy are potent stimulators of the JAK1/STAT3 signaling pathway in iCD3+IEL and thereby promote these cells survival (by blocking apoptosis) and proliferation. The small intestinal lesions also contain a tumor necrosis factor which stimulates iCD3+IEL survival and proliferation but does so by activating NF-κB, MAPK, and/or c-Jun N-terminal kinases rather than JAK1/STAT3 signaling pathway. These data suggest that: a) Type II RCD is a low grade lymphoma; 2) the intense inflammation in Type II RCD, perhaps amplified by the cited cytokines, promotes the proliferation, survival, genome instability, and consequential genetic abnormalities in IEL; and 3) one or more of these factors cause the transformation of Type II RD to EATL. As currently understood, the release of IL-15 by mucosal epithelial cells, the binding of IL-15 to the IL-15Rβ cell surface receptor on iCD3+IEL, and the stimulation thereby of these cells appears particularly important in driving Type II RCD to EATL in a significant number of cases.

Ulcerative jejunitis
Ulcerative jejunitis (also termed chronic ulcerative jejunitis, multifocal ulcerated microlymphomas, ulcerative jejunoilitis, and chronic ulcerative jejunoilitis) is regarded as a rare complications or severe form of Type II RCD in which the jejunum or jejunum plus ileum portions of the small intestine contain multifocal ulcers. Patients with this disorder have a higher risk of developing EATL than other Type II RCD patients.

EATL
Besides the genetic gene abnormalities found in Type II RCD, the malignant IEL in EATL consist of one or more subpopulations that have mutations: in other JAK-STAT pathway genes viz., STAT5B, JAK3, and SOCS1 (SOCS1 inhibits STAT signaling); tumor suppressor genes BCL11B and SETD2 (SETD2 is also involved in regulating lymphocyte development); another gene involved in lymphocyte development, PRDM1; a gene promoting activation of the tumor suppressor p53, IRF1; DNA repair genes BRIP1 and TERT (TERT is also involved in maintaining DNA telomeres and thereby chromosome stability); the NRAS and KRAS oncogenes; a gene involved in progression of the cell cycle and thereby cellular proliferation, STK10; a gene involved in promoting cell death by apoptosis, DAPK3; a gene involved in regulating Interferon gamma actions, inhibiting toll-like receptor signaling, and regulating activation of innate and adaptive immune systems, IRF4; a gene involved in cell signaling through various cell receptors, GNAS; a gene involved in production of the immunoglobulin, IgA, BBX; and two chromatin remodeling genes, TET2 and YLPM1. These cells also overexpress or under express various genes that impact cell survival, growth, and malignancy. It is likely that one or more of these genetic and gene expression abnormalities contribute to the malignant behavior of EATL.

Diagnosis

The diagnosis of EATL is based on endoscopic findings of: 1) flattened duodenal folds and small intestinal fissures and ulcers; 2) biopsy findings of small intestinal inflammation, increased IEL, villous atrophy, and crypt hyperplasia; 3) HLA-DG serology typing and/or gene allele analyses showing results compatible with coeliac disease (see above section on genetics); and 4) positive serology tests for IgA antitissue translutamase antibodies, IgA antibodies to deamidated gliadin peptides, IgG antibodies to deamidated gliadin peptides, and/or IgA antibodies to antitissue translutamase. About 35% of EATL cases will be found to have spread of the disease to extra-intestinal sites with lesions in the mesenteric lymph nodes (~35% of cases), bone marrow (<10% of cases), and, uncommonly, blood that contain IEL with the same genetic abnormalities and cell markers as those found in the IEL of their intestinal lesions. Intestinal biopsy specimens of EATL lesions also commonly show the presence of mucosal inflammatory cells (particularly eosinophils and histiocytes); a greatly  expanded population of medium- to large-sized or anaplastic IEL expressing iCD3 as well as cytotoxic and cell activation markers (e.g. granzyme B and usually TIA1 and perforin); and, frequently CD30. In most cases these IEL also show genetic abnormalities, particularly activating mutations in JAK1 and/or STAT3 and to lesser extents those cited in the above section on EATL. The malignant IEL in EATL do not express CD56.  Rarely, patients present with EATL who have no gastrointestinal symptoms of celiac disease but rather with extra-intestinal manifestations that are associated with the disease such as dermatitis herpetiformis, psoriasis, other chronic skin conditions, dental enamel defects, gluten-induced cerebellar ataxia, arthritis, and  arthralgias.

Differential diagnosis
Other gastrointestinal T-cell lymphomas can resemble, and therefore need to be differentiated from, EATL. These include:
 Monomorphic epitheliotropic intestinal T cell lymphoma is distinguished from EATL in that it is not associated with coeliac disease; is more common in Asians than Northern Europeans; and their small intestine lesions show little or no inflammatory cells plus numerous small- to medium-sized, normal appearing IEL that express CD56 but may not express CD30. The genetic abnormalities found in Monomorphic epitheliotropic intestinal T cell lymphoma are similar to those in EATL.
 Small intestinal adenocarcinoma, while rare, is far more frequent in coeliac disease than in the general population. Unlike EATL, it often occurs in celiac disease patients who, while otherwise well-maintained on a gluten-free diet, have vague gastrointestinal symptoms such as fatigue, malaise, and weight loss. However, it can cause severe symptoms such as bowel obstruction and intestinal bleeding. Also unlike EATL, the adenocarcinoma often occurs in women and younger (<50 years old) individuals; is more likely to begin as a non-maligant adenoma; and has the histology typical of an adenocarcinoma.
 Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and anaplastic large cell lymphoma (ALCL) are heterogeneous sets of aggressive T cell lymphomas that exhibit variable morphologies. Unlike EATL, they are not associated with coeliac disease and rarely present as an intestinal lymphoma without involvement of extra-intestinal tissues. PTCL-NOS's genetic abnormalities differ from those in EATL: its malignant cells have recurrent mutations in TET2, IDH2, DNMT3A, RHOA, VAV1, and/or CD28 genes, rearrangements of the ITK gene with the SYK, FER, and ERBB4 genes, and/or rearrangements of the TP63 gene. ALCL likewise exhibits different mutations than those occurring in EATL; its malignant cells, similar to those in PTCL-NOS, have recurrent mutations in VAV1, rearrangements of the ITK gene with the SYK, FER, and ERBB genes, and/or rearrangements of the TP63 gene. However, ALCL also has distinctive genetic abnormalities: malignant cells in the ALK+ form of ALCL have a translocation between the NPM1 and ALK genes to form a gene encoding the chimeric protein, NPM-ALK while the malignant cells in the ALK- form of ALCL have translocations of either the DUSP22 or TP63 genes.
 Epstein–Barr virus–associated lymphoproliferative diseases are a large group of benign, pre-malignant and malignant lymphoproliferative diseases that are associated with the infection of lymphocytes by the Epstein–Barr virus. One of these diseases, Extranodal NK/T cell lymphoma, nasal type may develop primarily in the small intestine but unlike EATL often involves lesions in the nasal cavity, pharynx, lung, skin, or other tissues. Furthermore, the malignant T cells in this disease express readily detectable products encoded by the Epstein–Barr virus's genes whereas those of EATL are not infected with this virus and therefore do not express these viral products.
 Indolent T cell lymphoproliferative disorder of the gastrointestinal tract (ITCLD-GT)) is a rare, slowly progressive, and potentially premalignant disorder of the GI tract that may be mistaken of EATL, particularly with respect to the severity of its symptoms, the gross pathology of its intestinal lesions, and the presence in its intestinal lesions of T cells that have monoclonal rearrangements of their TCR as well as genetic abnormalities in the JAK/STAT signaling pathway. Unlike EATL, ITCLD-GT is not associated with coeliac disease; often involves symptomatic lesions of the upper GI tract (i.e. stomach, esophagus, and pharynx); and has GI tract lesions populated by T cells that express CD3 (rather than iCD3), do not express CD56, and, in many cases, express an abnormal STAT3-JAK2 fusion gene.

Prevention
Strict adherence to a gluten-free diet has been shown in some but not all studies to prevent in a significant number of cases the progression of coeliac disease to Type I RCD, Type II RCD, and EATL. For example, an Italian study of 1757 patients found that the morbidity of EATL over 3 years fell from 6.42 to 0.22 in coeliac disease patients kept on a strict gluten-free diet. While two other studies found that the risk of malignancy in the diseases did not fall on this diet, current opinion strongly favors using it in all stages of coeliac disease.

Management

Treatment of refractory celiac disease
Efforts have also been made to treat refractory coeliac disease in order to prevent EATL. Treatment with corticosteroids, particularly budesonide gives temporary improvement in symptoms and histological responses in 30-40% of patients but few have attained a good overall response. The addition of azathioprine, cyclosporin, or a monoclonal antibody directed against tumor necrosis factor-α to the corticosteroid regimen, the use, as single agents, of purine analogs (i.e. pentostatin, cladribine) or monoclonal antibody directed against CD52 as well as the use of intensive chemotherapy regimens have shown little therapeutic effects. Furthermore, azathioprine, anti-CD52 antibody, and cladribine have been reported to increase the disease's progression to EATL. In summary, the role these drugs, intensive chemotherapy regimens, and hematopoietic stem cell transplantation in the treatment of refractory coeliac disease is unclear and has not been shown to improve, and in some cases may worsen, the chances that Type I and Type II RCD, will progress to EATL.

Patients with refractory coeliac disease, especially those with Type II RCD, should be examined at regular intervals for the development of EATL using magnetic resonance imaging, capsule endoscopy, CT scan, and Positron emission tomography;. These examinations should also be used whenever patients with refractory disease experience worsening symptoms.

Treatment of EATL
In eligible patients, surgery where necessary (required in >80% of patients) to repair obstructed or perforated bowel or remove bulky disease followed by a conditioning regimen of high-dose chemotherapy (usually the CHOP regimen) and autologous stem cell transplantion has been the mainstay of treating EATL. Previous chemotherapy treatment regimens that did not use autologous stem cell transplantation reported poor prognoses with overal survival, progression free, and mortality rates over a 5-year period of 22%, 3%, and 81%. respectively whereas a regimen that included intensive chemotherapy, conditioning, and autologous stem cell transplantation had rates of 60%, 52%, and 39%, respectively.

Research

Clinical trials
A phase 2 study sponsored by the Imagine Institute and being conducted in Paris, France is recruiting patients to examine the efficacy and side effects of a new treatment regimen on EATL. The regimen consists of treatment with brentuximab vedotin plus CHP (i.e. cyclophosphamide, Adriamycin, prednisone) followed by consolidation chemotherapy and autologous hematopoietic stem cell transplantation. Brentuximab vedotin is a chimeric monoclonal antibody that is complexed to the antimitotic agent, monomethyl auristatin E; the drug binds to the cell-membrane protein CD30 to deliver thereby the antimitotic aged into CD30-bearing target cells. This study is based on a phase 1 study finding that a regimen consisting of brentuximab vedotin plus CHP achieved objective responses in all 26 patients tested, with complete remissions obtained in the only patient with EATL, all 6 patients with ALCL, and 16 of 19 patients with other types of T-cell/NK-cell lymphomas.

A phase 1 study sponsored by the National Institutes of Health Clinical Center is recruiting patients that have CD30-expressing lymphomas such as EATL to examine the effects of a conditioning drug regimen (i.e. cyclophosphamide and fludarabine) followed by infusions of the patients' chimeric antigen receptor T cells that have been modified to target and destroy cells bearing CD30.

A phase 1 study sponsored by the NIH and Mayo Clinic USA is recruiting patients with peripheral T-cell lymphomas, including EATL, to study the efficacy and toxicity of nivolumab. Nivolumab is monoclonal antibody checkpoint inhibitor that binds to the programmed cell death protein 1 (PD-1) thereby blocking this protein from being activated by programmed death-ligand 1 (PD-L1). Many types of cancer cells increase their expression of PD-LI in order to inhibit immune cells that express PD-1 from killing them. Nivolumab blocks this inhibition and has been found effective in suppressing the growth of certain cancers.

Clinical trials
A recently completed Phase 2, randomized, double-blinded, placebo-controlled, parallel group study evaluated the efficacy and safety of a monoclonal antibody (termed AMG 714) directed against IL-15 in adult patients with Type II RCD. The study found potential therapeutic effects of the treatment in that it halted the malignant progression of IEL in these patients. Expanded access or compassionate use requests for AMG 714 may be considered for adult patients with biopsy-proven Type II RCD who have failed all available treatment options and do not have EATL. To request access, use Responsible Party contact information found by hitting the "More info..." linkage on the following clinical trials page.

See also
 Lymphoma
 Mucosa-associated lymphoid tissue

References

External links

Lymphocytes
T cells
Lymphocytic disorders
Gastrointestinal tract disorders
Lymphoma
Non-Hodgkin lymphoma

Enteropathy-associated T-cell lymphoma


The Nobel Prize in Literature (here meaning for literature; ) is a Swedish literature prize that is awarded annually, since 1901, to an author from any country who has, in the words of the will of Swedish industrialist Alfred Nobel, "in the field of literature, produced the most outstanding work in an idealistic direction" (original ). Though individual works are sometimes cited as being particularly noteworthy, the award is based on an author's body of work as a whole. The Swedish Academy decides who, if anyone, will receive the prize. The academy announces the name of the laureate in early October. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895. Literature is traditionally the final award presented at the Nobel Prize ceremony. On some occasions, the award has been postponed to the following year, most recently in 2018 as of July 2023.

Background

Alfred Nobel stipulated in his last will and testament that his money be used to create a series of prizes for those who confer the "greatest benefit on mankind" in physics, chemistry, peace, physiology or medicine, and literature. Although Nobel wrote several wills during his lifetime, the last was written a little over a year before he died, and it was signed at the Swedish-Norwegian Club in Paris on 27 November 1895. Nobel bequeathed 94% of his total assets, 31 million Swedish kronor (US$198 million, €176 million in 2016), to establish and endow the five Nobel Prizes. Due to the level of scepticism surrounding the will, it was not until 26 April 1897 that the Storting (Norwegian Parliament) approved it. The executors of his will were Ragnar Sohlman and Rudolf Lilljequist, who formed the Nobel Foundation to take care of Nobel's fortune and organise the prizes.

The members of the Norwegian Nobel Committee that were to award the Peace Prize were appointed shortly after the will was approved. The prize-awarding organisations followed: the Karolinska Institutet on 7 June, the Swedish Academy on 9 June, and the Royal Swedish Academy of Sciences on 11 June. The Nobel Foundation then reached an agreement on guidelines for how the Nobel Prize should be awarded. In 1900, the Nobel Foundation's newly created statutes were promulgated by King Oscar II. According to Nobel's will, the prize in literature should be determined by "the Academy in Stockholm", which was specified by the statutes of the Nobel Foundation to mean the Swedish Academy.

Nomination and award procedure

Each year, the Swedish Academy sends out requests for nominations of candidates for the Nobel Prize in Literature. Members of the Academy, members of literature academies and societies, professors of literature and language, former Nobel literature laureates, and the presidents of writers' organisations are all allowed to nominate a candidate. It is not allowed to nominate oneself.

Thousands of requests are sent out each year, and  about 220 proposals were returned. These proposals must be received by the Academy by 1 February, after which they are examined by the Nobel Committee, a working group within the Academy comprising four to five members. By April, the committee narrows the field to around 20 candidates. By May, a shortlist of five names is approved by the Academy. The next four months are spent reading and reviewing the works of the five candidates. In October, members of the Academy vote, and the candidate who receives more than half of the votes is named the Nobel laureate in Literature. No one can get the prize without being on the list at least twice; thus, many authors reappear and are reviewed repeatedly over the years. The academicians read works in their original language, but when a candidate is shortlisted from a language that no member masters, they call on translators and oath-sworn experts to provide samples of that writer's work. Other elements of the process are similar to those of other Nobel Prizes. The Swedish Academy is composed of 18 members who are elected for life and, until 2018, not technically permitted to leave. On 2 May 2018, King Carl XVI Gustaf amended the rules of the academy and made it possible for members to resign. The new rules also mention that a member who has been inactive in the work of the academy for more than two years can be asked to resign. The members of the Nobel committee are elected for a period of three years from among the members of the academy and are assisted by specially appointed expert advisers.

The award is usually announced in October. Sometimes, however, the award has been announced the year after the nominal year, the latest such case being the 2018 award. In the midst of controversy surrounding claims of sexual assault, conflict of interest, and resignations by officials, on 4 May 2018, the Swedish Academy announced that the 2018 laureate would be announced in 2019 along with the 2019 laureate. Some years, such as in 1949, no candidate received the required majority of the votes, and for that reason, the prize was postponed and announced the following year.

Prizes
A Literature Nobel Prize laureate receives a gold medal, a diploma bearing a citation, and a sum of money. The amount of money awarded depends on the income of the Nobel Foundation that year. The literature prize can be shared between two, but not three, laureates. If a prize is awarded jointly, the prize money is split equally between them.

The prize money of the Nobel Prize has been fluctuating since its inauguration but  it stood at  (about ), previously it was . This was not the first time the prize amount was decreased—beginning with a nominal value of  in 1901 (worth 8,123,951 in 2011 SKr) the nominal value has been as low as  (2,370,660 in 2011 SKr) in 1945—but it has been uphill or stable since then, peaking at an SKr-2011 value of 11,659,016 in 2001.

The laureate is also invited to give a lecture during "Nobel Week" in Stockholm; the highlight is the prize-giving ceremony and banquet on 10 December. It is the second richest literary prize in the world.

Medals

The literature medal features a portrait of Alfred Nobel in left profile on the obverse. It was designed by Erik Lindberg. The reverse of the medal depicts a '... young man sitting under a laurel tree who, enchanted, listens to and writes down the song of the Muse'. It is inscribed "" ("It is beneficial to have improved (human) life through discovered arts"), an adaptation of "" from line 663 of book 6 of the Aeneid by the Roman poet Virgil. A plate below the figures is inscribed with the name of the recipient. The text "ACAD. SUEC." denoting the Swedish Academy is also inscribed on the reverse.

Between 1902 and 2010, the Nobel Prize medals were struck by the Myntverket, the Swedish royal mint, located in Eskilstuna. In 2011, the medals were made by the Det Norske Myntverket in Kongsberg. The medals have been made by Svenska Medalj in Eskilstuna since 2012.

Diplomas
Nobel laureates receive a diploma directly from the King of Sweden. Each diploma is uniquely designed by the prize-awarding institutions for the laureate who receives it. The diploma contains a picture and text that states the name of the laureate and normally a citation of why they received the prize.

Laureates

The Nobel Prize in Literature has been awarded 116 times between 1901 and 2023 to 120 individuals: 103 men and 17 women. The prize has been shared between two individuals on four occasions. It was not awarded on seven occasions. The laureates have included writers in 25 different languages. The youngest laureate was Rudyard Kipling, who was 41 years old when he was awarded in 1907. The oldest laureate to receive the prize was Doris Lessing, who was 88 when she was awarded in 2007. It has been awarded posthumously once, to Erik Axel Karlfeldt in 1931. On some occasions, the awarding institution, the Swedish Academy, has awarded the prize to its own members; Verner von Heidenstam in 1916, the posthumous prize to Karlfeldt in 1931, Pär Lagerkvist in 1951, and the shared prize to Eyvind Johnson and Harry Martinson in 1974. Selma Lagerlöf was elected a member of the Swedish Academy in 1914, five years after she was awarded the Nobel Prize in 1909. Two writers have declined the prize, Boris Pasternak in 1958 ("Accepted first, later caused by the authorities of his country (Soviet Union) to decline the Prize", according to the Nobel Foundation) and Jean-Paul Sartre in 1964.

Interpretations of Nobel's guidelines
Alfred Nobel's guidelines for the prize, stating that the candidate should have bestowed "the greatest benefit on mankind" and written "in an idealistic direction," have sparked much discussion. In the early history of the prize, Nobel's "idealism" was read as "a lofty and sound idealism." The set of criteria, characterised by its conservative idealism, holding church, state, and family sacred, resulted in prizes for Bjørnstjerne Bjørnson, Rudyard Kipling, and Paul Heyse. During World War I, there was a policy of neutrality, which partly explains the number of awards to Scandinavian writers. In the 1920s, "idealistic direction" was interpreted more generously as "wide-hearted humanity," leading to awards for writers like Anatole France, George Bernard Shaw, and Thomas Mann. In the 1930s, "the greatest benefit on mankind" was interpreted as writers within everybody's reach, with authors like Sinclair Lewis and Pearl Buck receiving recognition. From 1946, a renewed Academy changed focus and began to award literary pioneers like Hermann Hesse, André Gide, T. S. Eliot, and William Faulkner. During this era, "the greatest benefit on mankind" was interpreted in a more exclusive and generous way than before. Since the 1970s, the Academy has often given attention to important but internationally unnoticed writers, awarding writers like Isaac Bashevis Singer, Odysseus Elytis, Elias Canetti, and Jaroslav Seifert.

From 1986, the Academy acknowledged the international horizon in Nobel's will, which rejected any consideration of the nationality of the candidates, and awarded authors from all over the world, such as Wole Soyinka from Nigeria, Naguib Mahfouz from Egypt, Octavio Paz from Mexico, Nadine Gordimer from South Africa, Derek Walcott from St. Lucia, Toni Morrison, the first African-American on the list, Kenzaburo Oe from Japan, and Gao Xingjian, the first laureate to write in Chinese. In the 2000s, V. S. Naipaul, Mario Vargas Llosa, and the Chinese writer Mo Yan have been awarded, but the policy of "a prize for the whole world" has been less noticeable as the Academy has mostly awarded European and English-language writers from the Western literary tradition. In 2015, a rare prize to a non-fiction writer was awarded to Svetlana Alexievich.

Shared prize
The Nobel Prize in Literature can be shared between two individuals. However, the Academy has been reluctant to award shared prizes, mainly because divisions are liable to be interpreted as a result of a compromise. The shared prizes awarded to Frederic Mistral and José Echegaray in 1904 and to Karl Gjellerup and Henrik Pontoppidan in 1917 were, in fact, both results of compromises. The Academy has also hesitated to divide the prize between two authors, as a shared prize runs the risk of being regarded as only half a laurel. Shared prizes are exceptional, and more recently, the Academy has awarded a shared prize on only two occasions, to Shmuel Yosef Agnon and Nelly Sachs in 1966, and to Eyvind Johnson and Harry Martinson in 1974.

Recognition of a specific work
Nobel Prize Laureates in Literature are awarded for the author's life work, but on some occasions, the Academy has singled out a specific work for particular recognition. For example, Knut Hamsun was awarded in 1920 "for his monumental work, Growth of the Soil," Thomas Mann in 1929 "principally for his great novel, Buddenbrooks, which has won steadily increased recognition as one of the classic works of contemporary literature," John Galsworthy in 1932 "for his distinguished art of narration which takes its highest form in The Forsyte Saga," Roger Martin du Gard in 1937 "for the artistic power and truth with which he has depicted human conflict as well as some fundamental aspects of contemporary life in his novel-cycle Les Thibault'," Ernest Hemingway in 1954 "for his mastery of the art of narrative, most recently demonstrated in The Old Man and the Sea, and for the influence that he has exerted on contemporary style," and Mikhail Sholokhov in 1965 "for the artistic power and integrity with which, in his epic of the Don, he has given expression to a historic phase in the life of the Russian people".

 Potential candidates
Nominations are kept secret for fifty years until they are publicly available at The Nomination Database for the Nobel Prize in Literature. Currently, only nominations submitted between 1901 and 1971 are available for public viewing.

 Criticism
Although the Nobel Prize in Literature has become the world's most prestigious literature prize, the Swedish Academy has attracted significant criticism for its handling of the award. Many authors who have won the prize have fallen into obscurity, while others rejected by the jury remain widely studied and read. In the Wall Street Journal, Joseph Epstein wrote, "You might not know it, but you and I are members of a club whose fellow members include Leo Tolstoy, Henry James, Anton Chekhov, Mark Twain, Henrik Ibsen, Marcel Proust, James Joyce, Jorge Luis Borges and Vladimir Nabokov. The club is the Non-Winners of the Nobel Prize in Literature. All these authentically great writers, still alive when the prize, initiated in 1901, was being awarded, didn't win it." Other notable names from the non-western canon who were ignored despite being nominated several times for the prize include Sri Aurobindo and Dr. Sarvepalli Radhakrishnan. The prize has "become widely seen as a political one – a peace prize in literary disguise", whose judges are prejudiced against authors with political tastes different from theirs.  Tim Parks has expressed skepticism that it is possible for "Swedish professors ... [to] compar[e] a poet from Indonesia, perhaps translated into English with a novelist from Cameroon, perhaps available only in French, and another who writes in Afrikaans but is published in German and Dutch...". As of 2021, 16 of the 118 recipients have been of Scandinavian origin. The Academy has often been alleged to be biased towards European, and in particular Swedish, authors.

Nobel's "vague" wording for the criteria for the prize has led to recurrent controversy. In the original Swedish, the word idealisk translates as "ideal." The Nobel Committee's interpretation has varied over the years. In recent years, this means a kind of idealism championing human rights on a broad scale.

 Controversies about Nobel laureate selections

From 1901 to 1912, the committee, led by the conservative Carl David af Wirsén, assessed the literary quality of a work in relation to its contribution to humanity's pursuit of the "ideal." Leo Tolstoy, Henrik Ibsen, Émile Zola, and Mark Twain were rejected in favour of authors who are little read today.

Later, the prize has often been controversial due to the Swedish Academy's Eurocentric choices of laureates for political reasons, as seen in the years 1970, 2005, and 2019, and for the Academy awarding its own members, as happened in 1974.

 Nationality-based criticism

The prize's focus on European men, and Swedes in particular, has been the subject of criticism, even from Swedish newspapers. The majority of laureates have been European, with Sweden itself receiving more prizes (8) than all of Asia (7, if Turkish Orhan Pamuk is included), as well as all of Latin America (7, if Saint Lucian Derek Walcott is included). In 2009, Horace Engdahl, then the permanent secretary of the Academy, declared that "Europe still is the centre of the literary world" and that "the US is too isolated, too insular. They don't translate enough and don't really participate in the big dialogue of literature."

In 2009, Engdahl's replacement, Peter Englund, rejected this sentiment ("In most language areas ... there are authors that really deserve and could get the Nobel Prize and that goes for the United States and the Americas, as well") and acknowledged the Eurocentric nature of the award, saying that, "I think that is a problem. We tend to relate more easily to literature written in Europe and in the European tradition." American critics are known to object that those from their own country, like Philip Roth, Thomas Pynchon, and Cormac McCarthy, have been overlooked, as have Latin Americans such as Jorge Luis Borges, Julio Cortázar, and Carlos Fuentes, while in their place Europeans lesser-known to that continent have triumphed. The 2009 award to Herta Müller, previously little-known outside Germany but many times named favourite for the Nobel Prize, re-ignited the viewpoint that the Swedish Academy was biased and Eurocentric.

The 2010 prize was awarded to Mario Vargas Llosa, a native of Peru in South America, a generally well-regarded decision. When the 2011 prize was awarded to the Swedish poet Tomas Tranströmer, permanent secretary of the Swedish Academy Peter Englund said the prize was not decided based on politics, describing such a notion as "literature for dummies." The Swedish Academy awarded the next two prizes to non-Europeans, Chinese author Mo Yan and Canadian short story writer Alice Munro. French writer Patrick Modiano's win in 2014 renewed questions of Eurocentrism; when asked by The Wall Street Journal "So no American this year, yet again. Why is that?", Englund reminded Americans of the Canadian origins of the previous year's recipient, the Academy's desire for literary quality and the impossibility of rewarding everyone who deserves the prize.

 Overlooked literary achievements
In the history of the Nobel Prize in Literature, many critical literary figures were ignored. The literary historian Kjell Espmark admitted that "as to the early prizes, the censure of bad choices and blatant omissions is often justified. Tolstoy, Ibsen, and Henry James should have been rewarded instead of, for instance, Sully Prudhomme, Eucken, and Heyse." There are omissions which are beyond the control of the Nobel Committee such as the early death of an author as was the case with Marcel Proust, Italo Calvino, and Roberto Bolaño. According to Kjell Espmark, "the main works of Kafka, Cavafy, and Pessoa were not published until after their deaths, and the true dimensions of Mandelstam's poetry were revealed above all in the unpublished poems that his wife saved from extinction and gave to the world long after he had perished in his Siberian exile." British novelist Tim Parks ascribed the never-ending controversy surrounding the decisions of the Nobel Committee to the "essential silliness of the prize and our own foolishness at taking it seriously" and noted that "eighteen (or sixteen) Swedish nationals will have a certain credibility when weighing up works of Swedish literature, but what group could ever really get its mind round the infinitely varied work of scores of different traditions. And why should we ask them to do that?"

Although several Scandinavians were awarded, two of the most celebrated writers, Norwegian playwright Henrik Ibsen and Swedish author August Strindberg, were repeatedly bypassed by the committee, but Strindberg holds the singular distinction of being awarded an Anti-Nobel Prize, conferred by popular acclaim and national subscription and presented to him in 1912 by future prime minister Hjalmar Branting.

Paul Valéry was nominated twelve times between 1930 and 1945 but died just as the Academy intended to award him the prize in 1945.

James Joyce wrote the books that rank 1st and 3rd on the Modern Library 100 Best Novels – Ulysses and Portrait of the Artist as a Young Man – but Joyce was never nominated for the prize. Kjell Espmark, a member of the Nobel Prize committee and author of the history of the prize, claimed that Joyce's "stature was not properly recognized even in the English-speaking world," but that Joyce doubtless would have been awarded if he had lived in the late 1940s when the Academy began to award literary pioneers like T. S. Eliot.

Argentine writer Jorge Luis Borges was nominated for the prize several times, but the Academy did not award it to him, though he was among the final candidates some years in the 1960s.

Graham Greene was nominated for the prize twenty times between the years 1950 and 1966. Greene was a celebrated candidate to be awarded the prize in the 1960s and 1970s, and the Academy was criticised for passing him over.

French novelist and intellectual André Malraux was seriously considered for the prize in the 1950s. Malraux was competing with Albert Camus but was rejected several times, especially in 1954 and 1955, "so long as he does not come back to novel." Thus, Camus was awarded the prize in 1957. Malraux was again considered in 1969 when he was competing with Samuel Beckett for the prize. Some members of the Nobel committee supported a prize to Malraux, but Beckett was awarded.

W. H. Auden was nominated for the Nobel Prize in Literature ten times in the 1960s and was among the final candidates for the prize several times, but the Academy favoured other writers. In 1964 Auden and Jean-Paul Sartre were the leading candidates, and the Academy favoured Sartre as Auden's best work was thought "too far back in time." In 1967 Auden was one of three final candidates along with Graham Greene and the awarded Guatemalan author Miguel Ángel Asturias.Burton Feldman: The Nobel Prize: A History of Genius, Controversy and Prestige Google Books.

 Controversies about Swedish Academy board members
Membership in the 18-member academy, who select the recipients, is technically for life. Until 2018, members were not allowed to leave, although they might refuse to participate. For members who did not participate, their board seat was left vacant until they died. Twelve active/participating members are required for a quorum.

In 1989, three members, including the former permanent secretary Lars Gyllensten, resigned in protest after the academy refused to denounce Ayatollah Ruhollah Khomeini for calling for the death of Salman Rushdie, author of The Satanic Verses. A fourth member, Knut Ahnlund, decided to remain in the academy but later refused to participate in their work and resigned in 2005 in protest of the Nobel Prize in Literature awarded to Elfriede Jelinek. According to Ahnlund, the decision to award Jelinek ruined the worth of the Nobel Prize in Literature for a long time.Knut Ahnlund död Svenska Yle 30 November 2012

2018 controversy and award cancellation
In April 2018, three members of the academy board resigned in response to a sexual misconduct investigation involving author Jean-Claude Arnault, who is married to board member Katarina Frostenson. Arnault was accused by at least 18 women of sexual assault and harassment. He and his wife were also accused of leaking the names of prize recipients on at least seven occasions so friends could profit from bets. He denied all accusations, although he was later convicted of rape and sentenced to two years and six months in prison.  Sara Danius, the board secretary, hired a law firm to investigate if Frostenson had leaked confidential information and if Arnault had any influence on the Academy, but no legal action was taken. The investigation caused a split within the Academy. Following a vote to exclude board member Frostenson, the three members resigned in protest over the decisions by the Academy. Two former permanent secretaries, Sture Allén and Horace Engdahl, called Danius a weak leader.

On 10 April, Danius was asked to resign from her position by the Academy, bringing the number of empty seats to four. Although the Academy voted against removing Katarina Frostenson from the committee, she voluntarily agreed to withdraw from participating in the academy, bringing the total of withdrawals to five. Because two other seats were still vacant from the Rushdie affair, this left only 11 active members, one short of the quorum needed to vote in replacements. On 4 May 2018, the Swedish Academy announced that the selection would be postponed until 2019, when two laureates would be chosen. It was still technically possible to choose a 2018 laureate, as only eight active members are required to choose a recipient. However, there were concerns that the academy was not in any condition to credibly present the award. The New Academy Prize in Literature, not affiliated with either the Nobel Foundation or the Swedish Academy, was created as an alternative award for 2018 only.

The scandal was widely seen as damaging to the credibility of the prize and its authority. As noted by Andrew Brown in The Guardian'' in a lengthy deconstruction of the scandal:

King Carl XVI Gustaf of Sweden said a reform of the rules may be evaluated, including the introduction of the right to resign in respect of the current lifelong membership of the committee. On 5 March 2019, it was announced that the Nobel Prize in Literature would once again be awarded, and laureates for both 2018 and 2019 would be announced together. The decision came after several changes were made to the structure of the Swedish Academy as well as to the Nobel Committee members selection, in order to "[restore] trust in the Academy as a prize-awarding institution".

Similar international prizes
The Nobel Prize in Literature is not the only literary prize for which all nationalities are eligible. Other notable international literary prizes include the Neustadt International Prize for Literature, the Jerusalem Prize, Franz Kafka Prize, the International Booker Prize, and the Formentor Prix International. The journalist Hephzibah Anderson has noted that the International Booker Prize "is fast becoming the more significant award, appearing an ever more competent alternative to the Nobel". However, since 2016, the International Booker Prize now recognises an annual book of fiction translated into English. Previous winners of the International Booker Prize who have gone on to win the Nobel Prize in Literature include Alice Munro and Olga Tokarczuk. The Neustadt International Prize for Literature is regarded as one of the most prestigious international literary prizes, often referred to as the American equivalent of the Nobel Prize. Like the Nobel Prize, it is awarded not for any one work but for an entire body of work. It is frequently seen as an indicator of who may be awarded the Nobel Prize in Literature. Gabriel García Márquez (1972 Neustadt, 1982 Nobel), Czesław Miłosz (1978 Neustadt, 1980 Nobel), Octavio Paz (1982 Neustadt, 1990 Nobel), Tomas Tranströmer (1990 Neustadt, 2011 Nobel) were first awarded the Neustadt International Prize for Literature before being awarded the Nobel Prize in Literature.

Another award of note is the Spanish Princess of Asturias Award (formerly Prince of Asturias Award) in Letters. During the first years of its existence, it was almost exclusively awarded to writers in the Spanish language, but in more recent times, writers in other languages have been awarded as well. Writers who have won both the Asturias Award in Letters and the Nobel Prize in Literature include Camilo José Cela, Günter Grass, Doris Lessing, and Mario Vargas Llosa.

The non-monetary America Award in Literature presents itself as an alternative to the Nobel Prize. To date, Peter Handke, Harold Pinter, José Saramago, and Mario Vargas Llosa are the only writers to have received both the America Award and the Nobel Prize in Literature.

There are also prizes for honouring the lifetime achievement of writers in specific languages, like the Miguel de Cervantes Prize (for Spanish language, established in 1976) and the Camões Prize (for Portuguese language, established in 1989). Nobel laureates who were also awarded the Miguel de Cervantes Prize include Octavio Paz (1981 Cervantes, 1990 Nobel); Mario Vargas Llosa (1994 Cervantes, 2010 Nobel); and Camilo José Cela (1995 Cervantes, 1989 Nobel). José Saramago is the only author to receive both the Camões Prize (1995) and the Nobel Prize (1998) to date.

The Hans Christian Andersen Award is sometimes referred to as "the Little Nobel". The award has earned this appellation since, in a similar manner to the Nobel Prize in Literature, it recognises the lifetime achievement of writers, though the Andersen Award focuses on a single category of literary works (children's literature).

See also

 The Big Read
 List of literary awards
 List of Nobel laureates
 List of Nobel laureates in Literature
 List of nominees for the Nobel Prize in Literature
 Lists of 100 best books
 Nobel Library
 Swedish Academy Nordic Prize
 World literature

References

External links

 The Nobel Prize Medal for Literature –  Official webpage of the Nobel Foundation.
 Graphics: National Literature Nobel Prize shares 1901–2009 by citizenship at the time of the award and by country of birth. From J. Schmidhuber (2010), Evolution of National Nobel Prize Shares in the 20th Century at arXiv:1009.2634v1
 What the Nobel Laureates Receive – Featured link in "The Nobel Prize Award Ceremonies" on the official site of the Nobel Foundation.
 "The rise of the Prize" – Article by Nilanjana Roy dealing with the history of the award by decade, from the 1900s to the 2000s.
 Alternative Nobel literature prize planned in Sweden

Literature
International literary awards
Literary awards honoring writers
Swedish Academy

Nobel Prize in Literature


The ;  ; ) is a layer of tissue in the eye of many vertebrates and some other animals. Lying immediately behind the retina, it is a retroreflector. It reflects visible light back through the retina, increasing the light available to the photoreceptors (although slightly blurring the image). The tapetum lucidum contributes to the superior night vision of some animals. Many of these animals are nocturnal, especially carnivores, while others are deep sea animals.

Similar adaptations occur in some species of spiders. Haplorhine primates, including humans, are diurnal and lack a tapetum lucidum.

Function and mechanism

Presence of a tapetum lucidum enables animals to see in dimmer light than would otherwise be possible. The tapetum lucidum, which is iridescent, reflects light roughly on the interference principles of thin-film optics, as seen in other iridescent tissues. However, the tapetum lucidum cells are leucophores, not iridophores.

The tapetum functions as a retroreflector which reflects light directly back along the light path. This serves to match the original and reflected light, thus maintaining the sharpness and contrast of the image on the retina. The tapetum lucidum reflects with constructive interference, thus increasing the quantity of light passing through the retina. In the cat, the tapetum lucidum increases the sensitivity of vision by 44%, allowing the cat to see light that is imperceptible to human eyes.

It has been speculated that some flashlight fish may use eyeshine both to detect and to communicate with other flashlight fish. American scientist Nathan H. Lents has proposed that the tapetum lucidum evolved in vertebrates, but not in cephalopods, which have a very similar eye, because of the backwards-facing nature of vertebrate photoreceptors. The tapetum boosts photosensitivity under conditions of low illumination, thus compensating for the suboptimal design of the vertebrate retina.

Classification
A classification of anatomical variants of tapeta lucida defines four types:
 Retinal tapetum, as seen in teleosts (with a variety of reflecting materials from lipids to phenols), crocodiles (with guanine), marsupials (with lipid spheres), and fruit bats (with phospholipids). The tapetum lucidum is within the retinal pigment epithelium; in the other three types the tapetum is within the choroid behind the retina. Two anatomical classes can be distinguished: occlusible and non-occlusible.
 The brownsnout spookfish has an extraordinary focusing mirror derived from a retinal tapetum.
 Choroidal guainine tapetum, as seen in cartilaginous fish The tapetum is a palisade of cells containing stacks of flat hexagonal crystals of guanine.
 Choroidal tapetum cellulosum, as seen in carnivores, rodents and cetacea. The tapetum consists of layers of cells containing organized, highly refractive crystals. These crystals are diverse in shape and makeup: dogs and ferrets use zinc, cats use riboflavin and zinc, and lemurs use only riboflavin.
 Choroidal tapetum fibrosum, as seen in cows, sheep, goats and horses. The tapetum is an array of extracellular fibers, most commonly collagen.

The functional differences between these four structural classes of tapeta lucida are not known.

This classification does not include tapeta lucida in birds. Kiwis, stone-curlews, the boat-billed heron, the flightless kakapo and many nightjars, owls, and other night birds such as the swallow-tailed gull also possess a tapetum lucidum. Nightjars use a retinal tapetum lucidum composed of lipids.

Like humans, some animals lack a tapetum lucidum and they usually are diurnal. These include haplorhine primates, squirrels, some birds, red kangaroo, and pigs. Strepsirrhine primates are mostly nocturnal and, with the exception of several diurnal Eulemur species, have a tapetum lucidum of riboflavin crystals.

When a tapetum lucidum is present, its location on the eyeball varies with the placement of the eyeball in the head, such that in all cases the tapetum lucidum enhances night vision in the center of the animal's field of view.

Apart from its eyeshine, the tapetum lucidum itself has a color. It is often described as iridescent. In tigers it is greenish. In ruminants it may be golden green with a blue periphery, or whitish or pale blue with a lavender periphery. In dogs it may be whitish with a blue periphery. The color in reindeer changes seasonally, allowing the animals to better avoid predators in low-light winter at the price of blurrier vision.

Eyeshine

Eyeshine is a visible effect of the tapetum lucidum. When light shines into the eye of an animal having a tapetum lucidum, the pupil appears to glow. Eyeshine can be seen in many animals, in nature and in flash photographs. In low light, a hand-held flashlight is sufficient to produce eyeshine that is highly visible to humans (despite their inferior night vision). Eyeshine occurs in a wide variety of colors including white, blue, green, yellow, pink and red. However, since eyeshine is a type of iridescence, the color varies with the angle at which it is seen and the minerals which make up the reflective tapetum-lucidum crystals.

White eyeshine occurs in many fish, especially walleye; blue eyeshine occurs in many mammals such as horses; green eyeshine occurs in mammals such as cats, dogs, and raccoons; and red eyeshine occurs in coyote, rodents, opossums and birds.

Although human eyes lack a tapetum lucidum, they still exhibit a weak reflection from the choroid, as can be seen in photography with the red-eye effect and with near-infrared eyeshine. Another effect in humans and other animals that may resemble eyeshine is leukocoria, which is a white shine indicative of abnormalities such as cataracts and cancers.

In blue-eyed cats and dogs

Cats and dogs with a blue eye color may display both eyeshine and red-eye effect. Both species have a tapetum lucidum, so their pupils may display eyeshine. In flash color photographs, however, individuals with blue eyes may also display a distinctive red eyeshine. Individuals with heterochromia may display red eyeshine in the blue eye and normal yellow/green/blue/white eyeshine in the other eye. These include odd-eyed cats and bi-eyed dogs. The red-eye effect is independent of the eyeshine: in some photographs of individuals with a tapetum lucidum and heterochromia, the eyeshine is dim, yet the pupil of the blue eye still appears red. This is most apparent when the individual is not looking into the camera because the tapetum lucidum is far less extensive than the retina.

In spiders
Most species of spider also have a tapetum, which is located only in their smaller, lateral eyes; the larger central eyes have no such structure. This consists of reflective crystalline deposits, and is thought to have a similar function to the structure of the same name in vertebrates. Four general patterns can be distinguished in spiders:
 Primitive type (e.g. Mesothelae, Orthognatha)a simple sheet behind the retina
 Canoe-shape type (e.g. Araneidae, Theridiidae)two lateral walls separated by a gap for the nerve fibres
 Grated type (e.g. Lycosidae, Pisauridae)a relatively complex, grill-shaped structure
 No tapetum (e.g. Salticidae)

Uses by humans

Humans use scanning for reflected eyeshine to detect and identify the species of animals in the dark, and deploying trained search dogs and search horses at night, as these animals benefit from improved night vision through this effect.

Using eyeshine to identify animals in the dark employs not only its color but also several other features. The color corresponds approximately to the type of tapetum lucidum, with some variation between species. Other features include the distance between pupils relative to their size; the height above ground; the manner of blinking (if any); and the movement of the eyeshine (bobbing, weaving, hopping, leaping, climbing, flying).

Artificial tapetum lucidum
Manufactured retroreflectors modeled after a tapetum lucidum are described in numerous patents and today have many uses. The earliest patent, first used in "Catseye" brand raised pavement markers, was inspired by the tapetum lucidum of a cat's eye.

Pathology
In dogs, certain drugs are known to disturb the precise organization of the crystals of the tapetum lucidum, thus compromising the dog's ability to see in low light. These drugs include ethambutol, macrolide antibiotics, dithizone, antimalarial medications, some receptor H2-antagonists, and cardiovascular agents. The disturbance "is attributed to the chelating action which removes zinc from the tapetal cells."

Gallery
Traditionally it has been difficult to take retinal images of animals with a tapetum lucidum because ophthalmoscopy devices designed for humans rely on a high level of on-axis illumination. This kind of illumination causes a great deal of reflex, or back-scatter, when it interacts with the tapetum. New devices with variable illumination can make this possible, however.

See also
 Defense mechanism (biology)
 Emission theory (vision)
 Nocturnal bottleneck
 Walleye

Notes

References

External links

Vertebrate anatomy
Animal communication
Science of photography
Eye anatomy

Tapetum lucidum


The Pierre Werner Cricket Ground, also known as the Walferdange Cricket Ground, is a cricket ground in Walferdange, in central Luxembourg. It is the premier cricket venue in Luxembourg, being the home ground of the country's top club, the Optimists Cricket Club, which plays in the Belgian Cricket League, and of the Luxembourg national team.

The ground was opened in 1991. In 2002 the ground was given its present name to commemorate Pierre Werner (1913–2002), formerly Prime Minister of Luxembourg and honorary president of Optimists Cricket Club. The ground was established on land donated by the Walferdange commune, adjacent to the Alzette river.

The ground has hosted matches between the Luxembourg national team and various other teams, including the Belgium national team and the MCC. The heavy use of the ground is illustrated by the programme in 2003, when it "was in use almost every day between mid-April and early October". That year two internationals against France and one against Belgium were played on the ground (though one of the games against France was rained off). A six-a-side tournament was hosted in 2007.

The ground is the only outdoor venue regularly used for cricket in Luxembourg, with the only other venue being Robert Schuman Oval, located  over the French border in Évrange. The ground's pitch is artificial matting on concrete.

The ground hosts a one-week junior training academy each July. In 2010 this was attended by forty boys and girls of all ages, who were coached by a Level 3 coach from the UK and benefited from the ground's "excellent facilities".

In August 2020, the ground was selected to host the 2020 Luxembourg T20I Trophy, a tri-series between Luxembourg, Belgium and the Czech Republic.

List of International Centuries

Twenty20 Internationals

This is the list of centuries scored at the ground in Twenty20 Internationals.

References

Walferdange
Cricket grounds in Luxembourg

Pierre Werner Cricket Ground


Rubuubi Kyebambe IIl was Omukama of the Tooro Kingdom, in 1875 and from 1877 until 1879. He was the seventh (7th) Omukama of Tooro.

Claim to the throne
He was the fourth son of Kasunga Kyebambe Nyaika, Omukama of Tooro, from 1866 until 1871 and from 1871 until 1872. No mention is made of his mother. He ascended to the throne following the abdication of his elder brother, Rukirabasaija Isingoma Rukidi II in 1875.

Personal life
No mention is made about the marital life of Omukama Rububi Kyebambe II. It is not known how many children were fathered by Omukama Rububi Kyebambe II.

His reign
He became Omukama following the abdication of his brother, Rukidi II, in 1875. However, later that year, the Tooro Kingdom was invaded by the Bunyoro Army under the command of Chief Kikukule  of Bugangaizi. He fled to Buganda. Two years later, he returned and deposed his younger brother, Omukama Katera, in 1877. He ruled until he himself was deposed in 1879.

The final years
Omukama Rububi Kyebambe II deposed by his younger brother, Rukirabasaija Kakende Nyamuyonjo, in 1879, with the support of the Buganda Army. It is not known where and how Omukama Rububi Kyebambe died or what caused his death.

Succession table:First time

Succession table:Second time

See also
 Omukama of Tooro

References

Toro
19th-century monarchs in Africa

Rububi Kyebambe II of Tooro


Wu Ta-You () (27 September 1907 – 4 March 2000) was a Chinese physicist and writer who worked in the United States, Canada, mainland China and Taiwan. He has been called the Father of Chinese Physics.

Early life and education
Wu was born in Panyu, Guangzhou (Canton) in the last years of the Qing dynasty. In 1929 he took his undergraduate degree at Nankai University in Tianjin (Tientsin). He moved to the United States for graduate schooling and obtained a Doctor of Philosophy Degree from the University of Michigan in 1933.

Career
Wu returned to China (then Republic of China) after receiving his doctorate degree, and between 1934 and 1949 he taught at various institutions there, including Peking University in Beijing, and National Southwestern Associated University in Kunming. In 1949, the year of the defeat of the Nationalists by the Communists in the Chinese Civil War, Wu moved to Canada.

There he headed the Theoretical Physics Division of the National Research Council until 1963. In the 1960s, he was Chair of the Department of Physics and Astronomy at the University at Buffalo. After 1962, he held various positions in Taiwan (Republic of China), including the President of the Academia Sinica (1983–1994). He continued lecturing into his 90s and died on March 4, 2000.

Wu's PhD dissertation dealt with theoretical predictions of the chemical properties of the yet undiscovered transuranic elements of the actinide series, which includes such well known elements as plutonium and americium. Later in his career, he worked on solid-state physics, molecular physics, statistical physics and other areas of theoretical physics.  He was known as a teacher as much as a theoretician. His many illustrious students include Chen Ning Yang and Tsung-Dao Lee, co-winners of the Nobel Prize in Physics in 1957.

Wu wrote several books, best known of which are the monograph Vibrational Spectra and Structure of Polyatomic Molecules (1939) and the graduate level textbooks Quantum Mechanics (1986) and (as co-author) Relativistic Quantum Mechanics and Quantum Fields (1991).

Awards and honors
 Beginning from 2002, National Science Council of Republic of China (reformed as the Ministry of Science and Technology since 2014) gives out Wu Ta-You Memorial Award every year.
 The Department of Physics of the University of Michigan hosts Ta-You Wu Lecture.
 Asteroid 256892 Wutayou, discovered by astronomers Chi Sheng Lin and Ye Quanzhi in 2008, was named in his memory. The official  was published by the Minor Planet Center on 17 May 2011 ().

References

External links
 A Biographical Sketch of Dr. Ta-You Wu – Lee, Ting-Kuo (2007). AAPPS Bulletin 17, 5.
 A Chronology of Ta-You Wu's Life and Career, Hsu, Jong-Ping and Leonardo (1998). JingShin Theoretical Physics Symposium in Honor of Professor Ta-You Wu. World Scientific Publishing.

1907 births
2000 deaths
20th-century Taiwanese writers
Chinese Civil War refugees
Chinese expatriates in Canada
Chinese expatriates in the United States
Chinese nuclear physicists
Educators from Guangdong
Members of Academia Sinica
Ministers of Science and Technology of the Republic of China
Tianjin Nankai High School alumni
Nankai University alumni
Academic staff of the National Southwestern Associated University
Academic staff of Peking University
People from Panyu District
Physicists from Guangdong
Polytechnic Institute of New York University faculty
Recipients of the Order of Brilliant Star
20th-century Chinese science writers
Academic staff of Sichuan University
Taiwanese expatriates in the United States
Taiwanese male writers
Taiwanese people from Guangdong
20th-century Taiwanese physicists
University at Buffalo faculty
University of Michigan alumni
Writers from Guangzhou

Wu Ta-You


Wittenham Clumps are a pair of wooded chalk hills in the Thames Valley, in the civil parish of Little Wittenham, in the historic county of Berkshire, although since 1974 administered as part of South Oxfordshire district.

The higher of the two, Round Hill, is  above sea-level. The   Castle Hill is about  south-east and was the site of an Iron Age hill fort. A third hill, not normally considered one of The Clumps, is Brightwell Barrow, further to the south-east.

The grassed slopes of The Clumps lead up to summits wooded by the oldest beech tree plantings in England, dating to the 1740s. Standing over 70 metres above their surroundings, the Clumps have a prominent appearance and panoramic views, with the north slopes overlooking villages and towns whose sites mark some of the first settlements of the English. The view from The Clumps was described by the artist Paul Nash, who first saw them in 1911, as "a beautiful legendary country haunted by old gods long forgotten".

The Clumps are the most visited outdoor site in the administrative county of Oxfordshire, attracting over 200,000 visitors a year. A car park was added in 1971, and the extensive network of paths are accessible by foot all year round. A path through the wooded area at the top of Round Hill has enabled access since 2005, after being closed for twenty years. The site and its surroundings are maintained as a Nature Reserve by the Earth Trust.

Toponymy

Strictly speaking, the name Wittenham Clumps refers to the wooded summits of these hills, which are themselves more properly referred to as the Sinodun Hills, the name Sinodun deriving from Celtic, Seno-Dunum, meaning 'Old Fort'. Alternatively, it has been suggested that the name is a scholarly creation, punning on the Latin 'sinus' (bosom). Other lesser-used and more colloquial names for the Clumps include the Berkshire Bubs (since the Clumps are in the historic county of Berkshire, though this area was transferred to Oxfordshire administratively in 1974) and Mother Dunch's Buttocks (after a local Lady of the Manor named Dunch).

On Sinodun Hill is a hollow named the Money-Pit and a clump of trees named the Cuckoo Pen. The Money-Pit is supposedly the location of a treasure hoard guarded by a raven, and the Cuckoo Pen gets its name from the local belief that a trapped cuckoo would ensure eternal Summer.

Location

Wittenham Clumps are located at , close to the River Thames, and good views can be had from the Thames Path along the river. The panoramic views of the Berkshire and Oxfordshire countryside from the Clumps themselves are also spectacular; a viewpoint guide on the north side of Round Hill gives directions to many sights, the furthest being Faringdon Folly, a tower built on another Iron Age hillfort  to the west. Day's Lock and Dorchester Abbey are clearly visible in the valley to the north, with the 15-storey Plowman Tower in Northway, Oxford visible on the horizon,  away. The white-walled reactor buildings of the Joint European Torus, site of the world's first successful controlled nuclear fusion experiments, can be seen around 6 km to the north-west. To the west, there is the town of Didcot, with some of the chimneys of the gas-fired Didcot B Power Station visible. Formerly, the  cooling towers of Didcot A Power Station, constructed in the late 1960s, dominated the skyline around Didcot; they were demolished in phases from 2014 to 2020. To the north-east is Little Wittenham Wood, which borders the Thames, and to the south-east is Brightwell Barrow.

The wooded area at the top of Castle Hill, which contains a public footpath, is now closed indefinitely due to the danger of falling trees. The entrance to the wooded area atop Round Hill also carries a warning of falling branches due to fungal decay of many of its trees.

Archaeology
There is a hillfort on Castle Hill. The earliest earthworks date to the late Bronze Age. More banks and ditches were added during the early Iron Age. Excavation has revealed that the Iron Age inhabitants caught fish and wild boar as well as herding cattle and sheep. There is also evidence of cultivation of barley and wheat. The fort appears to have been abandoned by the late Iron Age, the next occupants being Romans. A 2004 episode of the Channel 4 archaeological television programme Time Team focused on the Clumps. In 2004 Castle Hill was under excavation by Oxford Archaeology, and Time Team was charged with investigating the surrounding landscape to find any trace of activity that could be associated with the Clumps.

Over a period of three days, Time Team surveyed a total of seven hectares using ground-penetrating radar. The original focus was the previously unexplored Round Hill, but difficulties in carrying out geophysical studies on its tree-covered crest forced the team to abandon their original goal. Moving down the southern slopes, however, many hidden features emerged, including enclosure ditches, pits, possible buildings and other clusters of anomalies. The geophysics highlighted a large rectilinear enclosure, which was subsequently singled out for excavation. This revealed the remains of a Romano-British house with tesserae (mosaic) floors and painted wall plaster on the southern slope of Round Hill. The area also contained an Iron-Age cobbled floor, together with post holes that could have related to a structure.

Further investigations found Iron Age rubbish pits distributed all over the valley, suggesting widespread settlement throughout the period. Pottery finds indicated that most activity took place in the earlier and later phases of the period, with a quieter occupation phase in the middle. The geophysics surveys also uncovered more suspected Iron Age enclosures along with what appeared to be a Roman road, which would have been associated with the site.

The overall chronology suggested by the excavations is of the site being occupied since the Bronze Age around 1000 BC, the hillfort and surrounding farms dating from around 600 BC, followed by a move down towards the southern part of the site around 300 BC. The area was then abandoned, until the construction of the Roman villa.

Among the many artefacts found in the area are an oval bronze shield around 35 cm in diameter, retrieved from the nearby river Isis in 1836 and the 70 cm long Wittenham Sword and scabbard, found in 1982 and dating from the Late Iron Age (120 BC - AD 43)

In February 2021, archaeologists headed by Chris Casswell from DigVentures announced the discovery of at least 15 roundhouses dating from 400 to 100 BC. and remains of Roman villa dating from 3rd to early 4th century CE. According to excavators, members of noble family would have lived in this Roman villa. Researchers have also revealed some Roman kitchen utensils and an Iron Age "fridge" or pantry-ceramic food storage containers to keep food cool and safe in a pit dug into the ground.

Poetry

The eastern side of Castle Hill is the location of the Victorian 'Poem Tree', a beech tree which had a poem carved into it by Joseph Tubb of Warborough Green in 1844–45. The tree, which died in the 1990s, collapsed in 2012; there is now a stone commemorating the 150th anniversary of the carving.

Wittenham Clumps is said to be where Matthew Prior wrote Henry and Emma, and this is commemorated by a plaque.

In 2021, Robin Alexander Lucas published a new poem about The Wittenham Clumps, the Money Pit and the Raven that is said to guard it, entitled The Money Pit – or – The Sinodun Hoard. It was printed on the reverse side of a decorative map of The Wittenham Clumps, published by Cittern Press, (ISBN 978-1-8384385-9-3, Cittern Press, 2021).

Usage in media
Wittenham Clumps were repeatedly painted by the 20th-century British artist Paul Nash.

The Clumps was the filming location for the Radiohead webcast video of the band's song "Faust Arp".

The climax of the third episode of the third season of the Netflix series Black Mirror takes place in the woods.

References

External links

 Earth Trust
 Little Wittenham at Royal Berkshire History
 Photograph, Geograph British Isles project
 Archaeological dig, Time Team, Channel 4

Forests and woodlands of Oxfordshire
Hill forts in Berkshire
Hills of Oxfordshire
Geography of the River Thames
Nature reserves in Oxfordshire
Former populated places in Oxfordshire

Wittenham Clumps


"Unplayed Piano" is a 2005 single by the Irish singer-songwriter duo Damien Rice and Lisa Hannigan. It was released in June 2005 and appeared in a total of six charts, spending a total of twenty-five weeks there. It spent twelve weeks in the Irish Singles Chart after entering on 23 June 2005, breaking into the Top 10 and achieving a peak of fourth position. It remained in fourth position for two weeks before falling to seventh position where it spent a further three weeks. The song peaked at number 24 in the UK Singles Chart and number 36 in the Eurochart Hot 100 Singles. "Unplayed Piano" was released on the DRM label and featured Rice's usual backing band of Vyvienne Long, Tom Osander and Shane Fitzsimons.

Background
"Unplayed Piano" was released as a single by Hannigan and Rice to support the Free Aung San Suu Kyi 60th Birthday campaign which was running at the time. Aung San Suu Kyi is a Nobel Peace Prize winner who had been under house arrest in Burma for various periods from 2002 to 2010. She was previously placed under house arrest by the country's ruling military junta in the former capital, Yangon on 19 July 1989 under martial law that allows for detention without charge or trial for three years. She was released on 10 July 1995 but re-arrested on 23 September 2000. On 6 May 2002 she was freed after nineteen months but on 30 May 2003, following the Depayin massacre she was held in secret detention for over three months before being returned to house arrest. Despite global protests in solidarity her detention was extended by the Myanmar military junta for one year periods in 2007 and 2008. She was finally released in 2010.

Rice was approached by the United States Campaign for Burma, which asked him to donate an existing song for their Free Aung San Suu Kyi 60th Birthday Campaign. Instead Rice constructed, "Unplayed Piano", and also scheduled a live show at the London Palladium to assist in increasing the public profile of the campaign. He also gave a rare interview to The Independent to highlight the issues which inspired the song, discussing his visit to Myanmar and confessing his prior ignorance of the situation there. He wishes not to be viewed as a political activist and is "no Bob Geldof... just a regular guy who has seen something that is wrong and is trying, in some small way, to help".

The Independent described "Unplayed Piano" as "a twinkly and beautiful thing". Rice is known for refusing to openly discuss the song after becoming incensed when a friend commented that it "didn't quite measure up to the clout of his earlier work". He insists that his other songs are more powerful because they originate deeper inside him.

Chart performance
"Unplayed Piano" first appeared in the Irish Singles Chart on 25 June 2005 in fourth position where it remained for a second consecutive week. The day after it first charted in Ireland the song charted in the United Kingdom at number 16. The song peaked at number 24 in the UK Singles Chart dropping out of the Top 40 at number 39. It remained in the Irish Singles Chart charting at number 7 for three consecutive weeks before dropping to number 8 on 27 July 2005. In August it charted consecutively at number 12, number 14, number 15 and number 20. The song entered the Eurochart Hot 100 Singles on 9 July 2005 at number 36 before dropping to number 52 and number 81 in the following two weeks.

References

2005 singles
Damien Rice songs
Lisa Hannigan songs
2005 songs
Songs written by Damien Rice

Unplayed Piano