Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Empirical Bayes estimates of age-standardized relative risks for use in disease mapping.

Abstract: There have been many attempts in recent years to map incidence and mortality from diseases such as cancer. Such maps usually display either relative rates in each district, as measured by a standardized mortality ratio (SMR) or some similar index, or the statistical significance level for a test of the difference between the rates in that district and elsewhere. Neither of these approaches is fully satisfactory and we propose a new approach using empirical Bayes estimation. The resulting estimators represent a weighted compromise between the SMR, the overall mean relative rate, and a local mean of the relative rate in nearby areas. The compromise solution depends on the reliability of each individual SMR and on estimates of the overall amount of dispersion of relative rates over different districts.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 10 × 10(-4)) In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 50 × 10(-8)), 3 of which we found after conditioning on previously identified variants Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals

The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis.

Abstract: A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.

Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia

Abstract: Familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML, MIM 601399) is an autosomal dominant disorder characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukaemia (AML). Informative recombination events in 6 FPD/AML pedigrees with evidence of linkage to markers on chromosome 21q identified an 880-kb interval containing the disease gene. Mutational analysis of regional candidate genes showed nonsense mutations or intragenic deletion of one allele of the haematopoietic transcription factor CBFA2 (formerly AML1) that co-segregated with the disease in four FPD/AML pedigrees. We identified heterozygous CBFA2 missense mutations that co-segregated with the disease in the remaining two FPD/AML pedigrees at phylogenetically conserved amino acids R166 and R201, respectively. Analysis of bone marrow or peripheral blood cells from affected FPD/AML individuals showed a decrement in megakaryocyte colony formation, demonstrating that CBFA2 dosage affects megakaryopoiesis. Our findings support a model for FPD/AML in which haploinsufficiency of CBFA2 causes an autosomal dominant congenital platelet defect and predisposes to the acquisition of additional mutations that cause leukaemia.