Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics

Abstract: The quantification of transmissibility during epidemics is essential to designing and adjusting public health responses. Transmissibility can be measured by the reproduction number R, the average number of secondary cases caused by an infected individual. Several methods have been proposed to estimate R over the course of an epidemic; however, they are usually difficult to implement for people without a strong background in statistical modeling. Here, we present a ready-to-use tool for estimating R from incidence time series, which is implemented in popular software including Microsoft Excel (Microsoft Corporation, Redmond, Washington). This tool produces novel, statistically robust analytical estimates of R and incorporates uncertainty in the distribution of the serial interval (the time between the onset of symptoms in a primary case and the onset of symptoms in secondary cases). We applied the method to 5 historical outbreaks; the resulting estimates of R are consistent with those presented in the literature. This tool should help epidemiologists quantify temporal changes in the transmission intensity of future epidemics by using surveillance data.

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

Sample Size Tables for Clinical Studies

Abstract: Preface to the Second Edition Preface to the First Edition 1. Basic Design Considerations 2. The Normal Distribution 3. Comparing Independent Groups for Binary, Ordered Categorical and Continuous Data 4. Comparing Paired Groups for Binary, Ordered Categorical and Continuous Outcomes 5. Demonstrating Equivalence 6. Confidence Intervals 7. Post-Marketing Surveillance 8. The Correlation Coefficient 9. Comparing Two Survival Curves 10. Phase II Trials 11. Observer Agreement Studies 12. Randomization Cumalative References Author Index Subject Index

Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria.

Abstract: Tumour-necrosis factor-alpha (TNF-alpha) is believed to have an important role in the pathogenesis of severe infectious disease and fatal cerebral malaria is associated with high circulating levels of this cytokine. In a large case-control study in Gambian children we find that homozygotes for the TNF2 allele, a variant of the TNF-alpha gene promoter region, have a relative risk of 7 for death or severe neurological sequelae due to cerebral malaria. Although the TNF2 allele is in linkage disequilibrium with several neighbouring HLA alleles, we show that this disease association is independent of HLA class I and class II variation. These data suggest that regulatory polymorphisms of cytokine genes can affect the outcome of severe infection. The maintenance of the TNF2 allele at a gene frequency of 0.16 in The Gambia implies that the increased risk of cerebral malaria in homozygotes is counterbalanced by some biological advantage.

Targeting MET in cancer: rationale and progress

Abstract: Uncontrolled cell survival, growth, angiogenesis and metastasis are essential hallmarks of cancer. Genetic and biochemical data have demonstrated that the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the tyrosine kinase MET, have a causal role in all of these processes, thus providing a strong rationale for targeting these molecules in cancer. Parallel progress in understanding the structure and function of HGF/SF, MET and associated signalling components has led to the successful development of blocking antibodies and a large number of small-molecule MET kinase inhibitors. In this Review, we discuss these advances, as well as results from recent clinical studies that demonstrate that inhibiting MET signalling in several types of solid human tumours has major therapeutic value.