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 genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice.

Abstract: Aims/hypothesis C57BL/6J mice exhibit impaired glucose tolerance. The aims of this study were to map the genetic loci underlying this phenotype, to further characterise the physiological defects and to identify candidate genes.

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review

Abstract: In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship. A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken. There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol. The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.

Breadth and Magnitude of Antibody Responses to Multiple Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Clinical Malaria

Abstract: Individuals living in areas where malaria is endemic are repeatedly exposed to many different malaria parasite antigens. Studies on naturally acquired antibody-mediated immunity to clinical malaria have largely focused on the presence of responses to individual antigens and their associations with decreased morbidity. We hypothesized that the breadth (number of important targets to which antibodies were made) and magnitude (antibody level measured in a random serum sample) of the antibody response were important predictors of protection from clinical malaria. We analyzed naturally acquired antibodies to five leading Plasmodium falciparum merozoite-stage vaccine candidate antigens, and schizont extract, in Kenyan children monitored for uncomplicated malaria for 6 months (n 119). Serum antibody levels to apical membrane antigen 1 (AMA1) and merozoite surface protein antigens (MSP-1 block 2, MSP-2, and MSP-3) were inversely related to the probability of developing malaria, but levels to MSP-119 and erythrocyte binding antigen (EBA-175) were not. The risk of malaria was also inversely associated with increasing breadth of antibody specificities, with none of the children who simultaneously had high antibody levels to five or more antigens experiencing a clinical episode (17/119; 15%; P 0.0006). Particular combinations of antibodies (AMA1, MSP-2, and MSP-3) were more strongly predictive of protection than others. The results were validated in a larger, separate case-control study whose end point was malaria severe enough to warrant hospital admission (n 387). These findings suggest that under natural exposure, immunity to malaria may result from high titers antibodies to multiple antigenic targets and support the idea of testing combination blood-stage vaccines optimized to induce similar antibody profiles.

Performance indicators: good, bad, and ugly

Abstract: Summary. A striking feature of UK public services in the 1990s was the rise of performance monitoring (PM), which records, analyses and publishes data in order to give the public a better idea of how Government policies change the public services and to improve their effectiveness. PM done well is broadly productive for those concerned. Done badly, it can be very costly and not merely ineffective but harmful and indeed destructive. Performance indicators (PIs) for the public services have typically been designed to assess the impact of Government policies on those services, or to identify well performing or underperforming institutions and public servants. PIs’ third role, which is the public accountability of Ministers for their stewardship of the public services, deserves equal recognition. Hence, Government is both monitoring the public services and being monitored by PIs. Especially because of the Government's dual role, PM must be done with integrity and shielded from undue political influence, in the way that National Statistics are shielded. It is in everyone's interest that Ministers, Parliament, the professions, practitioners and the wider public can have confidence in the PM process, and find the conclusions from it convincing. Before introducing PM in any public service, a PM protocol should be written. This is an orderly record not only of decisions made but also of the reasoning or calculations that led to those decisions. A PM protocol should cover objectives, design considerations and the definition of PIs, sampling versus complete enumeration, the information to be collected about context, the likely perverse behaviours or side-effects that might be induced as a reaction to the monitoring process, and also the practicalities of implementation. Procedures for data collection, analysis, presentation of uncertainty and adjustment for context, together with dissemination rules, should be explicitly defined and reflect good statistical practice. Because of their usually tentative nature, PIs should be seen as ‘screening devices’ and not overinterpreted. If quantitative performance targets are to be set, they need to have a sound basis, take account of prior (and emerging) knowledge about key sources of variation, and be integral to the PM design. Aspirational targets have a distinctive role, but one which is largely irrelevant in the design of a PM procedure; motivational targets which are not rationally based may demoralize and distort. Anticipated and actual side-effects of PM, including on individuals’ behaviour and priorities, may need to be monitored as an intrinsic part of the PM process. Independent scrutiny of PM schemes for the public services should be set up and must report publicly. The extent and nature of this scrutiny should be related to the assessed drawbacks and benefits, reflect ethical concerns, and conform with good statistical practice. Research is needed into the merits of different strategies for identifying institutions or individuals in the public release of PM data, into how new PM schemes should be evaluated, and into efficient designs for evaluating a series of new policies which are monitored by PIs. The Royal Statistical Society considers that attempts to educate the wider public, as well as policy makers, about the issues surrounding the use of PIs are very important. High priority should be given to sponsoring well-informed public debate, and to disseminating good practices by implementing them across Government.