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.

Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects

Abstract: We investigated the functional anatomy of self-initiated and externally triggered movements. Six patients with Parkinson's disease off medication and six age-matched normals were assessed. All subjects had regional cerebral blood flow (rCBF) measurement with PET and recording of movement-related cortical potentials (MRPs) from frontal (F), fronto-central (FC), central (C) and parietal (P) sites to obtain measures of the Bereitschaftspotential (BP). The tasks were (i) self-initiated extension of the right index finger on average once every 3 s, (ii) externally triggered finger extension with the rate yoked to the self-initiated task, and (iii) rest condition with tones presented at a rate yoked with the self-initiated task. For the self-initiated movements, the amplitude of the early and peak BP were lower in Parkinson's disease relative to normals. For the externally triggered movements, the patients and the normals did not differ on any of the measures of cortical negativity prior to movement. For both groups, the late and peak BP components, but not the early component, had a lower amplitude in the externally triggered than the self-initiated movements. In normals, the left primary sensorimotor cortex, the supplementary motor area bilaterally, anterior cingulate, the lateral premotor cortex bilaterally, the insular cortex bilaterally, the left thalamus and the left putamen, parietal area 40 bilaterally and the right dorsolateral prefrontal cortex (DLPFC) were significantly activated during the self-initiated movements relative to rest. For the normals, greater activation of the right DLPFC during the self-initiated movements was the only area that significantly differentiated them from the externally triggered movements. When Parkinson's disease patients and normals were compared for the self-initiated movements relative to rest, normals showed greater activation of the supplementary motor area and anterior cingulate, left putamen, left insular cortex, right DLPFC and right parietal area 40. When the groups were compared for the externally triggered movements relative to rest, the global pattern of blood flow and rCBF change in the two groups did not differ, confirming the absence of group differences in BPs for the externally triggered movements. During the self-initiated movements, the lower amplitude of the early BP in patients with Parkinson's disease as well as the underactivation of the supplementary motor area relative to normals support the premises that (i) the supplementary motor area contributes to the early BP, and (ii) the deficit is self-initiated movements in Parkinson's disease is due to supplementary motor area underactivation. The DLPFC is activated in situations requiring non-routine decision making as in the self-initiated movements.

C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction

Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P = 20%) (P = 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

The role of strong syllables in segmentation for lexical access

Abstract: A model of speech segmentation in a stress language is proposed, according to which the occurrence of a strong syllable triggers segmentation of the speech signal, whereas occurrence of a weak syllable does not trigger segmentation. We report experiments in which listeners detected words embedded in nonsense bisyllables more slowly when the bisyllable had two strong syllables than when it had a strong and a weak syllable; mint was detected more slowly in mintayve than in minlesh. According to our proposed model, this result is an effect of segmentation: When the second syllable is strong, it is segmented from the first syllable, and successful detection of the embedded word therefore requires assembly of speech material across a segmentation position. Speech recognition models involving phonemic or syllabic receding, or based on strictly left-toright processes, do not predict this result. It is argued that segmentation at strong syllables in continuous speech recognition serves the purpose of detecting the most efficient locations at which to initiate lexical access.

High-throughput discovery of novel developmental phenotypes

Abstract: Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.