Institution
Royal Devon and Exeter Hospital
Healthcare•Exeter, United Kingdom•
About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.
Papers published on a yearly basis
Papers
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TL;DR: It is shown that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders and a significant twofold enrichment of recurrently mutated elements.
Abstract: We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.
226 citations
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TL;DR: The results demonstrated that it was likely that many drug errors were not reported, for a variety of reasons, and it was recommended that all of these issues are addressed as a matter of urgency, for the sake of both patients and nurse practitioners.
Abstract: Drug administration is one of the highest risk areas of nursing practice and a matter of considerable concern for both managers and practitioners. The aim of this study, carried out in a district general hospital, was to identify any common themes that underlie the occurrence and reporting of drug administration errors. Data were collected from a variety of sources: drug error reports, questionnaires to nurses and nurse managers, and interviews with nurses who had been involved in drug errors. Several areas of particular concern emerged, including: the nurses' confusion regarding the definition of drug errors and the appropriate actions to take when they occurred; their fear of disciplinary action; their loss of clinical confidence; the variation in managerial response; and a possible lack of nurses' mathematical skills. The results from the study demonstrated that it was likely that many drug errors were not reported, for a variety of reasons. It is recommended that all of these issues are addressed as a matter of urgency, for the sake of both patients and nurse practitioners.
225 citations
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TL;DR: This work has used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD, and reinforces the hypothesis that proper regulation of the Notch signaling pathway is an absolute requirement for the correct patterning of the axial skeleton.
Abstract: The spondylocostal dysostoses (SCDs) are a heterogeneous group of vertebral malsegmentation disorders that arise during embryonic development by a disruption of somitogenesis. Previously, we had identified two genes that cause a subset of autosomal recessive forms of this disease: DLL3 (SCD1) and MESP2 (SCD2). These genes are important components of the Notch signaling pathway, which has multiple roles in development and disease. Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD. LFNG encodes a glycosyltransferase that modifies the Notch family of cell-surface receptors, a key step in the regulation of this signaling pathway. A missense mutation was identified in a highly conserved phenylalanine close to the active site of the enzyme. Functional analysis revealed that the mutant LFNG was not localized to the correct compartment of the cell, was unable to modulate Notch signaling in a cell-based assay, and was enzymatically inactive. This represents the first known mutation in the human LFNG gene and reinforces the hypothesis that proper regulation of the Notch signaling pathway is an absolute requirement for the correct patterning of the axial skeleton.
224 citations
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TL;DR: EDMD was delineated as a separate form of muscular dystrophy nearly 40 years ago, based on the distinctive clinical features of early contractures and humero-peroneal weakness, and cardiac conduction defects.
222 citations
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TL;DR: Support is provided for the validity of the SURG-TLX instrument and the importance of considering how different stressors may load surgeons is highlighted, and modifications to the scale to enhance clinical utility are suggested.
Abstract: Background
The purpose of the present study was to develop and validate a multidimensional, surgery-specific workload measure (the SURG-TLX), and to determine its utility in providing diagnostic information about the impact of various sources of stress on the perceived demands of trained surgical operators. As a wide range of stressors have been identified for surgeons in the operating room, the current approach of considering stress as a unidimensional construct may not only limit the degree to which underlying mechanisms may be understood but also the degree to which training interventions may be successfully matched to particular sources of stress.
219 citations
Authors
Showing all 2288 results
Name | H-index | Papers | Citations |
---|---|---|---|
Andrew T. Hattersley | 146 | 768 | 106949 |
Timothy M. Frayling | 133 | 500 | 100344 |
Gordon D.O. Lowe | 105 | 560 | 44327 |
Rod S Taylor | 104 | 524 | 39332 |
Sian Ellard | 97 | 636 | 36847 |
Zoltán Kutalik | 90 | 321 | 42901 |
Michael N. Weedon | 87 | 201 | 60701 |
Masud Husain | 81 | 398 | 25682 |
David Melzer | 80 | 328 | 33458 |
Jonathan Mill | 78 | 301 | 36343 |
A. John Camm | 76 | 368 | 49804 |
David Silver | 74 | 227 | 81103 |
Jason D. Warren | 73 | 384 | 20588 |
Nicholas J. Talbot | 71 | 240 | 29205 |
Andrew R. Wood | 70 | 214 | 36203 |