Royal Devon and Exeter Hospital

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.

Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

Abstract: Clinical genetic testing of protein-coding regions identifies a likely causative variant in only around half of developmental disorder (DD) cases. The contribution of regulatory variation in non-coding regions to rare disease, including DD, remains very poorly understood. We screened 9,858 probands from the Deciphering Developmental Disorders (DDD) study for de novo mutations in the 5' untranslated regions (5' UTRs) of genes within which variants have previously been shown to cause DD through a dominant haploinsufficient mechanism. We identified four single-nucleotide variants and two copy-number variants upstream of MEF2C in a total of ten individual probands. We developed multiple bespoke and orthogonal experimental approaches to demonstrate that these variants cause DD through three distinct loss-of-function mechanisms, disrupting transcription, translation, and/or protein function. These non-coding region variants represent 23% of likely diagnoses identified in MEF2C in the DDD cohort, but these would all be missed in standard clinical genetics approaches. Nonetheless, these variants are readily detectable in exome sequence data, with 30.7% of 5' UTR bases across all genes well covered in the DDD dataset. Our analyses show that non-coding variants upstream of genes within which coding variants are known to cause DD are an important cause of severe disease and demonstrate that analyzing 5' UTRs can increase diagnostic yield. We also show how non-coding variants can help inform both the disease-causing mechanism underlying protein-coding variants and dosage tolerance of the gene.

Recontacting in clinical practice: an investigation of the views of healthcare professionals and clinical scientists in the United Kingdom

Abstract: This article explores the views and experiences of healthcare professionals and clinical scientists in genetics about the existence of a duty and/or responsibility to recontact former patients when the genetic information relevant to their health, or that of family members, changes in a potentially important manner. It is based on N=30 semi-structured interviews guided by vignettes of recontacting scenarios. The sample included healthcare professionals in the United Kingdom from different medical specialties (clinical genetics, other ‘mainstream’ specialties now offering genetic testing), and scientists from regional genetics laboratories. While viewing recontacting as desirable under certain circumstances, most respondents expressed concerns about its feasibility within the current constraints of the National Health Service (NHS). The main barriers identified were insufficient resources (time, staff, and suitable IT infrastructures) and lack of clarity about role boundaries and responsibilities. All of these are further complicated by genetic testing being increasingly offered by mainstream specialties. Reaching a consensus about roles and responsibilities of clinical specialties with regard to recontacting former patients in the light of evolving genetic information, and about what resources and infrastructures would be needed, was generally seen as a pre-requisite to developing guidelines about recontact.

Managing Head Lice in an Era of Increasing Resistance to Insecticides

Abstract: Head lice are present in all age groups, however, the peak age for infestation is 7–8 years and the incidence varies throughout the year with higher incidence during the winter. Different insecticides have been used over the past 60 years to manage this condition. There is now strong evidence of insecticide resistance established in many countries to such an extent that some of these chemicals have become obsolete. Resistance to some pediculicides can vary from country to country and region to region within a country. The lack of a local monitoring system of resistance patterns means that parents and pupils are hampered in making an informed decision regarding how to treat head lice. One should no longer assume that treatment failure is due to poor treatment compliance or re-infestation. Clear treatment guidelines drawn up by healthcare professionals with an interest in head lice and taking into account regional/national resistance patterns should be implemented. These guidelines should combine chemical and non-chemical approaches to treatment and be coordinated and regularly reviewed by local public health departments. Drug companies should be made to provide up-to-date efficacy of their products.

Adjustment processes in chronic aphasia after stroke: Exploring multiple perspectives in the context of a community-based intervention

Abstract: Background: The impact of chronic aphasia following stroke on quality of life (QOL) is widely acknowledged, with improved QOL recognised as an important outcome in aphasia recovery and supported by emerging quantitative measures. One of the key constructs recognised as contributing to QOL in other chronic conditions is psychosocial adjustment, the mechanisms of which are little understood for the person with aphasia. Aims: This study addressed adjustment processes in aphasia by exploring multiple perspectives from people engaged in the Communication Hub for Aphasia in North Tyneside (CHANT), a two-year community intervention for long-term aphasia. The study aimed to explore the adjustment process over time in people with aphasia using thematic analysis of personal narratives derived from a combination of sources: semi-structured interviews with reflections on experiences, quantitative measures of change in QOL and self-assessments of change. Methods & Procedures: Three people with mild or moderate chronic...