44 research outputs found

    A real thirst?

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    It's not all about healthy eating ‚Äď what about healthy drinking? Dr Kristy Howells and Dr Jackie Musgrave explain how to ensure young children are achieving good hydratio

    ‚ÄėEarly childhood studies is more than a degree; it is an experience‚Äô: undergraduate students‚Äô motivations, professional aspirations and attributes

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    This mixed methods study sought the views of early childhood studies students from three universities in England. The research explored motivations, professional aspirations and the attributes they believed were required to work in early childhood. Findings highlighted that the holistic study of early childhood is valued by students and placements offered a space where they grew and flourished, as they made sense of where their personal intersected with wider theoretical, practice and political systems embedded in early childhood. Students follow a range of career trajectories, either by choice or because there is no specific practitioner role underpinned by the holistic study of early childhood. This study also revealed factors that led to their choice and place of study, as well as the ways that students’ personal circumstances affected their studies, reinforcing the importance of academic and pastoral support. Very significantly, this research led to discussions about the core purpose of the early childhood studies degree and helped to inform the development of the Graduate Competencies as an addition to ECS degrees that included placements

    Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

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    The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008‚Äď11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003‚Äď13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0¬∑674), and with age at onset (TRACK-HD, r=0¬∑315; REGISTRY, r=0¬∑234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1¬∑12 √ó 10‚ąí10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2¬∑94 √ó 10‚ąí8 DHFR p=8¬∑37 √ó 10‚ąí7 MTRNR2L2 p=2¬∑15 √ó 10‚ąí9) and to a lesser extent in REGISTRY (MSH3 p=9¬∑36 √ó 10‚ąí4 DHFR p=8¬∑45 √ó 10‚ąí4 MTRNR2L2 p=1¬∑20 √ó 10‚ąí3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1¬∑58 √ó 10‚ąí8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0¬∑4 units per year (95% CI 0¬∑16‚Äď0¬∑66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0¬∑12 units per year (95% CI 0¬∑06‚Äď0¬∑18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    Supporting children with chronic medical conditions in the Early Years Foundation Stage: a case for discrimination?

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    In April 2014, section 100 of the Children and Families Act (2014) legislated to strengthen the support given to children in schools with chronic medical conditions. However, the Act does not include children in the foundation stage because the former Education Minister, Michael Gove, stated in a Written Ministerial Statement (DfE, 2014) that the supporting pupils with chronic medical conditions guidance ‚Äúwill not apply to early years provision as there is already sufficient coverage of this issue in the statutory Early Years Foundation Stage‚ÄĚ. This assertion has made me reflect on the possible implications for children with chronic medical conditions in the early years. Excluding children in the foundation stage from the aims of the legislation may lead to inequality in care and education because the health needs of such children may be over-looked
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