The Skills Framework at key stage 2: an evaluation of the impact of the non-statutory Sskills framework for 3 to 19-year-olds in Wales at key stage 2

1 The non-statutory Skills framework for 3 to 19-year-olds in Wales provides guidance on developing pupils’ skills in thinking, communication, ICT and number. The Skills framework is designed to underpin the National Curriculum Subject Orders and teaching and learning in all subject areas. 2 The Skills framework is not used well for planning progression in pupils’ skills. Few schools use the Skills framework as a starting point for planning their work. Most schools use the National Curriculum Subject Orders to plan schemes of work first and then identify opportunities for developing pupils’ skills afterwards. As a result, few schools are planning a ‘skills-based’ curriculum consisting of progressively more complex activities designed to develop pupils’ thinking, communication, ICT and number skills. 3 Although the Skills framework has increased teachers’ awareness of the importance of improving pupils’ skills, too often teachers plan the curriculum as separate subjects, without giving enough attention to how subjects, such as history or geography, provide a context for the development of literacy, numeracy and other skills. These skills do not form the core organising elements or backbone of teachers’ schemes of work. Consequently, there are not enough opportunities for pupils to use and develop their number, reading and extended writing skills across all of the curriculum. 4 Assessing or tracking pupils’ progress in skills is one of the weakest aspects of the schools visited. Teachers are not aware of pupils’ prio

Supporting more able and talented pupils in primary schools

"This survey evaluates the effectiveness of strategies used by primary schools and local authorities to support and challenge more able and talented pupils. Overall, most more able and talented pupils are not challenged enough and too few pupils achieve above the expected levels at the end of key stages 1 and 2. Provision for more able and talented pupils varies too much across Wales. In the few primary schools with the best provision, thorough analysis of data and assessment outcomes helps to identify more able and talented pupils. In these few schools, more able and talented pupils are supported through a range of additional provision and their progress tracked and monitored carefully. Parents understand the school’s approach to providing additional support for more able and talented pupils. More able and talented pupils gain most in schools that promote individualised or personalised approaches to learning and they benefit particularly from having control over how and what they learn. However, in the majority of primary schools, more able and talented pupils are not identified and do not receive appropriate support. Teachers in these schools do not have the expertise to identify, support or track the progress of more able and talented pupils. Transition arrangements between primary and secondary schools often do not provide enough continuity and progression in the education of more able and talented pupils. Few local authorities use data to monitor the progress of more able and talented pupils or promote the sharing of best practice between schools. School improvement officers rarely discuss more able and talented pupils during their visits to schools." - page 1

Seafood provides significant health benefits for men

Evidence supports the regular consumption of Omega-3 polyunsaturated fatty acids found (Omega 3s) with positive effects to men?s health. The best source of these essential fatty acids are seafood, particularly oily fish. This article summarises evidence pertaining to the benefits associated with regular dietary intake of fish on men?s health.Methods: An extensive review of international academic libraries, databases and published literature was conducted. Quality assessment ratings were applied and thematic classifications based on major health issues relevant to men constructed.Results: A total of 168 articles from peer reviewed journals were identified with 60 studies providing moderate to high level evidence of an association between the consumption of Omega 3s and health benefit for men. The majority of the studies showed a positive link between the intake of Omega 3s and the prevention and management of chronic disease in men. Evidence also shows a reduced risk of prostate cancer and lower lung cancer mortality in men who consume a high seafood diets. Conclusion: There is conclusive evidence of an association between the dietary intake of Omega 3s and health benefits for men. However, men are less likely to consume fish when compared to red or white meats. Health promotion interventions should consider: the attitudes of men toward food and the impact of these attitudes on food choices; the association between seafood and other protein sources within the male psyche; and the role that particular foods play for males in social situations

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function

Levels of DNA methylation vary at CpG sites across the BRCA1 promoter, and differ according to triple negative and "BRCA-like" status, in both blood and tumour DNA

Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies

Loci influencing blood pressure identified using a cardiovascular gene-centric array

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.</p

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation