21 research outputs found

    Validity of a pictorial perceived exertion scale for effort estimation and effort production during stepping exercise in adolescent children

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    This is the author's PDF version of an article published in European Physical Education Review ©2002. The definitive version is available at http://epe.sagepub.com.Recent developments in the study of paediatric effort perception have continued to emphasise the importance of child-specific rating scales. The purpose of this study was to examine the validity of an illustrated 1 – 10 perceived exertion scale; the Pictorial Children’s Effort Rating Table (PCERT). 4 class groups comprising 104 children; 27 boys and 29 girls, aged 12.1±0.3 years and 26 boys, 22 girls, aged 15.3±0.2 years were selected from two schools and participated in the initial development of the PCERT. Subsequently, 48 of these children, 12 boys and 12 girls from each age group were randomly selected to participate in the PCERT validation study. Exercise trials were divided into 2 phases and took place 7 to 10 days apart. During phase 1, children completed 5 x 3-minute incremental stepping exercise bouts interspersed with 2-minute recovery periods. Heart rate (HR) and ratings of exertion were recorded during the final 15 s of each exercise bout. In phase 2 the children were asked to regulate their exercising effort during 4 x 4-minute bouts of stepping so that it matched randomly prescribed PCERT levels (3, 5, 7 and 9). Analysis of data from Phase 1 yielded significant (P<0.01) relationships between perceived and objective (HR) effort measures for girls. In addition, the main effects of exercise intensity on perceived exertion and HR were significant (P<0.01); perceived exertion increased as exercise intensity increased and this was reflected in simultaneous significant rises in HR. During phase 2, HR and estimated power output (POapprox) produced at each of the four prescribed effort levels were significantly different (P<0.01). The children in this study were able to discriminate between 4 different exercise intensities and regulate their exercise intensity according to 4 prescribed levels of perceived exertion. In seeking to contribute towards children’s recommended physical activity levels and helping them understand how to self-regulate their activity, the application of the PCERT within the context of physical education is a desirable direction for future research

    Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

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    Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

    Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

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    Background The association of fitness with cancer risk is not clear. Methods We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. Results After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. Discussion Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention

    An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

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    It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for Cp

    Large-scale transcriptome-wide association study identifies new prostate cancer risk regions

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    Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are region

    Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

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    Several susceptibility loci for classical Hodgkin lymphoma (cHL) have been reported, however much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies (GWAS), a new GWAS, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all cHL at 6q22.33 (rs9482849, P=1.52 × 10-8) and for nodular sclerosis HL (NSHL) at 3q28 (rs4459895, P=9.43 × 10-17), 6q23.3 (rs6928977, P=4.62 × 10-55 11), 10p14 (rs3781093, P=9.49 × 10-13), 13q34 (rs112998813, P=4.58 × 10-8) and 16p13.13 (rs34972832, P=2.12 × 10-8). Additionally, independent loci within the HLA region are observed for NSHL (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity HL (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. For further information, please visit the publishr's website

    Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

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    Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

    Geometrical transformation approximation for 2D/3D intensity-based registration of portal images and CT scan

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    Conformal radiotherapy treatments need accurate patient positioning in order to spare normal tissues. Patient pose can be evaluated by registering portal images (PI) with Digitally Reconstructed Radiographs (DRR). Several methods involve segmentation which is known to be a dicult task for noisy PI. In this paper, we study another approach by using a fully 3D intensity-based registration method, without segmentation. Our approach uses the correlation ratio as similarity measure and replace DRR generation with a treatment on pre-computed DRR. A specic geometrical transformation is applied to approximate a given projection by the composition of out-of-plane rotations and inplane transformation. Some preliminary experiments on both simulated and real portal images, lead to good results (RMS error lower than 2 mm). 1 Medical contex
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