66 research outputs found
Manipulating mud: (re-)constructing cosmogonical landscapes in the Nile Valley, Thebes, Egypt
N
Recommended from our members
Application of the risk-based strategy to the Hanford tank waste organic-nitrate safety issue
This report describes the results from application of the Risk-Based Decision Management Approach for Justifying Characterization of Hanford Tank Waste to the organic-nitrate safety issue in Hanford single-shell tanks (SSTs). Existing chemical and physical models were used, taking advantage of the most current (mid-1997) sampling and analysis data. The purpose of this study is to make specific recommendations for planning characterization to help ensure the safety of each SST as it relates to the organic-nitrate safety issue. An additional objective is to demonstrate the viability of the Risk-Based Strategy for addressing Hanford tank waste safety issues
Socioeconomic disparities in physical health among Aboriginal and Torres Strait Islander children in Western Australia
Objective. Few empirical studies have specifically examined the relationship between socio-economic status (SES) and health in Indigenous populations of Australia. We sought to provide insights into the nature of this relationship by examining socio-economic disparities in physical health outcomes among Aboriginal and Torres Strait Islander children in Western Australia.
Design. We used a diverse set of health and SES indicators from a representative survey conducted in 20002002 on the health and development of 5289 Indigenous children aged 017 years in Western Australia. Analysis was conducted using multivariate logistic regression within a multilevel framework. Results. After controlling for age and sex, we found statistically significant socio- economic disparities in health in almost half of the associations that were investigated, although the direction, shape and magnitude of associations differed. For ear infections, recurring chest infections and sensory function problems, the patterns were generally consistent with a positive socio-economic gradient where better health was associated with higher SES. The reverse pattern was found for asthma, accidents and injuries, and oral health problems, although this was primarily observed for area-level SES indicators.
Conclusion. Conventional notions of social position and class have some influence on the physical health of Indigenous children, although the diversity of results implies that there are other ways of conceptualising and measuring SES that are important for Indigenous populations. We need to consider factors that relate specifically to Indigenous circumstances and culture in the past and present day, and give more thought to how we measure social position in the Indigenous community, to gain a better understanding of the pathways from SES to Indigenous child health
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
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
An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk
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
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
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP
microarray intensity data of 38,303 women from cancer genome-wide association studies
(20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%)
women. Here we show rates for X-chromosome mosaicism are four times higher than mean
autosomal rates; X mosaic events more often include the entire chromosome and participants
with X events more likely harbour autosomal mosaic events. X mosaicism frequency
increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and
autosomes. Methylation array analyses of 33 women with X mosaicism indicate events
preferentially involve the inactive X chromosome. Our results provide further evidence that
the sex chromosomes undergo mosaic events more frequently than autosomes, which could
have implications for understanding the underlying mechanisms of mosaic events and their
possible contribution to risk for chronic diseases
Detectable clonal mosaicism and its relationship to aging and cancer
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases
Recommended from our members
A risk-based focused decision-management approach for justifying characterization of Hanford tank waste. June 1996, Revision 1; April 1997, Revision 2
This report describes a disciplined, risk-based decision-making approach for determining characterization needs and resolving safety issues during the storage and remediation of radioactive waste stored in Hanford tanks. The strategy recommended uses interactive problem evaluation and decision analysis methods commonly used in industry to solve problems under conditions of uncertainty (i.e., lack of perfect knowledge). It acknowledges that problem resolution comes through both the application of high-quality science and human decisions based upon preferences and sometimes hard-to-compare choices. It recognizes that to firmly resolve a safety problem, the controlling waste characteristics and chemical phenomena must be measurable or estimated to an acceptable level of confidence tailored to the decision being made
- …