987 resultados para Farrell, Steve


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The Bronze Age in Britain was a time of major social and cultural changes, reflected in the division of the landscape into field systems and the establishment of new belief systems and ritual practices. Several hypotheses have been advanced to explain these changes, and assessment of many of them is dependent on the availability of detailed palaeoenvironmental data from the sites concerned. This paper explores the development of a later prehistoric landscape in Orkney, where a Bronze Age field system and an apparently ritually-deposited late Bronze Age axe head are located in an area of deep blanket peat from which high-resolution palaeoenvironmental sequences have been recovered. There is no indication that the field system was constructed to facilitate agricultural intensification, and it more likely reflects a cultural response to social fragmentation associated with a more dispersed settlement pattern. There is evidence for wetter conditions during the later Bronze Age, and the apparent votive deposit may reflect the efforts of the local population to maintain community integrity during a time of perceptible environmental change leading to loss of farmland. The study emphasises the advantages of close integration of palaeoenvironmental and archaeological data for interpretation of prehistoric human activity. The palaeoenvironmental data also provide further evidence for the complexity of prehistoric woodland communities in Orkney, hinting at greater diversity than is often assumed. Additionally, differing dates for woodland decline in the two sequences highlight the dangers of over-extrapolation from trends observed in a single pollen profile, even at a very local scale.

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Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

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Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

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There have been important recent developments in law, research, policy and practice relating to supporting people with decision-making impairments, in particular when a person’s wishes and preferences are unclear or inaccessible. A driver in this respect is the United Nations Convention on the Rights of Persons with Disabilities (CRPD); the implications of the CRPD for policy and professional practices are currently debated. This article reviews and compares four legal frameworks for supported and substitute decision-making for people whose decision-making ability is impaired. In particular, it explores how these frameworks may apply to people with mental health problems. The four jurisdictions are: Ontario, Canada; Victoria, Australia; England and Wales, United Kingdom (UK); and Northern Ireland, UK. Comparisons and contrasts are made in the key areas of: the legal framework for supported and substitute decision-making; the criteria for intervention; the assessment process; the safeguards; and issues in practice. Thus Ontario has developed a relatively comprehensive, progressive and influential legal framework over the past thirty years but there remain concerns about the standardisation of decision-making ability assessments and how the laws work together. In Australia, the Victorian Law Reform Commission (2012) has recommended that the six different types of substitute decision-making under the three laws in that jurisdiction, need to be simplified, and integrated into a spectrum that includes supported decision-making. In England and Wales the Mental Capacity Act 2005 has a complex interface with mental health law. In Northern Ireland it is proposed to introduce a new Mental Capacity (Health, Welfare and Finance) Bill that will provide a unified structure for all substitute decision-making. The discussion will consider the key strengths and limitations of the approaches in each jurisdiction and identify possible ways that further progress can be made in law, policy and practice.

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Reversible work extraction from identical quantum systems via collective operations was shown to be possible even without producing entanglement among the sub-parts. Here, we show that implementing such global operations necessarily imply the creation of quantum correlations, as measured by quantum discord. We also reanalyze the conditions under which global transformations outperform local gates as far as maximal work extraction is considered by deriving a necessary and sufficient condition that is based on classical correlations.

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The mineral concentrations in cereals are important for human health, especially for individuals who consume a cereal subsistence diet. A number of elements, such as zinc, are required within the diet, while some elements are toxic to humans, for example arsenic. In this study we carry out genome-wide association (GWA) mapping of grain concentrations of arsenic, copper, molybdenum and zinc in brown rice using an established rice diversity panel of,300 accessions and 36.9 k single nucleotide polymorphisms (SNPs). The study was performed across five environments: one field site in Bangladesh, one in China and two in the US, with one of the US sites repeated over two years. GWA mapping on the whole dataset and on separate subpopulations of rice revealed a large number of loci significantly associated with variation in grain arsenic, copper, molybdenum and zinc. Seventeen of these loci were detected in data obtained from grain cultivated in more than one field location, and six co-localise with previously identified quantitative trait loci. Additionally, a number of candidate genes for the uptake or transport of these elements were located near significantly associated SNPs (within 200 kb, the estimated global linkage disequilibrium previously employed in this rice panel). This analysis highlights a number of genomic regions and candidate genes for further analysis as well as the challenges faced when mapping environmentally-variable traits in a highly genetically structured diversity panel.