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Sökning: WFRF:(Hall Jim W.)

  • Resultat 1-7 av 7
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  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
  • Sawcer, Stephen, et al. (författare)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
  • Beven, Keith, et al. (författare)
  • Epistemic uncertainties and natural hazard risk assessment - Part 2 : What should constitute good practice?
  • 2018
  • Ingår i: Natural hazards and earth system sciences. - : COPERNICUS GESELLSCHAFT MBH. - 1561-8633 .- 1684-9981. ; 18:10, s. 2769-2783
  • Tidskriftsartikel (refereegranskat)abstract
    • Part 1 of this paper has discussed the uncertainties arising from gaps in knowledge or limited understanding of the processes involved in different natural hazard areas. Such deficits may include uncertainties about frequencies, process representations, parameters, present and future boundary conditions, consequences and impacts, and the meaning of observations in evaluating simulation models. These are the epistemic uncertainties that can be difficult to constrain, especially in terms of event or scenario probabilities, even as elicited probabilities rationalized on the basis of expert judgements. This paper reviews the issues raised by trying to quantify the effects of epistemic uncertainties. Such scientific uncertainties might have significant influence on decisions made, say, for risk management, so it is important to examine the sensitivity of such decisions to different feasible sets of assumptions, to communicate the meaning of associated uncertainty estimates, and to provide an audit trail for the analysis. A conceptual framework for good practice in dealing with epistemic uncertainties is outlined and the implications of applying the principles to natural hazard assessments are discussed. Six stages are recognized, with recommendations at each stage as follows: (1) framing the analysis, preferably with input from potential users; (2) evaluating the available data for epistemic uncertainties, especially when they might lead to inconsistencies; (3) eliciting information on sources of uncertainty from experts; (4) defining a workflow that will give reliable and accurate results; (5) assessing robustness to uncertainty, including the impact on any decisions that are dependent on the analysis; and (6) communicating the findings and meaning of the analysis to potential users, stakeholders, and decision makers. Visualizations are helpful in conveying the nature of the uncertainty outputs, while recognizing that the deeper epistemic uncertainties might not be readily amenable to visualizations.
  • Eggimann, Sven, et al. (författare)
  • How weather affects energy demand variability in the transition towards sustainable heating
  • 2020
  • Ingår i: Energy. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0360-5442 .- 1873-6785. ; 195
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrification of heat will impact demands on power systems, potentially increasing sensitivity to weather variability. We have developed a spatio-temporal methodology for assessing electricity demand in the context of weather variability. We analyse varying levels of electrification of heat in the United Kingdom and simulate local weather impacts with an ensemble of 100 weather realisations. Across the scenarios, the maximum simulated national electricity peak demand doubles compared to today. Assuming current weather pattern, the weather-induced variability in electricity peak is projected to range from 6.1-7.8 GW (10.2-15.2% of mean peak demand) in 2020 to 6.2-14.6 GW (9.8-22.2% of mean peak demand) in 2050. We find that future weather may exacerbate the impact of electrification of heat on peak demand. However, socio-economic uncertainty predominates weather-induced variability. Electrification of heat without reducing heating demands will result in dramatic increases in peak electricity demand as well as increased exposure to weather effects. Regions experiencing a combined increase in peak demand and weather variability will likely prove to be particularly challenging for balancing demand and supply. Switching to alternative fuels such as hydrogen or measures to lower heating demand reduces the need for additional peak electricity capacity as well as mitigating impacts of extreme weather events.
  • Oughton, Edward J., et al. (författare)
  • Infrastructure as a Complex Adaptive System
  • 2018
  • Ingår i: Complexity. - : Hindawi Publishing Corporation. - 1076-2787 .- 1099-0526. ; 2018, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • National infrastructure systems spanning energy, transport, digital, waste, and water are well recognised as complex and interdependent. While some policy makers have been keen to adopt the narrative of complexity, the application of complexity-based methods in public policy decision-making has been restricted by the lack of innovation in associated methodologies and tools. In this paper we firstly evaluate the application of complex adaptive systems theory to infrastructure systems, comparing and contrasting this approach with traditional systems theory. We secondly identify five key theoretical properties of complex adaptive systems including adaptive agents, diverse agents, dynamics, irreversibility, and emergence, which are exhibited across three hierarchical levels ranging from agents, to networks, to systems. With these properties in mind, we then present a case study on the development of a system-of-systems modelling approach based on complex adaptive systems theory capable of modelling an emergent national infrastructure system, driven by agent-level decisions with explicitly modelled interdependencies between energy, transport, digital, waste, and water. Indeed, the novel contribution of the paper is the articulation of the case study describing a decade of research which applies complex adaptive systems properties to the development of a national infrastructure system-of-systems model. This approach has been used by the UK National Infrastructure Commission to produce a National Infrastructure Assessment which is capable of coordinating infrastructure policy across a historically fragmented governance landscape spanning eight government departments. The application will continue to be pertinent moving forward due to the continuing complexity of interdependent infrastructure systems, particularly the challenges of increased electrification and the proliferation of the Internet of Things.
  • Yu, ChaoQing, et al. (författare)
  • Managing nitrogen to restore water quality in China
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 567:7749, s. 516-520
  • Tidskriftsartikel (refereegranskat)abstract
    • The nitrogen cycle has been radically changed by human activities(1). China consumes nearly one third of the world's nitrogen fertilizers. The excessive application of fertilizers(2,3) and increased nitrogen discharge from livestock, domestic and industrial sources have resulted in pervasive water pollution. Quantifying a nitrogen 'boundary'(4) in heterogeneous environments is important for the effective management of local water quality. Here we use a combination of water-quality observations and simulated nitrogen discharge from agricultural and other sources to estimate spatial patterns of nitrogen discharge into water bodies across China from 1955 to 2014. We find that the critical surface-water quality standard (1.0 milligrams of nitrogen per litre) was being exceeded in most provinces by the mid-1980s, and that current rates of anthropogenic nitrogen discharge (14.5 +/- 3.1 megatonnes of nitrogen per year) to fresh water are about 2.7 times the estimated 'safe' nitrogen discharge threshold (5.2 +/- 0.7 megatonnes of nitrogen per year). Current efforts to reduce pollution through wastewater treatment and by improving cropland nitrogen management can partially remedy this situation. Domestic wastewater treatment has helped to reduce net discharge by 0.7 +/- 0.1 megatonnes in 2014, but at high monetary and energy costs. Improved cropland nitrogen management could remove another 2.3 +/- 0.3 megatonnes of nitrogen per year-about 25 per cent of the excess discharge to fresh water. Successfully restoring a clean water environment in China will further require transformational changes to boost the national nutrient recycling rate from its current average of 36 per cent to about 87 per cent, which is a level typical of traditional Chinese agriculture. Although ambitious, such a high level of nitrogen recycling is technologically achievable at an estimated capital cost of approximately 100 billion US dollars and operating costs of 18-29 billion US dollars per year, and could provide co-benefits such as recycled wastewater for crop irrigation and improved environmental quality and ecosystem services.
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  • Resultat 1-7 av 7

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