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Sökning: WFRF:(Page Trevor)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Sawcer, Stephen, et al. (författare)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 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.
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  • 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.
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  • Rich, Rebecca L., et al. (författare)
  • A global benchmark study using affinity-based biosensors
  • 2009
  • Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
  • Tidskriftsartikel (refereegranskat)abstract
    • To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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