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Sökning: WFRF:(Leyland J)

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31.
  • Leyland, K. M., et al. (författare)
  • Harmonising measures of knee and hip osteoarthritis in population-based cohort studies : an international study
  • 2018
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 26:7, s. 872-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Population-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses. Method: International OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI). Results: OA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0–20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question. Conclusion: This research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.
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34.
  • Antoniou, Antonis C., et al. (författare)
  • Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
  • 2011
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
  • Tidskriftsartikel (refereegranskat)abstract
    • Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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37.
  • Beurskens, M. N. A., et al. (författare)
  • Global and pedestal confinement in JET with a Be/W metallic wall
  • 2014
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 54:4, s. 043001-
  • Tidskriftsartikel (refereegranskat)abstract
    • Type I ELMy H-mode operation in JET with the ITER-like Be/W wall (JET-ILW) generally occurs at lower pedestal pressures compared to those with the full carbon wall (JET-C). The pedestal density is similar but the pedestal temperature where type I ELMs occur is reduced and below to the so-called critical type I-type III transition temperature reported in JET-C experiments. Furthermore, the confinement factor H-98(y,H- 2) in type I ELMy H-mode baseline plasmas is generally lower in JET-ILWcompared to JET-C at low power fractions Ploss/P-thr,(08)< 2 (where P-loss is (P-in-dW/dt), and P-thr,(08) the L-H power threshold from Martin et al 2008 (J. Phys. Conf. Ser. 123 012033)). Higher power fractions have thus far not been achieved in the baseline plasmas. At Ploss/P-thr,P- 08 > 2, the confinement in JET-ILW hybrid plasmas is similar to that in JET-C. A reduction in pedestal pressure is the main reason for the reduced confinement in JET-ILW baseline ELMy H-mode plasmas where typically H-98((y, 2)) = 0.8 is obtained, compared to H-98((y, 2)) = 1.0 in JET-C. In JET-ILW hybrid plasmas a similarly reduced pedestal pressure is compensated by an increased peaking of the core pressure profile resulting in H-98((y, 2)) <= 1.25. The pedestal stability has significantly changed in high triangularity baseline plasmas where the confinement loss is also most apparent. Applying the same stability analysis for JET-C and JET-ILW, the measured pedestal in JET-ILW is stable with respect to the calculated peeling-ballooning stability limit and the ELM collapse time has increased to 2ms from typically 200 mu s in JET-C. This indicates that changes in the pedestal stability may have contributed to the reduced pedestal confinement in JET-ILW plasmas. A comparison of EPED1 pedestal pressure prediction with JET-ILW experimental data in over 500 JET-C and JET-ILW baseline and hybrid plasmas shows a good agreement with 0.8 < (measured p(ped))/(predicted p(ped), EPED) < 1.2, but that the role of triangularity is generally weaker in the JET-ILW experimental data than in the model predictions.
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38.
  • Beurskens, M. N. A., et al. (författare)
  • The effect of a metal wall on confinement in JET and ASDEX Upgrade
  • 2013
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 55:12, s. 124043-
  • Tidskriftsartikel (refereegranskat)abstract
    • In both JET and ASDEX Upgrade (AUG) the plasma energy confinement has been affected by the presence of a metal wall by the requirement of increased gas fuelling to avoid tungsten pollution of the plasma. In JET with a beryllium/tungsten wall the high triangularity baseline H-mode scenario (i.e. similar to the ITER reference scenario) has been the strongest affected and the benefit of high shaping to give good normalized confinement of H-98 similar to 1 at high Greenwald density fraction of f(GW) similar to 0.8 has not been recovered to date. In AUG with a full tungsten wall, a good normalized confinement H-98 similar to 1 could be achieved in the high triangularity baseline plasmas, albeit at elevated normalized pressure beta(N) > 2. The confinement lost with respect to the carbon devices can be largely recovered by the seeding of nitrogen in both JET and AUG. This suggests that the absence of carbon in JET and AUG with a metal wall may have affected the achievable confinement. Three mechanisms have been tested that could explain the effect of carbon or nitrogen (and the absence thereof) on the plasma confinement. First it has been seen in experiments and by means of nonlinear gyrokinetic simulations (with the GENE code), that nitrogen seeding does not significantly change the core temperature profile peaking and does not affect the critical ion temperature gradient. Secondly, the dilution of the edge ion density by the injection of nitrogen is not sufficient to explain the plasma temperature and pressure rise. For this latter mechanism to explain the confinement improvement with nitrogen seeding, strongly hollow Z(eff) profiles would be required which is not supported by experimental observations. The confinement improvement with nitrogen seeding cannot be explained with these two mechanisms. Thirdly, detailed pedestal structure analysis in JET high triangularity baseline plasmas have shown that the fuelling of either deuterium or nitrogen widens the pressure pedestal. However, in JET-ILW this only leads to a confinement benefit in the case of nitrogen seeding where, as the pedestal widens, the obtained pedestal pressure gradient is conserved. In the case of deuterium fuelling in JET-ILW the pressure gradient is strongly degraded in the fuelling scan leading to no net confinement gain due to the pedestal widening. The pedestal code EPED correctly predicts the pedestal pressure of the unseeded plasmas in JET-ILW within +/- 5%, however it does not capture the complex variation of pedestal width and gradient with fuelling and impurity seeding. Also it does not predict the observed increase of pedestal pressure by nitrogen seeding in JET-ILW. Ideal peeling ballooning MHD stability analysis shows that the widening of the pedestal leads to a down shift of the marginal stability boundary by only 10-20%. However, the variations in the pressure gradient observed in the JET-ILW fuelling experiment is much larger and spans a factor of more than two. As a result the experimental points move from deeply unstable to deeply stable on the stability diagram in a deuterium fuelling scan. In AUG-W nitrogen seeded plasmas, a widening of the pedestal has also been observed, consistent with the JET observations. The absence of carbon can thus affect the pedestal structure, and mainly the achieved pedestal gradient, which can be recovered by seeding nitrogen. The underlying physics mechanism is still under investigation and requires further understanding of the role of impurities on the pedestal stability and pedestal structure formation.
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40.
  • Leyland, M. J., et al. (författare)
  • Edge profile analysis of Joint European Torus (JET) Thomson scattering data : Quantifying the systematic error due to edge localised mode synchronisation
  • 2016
  • Ingår i: Review of Scientific Instruments. - : AMER INST PHYSICS. - 0034-6748 .- 1089-7623. ; 87:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Joint European Torus (JET) high resolution Thomson scattering (HRTS) system measures radial electron temperature and density profiles. One of the key capabilities of this diagnostic is measuring the steep pressure gradient, termed the pedestal, at the edge of JET plasmas. The pedestal is susceptible to limiting instabilities, such as Edge Localised Modes (ELMs), characterised by a periodic collapse of the steep gradient region. A common method to extract the pedestal width, gradient, and height, used on numerous machines, is by performing a modified hyperbolic tangent (mtanh) fit to overlaid profiles selected from the same region of the ELM cycle. This process of overlaying profiles, termed ELM synchronisation, maximises the number of data points defining the pedestal region for a given phase of the ELM cycle. When fitting to HRTS profiles, it is necessary to incorporate the diagnostic radial instrument function, particularly important when considering the pedestal width. A deconvolved fit is determined by a forward convolution method requiring knowledge of only the instrument function and profiles. The systematic error due to the deconvolution technique incorporated into the JET pedestal fitting tool has been documented by Frassinetti et al. [Rev. Sci. Instrum. 83, 013506 (2012)]. This paper seeks to understand and quantify the systematic error introduced to the pedestal width due to ELM synchronisation. Synthetic profiles, generated with error bars and point-to-point variation characteristic of real HRTS profiles, are used to evaluate the deviation from the underlying pedestal width. We find on JET that the ELM synchronisation systematic error is negligible in comparison to the statistical error when assuming ten overlaid profiles (typical for a pre-ELM fit to HRTS profiles). This confirms that fitting a mtanh to ELM synchronised profiles is a robust and practical technique for extracting the pedestal structure.
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