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Sökning: WFRF:(Simpson David) > (2010-2014)

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1.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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2.
  • Baigent, Colin, et al. (författare)
  • The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial
  • 2011
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
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5.
  • Mills, Gina, et al. (författare)
  • Evidence of widespread effects of ozone on crops and (semi-)natural vegetation in Europe (1990 - 2006) in relation to AOT40 - and flux-based risk maps
  • 2010
  • Ingår i: Global Change Biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 17:1, s. 592-613
  • Tidskriftsartikel (refereegranskat)abstract
    • Records of effects of ambient ozone pollution on vegetation have been compiled for Europe for the years 1990–2006. Sources include scientific papers, conference proceedings, reports to research funders, records of confirmed ozone injury symptoms and an international biomonitoring experiment coordinated by the ICP Vegetation. The latter involved ozone-sensitive (NC-S) and ozone-resistant (NC-R) biotypes of white clover (Trifolium repens L.) grown according to a common protocol and monitored for ozone injury and biomass differences in 17 European countries, from 1996 to 2006. Effects were separated into visible injury or growth/yield reduction. Of the 644 records of visible injury, 39% were for crops (27 species), 38.1% were for (semi-) natural vegetation (95 species) and 22.9% were for shrubs (49 species). Owing to inconsistencies in reporting effort from year to year it was not possible to determine geographical or temporal trends in the data. Nevertheless, this study has shown effects in ambient air in 18 European countries from Sweden in the north to Greece in the south. These effects data were superimposed on AOT40 (accumulated ozone concentrations over 40 ppb) and POD3gen (modelled accumulated stomatal flux over a threshold of 3 nmol m−2 s−1) maps generated by the EMEP Eulerian model (50 km × 50 km grid) that were parameterized for a generic crop based on wheat and NC-S/NC-R white clover. Many effects were found in areas where the AOT40 (crops) was below the critical level of 3 ppm h. In contrast, the majority of effects were detected in grid squares where POD3gen (crops) were in the mid-high range (>12 mmol m−2). Overall, maps based on POD3gen provided better fit to the effects data than those based on AOT40, with the POD3gen model for clover fitting the clover effects data better than that for a generic crop.
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6.
  • Aas, W., et al. (författare)
  • Lessons learnt from the first EMEP intensive measurement periods
  • 2012
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:17, s. 8073-8094
  • Tidskriftsartikel (refereegranskat)abstract
    • The first EMEP intensive measurement periods were held in June 2006 and January 2007. The measurements aimed to characterize the aerosol chemical compositions, including the gas/aerosol partitioning of inorganic compounds. The measurement program during these periods included daily or hourly measurements of the secondary inorganic components, with additional measurements of elemental- and organic carbon (EC and OC) and mineral dust in PM1, PM2.5 and PM10. These measurements have provided extended knowledge regarding the composition of particulate matter and the temporal and spatial variability of PM, as well as an extended database for the assessment of chemical transport models. This paper summarise the first experiences of making use of measurements from the first EMEP intensive measurement periods along with EMEP model results from the updated model version to characterise aerosol composition. We investigated how the PM chemical composition varies between the summer and the winter month and geographically. The observation and model data are in general agreement regarding the main features of PM10 and PM2.5 composition and the relative contribution of different components, though the EMEP model tends to give slightly lower estimates of PM10 and PM2.5 compared to measurements. The intensive measurement data has identified areas where improvements are needed. Hourly concurrent measurements of gaseous and particulate components for the first time facilitated testing of modelled diurnal variability of the gas/aerosol partitioning of nitrogen species. In general, the modelled diurnal cycles of nitrate and ammonium aerosols are in fair agreement with the measurements, but the diurnal variability of ammonia is not well captured. The largest differences between model and observations of aerosol mass are seen in Italy during winter, which to a large extent may be explained by an underestimation of residential wood burning sources. It should be noted that both primary and secondary OC has been included in the calculations for the first time, showing promising results. Mineral dust is important, especially in southern Europe, and the model seems to capture the dust episodes well. The lack of measurements of mineral dust hampers the possibility for model evaluation for this highly uncertain PM component. There are also lessons learnt regarding improved measurements for future intensive periods. There is a need for increased comparability between the measurements at different sites. For the nitrogen compounds it is clear that more measurements using artefact free methods based on continuous measurement methods and/or denuders are needed. For EC/OC, a reference methodology (both in field and laboratory) was lacking during these periods giving problems with comparability, though measurement protocols have recently been established and these should be followed by the Parties to the EMEP Protocol. For measurements with no defined protocols, it might be a good solution to use centralised laboratories to ensure comparability across the network. To cope with the introduction of these new measurements, new reporting guidelines have been developed to ensure that all proper information about the methodologies and data quality is given.
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7.
  • Abel, I, et al. (författare)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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8.
  • Angelbratt, Jon, 1981, et al. (författare)
  • Carbon monoxide (CO) and ethane (C2H6) trends from ground-based solar FTIR measurements at six European stations, comparison and sensitivity analysis with the EMEP model
  • 2011
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:17, s. 9253-9269
  • Tidskriftsartikel (refereegranskat)abstract
    • Trends in the CO and C(2)H(6) partial columns (similar to 0-15 km) have been estimated from four European ground-based solar FTIR (Fourier Transform InfraRed) stations for the 1996-2006 time period. The CO trends from the four stations Jungfraujoch, Zugspitze, Harestua and Kiruna have been estimated to -0.45 +/- 0.16%yr(-1), -1.00 +/- 0.24%yr(-1), -0.62 +/- 0.19%yr(-1) and -0.61 +/- 0.16%yr(-1), respectively. The corresponding trends for C(2)H(6) are -1.51 +/- 0.23%yr(-1), -2.11 +/- 0.30%yr(-1), -1.09 +/- 0.25%yr(-1) and -1.14 +/- 0.18%yr(-1). All trends are presented with their 2-sigma confidence intervals. To find possible reasons for the CO trends, the global-scale EMEP MSC-W chemical transport model has been used in a series of sensitivity scenarios. It is shown that the trends are consistent with the combination of a 20% decrease in the anthropogenic CO emissions seen in Europe and North America during the 1996-2006 period and a 20% increase in the anthropogenic CO emissions in East Asia, during the same time period. The possible impacts of CH(4) and biogenic volatile organic compounds (BVOCs) are also considered. The European and global-scale EMEP models have been evaluated against the measured CO and C(2)H(6) partial columns from Jungfraujoch, Zugspitze, Bremen, Harestua, Kiruna and Ny-Alesund. The European model reproduces, on average the measurements at the different sites fairly well and within 10-22% deviation for CO and 14-31% deviation for C(2)H(6). Their seasonal amplitude is captured within 6-35% and 9-124% for CO and C(2)H(6), respectively. However, 61-98% of the CO and C(2)H(6) partial columns in the European model are shown to arise from the boundary conditions, making the global-scale model a more suitable alternative when modeling these two species. In the evaluation of the global model the average partial columns for 2006 are shown to be within 1-9% and 37-50% of the measurements for CO and C(2)H(6), respectively. The global model sensitivity for assumptions made in this paper is also analyzed.
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9.
  • Bergström, Robert, et al. (författare)
  • Biotic stress: a significant contributor to organic aerosol in Europe?
  • 2014
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus Publications. - 1680-7316 .- 1680-7324. ; 14:24, s. 13643-13660
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated the potential impact on organic aerosol formation from biotic stress-induced emissions (SIE) of organic molecules from forests in Europe (north of lat. 45° N). Emission estimates for sesquiterpenes (SQT), methyl salicylate (MeSA) and unsaturated C17 compounds, due to different stressors, are based on experiments in the Jülich Plant Atmosphere Chamber (JPAC), combined with estimates of the fraction of stressed trees in Europe based on reported observed tree damage. SIE were introduced in the EMEP MSC-W chemical transport model and secondary organic aerosol (SOA) yields from the SIE were taken from the JPAC experiments. Based on estimates of current levels of infestation and the JPAC aerosol yields, the model results suggest that the contribution to SOA in large parts of Europe may be substantial. It is possible that SIE contributes as much, or more, to organic aerosol than the constitutive biogenic VOC emissions, at least during some periods. Based on the assumptions in this study, SIE-SOA are estimated to constitute between 50 and 70 % of the total biogenic SOA (BSOA) in a current-situation scenario where the biotic stress in northern and central European forests causes large SIE of MeSA and SQT. An alternative current-situation scenario with lower SIE, consisting solely of SQT, leads to lower SIE-SOA, between 20 and 40 % of the total BSOA. Hypothetical future scenarios with increased SIE, due to higher degrees of biotic stress, show that SOA formation due to SIE can become even larger. Unsaturated C17 BVOC (biogenic volatile organic compounds) emitted by spruce infested by the forest-honey generating bark louse, Cinara pilicornis, have a high SOA-forming potential. A model scenario investigating the effect of a regional, episodic infestation of Cinara pilicornis in Baden-Württemberg, corresponding to a year with high production of forest honey, shows that these types of events could lead to very large organic aerosol formation in the infested region. We have used the best available laboratory data on biotic SIE applicable to northern and central European forests. Using these data and associated assumptions, we have shown that SIE are potentially important for SOA formation but the magnitude of the impact is uncertain and needs to be constrained by further laboratory, field and modelling studies. As an example, the MeSA, which is released as a consequence of various types of biotic stress, is found to have a potentially large impact on SIE-SOA in Europe, but different assumptions regarding the nighttime chemistry of MeSA can change its SOA potential substantially. Thus, further investigations of the atmospheric chemistry of MeSA and observational field studies are needed to clarify the role of this compound in the atmosphere.
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10.
  • Bergström, Robert, et al. (författare)
  • Modelling of organic aerosols over Europe (2002-2007) using a volatility basis set (VBS) framework: application of different assumptions regarding the formation of secondary organic aerosol
  • 2012
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:18, s. 8499-8527
  • Tidskriftsartikel (refereegranskat)abstract
    • A new organic aerosol module has been implemented into the EMEP chemical transport model. Four different volatility basis set (VBS) schemes have been tested in long-term simulations for Europe, covering the six years 2002-2007. Different assumptions regarding partitioning of primary organic aerosol and aging of primary semi-volatile and intermediate volatility organic carbon (S/IVOC) species and secondary organic aerosol (SOA) have been explored. Model results are compared to filter measurements, aerosol mass spectrometry (AMS) data and source apportionment studies, as well as to other model studies. The present study indicates that many different sources contribute significantly to organic aerosol in Europe. Biogenic and anthropogenic SOA, residential wood combustion and vegetation fire emissions may all contribute more than 10% each over substantial parts of Europe. This study shows smaller contributions from biogenic SOA to organic aerosol in Europe than earlier work, but relatively greater anthropogenic SOA. Simple VBS based organic aerosol models can give reasonably good results for summer conditions but more observational studies are needed to constrain the VBS parameterisations and to help improve emission inventories. The volatility distribution of primary emissions is one important issue for further work. Emissions of volatile organic compounds from biogenic sources are also highly uncertain and need further validation. We can not reproduce winter levels of organic aerosol in Europe, and there are many indications that the present emission inventories substantially underestimate emissions from residential wood combustion in large parts of Europe.
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