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- Patel, Riyaz S., et al.
(author)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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- Patel, Riyaz S., et al.
(author)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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- Bellouin, N., et al.
(author)
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Bounding Global Aerosol Radiative Forcing of Climate Change
- 2020
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In: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:1
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Research review (peer-reviewed)abstract
- Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6Wm(-2), or -2.0 to -0.4Wm(-2) with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds. Plain Language Summary Human activities emit into the atmosphere small liquid and solid particles called aerosols. Those aerosols change the energy budget of the Earth and trigger climate changes, by scattering and absorbing solar and terrestrial radiation and playing important roles in the formation of cloud droplets and ice crystals. But because aerosols are much more varied in their chemical composition and much more heterogeneous in their spatial and temporal distributions than greenhouse gases, their perturbation to the energy budget, called radiative forcing, is much more uncertain. This review uses traceable and arguable lines of evidence, supported by aerosol studies published over the past 40 years, to quantify that uncertainty. It finds that there are two chances out of three that aerosols from human activities have increased scattering and absorption of solar radiation by 14% to 29% and cloud droplet number concentration by 5 to 17% in the period 2005-2015 compared to the year 1850. Those increases exert a radiative forcing that offsets between a fifth and a half of the radiative forcing by greenhouse gases. The degree to which human activities affect natural aerosol levels, and the response of clouds, and especially ice clouds, to aerosol perturbations remain particularly uncertain.
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- Breton, Simon-Philippe, et al.
(author)
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Comparative CFD study of the effect of the presence of downstream turbines on upstream ones using a rotational speed control system
- 2014
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In: Science of Making Torque from Wind 2012. - : IOP Publishing.
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Conference paper (peer-reviewed)abstract
- The effect of a downstream turbine on the production of a turbine located upstream of the latter is studied in this work. This is done through the use of two CFD simulation codes, namely OpenFOAM and EllipSys3D, which solve the Navier-Stokes equations in their incompressible form using a finite volume approach. In both EllipSys3D and Open Foam, the LES (Large Eddy Simulation) technique is used for modelling turbulence. The wind turbine rotors are modelled as actuator disks whose loading is determined through the use of tabulated airfoil data by applying the blade-element method. A generator torque controller is used in both simulation methods to ensure that the simulated turbines adapt, in terms of rotational velocity, to the inflow conditions they are submited to. Results from both simulation codes, although they differ slightly, show that the downstream turbine affects the upstream one when the spacing between the turbines is small. This is also suggested to be the case looking at measurements performed at the Lillgrund offshore wind farm, whose turbines are located unusually close to each other. However, for distances used in today's typical wind farms, this effect is shown by our calculations not to be significant.
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- Breton, Simon-Philippe, et al.
(author)
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Study of the influence of imposed turbulence on the asymptotic wake deficit in a very long line of wind turbines
- 2014
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In: Renewable energy. - : Elsevier BV. - 0960-1481 .- 1879-0682. ; 70, s. 153-163
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Journal article (peer-reviewed)abstract
- The influence of imposed turbulence on the development of the flow along a long row of wind turbines is studied, in search for an asymptotic wake deficit state. Calculations are performed using EllipSys3D, a CFD code that solves the Navier-Stokes equations in their incompressible form using a finite volume approach. In this code, the Large-Eddy Simulation technique is used for modeling turbulence, and the wind turbine rotors are represented as actuator discs whose loading is determined through the use of tabulated airfoil data by applying the blade-element method. Ten turbines are located along a row and separated from each other by seven rotor diameters, which is representative of the distance used in today's offshore wind farms. Turbulence is pre-generated with the Mann model, with imposed turbulence intensity levels of 4.5% and 8.9%. The aim with this study is to investigate features of the flow that depend solely on imposed turbulence and the presence of wind turbine rotors. For this reason, the turbines are isolated from their environment, and no effect from the presence of the atmospheric boundary layer is modeled, i.e., a non-sheared inflow is used. Analysis of the characteristics of the flow as a function of the position along the row of turbines is performed in terms of standard deviation of the velocity components, turbulence kinetic energy, mean velocity, and power spectra of the axial velocity fluctuations. The mean power production along the row of turbines is also used as an indicator. Calculations are performed below rated power, where a generator torque controller implemented in EllipSys3D renders it possible for the turbines to adapt to the flow conditions in which they operate. The results obtained for the standard deviation of the velocity components, turbulence kinetic energy, power and mean velocity as functions of downstream distance show that an asymptotic wake state seems close to be reached, in the conditions tested, near the end of the 10 turbine row. Significant changes towards this state are seen to happen faster when imposing turbulence in the domain. Power spectra of the axial velocity fluctuations are shown to provide interesting information about the turbulence in the flow, but are found not to be useful in determining if an asymptotic wake state is reached.
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- Rugenstein, Maria, et al.
(author)
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Equilibrium Climate Sensitivity Estimated by Equilibrating Climate Models
- 2020
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:4
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Journal article (peer-reviewed)abstract
- The methods to quantify equilibrium climate sensitivity are still debated. We collect millennial-length simulations of coupled climate models and show that the global mean equilibrium warming is higher than those obtained using extrapolation methods from shorter simulations. Specifically, 27 simulations with 15 climate models forced with a range of CO2 concentrations show a median 17% larger equilibrium warming than estimated from the first 150 years of the simulations. The spatial patterns of radiative feedbacks change continuously, in most regions reducing their tendency to stabilizing the climate. In the equatorial Pacific, however, feedbacks become more stabilizing with time. The global feedback evolution is initially dominated by the tropics, with eventual substantial contributions from the mid-latitudes. Time-dependent feedbacks underscore the need of a measure of climate sensitivity that accounts for the degree of equilibration, so that models, observations, and paleo proxies can be adequately compared and aggregated to estimate future warming.
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