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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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- Schollick, Julia M. H., et al.
(author)
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Segregated Ice Growth in a Suspension of Colloidal Particles
- 2016
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 120:16, s. 3941-3949
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Journal article (peer-reviewed)abstract
- We study the freezing of a dispersion of colloidal silica particles in water, focusing on the formation of segregated ice in the form of ice lenses. Local temperature measurements in combination with video microscopy give insight into the rich variety of factors that control ice lens formation. We observe the initiation of the lenses, their growth morphology, and their final thickness and spacing over a range of conditions, in particular the effect of the particle packing and the cooling rate. We find that increasing the particle density drastically reduces the thickness of lenses but has little effect on the lens spacing. Therefore, the fraction of segregated ice formed reduces. The effect of the cooling rate, which is the product of the temperature gradient and the pulling speed across the temperature gradient, depends on which parameter is varied. A larger temperature gradient causes ice lenses to be initiated more frequently, while a lower pulling speed allows for more time for ice lenses to grow: both increase the fraction of segregated ice. Surprisingly, we find that the growth rate of a lens does not depend on its undercooling. Finally, we have indications of pore ice in front of the warmest ice lens, which has important consequences for the interpretation of the measured trends. Our findings are relevant for ice segregation occurring in a wide range of situations, ranging from model lab experiments and theories to geological and industrial processes, like frost heave and frozen food production.
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- Seneviratne, Sonia I., et al.
(author)
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Impact of soil moisture-climate feedbacks on CMIP5 projections: First results from the GLACE-CMIP5 experiment
- 2013
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In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 1944-8007 .- 0094-8276. ; 40:19, s. 5212-5217
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Journal article (peer-reviewed)abstract
- The Global Land-Atmosphere Climate Experiment-Coupled Model Intercomparison Project phase 5 (GLACE-CMIP5) is a multimodel experiment investigating the impact of soil moisture-climate feedbacks in CMIP5 projections. We present here first GLACE-CMIP5 results based on five Earth System Models, focusing on impacts of projected changes in regional soil moisture dryness (mostly increases) on late 21st century climate. Projected soil moisture changes substantially impact climate in several regions in both boreal and austral summer. Strong and consistent effects are found on temperature, especially for extremes (about 1-1.5K for mean temperature and 2-2.5K for extreme daytime temperature). In the Northern Hemisphere, effects on mean and heavy precipitation are also found in most models, but the results are less consistent than for temperature. A direct scaling between soil moisture-induced changes in evaporative cooling and resulting changes in temperature mean and extremes is found in the simulations. In the Mediterranean region, the projected soil moisture changes affect about 25% of the projected changes in extreme temperature.
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- Stacchiotti, S., et al.
(author)
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Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
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Research review (peer-reviewed)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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- Stephens, Graeme L., et al.
(author)
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The changing nature of Earth's reflected sunlight
- 2022
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In: Proceedings of the Royal Society. Mathematical, Physical and Engineering Sciences. - : The Royal Society. - 1364-5021 .- 1471-2946. ; 478:2263
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Journal article (peer-reviewed)abstract
- The increased rate of sea-level rise suggests that Earth's energy imbalance is also increasing over time. This study assesses whether 20 years of direct observations of this energy imbalance from Earth-orbiting satellites support the existence of a real trend in this imbalance and the components of it and finds. Changes to the imbalance observed are found to be consistent across multiple sources of observations. The majority of recent studies now clearly point to this energy imbalance being positive, while forced by increasing greenhouse gas concentrations in the atmosphere, being amplified significantly by decreases to the amount of sunlight reflected by Earth to space. Here, we show that the global changes observed appear largely from reductions in the amount of sunlight scattered by Earth's atmosphere. These reductions, in turn, are found to be almost equally split between reduced reflection from the cloudy and clear regions of the atmosphere, with the latter being suggestive of reduced scattering by aerosol particles over the observational period. Climate models, however, show an almost exclusive response from clouds, and a slightly exaggerated darkening of the surface. Thus, models that match the global shortwave change do so for the wrong reasons.
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