| 1. |
- Leong, D. P., et al.
(författare)
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Medications for blood pressure, blood glucose, lipids, and anti-thrombotic medications: relationship with cardiovascular disease and death in adults from 21 high-, middle-, and low-income countries with an elevated body mass index
- 2022
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Ingår i: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 29:14, s. 1817-1826
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Tidskriftsartikel (refereegranskat)abstract
- Aims Elevated body mass index (BMI) is an important cause of cardiovascular disease (CVD). The population-level impact of pharmacologic strategies to mitigate the risk of CVD conferred by the metabolic consequences of an elevated BMI is not well described. Methods and results We conducted an analysis of 145 986 participants (mean age 50 years, 58% women) from 21 high-, middle-, and low-income countries in the Prospective Urban and Rural Epidemiology study who had no history of cancer, ischaemic heart disease, heart failure, or stroke. We evaluated whether the hazards of CVD (myocardial infarction, stroke, heart failure, or cardiovascular death) differed among those taking a cardiovascular medication (n = 29 174; including blood pressure-lowering, blood glucose-lowering, cholesterol-lowering, or anti-thrombotic medications) vs. those not taking a cardiovascular medication (n = 116 812) during 10.2 years of follow-up. Cox proportional hazard models with the community as a shared frailty were constructed by adjusting age, sex, education, geographic region, physical activity, tobacco, and alcohol use. We observed 7928 (5.4%) CVD events and 9863 (6.8%) deaths. Cardiovascular medication use was associated with different hazards of CVD (interaction P < 0.0001) and death (interaction P = 0.0020) as compared with no cardiovascular medication use. Among those not taking a cardiovascular medication, as compared with those with BMI 20 to <25 kg/m(2), the hazard ratio (HR) [95% confidence interval (95% CI)] for CVD were, respectively, 1.14 (1.06-1.23); 1.45 (1.30-1.61); and 1.53 (1.28-1.82) among those with BMI 25 to <30 kg/m(2); 30 to <35 kg/m(2); and >= 35 kg/m(2). However, among those taking a cardiovascular medication, the HR (95% CI) for CVD were, respectively, 0.79 (0.72-0.87); 0.90 (0.79-1.01); and 1.14 (0.98-1.33). Among those not taking a cardiovascular medication, the respective HR (95% CI) for death were 0.93 (0.87-1.00); 1.03 (0.93-1.15); and 1.44 (1.24-1.67) among those with BMI 25 to <30 kg/m(2); 30 to <35 kg/m(2); and >= 35 kg/m(2). However, among those taking a cardiovascular medication, the respective HR (95% CI) for death were 0.77 (0.69-0.84); 0.88 (0.78-0.99); and 1.12 (0.96-1.30). Blood pressure-lowering medications accounted for the largest population attributable benefit of cardiovascular medications. Conclusion To the extent that CVD risk among those with an elevated BMI is related to hypertension, diabetes, and an elevated thrombotic milieu, targeting these pathways pharmacologically may represent an important complementary means of reducing the CVD burden caused by an elevated BMI.
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| 2. |
- Hu, Weida, et al.
(författare)
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CLASSY VII Lyα Profiles : The Structure and Kinematics of Neutral Gas and Implications for LyC Escape in Reionization-era Analogs
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 956:1
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Tidskriftsartikel (refereegranskat)abstract
- Lyα line profiles are a powerful probe of interstellar medium (ISM) structure, outflow speed, and Lyman-continuum escape fraction. In this paper, we present the Lyα line profiles of the Cosmic Origins Spectrograph (COS) Legacy Archive Spectroscopic SurveY, a sample rich in spectroscopic analogs of reionization-era galaxies. A large fraction of the spectra show a complex profile, consisting of a double-peaked Lyα emission profile in the bottom of a damped, Lyα absorption trough. Such profiles reveal an inhomogeneous ISM. We successfully fit the damped Lyα absorption and the Lyα emission profiles separately, but with complementary covering factors, a surprising result because this approach requires no Lyα exchange between high-NH i and low-NH i paths. The combined distribution of column densities is qualitatively similar to the bimodal distributions observed in numerical simulations. We find an inverse relation between Lyα peak separation and the [O iii]/[O ii] flux ratio, confirming that the covering fraction of Lyman-continuum-thin sightlines increases as the Lyα peak separation decreases. We combine measurements of Lyα peak separation and Lyα red peak asymmetry in a diagnostic diagram, which identifies six Lyman-continuum leakers in the COS Legacy Archive Spectrocopy SurveY (CLASSY) sample. We find a strong correlation between the Lyα trough velocity and the outflow velocity measured from interstellar absorption lines. We argue that greater vignetting of the blueshifted Lyα peak, relative to the redshifted peak, is the source of the well-known discrepancy between shell-model parameters and directly measured outflow properties. The CLASSY sample illustrates how scattering of Lyα photons outside the spectroscopic aperture reshapes Lyα profiles because the distances to these compact starbursts span a large range.
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| 3. |
- Mansouri, Kamel, et al.
(författare)
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CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
- 2020
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:2, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
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