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- Kaptoge, S., et al.
(author)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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In: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Journal article (peer-reviewed)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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- Broadhurst, Edward T., et al.
(author)
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Polymorph evolution during crystal growth studied by 3D electron diffraction
- 2020
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In: IUCrJ. - 2052-2525. ; 7, s. 5-9
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Journal article (peer-reviewed)abstract
- 3D electron diffraction (3DED) has been used to follow polymorph evolution in the crystallization of glycine from aqueous solution. The three polymorphs of glycine which exist under ambient conditions follow the stability order beta < alpha < gamma. The least stable beta polymorph forms within the first 3 min, but this begins to yield the alpha-form after only 1 min more. Both structures could be determined from continuous rotation electron diffraction data collected in less than 20 s on crystals of thickness similar to 100 nm. Even though the gamma-form is thermodynamically the most stable polymorph, kinetics favour the alpha-form, which dominates after prolonged standing. In the same sample, some beta and one crystallite of the gamma polymorph were also observed.
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- Diego, J. M., et al.
(author)
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JWST's PEARLS : A new lens model for ACT-CL J0102-4915, "El Gordo," and the first red supergiant star at cosmological distances discovered by JWST
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
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Journal article (peer-reviewed)abstract
- The first James Webb Space Telescope (JWST) data on the massive colliding cluster El Gordo allow for 23 known families of multiply lensed images to be confirmed and for eight new members of these families to be identified. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and nine were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range 2 z z > 0.8 and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at z = 0.87 and has an estimated mass of 3.8 x 10(9) M-circle dot, making it the smallest substructure found at z > 0.5. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at z = 2.1878. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at z > 6, making more of them visible than in blank fields of a similar size, but there appears to be a deficiency of such objects.
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- Reinke, SN, et al.
(author)
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Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study
- 2022
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 59:6
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Journal article (peer-reviewed)abstract
- Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.MethodsBaseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.ResultsA total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.ConclusionsThis is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma.
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