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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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- Norberg, Peter, 1974, et al.
(author)
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Recombination of Globally Circulating Varicella-Zoster Virus
- 2015
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In: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 89:14, s. 7133-7146
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Journal article (peer-reviewed)abstract
- Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.
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- Lu, Ru-Sen, et al.
(author)
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Detection of Intrinsic Source Structure at similar to 3 Schwarzschild Radii with Millimeter-VLBI Observations of SAGITTARIUS A*
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 859:1
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Journal article (peer-reviewed)abstract
- We report results from very long baseline interferometric (VLBI) observations of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230 GHz). The observations were performed in 2013 March using six VLBI stations in Hawaii, California, Arizona, and Chile. Compared to earlier observations, the addition of the APEX telescope in Chile almost doubles the longest baseline length in the array, provides additional uv coverage in the N-S direction, and leads to a spatial resolution of similar to 30 mu as (similar to 3 Schwarzschild radii) for Sgr A*. The source is detected even at the longest baselines with visibility amplitudes of similar to 4%-13% of the total flux density. We argue that such flux densities cannot result from interstellar refractive scattering alone, but indicate the presence of compact intrinsic source structure on scales of similar to 3 Schwarzschild radii. The measured nonzero closure phases rule out point-symmetric emission. We discuss our results in the context of simple geometric models that capture the basic characteristics and brightness distributions of disk-and jet-dominated models and show that both can reproduce the observed data. Common to these models are the brightness asymmetry, the orientation, and characteristic sizes, which are comparable to the expected size of the black hole shadow. Future 1.3 mm VLBI observations with an expanded array and better sensitivity will allow more detailed imaging of the horizon-scale structure and bear the potential for a deep insight into the physical processes at the black hole boundary.
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- Nair, Arjun, et al.
(author)
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Variable radiological lung nodule evaluation leads to divergent management recommendations
- 2018
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:6, s. 1-12
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Journal article (peer-reviewed)abstract
- Radiological evaluation of incidentally detected lung nodules on computed tomography (CT) influences management. We assessed international radiological variation in 1) pulmonary nodule characterisation; 2) hypothetical guideline-derived management; and 3) radiologists' management recommendations.107 radiologists from 25 countries evaluated 69 CT-detected nodules, recording: 1) first-choice composition (solid, part-solid or ground-glass, with percentage confidence); 2) morphological features; 3) dimensions; 4) recommended management; and 5) decision-influencing factors. We modelled hypothetical management decisions on the 2005 and updated 2017 Fleischner Society, and both liberal and parsimonious interpretations of the British Thoracic Society 2015 guidelines.Overall agreement for first-choice nodule composition was good (Fleiss' κ=0.65), but poorest for part-solid nodules (weighted κ 0.62, interquartile range 0.50-0.71). Morphological variables, including spiculation (κ=0.35), showed poor-to-moderate agreement (κ=0.23-0.53). Variation in diameter was greatest at key thresholds (5 mm and 6 mm). Agreement for radiologists' recommendations was poor (κ=0.30); 21% disagreed with the majority. Although agreement within the four guideline-modelled management strategies was good (κ=0.63-0.73), 5-10% of radiologists would disagree with majority decisions if they applied guidelines strictly.Agreement was lowest for part-solid nodules, while significant measurement variation exists at important size thresholds. These variations resulted in generally good agreement for guideline-modelled management, but poor agreement for radiologists' actual recommendations.
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