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- Kaptoge, S., et al.
(författare)
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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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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Tidskriftsartikel (refereegranskat)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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- Gregson, J., et al.
(författare)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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- Jonkers, Y. M. H., et al.
(författare)
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DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients
- 2007
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 14:3, s. 769-779
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Tidskriftsartikel (refereegranskat)abstract
- The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size 2 cm, Ki67 proliferative index 2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan–Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P0.0004) and tumor-specific death (P0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index 2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.
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- Berner, G., et al.
(författare)
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LaAlO3/SrTiO3 oxide heterostructures studied by resonant inelastic x-ray scattering
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 82:24, s. 241405-
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Tidskriftsartikel (refereegranskat)abstract
- We report the application of resonant inelastic X-ray scattering to explore the nature of the single conducting interface in the oxide heterostructure LaAlO/sub 3//SrTiO/sub 3/. From the Ti 3d crystal-field excitations measured at the Ti L/sub 3/ resonance we not only derive information on the local geometry at the interface but are also able to follow the evolution of the sheet carrier density with the thickness of the LaAlO/sub 3/ overlayer. These findings confirm after calibration to previous hard X-ray photoelectron spectroscopy measurements that the charge density from spectroscopy exceeds the one derived from Hall-effect measurements, indicating the coexistence of itinerant /i and/ localized Ti 3d electrons at the interface. On the other hand, we observe a saturation of the charge-carrier concentration above a LaAlO/sub 3/ thickness of 6 unit cells at ~1*10/sup 14/ cm/sup -2/, well below the canonical value for ideal electronic reconstruction.
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- Fetscher, B., et al.
(författare)
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Making Random Judgments: Automatically Generating Well-Typed Terms from the Definition of a Type-System
- 2015
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Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. ; 9032, s. 383-405
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a generic method for randomly generating well-typed expressions. It starts from a specification of a typing judgment in PLT Redex and uses a specialized solver that employs randomness to find many different valid derivations of the judgment form. Our motivation for building these random terms is to more effectively falsify conjectures as part of the tool-support for semantics models specified in Redex. Accordingly, we evaluate the generator against the other available methods for Redex, as well as the best available custom well-typed term generator. Our results show that our new generator is much more effective than generation techniques that do not explicitly take types into account and is competitive with generation techniques that do, even though they are specialized to particular type-systems and ours is not.
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- Glawion, S., et al.
(författare)
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Two-Spinon and Orbital Excitations of the Spin-Peierls System TiOCl
- 2011
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 107:10, s. 107402-
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Tidskriftsartikel (refereegranskat)abstract
- We combine high-resolution resonant inelastic x-ray scattering with cluster calculations utilizing a recently derived effective magnetic scattering operator to analyze the polarization, excitation energy, and momentum-dependent excitation spectrum of the low-dimensional quantum magnet TiOCl in the range expected for orbital and magnetic excitations (0-2.5 eV). Ti 3d orbital excitations yield complete information on the temperature-dependent crystal-field splitting. In the spin-Peierls phase we observe a dispersive two-spinon excitation and estimate the inter- and intradimer magnetic exchange coupling from a comparison to cluster calculations.
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- Lopez, Juan R., et al.
(författare)
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Spectral Karyotypic and Comparative Genomic Analysis of the Endocrine Pancreatic Tumor Cell Line BON-1
- 2010
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 91:2, s. 131-141
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Tidskriftsartikel (refereegranskat)abstract
- BON-1 is a human serotonin-producing endocrine pancreatic tumor (EPT) cell line, which has been used for various studies of tumorigenesis and treatment. Because its genotype, phenotype and degree of differentiation may underlie events that are instrumental to the development of endocrine tumors and, moreover, may vary between labs and over time, we decided to comprehensively characterize the chromosomal constitution of BON-1 by applying conventional GTG-banding, spectral karyotyping (SKY), comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). BON-1 cells proved to be hyperdiploid containing a modal chromosome number of 57 (range 56–64). SKY identified a stemline containing 6 clonal aberrations including del(1p), t(9;12)del(9p)x2, der(10)t(5;10), der(19)t(8;19), der(14)t(9;14)t(9;10), and a sideline harboring an additional del(12q). CGH and FISH confirmed the SKY results and, in addition, highlighted the chromosomal regions involved in the rearrangements. Moreover, they identified a homozygous deletion of the key tumor suppressor genes CDKN2A and CDKN2B at 9p21.3, in accordance with absence of p16INK4A and p14ARF expression as revealed by immunocytochemistry. Apart from deregulation of the cell cycle and p53 pathway this finding indicates escape from replicative senescence (induced by mutated NRAS) and detachment-induced apoptosis as molecular mechanisms underlying the tumorigenesis of BON-1 cells. Immunostaining results for p53, MDM2 and pRb expression were consistent with previously published data using Western analysis. In conclusion, we provide here a comprehensive cytogenetic profile of BON-1. This cell line harbors both numerical and structural genomic alterations indicative for malignant EPTs.
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