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Sökning: WFRF:(Cesana A.)

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1.
  • Hageman, S., et al. (författare)
  • SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:25, s. 2439-2454
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe.
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2.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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3.
  • Ankowski, A., et al. (författare)
  • Energy reconstruction of electromagnetic showers from Ν0 decays with the ICARUS T600 liquid argon TPC
  • 2010
  • Ingår i: Acta Physica Polonica, Series B.. - 1509-5770 .- 0587-4254. ; 41:1, s. 103-125
  • Tidskriftsartikel (refereegranskat)abstract
    • We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π 0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γγ) invariant mass was found to be consistent with the value of the π 0 mass. The resolution of the reconstructed π 0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π 0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π 0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π 0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.
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4.
  • Ankowski, A, et al. (författare)
  • Energy reconstruction of electromagnetic showers from π0 decays with the ICARUS T600 liquid argon TPC
  • 2010
  • Ingår i: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 41:1, s. 103-125
  • Tidskriftsartikel (refereegranskat)abstract
    • We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γ,γ) invariant mass was found to be consistent with the value of the π0 mass. The resolution of the reconstructed π0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.
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  • Rubbia, C, et al. (författare)
  • Underground operation of the ICARUS T600 LAr-TPC : first results
  • 2011
  • Ingår i: Journal of Instrumentation. ; 6:07
  • Tidskriftsartikel (refereegranskat)abstract
    • Important open questions are still present in fundamental Physics and Cosmology, like the nature of Dark Matter, the matter-antimatter asymmetry and the validity of the Standard Model of particle interactions. Addressing these questions requires a new generation of massive particle detectors to explore the subatomic and astrophysical worlds. ICARUS T600 is the first large mass (760 tons) example of a new generation of detectors able to combine the imaging capabilities of the old famous “bubble chamber” with the excellent energy measurement of huge electronic detectors. ICARUS T600 now operates at the Gran Sasso underground laboratory and is used to study cosmic rays, neutrino oscillations and the proton decay. The potential for doing physics of this novel telescope is presented through a few examples of neutrino interactions reconstructed with unprecedented detail. Detector design and early operation are also reported.
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7.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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8.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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9.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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11.
  • Baroffio, L., et al. (författare)
  • Demo : Enabling image analysis tasks in visual sensor networks
  • 2014
  • Ingår i: Proceedings of the 8th ACM/IEEE International Conference on Distributed Smart Cameras, ICDSC 2014. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450329255 ; , s. a46-
  • Konferensbidrag (refereegranskat)abstract
    • This demo showcases some of the results obtained by the GreenEyes project, whose main objective is to enable visual analysis on resource-constrained multimedia sensor networks. The demo features a multi-hop visual sensor network operated by BeagleBones Linux computers with IEEE 802.15.4 communication capabilities, and capable of recognizing and tracking objects according to two different visual paradigms. In the traditional compress-then-analyze (CTA) paradigm, JPEG compressed images are transmitted through the network from a camera node to a central controller, where the analysis takes place. In the alternative analyze-then-compress (ATC) paradigm, the camera node extracts and compresses local binary visual features from the acquired images (either locally or in a distributed fashion) and transmits them to the central controller, where they are used to perform object recognition/tracking. We show that, in a bandwidth constrained scenario, the latter paradigm allows to reach better results in terms of application frame rates, still ensuring excellent analysis performance.
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14.
  • Kristensen, A., et al. (författare)
  • Simple cardiovascular risk stratification using anthropometric measures instead of serum cholesterol. The MORGAM Prospective Cohort Project
  • 2020
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:Suppl 2, s. 2913-2913
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Body composition predicts cardiovascular outcomes, but it is uncertain whether anthropometric measures can replace the more expensive serum total cholesterol for cardiovascular risk stratification in low resource settings.Purpose: The purpose of the study was to compare the additive prognostic ability of serum total cholesterol with that of body mass index (BMI), waist/hip ratio (WHR), and estimated fat mass (EFM, calculated using a validated prediction equation), individually and combined.Methods: We used data from the MORGAM (MONICA, Risk, Genetics, Archiving, and Monograph) Prospective Cohort Project, an international pooling of cardiovascular cohorts, to determine the relationship between anthropometric measures, serum cholesterol, and cardiovascular events, using multivariable Cox proportional-hazards regression analysis. We further investigated the ability of these measures to enhance prognostication beyond a simpler prediction model, consisting of age, sex, smoking status, systolic blood pressures, and country, using comparison of area under the receiver operating characteristics curve (AUCROC) derived from binary logistic regression models. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of death from coronary heart disease, myocardial infarction, or stroke.Results: The study population consisted of 52,188 apparently healthy subjects (56.3% men) aged 47±12 years ranging from 20 to 84, derived from 37 European cohorts, with baseline between 1982–2002 all followed for 10 years during which MACE occurred in 2465 (4.7%) subjects. All anthropometric measures (BMI: hazard ratio (HR) 1.04 [95% confidence interval (CI): 1.03–1.05] per kg/m2; WHR: HR 7.5 [4.0–14.0] per unit; EFM: HR 1.02 [1.01–1.02] per kg) as well as serum total cholesterol (HR 1.20 [1.16–1.24] per mmol/l) were significantly associated with MACE (P<0.001 for all), independently of age, sex, smoking status, systolic blood pressures, and country. The addition of serum cholesterol significantly improved the predictive ability of the simple model (AUCROC 0.818 vs. 0.814, P<0.001), as did the combination of WHR, BMI, and EFM (AUCROC 0.817 vs. 0.814, P=0.004). When assessed individually, BMI (AUCROC 0.816 vs. 0.814, P=0.004) and WHR (AUCROC 0.815 vs. 0.814, P=0.02) improved model performance, while EFM narrowly missed significance (AUCROC 0.815 vs. 0.814, P=0.06). There was no significant difference in the predictive ability of a model including serum cholesterol versus that including all three anthropometric measures (AUCROC 0.818 vs. 0.817, P=0.13). The figure shows the pertinent areas under the ROC curve in predicting MACE.Conclusion: In this large population-based cohort study, the addition of a combination of anthropometric measures, i.e. BMI, WHR, and EFM, raised the predictive ability of a simple prognostic model comparable to that obtained by the addition of serum total cholesterol.
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16.
  • Padmanabhan, Sandosh, et al. (författare)
  • Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
  • 2010
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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17.
  • Baroffio, L., et al. (författare)
  • GreenEyes : Networked energy-aware visual analysis
  • 2015
  • Ingår i: 2015 IEEE International Conference on Multimedia and Expo Workshops, ICMEW 2015. - : IEEE conference proceedings. - 9781479970797
  • Konferensbidrag (refereegranskat)abstract
    • The GreenEyes project aims at developing a comprehensive set of new methodologies, practical algorithms and protocols, to empower wireless sensor networks with vision capabilities. The key tenet of this research is that most visual analysis tasks can be carried out based on a succinct representation of the image, which entails both global and local features, while it disregards the underlying pixel-level representation. Specifically, GreenEyes will pursue the following goals: i) energy-constrained extraction of visual features; ii) rate-efficiency modelling and coding of visual feature; iii) networking streams of visual features. This will have a significant impact on several scenarios including, e.g., smart cities and environmental monitoring.
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