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Sökning: WFRF:(Leander John)

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1.
  • 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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2.
  • Peden, John F., et al. (författare)
  • A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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3.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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4.
  • Abbasi, Rasha, et al. (författare)
  • IceCube search for neutrinos from GRB 221009A
  • 2023
  • Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
  • Konferensbidrag (refereegranskat)abstract
    •  GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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5.
  • Feitosa, Mary F., et al. (författare)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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6.
  • Schunkert, Heribert, et al. (författare)
  • Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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7.
  • de Vries, Paul S., et al. (författare)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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8.
  • Patel, Riyaz S., et al. (författare)
  • Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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9.
  • Patel, Riyaz S., et al. (författare)
  • Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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10.
  • Sung, Yun Ju, et al. (författare)
  • A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
  • 2019
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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11.
  • de las Fuentes, Lisa, et al. (författare)
  • Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
  • Tidskriftsartikel (refereegranskat)abstract
    • Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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12.
  • Gertow, Karl, et al. (författare)
  • Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
  • 2012
  • Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
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14.
  • Leander, John (författare)
  • Refining the fatigue assessment procedure of existing steel bridges
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis treats the fatigue assessment process of steel bridges. The purpose is to identify areas with potential of enhancement with an overall aim of attaining a longer service life. The aging bridge stock in Sweden and in many other developed countries is an impending economical burden. Many bridges have reached their expected service life and increased axle loads, speeds, and traffic intensity further accelerate the deterioration. An immediate replacement of all our bridges approaching their expected service life will not be possible. For economical and environmental reasons, effort should be put on extending the theoretically safe service life as far as possible. Fatigue is one of the major reasons limiting the service life of steel bridges .A specific example is the Söderström Bridge in Stockholm, Sweden. Fatigue cracks have been found in the webs of the main beams and theoretical assessments have shown an exhausted service life. As a mean to reduce the uncertainties in the theoretical assessments a monitoring campaign was started in 2008 and continued in periods until 2011. The first continuous period of 43 days of measurements in 2008 forms the experimental foundation for this thesis.A fatigue life prediction involves (i) an estimation of the load effect, (ii) an estimation of the resistance, and (iii) the selection of a prediction model. This thesis treats in some sense all three of them. Considering part (i), the load effect, a theoretical study on the influence of dynamics has been performed. The quasi static approach suggested in the standards does not necessarily reflect the true dynamic behavior of the structure. Performing a dynamic moving load analysis gives for all cases studied a more favorable fatigue life. A further enhancement of the assessment is to perform in situ measurements. The uncertainties related to dynamics, loads, and structural behavior are thereby captured in the response. Routines for processing the measured response and performing life predictions are treated, moreover the quality of the measured response.The resistance, part (ii), in form of the fatigue endurance has a funda- mental influence on the fatigue life. As an attempt to reach a more adequate fatigue endurance a refined assessment of a typical joint is performed using linear elastic fracture mechanics (LEFM). A descriptive detail category is suggested which renders a somewhat more favorable resistance.Part (iii), the prediction model, is treated considering the safety format. A reliability-based model is suggested which enables a consideration of the uncertainties in each stochastic variable. Thereby, all aforementioned parts and uncertainties can be combined within the same prediction. The reliability-based model is used for a code calibration of partial safety factors to be used in semi-probabilistic assessments according to the standards.The implementation of the suggested procedures is shown with a numerical example. The outcome should not be generalized but the example clearly shows an increase in fatigue life with the proposed enhancements of the assessment procedure.   
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15.
  • Maljaars, Johan, et al. (författare)
  • Models and methods for probabilistic safety assessment of steel structures subject to fatigue
  • 2024
  • Ingår i: Structural Safety. - : Elsevier BV. - 0167-4730 .- 1879-3355. ; , s. 102446-102446
  • Tidskriftsartikel (refereegranskat)abstract
    • We review of the state of the art in probabilistic modelling for fatigue reliability of civil engineering and offshore structures. The modeling of randomness and uncertainty in  fatigue resistance and fatigue load variables are presented in some detail. This is followed  by a review of the specifics of reliability analysis for fatigue limit states and a background  on the semi-probabilistic treatment of fatigue safety. We discuss the different life-cycle  reliability concepts and give an overview on probabilistic inspection planning. We describe  the choices made in the Probabilistic Model Code of the Joint Committee of Structural  Safety, present alternatives to these choices and suggest areas of future research.
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16.
  • Scott, Robert A., et al. (författare)
  • An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
  • 2017
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
  • Tidskriftsartikel (refereegranskat)abstract
    • To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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17.
  • Wang, Ruoqi, 1992- (författare)
  • Reliability-based fatigue assessment of existing steel bridges
  • 2020
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Fatigue is among the most critical forms of deterioration damage that occurs tosteel bridges. It causes a decline of the safety level of bridges over time. Therefore,the performance of steel bridges, which may be seriously affected by fatigue, shouldbe assessed and predicted. There are several levels of uncertainty involved in thecrack initiation and propagation process; therefore the probabilistic methods canprovide a better estimation of fatigue lives than deterministic methods. Whenthere are recurring similar details which may have correlation with each other andbe regarded as a system, there are distinct advantages to analyze them from asystem reliability perspective. It allows the engineer to identify the importance ofan individual detail or the interaction between details with respect to the overallperformance of the system.The main aim of this licentiate thesis is to evaluate probabilistic methods for reliabilityassessment of steel bridges, from both a single detail level and a systemlevel. For single details, an efficient simulation technique is desired. The widelyapplied Monte Carlo simulation method provides accurate estimation, however, isvery time-consuming. The Subset simulation method is investigated as an alternativeand it shows great feasibility in dealing with a multi-dimensional limit statefunction and nonlinear crack propagation. For larger systems, the spatial correlationis considered between details. An equicorrelation-based modelling approachhas been proposed as supplement to common simulation techniques to estimate thesystem reliability analytically and significantly reduce the simulation time. Withcorrelation considered, the information of one accessible detail could be used topredict the status of the system.While reliability analysis aims for a specific safety level, risk analysis aims to findthe most optimal solution. With consequences considered, a risk-based decisionsupport framework is formulated for the selected system, which is presented asa decision tree. It reveals that the decisions based on reliability assessment canbe different from those based on risk analysis, since they have different objectivecriteria.
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18.
  • Wang, Ruoqi, et al. (författare)
  • Reliability-based inspection planning for steel bridges considering fatigue
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Inspections are important for ensuring adequate safety and performance of a bridge throughout its desired service life. Traditionally, inspection planning mainly follows the code, standard, or past experience. However, this may lead to an unnecessary number of inspections, which will not fulfill an efficient management strategy. In this paper, a reliability-based optimised inspection planning concept has been proposed and applied to a selected steel bridge under fatigue degradation. It aims to provide a plan of inspections which maintains an acceptable level of safety of the structure and reduce unnecessary inspections and associated costs. Several inspection techniques are implemented with selected acceptance criteria to determine the impact of the quality of the inspections and the acceptance criterion on the planning and associated costs. The expected costs are estimated in parametric studies considering the net present value and consequences of a failure. It is apparent that an optimised strategy will reduce the number of required inspections and their associated costs and make each inspection more effective. The effect that the net present value has on the expected cost is not negligible. However, it is difficult to quantify a specific value. When the cost of failure is high to a certain extent, it becomes more dominant than the cost of inspections, consequently increasing the estimated expected costs.
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19.
  • al-Karawi, Hassan, 1993, et al. (författare)
  • Verification of the Maximum Stresses in Enhanced Welded Details via High-Frequency Mechanical Impact in Road Bridges
  • 2023
  • Ingår i: Buildings. - : MDPI AG. - 2075-5309. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • High-frequency mechanical impact (HFMI) is an efficient post-weld treatment technique that enhances fatigue strength in metallic welded structures. Steel or steel-concrete composite road bridges, where the fatigue limit state often governs the design, compose one category of structures that can benefit from the application of this technology. To assert an improvement in fatigue strength using HFMI, the induced compressive residual stresses must be stable. Therefore, the maximum service stresses that can be allowed on HFMI-treated joints should be controlled to avoid the relaxation of the induced beneficial compressive stresses by HFMI treatment. Using statistical analysis of recorded traffic, this paper compares the measured maximum traffic loads to those generated by a load model. More than 870,000 and 470,000 recorded vehicles from traffic measurements in Sweden and the Netherlands are used in this analysis. To capture the characteristic bending moment, the daily maxima of the resulting measured load effect are combined with the extreme value distribution of the bending moment. In addition, it is found that the characteristic load combination is the best-studied option to assess the maximum stress in HFMI-treated weldments in road bridges.
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20.
  • Andersson, Andreas, 1980-, et al. (författare)
  • Extending the fatigue service life of a railway bridge by local approaches
  • 2013
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, fatigue assessment of a steel railway bridge is presented. The bridge is located in central Stockholm, Sweden, and is one of the most vital links for the railway network. The bridge services both freight trains and commuter trains with more than 500 passages per day. The main load bearing structure is designed as a steel grillage of welded I-beams. Fatigue critical sections have been identified at locations where secondary bracing systems are welded to the flanges of the I-beams. Both numerical simulations and extensive field measurements have shown a significant exceedance of the theoretical fatigue service life. Based on analysis of local stress concentrations, improvement of fatigue critical details have been suggested. The decrease in stress concentration is demonstrated both by numerical simulations and in-situ field measurements and shows a significant improvement when estimating the remaining fatigue service life.
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21.
  • Arthur Hvidtfeldt, Ulla, et al. (författare)
  • Long-term exposure to fine particle elemental components and lung cancer incidence in the ELAPSE pooled cohort
  • 2021
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 193
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the Effects of Low-level Air Pollution: A Study in Europe (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence.Methods: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status).Results: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m(3) PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m(3) PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m(3) PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative.Conclusions: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.
  •  
22.
  • Avendaño, Juan Camilo (författare)
  • Detection and quantification of cracks in concrete bridges using drone-image inspection
  • 2024
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The assessment of civil infrastructure plays an important role in ensuring the safety of the general public and the durability of structures. Traditional inspection methods often involve manual labour and subjective evaluations, resulting in limitations in efficiency and accuracy. In recent years, there has been an increasing interest on using advanced technologies, such as unmanned aerial vehicles (UAVs), image analysis and machine learning techniques, to establish them as alternatives for the inspection process. These techniques provide different advantages compared with the manual method in terms of time, objectivity, and safety. The results of these techniques can allow the engineers in charge of the assessment and maintenance planning to obtain detailed results that can improve their efficiency but they are not without challenges. This research project aims to evaluate different methods used for damage detection and quantification and their integration with UAVs as an alternative to structural inspections. The proposed methodology combines image analysis techniques, Convolutional Neural Networks (CNNs) with drones to address the different aspects of inspections, from the data gathering to the damage detection and quantification. This methodology focuses on detecting and quantifying small cracks as narrow as 0.1 mm on concrete structures, aiming to achieve results comparable to those of traditional inspection. Furthermore, an application demonstrating the feasibility of the methodology in inside environments is also presented, focusing on the inspection of the internal section of a box girder bridge, including the creation of 3Dphotogrammetrical models to improve the inspection process. The results of the thesis highlight the methodology’s capabilities in detecting small cracks with a high probability and the possibility to use it for inside inspections without ideal conditions. This demonstrates the potential of integrating the different methods to transform structural inspections toward more efficient methodologies. Furthermore, the analysis of the results evaluates the drawbacks encountered and outlines future research directions aimed at advancing image-based inspections and their practical application.
  •  
23.
  • Avendãno, Juan Camilo, et al. (författare)
  • Drone-based photogrammetric inspection of interior box girder bridges
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Digital inspections methods have gained increasing interest in the civil engineering field for assessing the condition of various structures including buildings and bridges. These methods are used primarily to evaluate the external surface condition of the structure. However, in the case of bridges, their application when inspecting the interior of these structures remains uncommon. This paper presents a case study for inspecting the interior of a concrete box girder bridge, the Strängnäs bridge. The inspection involved gathering data using a commercial drone, creating a photogrammetrical model, detecting and quantifying damages by employing a Convolutional Neural Network (CNN). The analysis successfully detected 60 cm long concrete cracks, a total area of 3.5 m2 leakage and corrosion over 40 cm. The study addressed the difficulties such as insufficient lighting, lack of GPS signal and dust clouds reducing visibility. Despite these obstacles, the study demonstrated the effectiveness of indoor drone-based inspections.
  •  
24.
  • Avendãno, Juan Camilo, et al. (författare)
  • Image-Based Concrete Crack Detection Method Using the Median Absolute Deviation
  • 2024
  • Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 24:9, s. 2736-2752
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper proposes an innovative approach for detecting and quantifying concrete cracks using an adaptive threshold method based on Median Absolute Deviation (MAD) in images. The technique applies limited pre-processing steps and then dynamically determines a threshold adapted for each sub-image depending on the greyscale distribution of the pixels, resulting in tailored crack segmentation. The edges of the crack are obtained using the Laplace edge detection method, and the width of the crack is obtained for each centreline point. The method’s performance is measured using the Probability of Detection (POD) curves as a function of the actual crack size, revealing remarkable capabilities. It was found that the proposed method could detect cracks as narrow as 0.1 mm, with a probability of 94% and 100% for cracks with larger widths. It was also found that the method had higher accuracy, precision, and F2 score values than the Otsu and Niblack methods.
  •  
25.
  • Avendãno, Juan Camilo, et al. (författare)
  • Image based inspection of concrete cracks using UAV photography
  • 2022
  • Ingår i: Bridge Safety, Maintenance, Management, Life-Cycle, Resilience and Sustainability. - London : CRC Press.
  • Konferensbidrag (refereegranskat)abstract
    • Traditional inspections are typically performed manually. They require specialized  equipment, which usually is expensive, time-consuming and can often be a source of risk.  Unmanned Aerial Vehicles (UAV) provide an alternative to overcome the challenges of  traditional manual inspections. This has been stud-ied as well as the use of machine  learning and image analysis algorithms for detection and quantification of damages, in  particular cracks. This paper presents a framework for inspections that combines data  acquisition, crack detection, and the quantification of essential parameters of concrete  cracks. From this method, the width and length of cracks are determined and compared  with control measurements to estimate the accuracy of the method. The results show that  using the pre-trained network to detect cracks, only a few to no false negatives are  obtained. From the images classified as containing cracks, the quantification methodology is performed obtaining measurements of crack width down to 0.13 mm. 
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26.
  • Aygül, Mustafa, 1970, et al. (författare)
  • An investigation of distortion-induced fatigue cracking under variable amplitude loading using 3D crack propagation analysis
  • 2014
  • Ingår i: Engineering Failure Analysis. - : Elsevier BV. - 1350-6307 .- 1873-1961. ; 45, s. 151-163
  • Tidskriftsartikel (refereegranskat)abstract
    • The distortion-induced fatigue cracks in the welded details of the Soderstrom Bridge are analytically and numerically investigated by performing 3D crack propagation analyses with variable amplitude fatigue loading. In the crack propagation analyses, the effects of bridge loading are defined on the basis of the field measurements in order to simulate crack growth and predict the residual fatigue life of the studied detail as accurately as possible. The effect of crack closure and crack direction while considering the most common criteria is also studied. The results are compared with those obtained from the crack propagation analyses with constant amplitude fatigue loading presented in Ayg l et al. [1]. The results of the crack growth simulations with variable amplitude fatigue loading have generally shown good agreement with the real crack formation and reveal that the crack growth rates are different in different directions. The crack behaviour in the damaged detail is mainly controlled by the loading and geometrical arrangement of the detail components. There is generally a significant difference between constant and variable amplitude fatigue crack growth analyses and the variable amplitude fatigue crack growth analyses yield more conservative results. The main reason for this difference is the bridge loading and the number of stress cycles defined in the analyses. The crack direction criteria studied in this investigation showed basically the same crack formation and crack growth rate.
  •  
27.
  • Aygül, Mustafa, 1970, et al. (författare)
  • Investigation of distortion-induced fatigue cracked welded details using 3D crack propagation analysis
  • 2014
  • Ingår i: International Journal of Fatigue. - : Elsevier BV. - 0142-1123 .- 1879-3452. ; 64, s. 54-66
  • Tidskriftsartikel (refereegranskat)abstract
    • The behaviour of distortion-induced fatigue cracks in welded details in an existing bridge was studied analytically by performing crack propagation analysis based on linear elastic fracture mechanics. The real load history of the bridge was obtained from strain measurements. These loads were utilised to examine the crack growth rate and the residual service life of the cracked detail. Moreover, the effectiveness, accuracy and applicability of the crack propagation analysis on bridge structures were investigated by simulating a complex case of fatigue cracking using several crack propagation analyses. The results of the analyses revealed that the fatigue crack in the studied details had significantly different crack growth characteristics in different directions. In the thickness direction, for instance, the crack was seen to propagate at a certain rate, which increased with the propagated crack from the beginning and, as expected, the crack propagation rate decreased when the crack grew longer. The crack was subsequently arrested half way through the thickness of the plate. In the longitudinal direction, the crack was not, however, arrested in the same way as in the thickness direction and it continued to propagate at a reduced yet constant crack growth rate. The results also revealed that, even though distortion-induced fatigue cracking was usually caused by a mixed-mode condition (i.e. a combination of modes I, II and III), the governing propagation mode is still mode I. Furthermore, it was also observed that the contribution of modes II and III to crack propagation was very little and dependent on the location of the propagated crack front, as well as the geometrical configuration of the cross-beam. (C) 2014 Elsevier Ltd. All rights reserved.
  •  
28.
  • Bayane, Imane, et al. (författare)
  • An unsupervised machine learning approach for real-time damage detection in bridges
  • 2024
  • Ingår i: Engineering structures. - : Elsevier BV. - 0141-0296 .- 1873-7323. ; 308
  • Tidskriftsartikel (refereegranskat)abstract
    • The bridge network is progressively aging, with an alarming proportion of bridges over 100 years. This situation engenders substantial risks to the overall reliability of transportation networks, requiring innovative methods for efficient management. Monitoring can provide a direct source of information about structural behavior generating alerts when changes occur. Real-time alerts enable effective infrastructure management and decision-making during damage or anomalous situations. However, monitoring can result in a large amount of data that is often difficult to convert into valuable information in real time. This paper presents an approach for real-time detection of abrupt damage occurrence in bridges using unsupervised anomaly detection algorithms and strain/acceleration measurements. The approach incorporates the separation of measurements into events having the same loading nature and the construction of three feature matrices based on statistical features, time-frequency features, and wavelet spectrum features. It includes the evaluation of five anomaly detection algorithms including Isolation Forest, One-Class Support Vector Machine, Robust Random Cut Forest, Local Outlier Factor, and Mahalanobis Distance. The approach is illustrated with a case study of a steel-bascule-railway bridge, that has experienced a brittle cracking event during monitoring. Results highlight the robustness of One-Class Support Vector Machine, Isolation Forest, and Local Outlier Factor algorithms in promptly detecting abrupt changes across different features. The separation of strain and acceleration data into loading-based events, coupled with the comparison of previous and new event features, provides robust feature matrices for effective damage detection. Enhanced detection and higher scores are particularly attributed to time-frequency domain features during damage occurrence. The presented approach can be used as a base on how to perform real-time anomaly detection within the context of bridge monitoring.
  •  
29.
  • Bayane, Imane, et al. (författare)
  • Real-Time Crack Detection in Bridges Using Monitoring and Machine Learning-Verified with an Actual Damage Case
  • 2023
  • Ingår i: Structural Health Monitoring 2023: Designing SHM for Sustainability, Maintainability, and Reliability - Proceedings of the 14th International Workshop on Structural Health Monitoring. - : DEStech Publications. ; , s. 1636-1644
  • Konferensbidrag (refereegranskat)abstract
    • Detecting damage in bridges that present signs of deterioration or have exceeded the expected lifespan is critical for ensuring safety in service. This paper suggests an approach for real-time damage detection for such bridges through monitoring and machine learning algorithms, which serve as timely alarms for decision-making and subsequent damage identification. The approach involves five steps: monitoring, data collection, data separation, feature extraction, and anomaly detection in real-time. Monitoring is ensured by strain gauges, accelerometers, and a temperature sensor. Data collection is ensured at high frequency continuously to capture the dynamic effects of loading. Data separation is provided to classify monitoring data according to loading events, which is in the case of the study characterized by the bridge opening, the bridge closing, and train passages. Feature extraction is provided to characterize monitoring data for each loading event. Anomaly detection is performed by the Isolation Forest and the One-Class Support Vector Machine algorithms. The algorithms are implemented in real-time for each new event. The approach is illustrated in a full-scale post-damage case study of a steel-bascule-railway bridge, in service since 1916, with signs of corrosion and fatigue. The results demonstrate the ability of the approach to capture a cracking event in real-time. The Isolation Forest algorithm is found to be more robust for damage detection compared to the One-Class Support Vector Machine. It assigned high scores to the events occurring during and after the cracking, highlighting its ability to capture such incidents promptly. These findings have significant implications for bridge owners as they can identify damage in components in real time, enabling them to take timely measures such as traffic interruption and subsequent repairs.
  •  
30.
  • Björnsson, Ivar, et al. (författare)
  • Decision support framework for bridge condition assessments
  • 2019
  • Ingår i: Structural Safety. - : Elsevier BV. - 0167-4730 .- 1879-3355. ; 81
  • Tidskriftsartikel (refereegranskat)abstract
    • An essential aspect in the maintenance of existing bridges is the ability to adequately and accurately assess and evaluate the condition of the structure. Condition assessments, which can be carried out in any number of ways, provide valuable information concerning the actual state of a bridge, including the severity of potential damages, and form the basis for further maintenance decisions. Any decision support concerning the management of existing structures thus requires attention towards the uncertainties associated with the assessment methods when applied in practice as well as the maintenance actions these support. These uncertainties cannot be solely described as model uncertainties but are also a result of the variation in engineering performance observed in practice. In the current paper a rational and systematic framework is presented which provides practical decision support concerning whether condition assessments are necessary, what assessment methods are recommended, if invasive actions are needed, or if some other non-invasive option may be more appropriate. The framework takes into account three main attributes of an enhanced condition assessment, namely, modelling sophistication, considerations of uncertainties and risks, and knowledge/information content. Increasing the level of one or more of these attributes may be advantageous only if the expected benefits or added value of information is considered appropriate in relation to the cost of implementation in practice. A decision making model, based on Bayesian decision theory, is adopted to evaluate this problem. Two case studies, in which the framework is applied, are provided for illustrative purposes; the first is a generic numerical example and the second a decision scenario related to the fatigue assessment of an existing railway bridge.
  •  
31.
  • Blasiak, Robert, et al. (författare)
  • Corporations and plastic pollution : Trends in reporting
  • 2021
  • Ingår i: Sustainable Futures. - : Elsevier BV. - 2666-1888. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on pathways to reducing plastic pollution often concludes that greater action is needed by the private sector. Yet the private sector is not a monolithic or homogeneous entity. We compiled a novel library of 2,317 corporate reports from the world's 200 largest companies, by revenue, over a ten-year period (2010–2019) and used text mining tools to identify pronounced regional and sectoral variability in the extent to which plastic waste and pollution is of material importance to corporate operations. The results show a dominant focus on recycling, with far less attention to the other stages of the life cycle of plastic. While green clubs have emerged in recent years to mobilize voluntary actions by companies seeking to position themselves as leaders in this context, we see regional and sectoral gaps in green club membership, as well as a tendency for members to be those companies that already had a history of reporting on plastics issues. This analysis provides a starting point for a more nuanced consideration of the private sector's role in addressing plastic pollution, and suggests sectors and regions for prioritization by policymakers and civil society actors seeking to broaden the range of committed corporate actors.
  •  
32.
  • Chen, Jie, et al. (författare)
  • Long-term exposure to ambient air pollution and bladder cancer incidence in a pooled European cohort : the ELAPSE project
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 126:10, s. 1499-1507
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The evidence linking ambient air pollution to bladder cancer is limited and mixed.Methods: We assessed the associations of bladder cancer incidence with residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight PM2.5 elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) in a pooled cohort (N = 302,493). Exposures were primarily assessed based on 2010 measurements and back-extrapolated to the baseline years. We applied Cox proportional hazard models adjusting for individual- and area-level potential confounders.Results: During an average of 18.2 years follow-up, 967 bladder cancer cases occurred. We observed a positive though statistically non-significant association between PM2.5 and bladder cancer incidence. Hazard Ratios (HR) were 1.09 (95% confidence interval (CI): 0.93–1.27) per 5 µg/m3 for 2010 exposure and 1.06 (95% CI: 0.99–1.14) for baseline exposure. Effect estimates for NO2, BC and O3 were close to unity. A positive association was observed with PM2.5 zinc (HR 1.08; 95% CI: 1.00–1.16 per 10 ng/m3).Conclusions: We found suggestive evidence of an association between long-term PM2.5 mass exposure and bladder cancer, strengthening the evidence from the few previous studies. The association with zinc in PM2.5 suggests the importance of industrial emissions.
  •  
33.
  • Chen, Jie, et al. (författare)
  • Long-Term Exposure to Source-Specific Fine Particles and Mortality-A Pooled Analysis of 14 European Cohorts within the ELAPSE Project
  • 2022
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:13, s. 9277-9290
  • Tidskriftsartikel (refereegranskat)abstract
    • We assessed mortality risks associated with sourcespecific fine particles (PM2.5) in a pooled European cohort of 323,782 participants. Cox proportional hazard models were applied to estimate mortality hazard ratios (HRs) for source-specific PM2.5 identified through a source apportionment analysis. Exposure to 2010 annual average concentrations of source-specific PM2.5 components was assessed at baseline residential addresses. The source apportionment resulted in the identification of five sources: traffic, residual oil combustion, soil, biomass and agriculture, and industry. In single-source analysis, all identified sources were significantly positively associated with increased natural mortality risks. In multisource analysis, associations with all sources attenuated but remained statistically significant with traffic, oil, and biomass and agriculture. The highest association per interquartile increase was observed for the traffic component (HR: 1.06; 95% CI: 1.04 and 1.08 per 2.86 mu g/m(3) increase) across five identified sources. On a 1 mu g/m(3) basis, the residual oil-related PM2.5 had the strongest association (HR: 1.13; 95% CI: 1.05 and 1.22), which was substantially higher than that for generic PM2.5 mass, suggesting that past estimates using the generic PM2.5 exposure response function have underestimated the potential clean air health benefits of reducing fossil-fuel combustion. Source-specific associations with cause-specific mortality were in general consistent with findings of natural mortality.
  •  
34.
  • Cole-Hunter, Thomas, et al. (författare)
  • Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort : An ELAPSE study
  • 2023
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson’s Disease (PD) remains limited.Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts.Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders.Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5.Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.
  •  
35.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
  •  
36.
  • Honfi, Daniel, et al. (författare)
  • A practical approach for supporting decisions in bridge condition assessment and monitoring
  • 2019
  • Ingår i: 20th Congress of IABSE, New York City 2019. - : International Association for Bridge and Structural Engineering (IABSE). - 9783857481659 ; , s. 2137-2142, s. 2137-2142
  • Konferensbidrag (refereegranskat)abstract
    • In this contribution a practical and rational decision-making approach is presented to be applied for common bridges typically managed by public authorities. The authors have developed a model with the intention to be applicable for practical cases for common bridges in the daily work of bride operators responsible for a large number of assets, yet still maintain the principles of more generic frameworks based on probabilistic decision-theory. Three main attributes of the verification of sufficiency of structural performance are considered, namely: 1) the level of sophistication of modelling performance, 2) the degree of verification and acceptance criteria in terms of dealing with uncertainties and consequences, 3) the extent of information is obtained and incorporated in the verification. The simplicity of the approach is demonstrated through an illustrative case study inspired by practical condition assessment decision problems. It is argued that in practical cases it may be desirable to utilize less advanced methods owing to constraints in resources or lack of reliable data (e.g. based on structural health monitoring or other on-site measurement techniques). 
  •  
37.
  • Honfi, Daniel, et al. (författare)
  • Decision support for bridge condition assessment
  • 2017
  • Ingår i: SMAR 2017 Proceedings.
  • Konferensbidrag (refereegranskat)abstract
    • The paper presents the first steps of the development of a theoretical framework for a rational yet practical decision making process concerning the condition assessment of existing bridges in Sweden. The main focus is on how to choose the appropriate level of enhanced conditions assessment considering aspects of model sophistication, uncertainty consideration and knowledge content utilisation. A conceptual case study is presented exemplifying how the framework can be used to structure the assessment actions of a steel bridge subjected to fatigue deterioration.
  •  
38.
  • Honfi, Daniel, et al. (författare)
  • Decision support for maintenance and upgrading of existing bridges
  • 2017
  • Ingår i: IABSE Conference, Vancouver 2017. - : International Association for Bridge and Structural Engineering (IABSE). - 9783857481536 ; , s. 336-345, s. 336-345
  • Konferensbidrag (refereegranskat)abstract
    • Maintenance of transportation infrastructure assets can be relatively expensive, since it does not only include the direct cost of interventions, but also the indirect consequences of traffic disruptions. To make optimal decisions about maintenance actions, including rehabilitation and upgrading, reliable information about the performance of existing structures is needed. However, obtaining such information might require significant efforts and can be done in various ways. The purpose of an ongoing Swedish research project BIG BRO is to develop a framework for a decision support methodology that can be used for implementing maintenance strategies for bridges on a rational basis. The present paper provides a brief overview about the project as well as describes some of the ongoing work. 
  •  
39.
  • Honfi, Daniel, et al. (författare)
  • Informed successive condition assessments in bridge maintenance
  • 2020
  • Ingår i: Journal of Civil Structural Health Monitoring. - : Springer. - 2190-5452 .- 2190-5479. ; 10:4, s. 729-737
  • Tidskriftsartikel (refereegranskat)abstract
    • The condition assessment of bridges considers a combination of information from different sources rendering multiple levels of assessment possible. This paper illustrates how successive condition assessment strategies increase the expected utility compared to single choice decisions through Bayesian inference. Multiple levels of assessment allow for additional possibilities for obtaining structural health information and updating one's beliefs about structural condition. Thus, more informed decision-making is possible with respect to the gain in accuracy versus the costs of the assessment options. The paper aims to introduce how the successive approach can be implemented and in which scenarios it provides an increase in expected utility in comparison to one instant decision. To highlight this, a few pedagogical numerical examples are provided. 
  •  
40.
  • Honfi, Daniel, et al. (författare)
  • Inspection and monitoring of bridges in Sweden
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report provides an overview about recent research activities and current practice concerning inspection and monitoring of the structural performance of bridges and the related decision-making process. A brief review of common methods of collecting information on structural performance of bridges is presented, followed by a description of the use of the information collected in structural analysis and maintenance planning. An overview about the state of the art is given including recent scientific developments. Finally, the current Swedish practice for bridge management is presented.
  •  
41.
  • Hvidtfeldt, Ulla Arthur, et al. (författare)
  • Long term exposure to air pollution and kidney parenchyma cancer – Effects of low-level air pollution : a Study in Europe (ELAPSE)
  • 2022
  • Ingår i: Environmental Research. - : Academic Press Inc.. - 0013-9351 .- 1096-0953. ; 215
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited.METHODS: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level.RESULTS: The participants were followed from baseline (1985–2005) to 2011–2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5–95%) exposure levels of NO2, PM2.5, BC and O3 were 24.1 μg/m3 (12.8–39.2), 15.3 μg/m3 (8.6–19.2), 1.6 10−5 m−1 (0.7–2.1), and 87.0 μg/m3 (70.3–97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 μg/m³ NO2, 1.04 (95% CI: 0.88, 1.21) per 5 μg/m³ PM2.5, 0.99 (95% CI: 0.89, 1.11) per 0.5 10−5 m−1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 μg/m³ O3. We did not find associations between any of the elemental components of PM2.5 and cancer of the kidney parenchyma.CONCLUSION: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer.
  •  
42.
  • Hvidtfeldt, Ulla Arthur, et al. (författare)
  • Long-term low-level ambient air pollution exposure and risk of lung cancer - A pooled analysis of 7 European cohorts
  • 2021
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/aim: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence.Methods: The Effects of Low-level Air Pollution: a Study in Europe (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O-3) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socioeconomic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines.Results: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O-3 (warm season) were 24.2 mu g/m(3) (19.5, 29.7), 15.4 mu g/m(3) (12.8, 17.3), 1.6 10(-5)m(-1) (1.3, 1.8), and 86.6 mu g/m(3) (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 mu g/m(3)). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 mu g/m(3). We did not observe associations between NO2, BC or O-3 and lung cancer incidence.Conclusions: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.
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43.
  • Justice, A. E., et al. (författare)
  • Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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44.
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45.
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46.
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47.
  • Larsson Ivanov, Oskar, et al. (författare)
  • The practical value of structural health information for time dependence in bridge maintenance
  • 2021
  • Ingår i: Structure and Infrastructure Engineering. - : Informa UK Limited. - 1573-2479 .- 1744-8980. ; , s. 1-16
  • Tidskriftsartikel (refereegranskat)abstract
    • For practical decisions on common recurring maintenance actions, the information from routine inspections form a decision basis for the bridge manager. It is often difficult to assess whether this information is sufficient for deciding on a repair action, or if more information is needed. For many bridges the information for supporting decisions may be limited, although those bridges cause large yearly maintenance costs for the society. The purpose of the study presented in this paper is to show how two different models for decision making based on Bayesian decision theory, a point-in-time decision model and a sequential updating decision model, can be used to improve the decision-making process for common maintenance decisions. The models use information from routine inspections and incorporates time dependent aspects such as material degradation and time value of money to improve the decision-making process. The focus is on presenting the methodology with a case study of a concrete bridge in Sweden where the edge beams may have to be replaced. Three assessment approaches are considered: (i) no assessment, (ii) desktop evaluation and (iii) measurements. The main finding is that sequential updating decision making will provide a higher benefit than a point-in-time decision, and thus give higher Value of Information. This value becomes even higher when the measurements are selected for the assessment. The results also show that the edge beams should be replaced. The general approach presented can be applicable to many decision scenarios related to maintenance of deteriorating structures.
  •  
48.
  • Leander, John, et al. (författare)
  • A calibrated verification model for fatigue assessment of road bridges
  • 2019
  • Ingår i: Proceeding of Nordic Steel 2019. - : Wiley.
  • Konferensbidrag (refereegranskat)abstract
    • The format suggested in the Eurocode for fatigue verification of road bridges is under scrutiny in thispaper. The model is easy to use in practice, which is important for design purposes, but its accuracyhas been questioned. For this reason, a reliability-based evaluation of the safety level has beenperformed and is briefly recapitulated in this paper. It shows a large scatter in reliability index rangingfrom unacceptably low to overly conservative. A calibration of the existing model has been performedshowing a more consistent reliability level. Results from comparisons of the existing and calibratedmodels are shown for real bridges considering the influence on design stress ranges. The results showthat the Eurocode model is conservative for short span bridges subjected to low traffic volume. Forother cases, the Eurocode model is non-conservative.
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49.
  • Leander, John, 1976- (författare)
  • A code calibration for heavy special transports on railway bridges
  • 2023
  • Konferensbidrag (refereegranskat)abstract
    • The current paper summarizes a code calibration project for heavy special transports  on railway bridges. The basis is the Swedish code for assessing existing bridges, which has a  safety formatbased on partial factors. Reliability-based models have been established for  different bridge types andfailure modes, covering the most common railway bridges and  relations between permanent and variableloads. A sample of special transport vehicles from previous admission applications was considered andmodelled with stochastic properties  reflecting known axle loads and gross weights. Statistical data forstochastic variables were  collected from the literature, but additional input had to be evaluated fromrecent  measurements. The results include safety indices for the present partial factors and a  suggestion for a reduced factor for vehicles with a known weight. With a target value of β = 3.7, applicable toexisting bridges, the partial factor for vehicles can be reduced from 1.5 to  1.3. 
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50.
  • Leander, John, et al. (författare)
  • A decision support framework for fatigue assessment of steel bridges
  • 2018
  • Ingår i: Engineering Failure Analysis. - : Elsevier BV. - 1350-6307 .- 1873-1961. ; 91, s. 306-314
  • Tidskriftsartikel (refereegranskat)abstract
    • Many bridges are approaching or have already passed their expected service life. For steel bridges, fatigue is often the decisive degradation phenomenon that theoretically puts restrictions on a continued use. At the same time, fatigue is also afflicted with large uncertainties on the resistance side as well as on the action effect side. An accurate assessment of the service life will require measures outside the governing regulations but understanding what steps to take and how to consider the outcome for decisions on interventions can be a difficult task for a non-expert. This paper presents possible assessment actions and a decision support framework for rational decisions on interventions to extend the theoretical service life of existing bridges. A case study of a critical railway bridge is incorporated to demonstrate the framework. The aim is to provide a tool for bridge managers on how to evaluate and procure different assessment actions.
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