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41.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 42:11, s. 53-937
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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42.
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43.
  • Spühler, Jeannette H., et al. (författare)
  • 3D Fluid-Structure Interaction Simulation of Aortic Valves Using a Unified Continuum ALE FEM Model
  • 2018
  • Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X .- 1664-042X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to advances in medical imaging, computational fluid dynamics algorithms and high performance computing, computer simulation is developing into an important tool for understanding the relationship between cardiovascular diseases and intraventricular blood flow. The field of cardiac flow simulation is challenging and highly interdisciplinary. We apply a computational framework for automated solutions of partial differential equations using Finite Element Methods where any mathematical description directly can be translated to code. This allows us to develop a cardiac model where specific properties of the heart such as fluid-structure interaction of the aortic valve can be added in a modular way without extensive efforts. In previous work, we simulated the blood flow in the left ventricle of the heart. In this paper, we extend this model by placing prototypes of both a native and a mechanical aortic valve in the outflow region of the left ventricle. Numerical simulation of the blood flow in the vicinity of the valve offers the possibility to improve the treatment of aortic valve diseases as aortic stenosis (narrowing of the valve opening) or regurgitation (leaking) and to optimize the design of prosthetic heart valves in a controlled and specific way. The fluid-structure interaction and contact problem are formulated in a unified continuum model using the conservation laws for mass and momentum and a phase function. The discretization is based on an Arbitrary Lagrangian-Eulerian space-time finite element method with streamline diffusion stabilization, and it is implemented in the open source software Unicorn which shows near optimal scaling up to thousands of cores. Computational results are presented to demonstrate the capability of our framework.
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44.
  • Spühler, Jeannette Hiromi, 1981-, et al. (författare)
  • A finite element framework for high performance computer simulation of blood flow in the left ventricle of the human heart
  • 2015
  • Rapport (övrigt vetenskapligt)abstract
    • Progress in medical imaging, computational fluid dynamics and high performance computing (HPC) enables computer simulations to emerge as a significant tool to enhance our understanding of the relationship between cardiac diseases and hemodynamics. The field of cardiac modelling is diverse, covering different aspects on microscopic and macroscopic level. In our research, we develop a cardiac model which is embedded in a computational environment where specific properties of the heart such as fluid-structure interaction of the aortic valve can be modeled, or numerical and computational algorithms as parallel computing or adaptivity can be added in a modular way without extensive efforts. In this paper, we present a patient-specific Arbitrary Lagrangian-Eulerian (ALE) finite element framework for simulating the blood flow in the left ventricle of a human heart using HPC, which forms the core of our cardiac model. The mathematical model is described together with the discretization method, mesh smoothing algorithms, and the parallel implementation in Unicorn which is part of the open source software framework FEniCS-HPC. The parallel performance is demonstrated, a convergence study is conducted and intraventricular flow patterns are visualized. The results capture essential features observed with other computational models and imaging techniques, and thus indicate that our framework possesses the potential to provide relevant clinical information for diagnosis and medical treatment. Several studies have been conducted to simulate the three dimensional blood flow in the left ventricle of the human heart with prescribed wall movement. Our contribution to the field of cardiac research lies in establishing an open source framework modular both in modelling and numerical algorithms.
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45.
  • Spühler, Jeannette Hiromi, 1981-, et al. (författare)
  • A High Performance Computing Framework for Finite Element Simulation of Blood Flow in the Left Ventricle of the Human Heart
  • 2020
  • Ingår i: Lecture Notes in Computational Science and Engineering. - : Springer. - 9783030307042 ; , s. 155-164
  • Konferensbidrag (refereegranskat)abstract
    • We present a high performance computing framework for finite element simulation of blood flow in the left ventricle of the human heart. The mathematical model is described together with the discretization method and the parallel implementation in Unicorn which is part of the open source software framework FEniCS-HPC. We show results based on patient-specific data that capture essential features observed with other computational models and imaging techniques, and thus indicate that our framework possesses the potential to provide relevant clinical information for diagnosis and medical treatment. Several other studies have been conducted to simulate the three dimensional blood flow in the left ventricle of the human heart with prescribed wall movement. Our contribution to the field of cardiac research lies in establishing an open source framework modular both in modelling and numerical algorithms. © Springer Nature Switzerland AG 2020.
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46.
  • Van Guelpen, B, et al. (författare)
  • Plasma folate and total homocysteine levels are associated with the risk of myocardial infarction, independently of each other and of renal function.
  • 2009
  • Ingår i: Journal of internal medicine. - : Wiley: 12 months. - 1365-2796 .- 0954-6820. ; 266:2, s. 182-95
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the relationship between plasma folate, vitamin B12 and total homocysteine concentrations, dietary intake of folate and vitamins B12, B6 and B2, and the risk of first acute myocardial infarction (MI). DESIGN: Nested case-referent study with up to 13 years of follow-up. SETTING: The population-based Northern Sweden Health and Disease Study, with 73 879 participants at the time of case ascertainment. SUBJECTS: A total of 571 MI cases (406 men) and 1569 matched referents. Of the cases, 530 had plasma samples available, and 247 had dietary B-vitamin intake data. RESULTS: Plasma concentrations of folate were inversely associated, and total homocysteine positively associated, with the risk of MI, independently of each other and of a number of established and novel cardiovascular risk factors, including renal function [multivariate odds ratio for highest vs. lowest quintile of folate 0.52 (95% CI 0.31-0.84), P for trend = 0.036, and homocysteine 1.92 (95% CI 1.20-3.09), P for trend = 0.006]. For plasma vitamin B12 concentrations, and vitamin B12, B6 and B2 intake, no clear risk relationship was apparent. Though not statistically significant, the results for folate intake were consistent with those for plasma concentrations. CONCLUSIONS: In this large prospective study of a population without mandatory folic acid fortification, both folate and homocysteine were strongly associated with the risk of myocardial infarction, independently of each other and of renal function. Although randomized trials of folic acid supplementation are needed to determine causality, our findings highlight the potential importance of folate, or sources of folate, in incident cardiovascular disease.
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47.
  • Willing, Ben P., et al. (författare)
  • A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary With Inflammatory Bowel Disease Phenotypes
  • 2010
  • Ingår i: Gastroenterology. - : Elsevier: 12 months. - 0016-5085 .- 1528-0012. ; 139:6, s. 1844-U105
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: The composition of the gastrointestinal microbiota is thought to have an important role in the etiology of inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC). Interindividual variation and an inability to detect less abundant bacteria have made it difficult to correlate specific bacteria with disease. METHODS: We used 454 pyrotag sequencing to determine the compositions of microbial communities in feces samples collected from a cohort of 40 twin pairs who were concordant or discordant for CD or UC, and in mucosal samples from a subset of the cohort. The cohort primarily comprised patients who were in remission, but also some with active disease. RESULTS: The profiles of the microbial community differed with disease phenotypes; relative amounts of bacterial populations correlated with IBD phenotypes. The microbial compositions of individuals with CD differed from those of healthy individuals, but were similar between healthy individuals and individuals with UC. Profiles from individuals with CD that predominantly involved the ileum differed from those with CD that predominantly involved the colon; several bacterial populations increased or decreased with disease type. Changes specific to patients with ileal CD included the disappearance of core bacteria, such as Faecalibacterium and Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus gnavus. CONCLUSIONS: Bacterial populations differ in abundance among individuals with different phenotypes of CD. Specific species of bacteria are associated with ileal CD; further studies should investigate their role in pathogenesis.
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48.
  • Willing, Ben, et al. (författare)
  • Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease
  • 2009
  • Ingår i: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).METHODS: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).RESULTS: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.CONCLUSIONS: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.
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49.
  • Albrektsson, Joakim, et al. (författare)
  • Assessment of fire exposed concrete structures
  • 2012
  • Ingår i: fib Symposium 2012: Concrete Structures for Sustainable Community. - 9789198009811 ; , s. 619-622, s. 619-622
  • Konferensbidrag (refereegranskat)abstract
    • Annually, several concrete structures, such as buildings, bridges, parking garages and tunnels are exposed to fires. An assessment is then necessary to decide whether the structure can be repaired or needs to be replaced. In a recent research project, recommendations for assessments of fire exposed concrete structures have been developed. The recommendations are based on a literature survey, results from an experimental study, where ultrasonic measurements, microscopy, Digital Image Correlation (DIC) measurement on loaded core samples were used and practical experience of real post-fire structural assessments. A refined assessment of the fire damage is obtained by combining these test methods.
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50.
  • Berlin, Mats, et al. (författare)
  • The effect of fertilization on genetic parameters in Picea abies clones in central Sweden and consequences for breeding and deployment
  • 2012
  • Ingår i: Forest Ecology and Management. - : Elsevier. - 0378-1127 .- 1872-7042. ; 270, s. 239-247
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to analyze the effect of repeated fertilizer application on the genetic parameters of Norway spruce. Genetic and environmental variances of growth and phenological traits were estimated to find differences between fertilized and control treatments in broad sense heritability and accuracy of estimated genotypic value. Furthermore, genotype × environment interactions (GxE) between the two treatments were investigated. Two Norway spruce clonal field trials in central Sweden were subjected to both treatments and were measured at various points in time up to a field age of 15 years, to monitor the effects of fertilization. For growth traits, trees in the fertilized treatment exhibited lower environmental variance than those in the non-fertilized treatment; consequently, fertilization yielded higher heritability and greater accuracy of estimated genotypic value. Furthermore, the GxE increased as the effects of fertilization became more pronounced; the genetic correlation between treatments dropped to around 0.5 in the last measured growth period. For phenological traits, no GxE but a slight increase in heritability of prolepsis on the leader shoot was found. The results from this study show that, for the conditions encountered in central Sweden, Norway spruce clones should be tested and selected under the conditions in which they are to be deployed. If repeated fertilizer application is to be adopted under operational conditions, substantial losses in genetic gain for growth can be expected when using current selected clones due to the induced GxE. While the fertilized treatment yielded a higher heritability and accuracy of estimated genotypic value for growth traits than did the control, the Swedish Norway spruce breeding program will not benefit from fertilizing genetic field trials because the increased accuracy of estimated genotypic value is nullified by the GxE.
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