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Träfflista för sökning "WFRF:(Holmén Martin) ;lar1:(lu)"

Sökning: WFRF:(Holmén Martin) > Lunds universitet

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1.
  • Crosby, Jacy, et al. (författare)
  • Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
  • 2014
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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2.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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3.
  • Dahlin, Torleif, et al. (författare)
  • ASSERT - Kontroll av markstabilisering med resistivitetstomografi (ERT)
  • 2023
  • Ingår i: ; , s. 219-228
  • Konferensbidrag (refereegranskat)abstract
    • Soil stabilisation is becoming increasingly common for the development of areas withpoor bearing capacity. However, there is a need for better and volume-wide controlmethods for quality assurance. The control methods can be divided into two steps,where the first takes place in immediate connection to the mixing of binders to checkwhether the entire intended volume has been successfully treated, or whether thereare zones that need completion. The second step focuses on the strength of thestabilised volume and assumes that the binder has cured.The R&D project ASSERT focuses on quality control using electrical resistivitytomography (ERT). The idea is to use the method in immediate connection with themixing of binders to delineate the soil volume that has been treated with binders fromuntreated parts. ERT could then be used to quickly check the results of thestabilisation, so that supplementary measures can be taken in zones of insufficienttreatment while personnel and equipment are in place. Furthermore, there is potentialfor volume-wide quantification of strength growth via correlation between change inresistivity and change in strength during the curing process, but this would probablyneed to be done on a site specific basis.Testing and verification of the method takes place in different geomaterials in thelaboratory and in the field, including full-scale tests for different types ofstabilisations. Furthermore, method development and adaptation for the applicationare included, so that the method becomes sufficiently robust and fast to be usedroutinely in a sustainable manner. Field trials have been carried out by installingelectrodes in lime-cement columns and jet columns in direct connection to thestabilisation. Laboratory tests have so far been carried out for lime-cementstabilisation of clay and for stabilisation of dredged masses.
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5.
  • Holmen, Martin, 1976, et al. (författare)
  • Economic Preferences and Personality Traits Among Finance Professionals and the General Population
  • 2023
  • Ingår i: Economic Journal. - 0013-0133 .- 1468-0297. ; 133:656
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on artefactual field experiments, we investigate whether finance professionals differ from a sample of the working population in terms of industry-relevant preferences and personality traits. When adjusting for socioeconomic characteristics, we find only few and less marked differences: finance professionals are less risk averse, less trustworthy, show higher levels of psychopathy and are more competitive than participants from the general population. In an additional survey, experts with hiring experience consider industry selection, self-selection and imprinting by industry norms as explanatory for the observed subject pool differences.
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6.
  • Holmén Notander, Jesper, et al. (författare)
  • A Model-Based Framework for Flexible Safety-Critical Software Development - A Design Study
  • 2013
  • Ingår i: Proceedings of the ACM Symposium on Applied Computing/SAC '13. - 9781450316569 ; , s. 1137-1144
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents the findings from a design study of a model-based framework for safety-critical software development, called SimPal. The objective of the study was to better understand the necessary properties of such a framework and to learn more about the challenges of realizing it. Our research approach can be labeled as design research, which means that we try to answer our research questions by developing an artifact, in our case SimPal, and analyzing our experiences from the design of the artifact. In the paper we present what we identify as the necessary quality characteristics, using the ISO25010 quality in use quality model, of a framework like SimPal. These characteristics are then used to evaluate the SimPal framework in combination with a simple design case where we design a soft safety controller. We show that our approach has potential considering safety-critical software development. Although, there are some concerns about its run-time performance, from our results we conclude that the ideas behind the SimPal framework are sound but more work is required to investigate how they can be realized. In the future more effort should be spent on increasing performance and adding more features to the framework.
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7.
  • Holmén Notander, Jesper, et al. (författare)
  • Challenges in Flexible Safety-Critical Software Development -- An Industrial Qualitative Survey
  • 2013
  • Ingår i: Lecture Notes in Computer Science/Product-Focused Software Process Improvement. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0302-9743 .- 1611-3349. - 9783642392580 ; 7983, s. 283-297
  • Konferensbidrag (refereegranskat)abstract
    • Context. Development of safety-critical systems is mostly governed by process-heavy paradigms, while increasing demands on flexibility and agility also reach this domain. Objectives. We wanted to explore in more detail the industrial needs and challenges when facing this trend. Method. We launched a qualitative survey, interviewing engineers from four companies in four different industry domains. Results. The survey identifies human factors (skills, experience, and attitudes) being key in safety-critical systems development, as well as good documentation. Certification cost is related to change frequency, which is limiting flexibility. Component reuse and iterative processes were found to increase adaptability to changing customer needs. Conclusions. We conclude that agile development and flexibility may co-exist with safety-critical software development, although there are specific challenges to address.
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8.
  • Holzmeister, Felix, et al. (författare)
  • Delegation Decisions in Finance
  • 2020
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • We run an online experiment with finance professionals and subjects from the general population (clients) to examine drivers and implications of clients' delegation decisions. We find that clients favor delegation to investment algorithms, followed by delegation to finance professionals with aligned incentives and lastly to those with fixed incentives. We also show that trust in investment algorithms or money managers (finance professionals), respectively, and clients' propensity to shift blame on others increases the likelihood of delegation, whereas own decision-making quality is associated with a decrease. In measuring the implications of clients' delegation decisions, we report high variability among finance professionals' perceptions of clients' preferred risk levels. We show that this results in overlaps in portfolio risk across risk-levels of clients, indicating problems of risk communication between clients and their money managers.
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9.
  • Holzmeister, Felix, et al. (författare)
  • Delegation Decisions in Finance
  • 2023
  • Ingår i: Management Science. - : Institute for Operations Research and the Management Sciences (INFORMS). - 0025-1909 .- 1526-5501. ; 69:8, s. 4828-4844
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on an online experimentwith a sample of finance professionals and participants from the general population (acting as clients), we examine drivers and motives of clients' choices to delegate investment decisions to agents.We find that clients favor delegation to investment algorithms, followed by delegation to finance professionals compensated with an aligned incentive scheme, and lastly to finance professionals receiving a fixed payment for investing on behalf of others. We show that trust in investment algorithms or finance professionals, and clients' propensity to shift blame on others increase the likelihood of delegation, whereas clients' own decision-making quality is associated with a decrease in delegation frequency.
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10.
  • Lange, Leslie A, et al. (författare)
  • Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
  • 2014
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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