| 11. |
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| 12. |
- Gustafsson, Stefan, et al.
(författare)
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Markers of imminent myocardial infarction
- 2024
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Ingår i: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590.
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.
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| 13. |
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| 14. |
- Ingelsson, Urban, et al.
(författare)
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Abort-on-Fail Test Scheduling for Modular SOCs without and with Preemption
- 2015
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Ingår i: IEEE Transactions on Computers. - 0018-9340. ; 64:12, s. 3335-3347
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Tidskriftsartikel (refereegranskat)abstract
- System-on-chips (SOCs) and 3D stacked ICs are often tested for manufacturing defects in a modular fashion, enabling us to record the module test pass probability. We use this pass probability to exploit the abort-on-fail feature of automatic test equipment (ATE) and hence reduce the expected test time in the context of single-site testing. We present a model for calculation of expected test time, for which the abortable test unit can be a module test, a test pattern or a clock cycle. Given an SOC, with test architecture consisting of module test wrappers and test access mechanisms (TAMs), and given module test pass probabilities, we schedule the tests on each TAM to minimize the expected test time. We describe four scheduling heuristics, one without and three with preemption. Experimental results for the ITC’02 SOC Test Benchmarks show 3.5% and 20% reduction of expected test time in SOCs with 0.89 and 0.71 SOC test pass probability respectively, without modification of SOC or ATE. Further experiments show how accurate estimates for the module test pass probability or the distribution of pass probability over test patterns need to be to lead to effective test schedulng.
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| 15. |
- Ingelsson, Urban, et al.
(författare)
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Test Scheduling for Modular SOCs in an Abort-on-Fail Environment
- 2005
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Ingår i: IEEE European Test Symposium ETS 05,2005. - Tallinn, Estonia : IEEE Computer Society Press.
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Konferensbidrag (refereegranskat)abstract
- Complex SOCs are increasingly tested in a modular fashion, which enables us to record the yield-per-module. In this paper, we consider the yield-per-module as the pass probability of the module s manufacturing test. We use it to exploit the abort-on-fail feature of ATEs, in order to reduce the expected test application time. We present a model for expected test application time, which obtains increasing accuracy due to decreasing granularity of the abortable test unit. For a given SOC, with a modular test architecture consisting of wrappers and disjunct TAMs, and for given pass probabilities per module test, we schedule the tests on each TAM such that the expected test application time is minimized. We describe two heuristic scheduling approaches, one without and one with preemption. Experimental results for the ITC 02 SOC Test Benchmarks demonstrate the effectiveness of our approach, as we achieve up to 97% reduction in the expected test application time, without any modification to the SOC or ATE.
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| 16. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 17. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 18. |
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| 19. |
- Lind, Lars, et al.
(författare)
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Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
- 2017
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.
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| 20. |
- Lind, Lars, et al.
(författare)
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Longitudinal effects of aging on plasma proteins levels in older adults : associations with kidney function and hemoglobin levels
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels.MATERIAL AND METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured.RESULTS: Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships.CONCLUSION: The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.
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