| 1. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 8. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 9. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 10. |
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| 11. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 14. |
- Jiang, X., et al.
(författare)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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| 17. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 18. |
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| 19. |
- Arnau-Soler, A, et al.
(författare)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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| 20. |
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| 24. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 25. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 26. |
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| 27. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 28. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 29. |
- Vidal, R. M., et al.
(författare)
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Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS)
- 2019
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Ingår i: Plos Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2735. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. Methodology/Principal findings MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence 5% and significant association with MSD. Conclusions/Significance Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to similar to 77%. Author summary Enterotoxigenic Escherichia coli (ETEC) were found to be one of the four most consistently important agents that cause moderate-to-severe diarrhea among children <5 years of age in a large case-control study, the Global Enteric Multicenter Study, performed in four countries in sub-Saharan Africa and three in South Asia. ETEC attach to the lining of the human small intestine by means of protein colonization factors (CFs), after which bacterial toxins stimulate intestinal secretion resulting in diarrhea. Moderate-to-severe diarrhea in young children in developing countries can lead to malnutrition and death. Vaccines are being developed to prevent ETEC diarrhea and its consequences. Several ETEC vaccines aim to stimulate antibodies (protective proteins) that will bind CFs and prevent the bacteria from attaching to intestinal cells, which should, in turn, prevent ETEC diarrhea. Different types of CFs exist. To guide the development of vaccines intending to provide broad protection against ETEC, one must know the frequency with which the different major CFs are produced by ETEC. This paper reports an extensive systematic survey of ETEC CFs and provides helpful information to guide the development of ETEC vaccines.
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| 30. |
- Hampton, Stephanie E., et al.
(författare)
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Ecology under lake ice
- 2017
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:1, s. 98-111
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Forskningsöversikt (refereegranskat)abstract
- Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.
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| 31. |
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| 32. |
- Petimar, J, et al.
(författare)
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Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.
- 2019
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 26:3, s. 468-475
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality.METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures.RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously.CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.
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| 33. |
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| 34. |
- Bouchouireb, Hamza, 1991-
(författare)
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Advancing the life cycle energy optimisation methodology
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle-to-production of materials, operation of the vehicle, and end-of-life phases. This work further develops the LCEO methodology and expands its scope through three main methodological contributions which, for illustrative purposes, were applied to a vehicle sub-system design case study.An End-Of-Life (EOL) model, based on the substitution with a correction factor method, is included to estimate the energy credits and burdens that originate from EOL vehicle processing. Multiple recycling scenarios with different levels of assumed induced recyclate material property degradation were built, and their impact on the LCEO methodology's outcomes was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the inclusion of EOL modelling in the LCEO methodology can alter material use patterns and significantly effect the life cycle energy of the optimal designs.Furthermore, the previous model is expanded to enable holistic vehicle product system design with the LCEO methodology. The constrained optimisation of a vehicle sub-system, and the design of a subset of the processes which are applied to it during its life cycle, are simultaneously optimised for a minimal product system life cycle energy. In particular, a subset of the EOL processes' parameters are considered as continuous design variables with associated barrier functions that control their feasibility. The results show that the LCEO methodology can be used to find an optimal design along with its associated ideal synthetic EOL scenario. Moreover, the ability of the method to identify the underlying mechanisms enabling the optimal solution's trade-offs is further demonstrated.Finally, the functional scope of the methodology is expanded through the inclusion of shape-related variables and aerodynamic drag estimations. Here, vehicle curvature is taken into account in the LCEO methodology through its impact on the aerodynamic drag and therewith its related operational energy demand. In turn, aerodynamic drag is considered through the estimation of the drag coefficient of a vehicle body shape using computational fluid dynamics simulations. The aforementioned coefficient is further used to estimate the energy required by the vehicle to overcome aerodynamic drag. The results demonstrate the ability of the LCEO methodology to capitalise on the underlying functional alignment of the structural and aerodynamic requirements, as well as the need for an allocation strategy for the aerodynamic drag energy within the context of vehicle sub-system redesign.Overall, these methodological developments contributed to the exploration of the ability of the LCEO methodology to handle life cycle and functional trade-offs to achieve life cycle energy optimal vehicle designs.
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| 35. |
- Bouchouireb, Hamza, et al.
(författare)
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The inclusion of vehicle shape and aerodynamic drag estimations within the life cycle energy optimisation methodology
- 2019
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Ingår i: Procedia CIRP. - : Elsevier. - 2212-8271 .- 2212-8271. ; 84, s. 902-907
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Tidskriftsartikel (refereegranskat)abstract
- The present work describes a widening of the scope of the Life Cycle Energy Optimisation (LCEO) methodology with the addition of shape-related design variables. They describe the curvature of a vehicle which impacts its aerodynamic drag and therewith its operational energy demand. Aerodynamic drag is taken into account through the estimation of the drag coefficient of the vehicle body shape using computational fluid dynamics simulations. Subsequently, the aforementioned coefficient is used to calculate the operational energy demand associated with the vehicle. The methodology is applied to the design of the roof of a simplified 2D vehicle model which is both mechanically and geometrically constrained. The roof is modelled as a sandwich structure with its design variables consisting of the material compositions of the different layers, their thicknesses as well as the shape variables. The efficacy of the LCEO methodology is displayed through its ability to deal with the arising functional conflicts while simultaneously leveraging the design benefits of the underlying functional alignments. On average, the optimisation process resulted in 2.5 times lighter and 4.5 times less life cycle energy-intensive free shape designs. This redesign process has also underlined the necessity of defining an allocation strategy for the energy necessary to overcome drag within the context of vehicle sub-system redesign.
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| 36. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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Towards holistic energy-efficient vehicle product system design: The case for a penalized continuous end-of-life model in the life cycle energy optimisation methodology
- 2019
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Ingår i: Proceedings of the International Conference on Engineering Design. - : Cambridge University Press. - 2220-4334 .- 2220-4342. ; 1, s. 2901-2910
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Tidskriftsartikel (refereegranskat)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle-to-production of materials, operation of the vehicle, and end-of-life phases. The present work describes the extension of the LCEO methodology to perform holistic product system optimisation. The constrained design of an automotive component and the design of a subset of the processes which are applied to it during its life cycle are simultaneously optimised to achieve a minimal product system life cycle energy. A subset of the processes of the end-of-life phase of a vehicle’s roof are modelled through a continuous formulation. The roof is modelled as a sandwich structure with its design variables being the material compositions and the thicknesses of the different layers. The results show the applicability of the LCEO methodology to product system design and the use of penalisation to ensure solution feasibility.
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| 37. |
- Gidlöf, Olof, et al.
(författare)
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Ischemic Preconditioning Confers Epigenetic Repression of Mtor and Induction of Autophagy Through G9a-Dependent H3K9 Dimethylation
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ischemic preconditioning (IPC) protects the heart from prolonged ischemic insult and reperfusion injury through a poorly understood mechanism. Post-translational modifications of histone residues can confer rapid and drastic switches in gene expression in response to various stimuli, including ischemia. The aim of this study was to investigate the effect of histone methylation in the response to cardiac ischemic preconditioning.METHODS AND RESULTS: We used cardiac biopsies from mice subjected to IPC to quantify global levels of 3 of the most well-studied histone methylation marks (H3K9me2, H3K27me3, and H3K4me3) with Western blot and found that H3K9me2 levels were significantly increased in the area at risk compared to remote myocardium. In order to assess which genes were affected by the increase in H3K9me2 levels, we performed ChIP-Seq and transcriptome profiling using microarray. Two hundred thirty-seven genes were both transcriptionally repressed and enriched in H3K9me2 in the area at risk of IPC mice. Of these, Mtor (Mechanistic target of rapamycin) was chosen for mechanistic studies. Knockdown of the major H3K9 methyltransferase G9a resulted in a significant decrease in H3K9me2 levels across Mtor, increased Mtor expression, as well as decreased autophagic activity in response to rapamycin and serum starvation.CONCLUSIONS: IPC confers an increase of H3K9me2 levels throughout the Mtor gene-a master regulator of cellular metabolism and a key player in the cardioprotective effect of IPC-leading to transcriptional repression via the methyltransferase G9a. The results of this study indicate that G9a has an important role in regulating cardiac autophagy and the cardioprotective effect of IPC.
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| 38. |
- Jank, Merle-Hendrikje, et al.
(författare)
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Advancing energy efficient early-stage vehicle design through inclusion of end-of-life phase in the life cycle energy optimisation methodology
- 2017
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Ingår i: 12th International Conference on Ecological Vehicles and Renewable Energies Conference, EVER.
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Konferensbidrag (refereegranskat)abstract
- Environmentally-friendly energy-efficient vehicles are an important contributor to meet future global transportation needs. To minimise the environmental impact of a vehicle throughout its entire life cycle, the life cycle energy optimisation (LCEO) methodology has been proposed. Using the proxy of life cycle energy, this methodology balances the energy consumption of vehicle production, operation and end-of-life scenarios. The overall aim is to design a vehicle where life cycle energy is at a minimum. While previous work only included vehicle production and operation, this paper aims at advancing the LCEO methodology by including an end-of-life phase. A simplified design study was conducted to illustrate how vehicle design changes when end-of-life treatment is included. Landfilling, incineration and recycling have been compared as end-of-life treatments, although the focus was put on recycling. The results reveal that the optimal design not only changes with the inclusion of an end-of-life phase but it changes with specific end-of-life treatment.
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| 39. |
- Kivimäki, Mika, et al.
(författare)
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Long working hours and risk of coronary heart disease and stroke : a systematic review and meta-analysis of published and unpublished data for 603 838 individuals
- 2015
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Ingår i: The Lancet. - : The Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 386:10005, s. 1739-1746
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Tidskriftsartikel (refereegranskat)abstract
- Background Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. Methods We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. Findings We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5.1 million person-years (mean 8.5 years), in which 4768 events were recorded, and for stroke was 3.8 million person-years (mean 7.2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (>= 55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1.13, 95% CI 1.02-1.26; p=0.02) and incident stroke (1.33, 1.11-1.61; p=0.002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1.30-1.42). We recorded a dose-response association for stroke, with RR estimates of 1.10 (95% CI 0.94-1.28; p=0.24) for 41-48 working hours, 1.27 (1.03-1.56; p=0.03) for 49-54 working hours, and 1.33 (1.11-1.61; p=0.002) for 55 working hours or more per week compared with standard working hours (p(trend)<0.0001). Interpretation Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours.
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| 40. |
- O'Reilly, Ciarán J., et al.
(författare)
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Investigation of a jet-noise-shielding methodology
- 2015
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Ingår i: AIAA Journal. - : American Institute of Aeronautics and Astronautics. - 0001-1452 .- 1533-385X. ; 53:11, s. 3286-3296
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Tidskriftsartikel (refereegranskat)abstract
- Ongoing research toward the reduction of environmental noise from aircraft is investigating the possible shielding of engine-noise sources by novel airframe configurations. To assess the noise-reduction benefits attainable from such configurations, it is necessary to develop appropriate acoustic evaluation tools. In this paper, a jet-noise-shielding- prediction methodology is described. The Tam–Auriault (“Jet Mixing Noise from Fine-Scale Turbulence,” AIAA Journal, Vol. 37, No. 2, 1999, pp. 145–153) jet-noise model with a Reynolds-averaged Navier–Stokes solution input, together with a Fresnel–Kirchhoff diffraction method (Fundamentals of Physical Acoustics, Wiley-Interscience, New York, 2000, pp. 472–494), is used to make isolated and shielded far-field jet-noise predictions. This methodology is employed as a sensitivity-analysis tool to establish the relative importance of the source location, spatial extent, and directivity in jet-noise-shielding predictions. Predictions have been made for a shielded single-stream Mach 0.9 jet, and compared with experimental data. Good qualitative agreement is observed, and the disagreement in the shielding levels is most likely due to underestimation of the source axial extent by the jet-noise model.
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| 41. |
- O'Reilly, Ciarán J., et al.
(författare)
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Life cycle energy optimisation : A proposed methodology for integrating environmental considerations early in the vehicle engineering design process
- 2016
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Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 135, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- To enable the consideration of life cycle environmental impacts in the early stages of vehicle design, a methodology using the proxy of life cycle energy is proposed in this paper. The trade-offs in energy between vehicle production, operational performance and end-of-life are formulated as a mathematical problem, and simultaneously balanced with other transport-related functionalities, and may be optimised. The methodology is illustrated through an example design study, which is deliberately kept simple in order to emphasise the conceptual idea. The obtained optimisation results demonstrate that there is a unique driving-scenario-specific design solution, which meets functional requirements with a minimum life cycle energy cost. The results also suggest that a use-phase focussed design may result in a solution, which is sub-optimal from a life cycle point-of-view. © 2016 The Authors
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| 42. |
- Pignier, Nicolas J., et al.
(författare)
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A Kirchhoff approximation-based numerical method to compute multiple acoustic scattering of a moving source
- 2015
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Ingår i: Applied Acoustics. - : Elsevier. - 0003-682X .- 1872-910X. ; 96, s. 108-117
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Tidskriftsartikel (refereegranskat)abstract
- Within the scope of a study of external noise propagation from moving ground vehicles, a numerical method is developed to compute the acoustic field emitted by a moving source in the presence of scattering objects such as roads, buildings or noise-shields. This method is developed with the purpose of being used in a vehicle design process and therefore it must have a low computational cost, which requires a certain number of approximations. The case of a fixed point source is studied first then the effect of a movement of the source is taken into account through the introduction of a retarded time. The acoustic source is assumed to be represented by one or many harmonic monopoles of possibly different frequency moving with a constant speed in a quiescent flow field. Scattering from nearby perfectly reflecting objects is computed through a Kirchhoff–Helmholtz integral equation applying the Kirchhoff approximation. A ray-surface intersection algorithm to compute shadow areas is proposed. The method is validated against analytical solutions and experimental results for a fixed source, and against a higher-order finite difference time-domain method for the multiple scattering of a moving source. Results are good and show that this method can potentially be used to predict urban noise.
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| 43. |
- Proenza, J. A., et al.
(författare)
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Cold plumes trigger contamination of oceanic mantle wedges with continental crust-derived sediments: Evidence from chromitite zircon grains of eastern Cuban ophiolites
- 2018
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Ingår i: Geoscience Frontiers. - : Elsevier. - 1674-9871. ; 9:6, s. 1921-1936
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Tidskriftsartikel (refereegranskat)abstract
- The origin of zircon grains, and other exotic minerals of typical crustal origin, in mantle-hosted ophiolitic chromitites are hotly debated. We report a population of zircon grains with ages ranging from Cretaceous (99 Ma) to Neoarchean (2750 Ma), separated from massive chromitite bodies hosted in the mantle section of the supra-subduction (SSZ)-type Mayarí-Baracoa Ophiolitic Belt in eastern Cuba. Most analyzed zircon grains (n = 20, 287 ± 3 Ma to 2750 ± 60 Ma) are older than the early Cretaceous age of the ophiolite body, show negative εHf(t) (−26 to −0.6) and occasional inclusions of quartz, K-feldspar, biotite, and apatite that indicate derivation from a granitic continental crust. In contrast, 5 mainly rounded zircon grains (297 ± 5 Ma to 2126 ± 27 Ma) show positive εHf(t) (+0.7 to +13.5) and occasional apatite inclusions, suggesting their possible crystallization from melts derived from juvenile (mantle) sources. Interestingly, younger zircon grains are mainly euhedral to subhedral crystals, whereas older zircon grains are predominantly rounded grains. A comparison of the ages and Hf isotopic compositions of the zircon grains with those of nearby exposed crustal terranes suggest that chromitite zircon grains are similar to those reported from terranes of Mexico and northern South America. Hence, chromitite zircon grains are interpreted as sedimentary-derived xenocrystic grains that were delivered into the mantle wedge beneath the Greater Antilles intra-oceanic volcanic arc by metasomatic fluids/melts during subduction processes. Thus, continental crust recycling by subduction could explain all populations of old xenocrystic zircon in Cretaceous mantle-hosted chromitites from eastern Cuba ophiolite. We integrate the results of this study with petrological-thermomechanical modeling and existing geodynamic models to propose that ancient zircon xenocrysts, with a wide spectrum of ages and Hf isotopic compositions, can be transferred to the mantle wedge above subducting slabs by cold plumes.
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| 44. |
- Rasam, Amin, et al.
(författare)
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Aerodynamic noise prediction for a wind turbine using numerical flow simulations and semi-empirical modelling approaches
- 2016
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Ingår i: 22nd AIAA/CEAS Aeroacoustics Conference. - Reston, Virginia : American Institute of Aeronautics and Astronautics.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, aerodynamic and aero-acoustic simulations are performed for a small horizontal axis wind turbine, suitable for the integration of wind energy in urban and peri-urban areas. Detached-eddy simulation (DES) of compressible flow is performed to compute the flow field over the wind turbine. The far-field noise is computed using the Ffowcs - Williams and Hawkings acoustic analogy. Furthermore, the blade element momentum theory is used with a semi-empirical acoustic modeling approach to predict the wind turbine noise. The acoustic modeling approach is based on a semi-empirical formulation for airfoil self noise and an analytic formulation for inflow noise.
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| 45. |
- Tin, T., et al.
(författare)
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Preservation amenity, research laboratory, or mineral reserve? International perspectives on the values of Antarctica
- 2019
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Ingår i: Polar Record. - 0032-2474. ; 55:2, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- Inspired by notions of interest of humankind and intergenerational equity, we explored Antarctic perceptions of a subset of future generations - university students. Students at three universities in Canada, the Netherlands, and the USA were surveyed to determine the relationships between nationality, academic major, opinions on values of Antarctica, and support for a range of human activities in Antarctica (n = 618). Logistic regression was used to model the relationship of these variables with support for designation of Antarctica as a wilderness reserve, construction of new research stations, and mining. Compared with business and economics majors, biological sciences and natural resources/conservation majors were more likely to support wilderness designation and less likely to support mineral resource development. Nationality was not significantly associated with support for construction of new research stations and mineral resource development. Opinions on the value of Antarctica and support for activities also exhibited significant influences on dependent variables. Consistent with earlier studies of Antarctic scientists, personnel, tourists, and other members of the general public, university students valued Antarctica as one of the world's last great wildernesses (66%), an important component of the Earth's climate system (66%), and a science laboratory for the benefit of mankind (62%). © 2019 Cambridge University Press.
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| 46. |
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| 47. |
- Bouchouireb, Hamza, et al.
(författare)
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Identification of noise sources on a realistic landing gear using numerical phased array methods applied to computational data
- 2017
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Ingår i: 23rd AIAA/CEAS Aeroacoustics Conference. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624105043
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aerodynamic sound sources on a realistic landing gear are investigated using numerical phased array methods, based on array data extracted from compressible Detached-Eddy Simulations of the flow. Assuming monopole or monopole in a moving medium propagation, the sound sources are identified in the source region through various beamforming approaches: dual linear programming (dual-LP) deconvolution, orthogonal beamforming and CLEAN-SC. The predicted source locations are in good agreement with previous experimental results performed on the same nose landing gear configuration by industrial and academic partners within the ALLEGRA project. Additionally, the modeled sources are used to generate far-field spectra which are subsequently compared to the ones obtained with the Ffowcs Williams-Hawkings acoustic analogy. The results of the dual-LP approach show a good match between the far-field spectra up to a certain frequency threshold cor- responding to the quality of the mesh used. The results demonstrate the potential of numerical phased array methods as a legitimate modeling tool for aeroacoustic simulations in general and as a tool to gain insight into the noise generation mechanisms of landing gear components in particular.
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| 48. |
- Ghaneh, Paula, et al.
(författare)
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The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma
- 2019
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 269:3, s. 520-529
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Tidskriftsartikel (refereegranskat)abstract
- Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapiesMethods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.
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| 49. |
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| 50. |
- Hammar, Johan, 1979-
(författare)
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A Wave Expansion Method for Aeroacoustic Propagation
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although it is possible to directly solve an entire flow-acoustics problem in one computation, this approach remains prohibitively large in terms of the computational resource required for most practical applications. Aeroacoustic problems are therefore usually split into two parts; one consisting of the source computation and one of the source propagation. Although both these parts entail great challenges on the computational method, in terms of accuracy and efficiency, it is still better than the direct solution alternative. The source usually consists of highly turbulent flows, which for most cases will need to be, at least partly, resolved. Then, acoustic waves generated by these sources often have to be propagated for long distances compared to the wavelength and might be subjected to scattering by solid objects or convective effects by the flow. Numerical methods used solve these problems therefore have to possess low dispersion and dissipation error qualities for the solution to be accurate and resource efficient.The wave expansion method (WEM) is an efficient discretization technique, which is used for wave propagation problems. The method uses fundamental solutions to the wave operator in the discretization procedure and will thus produce accurate results at two to three points per wavelength. This thesis presents a method that uses the WEM in an aeroacoustic context. Addressing the propagation of acoustic waves and transfer of sources from flow to acoustic simulations. The proposed computational procedure is applied to a co-rotating vortex pair and a cylinder in cross-flow. Overall, the computed results agree well with analytical solutions.Although the WEM is efficient in terms of the spatial discretization, the procedure requires that a Moore-Penrose pseudo-inverse is evaluated at each unique node-neighbour stencil in the grid. This evaluation significantly slows the procedure. In this thesis, a method with a regular grid is explored to speed-up this process.
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