| 1. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 2. |
- Ellinor, Patrick T., et al.
(author)
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Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
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Journal article (peer-reviewed)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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| 3. |
- Gusarova, Viktoria, et al.
(author)
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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
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Journal article (peer-reviewed)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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| 4. |
- Jansson, John-Olov, 1954, et al.
(author)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Journal article (peer-reviewed)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 5. |
- Allentoft, Morten E., et al.
(author)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Journal article (peer-reviewed)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 6. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 7. |
- Andersson, Daniel, 1993-
(author)
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Berättelser om 1700-talet : frihetstiden och Gustav III:s regeringstid i svensk historiekultur från 1870-tal till 1990-tal
- 2023
-
Doctoral thesis (other academic/artistic)abstract
- This dissertation analyses historical-cultural change in Sweden during the nineteenth and twentieth centuries. The study focuses on historical narratives concerning the eighteenth-century epoch called the Age of Liberty and the subsequent reign of Gustav III. The overarching aim has been to study these narratives within a Swedish national historical culture from the 1870s to the 1990s. Three different arenas are examined in which history has been mediated in society: the historical research arena, the history textbook arena and history-mediating texts published in the press, what is here referred to as the press arena. The dissertation analyses the relationship between the mediation within these arenas, how this relationship has changed over time, and how they have taken part in influencing the overall image of the Age of Liberty and Gustav III's reign. The theoretical framework is largely based on history didactical perspectives concerning historical culture and the mediation of history. A two-pronged analytical method has been applied consisting of a hermeneutic analysis of mediation and a narrative analysis.This study shows that the three arenas are the most homogeneous in relation to each other during the period from the 1870s up until the 1920s. The historical culture is dominated by two main narratives during this period. One is a conservative, royalistic state idealist narrative, where the Age of Liberty functions as a cautionary tale about the dangers of party rule and a weak monarchy. The other narrative is a prodemocratic anti-Gustavian narrative, originating from the works of Anders Fryxell. However, this narrative is absent from the textbook arena, where the state idealist narrative is completely dominant. But overall, there is high level of temporal consistency between the three arenas during this time. This changes from the 1920s onwards, when the arenas drift apart and become more heterogeneous in relation to each other. As the arenas become more genre-specific, their roles as platforms for history mediation consequently begin to diverge. Which arena narratives are conveyed in, gradually attains greater importance for the historical-cultural communication.From the 1960s onwards, a Lagerrothian pro-parliamentary, prodemocratic narrative, which primarily originates from the research arena, becomes prominent in textbooks and press, but not as prominent in historical research. In this narrative, the Age of Liberty is presented as the precursor of the sound democratic, parliamentary system known in contemporary times, with people's rule, social equality, and without royal interference. The reign of Gustav III is described as an obstacle standing in the path of desirable social and political development. The narrative consolidates democratic ideals in its contemporary context by highlighting parliamentary and democratic traditions in the nation’s history. By the end of the twentieth century, the Lagerrothian narrative dominates both the textbook arena and the press arena. The shift from one dominant narrative to another suggests that the political applicability of research narratives in different times has a strong impact on historical cultural change within the framework of the nation. The study also shows that the most dominant narrative has not shifted chronologically from an old narrative to a newer one. Rather, the shift has been from one dominant narrative direction to another, while both have been mediated simultaneously for decades. It is concluded in the study that the view of a “lag” between historical research and other arenas must be nuanced and placed in the context of specific historical narratives.
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| 8. |
- Birnbaum, Daniel, et al.
(author)
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Thirteen questions about the object to Graham Harman
- 2020
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In: Artful objects : Graham Harman on art and the business of speculative realism. - Berlin ; Stockholm : Sternberg Press ; Stockholm School of Economics. - 9783956795244 ; , s. 43-72
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Book chapter (other academic/artistic)
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| 9. |
- Bjursten, Henrik, et al.
(author)
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Once after a full moon : acute type A aortic dissection and lunar phases
- 2022
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In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press. - 1569-9293 .- 1569-9285. ; 34:1, s. 105-110
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD.METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period).RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated.CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.
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| 10. |
- Bohlooly-Yeganeh, Mohammad, 1966, et al.
(author)
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Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.
- 2005
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In: Diabetes. - 0012-1797 .- 1939-327X. ; 54:1, s. 51-62
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Journal article (peer-reviewed)abstract
- It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.
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| 11. |
- Chambers, John C., et al.
(author)
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Genetic loci influencing kidney function and chronic kidney disease
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 373-375
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Journal article (peer-reviewed)abstract
- Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
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| 12. |
- Ede, Jacob, et al.
(author)
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Retrograde cerebral perfusion reduces embolic and watershed lesions after acute type a aortic dissection repair with deep hypothermic circulatory arrest
- 2024
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In: Journal of Cardiothoracic Surgery. - : BioMed Central (BMC). - 1749-8090. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: To assess whether retrograde cerebral perfusion reduces neurological injury and mortality in patients undergoing surgery for acute type A aortic dissection.Methods: Single-center, retrospective, observational study including all patients undergoing acute type A aortic dissection repair with deep hypothermic circulatory arrest between January 1998 and December 2022 with or without the adjunct of retrograde cerebral perfusion. 515 patients were included: 257 patients with hypothermic circulatory arrest only and 258 patients with hypothermic circulatory arrest and retrograde cerebral perfusion. The primary endpoints were clinical neurological injury, embolic lesions, and watershed lesions. Multivariable logistic regression was performed to identify independent predictors of the primary outcomes. Survival analysis was performed using Kaplan-Meier estimates.Results: Clinical neurological injury and embolic lesions were less frequent in patients with retrograde cerebral perfusion (20.2% vs. 28.4%, p = 0.041 and 13.7% vs. 23.4%, p = 0.010, respectively), but there was no significant difference in the occurrence of watershed lesions (3.0% vs. 6.1%, p = 0.156). However, after multivariable logistic regression, retrograde cerebral perfusion was associated with a significant reduction of clinical neurological injury (OR: 0.60; 95% CI 0.36–0.995, p = 0.049), embolic lesions (OR: 0.55; 95% CI 0.31–0.97, p = 0.041), and watershed lesions (OR: 0.25; 95%CI 0.07–0.80, p = 0.027). There was no significant difference in 30-day mortality (12.8% vs. 11.7%, p = ns) or long-term survival between groups.Conclusion: In this study, we showed that the addition of retrograde cerebral perfusion during hypothermic circulatory arrest in the setting of acute type A aortic dissection repair reduced the risk of clinical neurological injury, embolic lesions, and watershed lesions.
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| 13. |
- Edvardsson, Ulrika, 1967, et al.
(author)
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PPARalpha activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes.
- 2006
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In: Journal of lipid research. - 0022-2275. ; 47:2, s. 329-40
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Journal article (peer-reviewed)abstract
- Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and intracellular triglyceride mass. The triglyceride mass increased in spite of unchanged triglyceride biosynthesis and increased palmitic acid oxidation. However, Wy incubation decreased the secretion of newly synthesized triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased availability of triglycerides for VLDL assembly could help to explain the cellular accumulation of triglycerides after Wy treatment. We hypothesized that this effect could be mediated by increased ADRP expression. Similar to PPARalpha activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced cellular triglyceride mass and decreased the secretion of newly synthesized triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further decrease in triglyceride secretion. This effect of Wy was not attributable to decreased cellular triglycerides after increased fatty acid oxidation because the triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In summary, PPARalpha activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP.
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| 14. |
- Fedorowski, Artur, et al.
(author)
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Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.
- 2012
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In: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:18, s. 2331-2341
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Journal article (peer-reviewed)abstract
- Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85-0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75-0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87-0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02-1.24; P = 0.02, rs198358: 1.10, 1.01-1.20; P = 0.04, and rs5068: 1.22, 1.04-1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04).ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
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| 15. |
- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 16. |
- Hagen, Johannes, et al.
(author)
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A nudge to quit? The effect of a change in pension information on annuitization, labor supply and retirement choices among older workers
- 2018
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Reports (other academic/artistic)abstract
- Nudge is about affecting behavior in a certain way through small changes to the choice architecture. However, a nudge may also affect behaviors that the architect did not intend. We show that such spillover effects exist in a highly policy relevant context where the use of nudge is widespread; retirement. Specifically, we find that an exogenous application form change in the Swedish pension system that highlighted a five-year payout on the expense of a life annuity not only increased the demand for the nudged payout (as expected), but also induced individuals to retire earlier. We attribute the effects to decision-framing.
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| 17. |
- Hagen, Johannes, 1986-, et al.
(author)
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A Nudge to Quit? The Effect of a Change in Pension Information on Annuitization, Labour Supply, and Retirement Choices Among Older Workers
- 2022
-
In: Economic Journal. - : Oxford University Press. - 0013-0133 .- 1468-0297. ; 132:643, s. 1060-1094
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Journal article (peer-reviewed)abstract
- We study the effects of two exogenous modifications in the Swedish pension system application form nudging individuals towards a fixed-term payout. Meanwhile, the set of available options and the default option—life annuity—were unchanged during the period under study. We examine the effects on individuals’ payout decisions and the spillover effects on labour supply and other pensions using a difference-in-difference framework and detailed administrative data on actual payout decisions and a wide range of individual-level outcomes. Each modification increased the demand for the nudged payout by around 30 percentage points. The first modification also induced individuals to work less.
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| 18. |
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| 19. |
- Irving-Pease, Evan K., et al.
(author)
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The selection landscape and genetic legacy of ancient Eurasians
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 312-320
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Journal article (peer-reviewed)abstract
- The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes 1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.
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| 20. |
- Kurdve, Martin, et al.
(author)
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Production System Change Strategy in Lightweight Manufacturing
- 2016
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In: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; , s. 160-165
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Conference paper (peer-reviewed)abstract
- Two change management strategies: a minimum change, exploitation strategy (kaizen) and a maximum output, exploration strategy (kaikaku) have been applied in a manufacturing case study. Value stream mapping and discrete event simulation were used to analyse the production system changes, with regards to robustness and total lead-time, to increase knowledge of how to choose change management strategy. The results point out that available time is crucial. It is important to consider not only product specification and return of investment, but also the change and risk management. Future research should develop engineering change management further.
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| 21. |
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| 22. |
- Laird, Eamon, et al.
(author)
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Orthostatic hypotension and novel blood pressure associated gene variants in older adults : data from the TILDA Study
- 2020
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In: Journals of Gerontology. Series A: Biological Sciences & Medical Sciences. - : Oxford University Press (OUP). - 1758-535X. ; 75:11, s. 2074-2080
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Journal article (peer-reviewed)abstract
- Orthostatic hypotension (OH) is associated with increased risk of trauma and cardiovascular events. Recent studies have identified new genetic variants that influence orthostatic blood pressure (BP). The aim of this study was to investigate the associations of candidate gene loci with orthostatic BP responses in older adults. A total of 3,430 participants aged ≥50 years from The Irish Longitudinal Study on Ageing (TILDA) with BP measures and genetic data from twelve single-nucleotide polymorphism (SNP) linked to BP responses were analysed. Orthostatic BP responses were recorded at each 10 second interval and were defined as OH (SBP drop ≥20mmHg or DBP drop ≥10mmHg) at the time-points 40, 90 and 110 seconds. We defined sustained OH (SOH) as a drop that exceeded consensus BP thresholds for OH at 40, 90 and 110 seconds after standing. Logistic regression analyses modelled associations between the candidate SNP alleles and OH. We report no significant associations between OH and measured SNPs after correction for multiple comparisons apart from the SNP rs5068 where proportions of the minor allele was significantly different between cases and controls for SOH 40 (p=0.002). After adjustment for covariates in a logistic regression, those with the minor G allele (compared to the A allele) had a decreased incidence rate ratio (IRR) for SOH 40 (IRR 0.45, p=0.001, 95% CI 0.29-0.72). Only one SNP linked with increased natriuretic peptide concentrations was associated with OH. These results suggest that genetic variants may have a weak impact on OH but needs verification in other population studies.
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| 23. |
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| 24. |
- Nasr, Patrik, et al.
(author)
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A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease : the ACCESS-ESLD study protocol
- 2023
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In: BMC Gastroenterology. - : BioMed Central (BMC). - 1471-230X. ; 23:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .
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| 25. |
- Norman, Viktor
(author)
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Fatigue of Heavy-Vehicle Engine Materials : Experimental Analysis and Life Estimation
- 2015
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Licentiate thesis (other academic/artistic)abstract
- The heavy-vehicle automotive industry is constantly subjected to higher demands. In particular, new European emission standards are formulated with the intention of improving the environmental friendliness of newly-produced vehicles through reduced exhaust emission. In one way or another, this implies a successive improvement of the engine efficiency, which in turn, inevitably will require a higher combustion pressure and temperature. This is a respectable challenge for future engine constructions, but also for the engineering materials used to embody them. As higher thermal and mechanical loads must be sustained, there is a higher rate of wear, and consequently, a negative effect on the extent of the engine lifetime.The aim of the present thesis is to confront the expected increase in rate of wear, henceforth referred to as fatigue, by studying the effect on materials typically employed in heavy-vehicle engines, namely cast irons. Foremost, the intention has been to improve the understanding of the physical mechanisms of fatigue in these materials, in order to develop a lifetime estimation method designated to assist the mechanical design of heavy-vehicle engines.In essence, a large set of thermo-mechanical fatigue (TMF) and combined thermo-mechanical and high-cycle fatigue (TMF-HCF) tests has been conducted at engine load conditions on laboratory specimens of lamellar, compacted and spheroidal graphite irons. In this way, these three different material groups have been experimentally compared and the associated fatigue mechanism has been studied. In particular, a new property related to TMF-HCF conditions has been identified and measured, . Regarding the fatigue mechanism, it has been affirmed to consist of the initiation, propagation and coalescence of numerous microcracks. Based on this, a successful lifetime assessment model was formulated, allowing good estimations of the fatigue life of laboratory specimens subjected to both TMF and TMF-HCF conditions.
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| 26. |
- Noruzi, Farhad, et al.
(author)
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A holistic model for inter-plant knowledge transfer within an international manufacturing network
- 2020
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In: Journal of Knowledge Management. - 1758-7484 .- 1367-3270. ; 24:3, s. 535-552
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Journal article (peer-reviewed)abstract
- urpose This paper aims to provide a holistic view to support the choice of appropriate strategy for conducting a knowledge transfer (KT) project in an international manufacturing network (IMN) environment. It proposes a model that includes multiple aspects of a KT project along with guidelines on each aspect. Design/methodology/approach To achieve the research goals, multiple case study method was adopted. Data have been collected by conducting semi-structured interviews regarding five KT projects in three multinational corporations. Data were triangulated by means of comparisons to complementary data acquired through observations and archival documents. Findings The results of this paper detail the key issues of five KT projects. Furthermore, the paper proposes an aggregated model comprising the main aspects and strategies for a KT project within an IMN. Research limitations/implications Despite the abundant research on KT area, not many research projects provide holistic views on KT process. The focus has rather been sectional and concentrated on each specific aspect within the KT. Practical implications The paper guides practitioners to identify multiple aspects in KT that will eventually increase the odds for successfully performing such projects. Originality/value The proposed learning network model improves the performance of KT projects by providing a holistic view including several factors that the organization should emphasize to succeed with inter-plant KT.
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| 27. |
- Onerup, Aron, 1983, et al.
(author)
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Physical activity on prescription in accordance with the Swedish model increases physical activity: a systematic review.
- 2019
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In: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 53:6, s. 383-388
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Research review (peer-reviewed)abstract
- This study investigates the effects of the core elements of the Swedish model for physical activity on prescription (PAP) by evaluating studies that compared adults who received PAP with adults who did not receive PAP. All participants were adults identified by a healthcare professional as in need of increased physical activity. Primary outcome was level of physical activity.Systematic review. ELIGIBILITY CRITERIA: (1) Published 1999. (2) Systematic review, randomised controlled trial (RCT), non-RCT or case series (for adverse events). (3) ≥12 weeks' follow-up. (4) Performed in the Nordic countries. (5) Presented in English, Swedish, Norwegian or Danish.Systematic searches in PubMed, Embase, the Cochrane Library, AMED, CINAHL and SweMed+ in September 2017. Included articles were evaluated using checklists to determine risk of bias.Nine relevant articles were included: seven RCTs, one cohort study and one case series.Primary outcome was reported in seven articles from six studies (five RCTs, one cohort study, 642 participants). Positive results were reported from three of the five RCTs and from the cohort study. No study reported any negative results. Swedish PAP probably results in an increased level of physical activity (GRADE⊕⊕⊕Ο).Although the number of the reviewed articles was relatively modest, this systematic review shows that PAP in accordance with the Swedish model probably increases the level of physical activity. As a model for exercise prescription, Swedish PAP may be considered as part of regular healthcare to increase physical activity in patients.
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| 28. |
- Oudin, Anna, et al.
(author)
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Impact of national holidays and weekends on incidence of acute type A aortic dissection repair
- 2022
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54–0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68–0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.
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| 29. |
- Oudin Åström, Daniel, et al.
(author)
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Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics
- 2022
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In: Global health action. - : Informa UK Limited. - 1654-9880 .- 1654-9880 .- 1654-9716. ; 15:1
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Journal article (peer-reviewed)abstract
- We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (<=-5 degrees C) and hot temperatures (>= 21 degrees C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.
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| 30. |
- Rentoft, Matilda, et al.
(author)
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A geographically matched control population efficiently limits the number of candidate disease-causing variants in an unbiased whole-genome analysis
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 14:3
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing is a promising approach for human autosomal dominant disease studies. However, the vast number of genetic variants observed by this method constitutes a challenge when trying to identify the causal variants. This is often handled by restricting disease studies to the most damaging variants, e. g. those found in coding regions, and overlooking the remaining genetic variation. Such a biased approach explains in part why the genetic causes of many families with dominantly inherited diseases, in spite of being included in whole-genome sequencing studies, are left unsolved today. Here we explore the use of a geographically matched control population to minimize the number of candidate disease-causing variants without excluding variants based on assumptions on genomic position or functional predictions. To exemplify the benefit of the geographically matched control population we apply a typical disease variant filtering strategy in a family with an autosomal dominant form of colorectal cancer. With the use of the geographically matched control population we end up with 26 candidate variants genome wide. This is in contrast to the tens of thousands of candidates left when only making use of available public variant datasets. The effect of the local control population is dual, it (1) reduces the total number of candidate variants shared between affected individuals, and more importantly (2) increases the rate by which the number of candidate variants are reduced as additional affected family members are included in the filtering strategy. We demonstrate that the application of a geographically matched control population effectively limits the number of candidate disease-causing variants and may provide the means by which variants suitable for functional studies are identified genome wide.
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| 31. |
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| 32. |
- Sjögren, David, 1976-, et al.
(author)
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Nordic Journal of Educational History (NJEdH)
- 2015
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In: Connecting History of Education Scientific Journals as International Tools for a Global World. - Salamanca : FahrenHouse. - 9788494267581 ; , s. 151-159
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Book chapter (peer-reviewed)
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| 33. |
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| 34. |
- Sjögren, Hans, et al.
(author)
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The Timing of the Popping : Using the Log-Periodic Power Law Model to Predict the Bursting of Bubbles on Financial Markets
- 2016
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In: Financial History Review. - 0968-5650 .- 1474-0052. ; 23:2, s. 193-217
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Journal article (peer-reviewed)abstract
- The occurrence and unpredictability of speculative bubbles on financial markets, and their accompanying crashes, have confounded economists and economic historians worldwide. We examine the ability of the log-periodic power law model (LPPL-model) to accurately predict the end dates of speculative bubbles on financial markets through modeling of asset price dynamics on a selection of historical bubbles. The method is based on a nonlinear least squares estimation which yields predictions of when the bubble will change regime. Previous studies have only presented results where the predictions turn out to be successful. This study is the first to highlight both the potential and the limitations of the LPPL-model.We find evidence which support the characteristic patterns as proposed by the LPPL-framework leading up to the change in regime; asset prices during bubble periods seem to oscillate around a faster-than-exponential growth. In most cases the estimation yields accurate predictions, although we conclude that the predictions are quite dependent on the point in time at which the prediction is conducted. We also find that the end of a speculative bubble seems to be influenced by both endogenous speculative growth and exogenous factors. For this reason we propose a new way of interpreting the predictions of the model, where the end dates should be interpreted as the start of a time period where the asset prices are especially sensitive to exogenous events. We propose that negative news during this time period results in a regime shift and the bursting of the bubble. Thus, the model has the ability to predict sensitivity to exogenous events ex-ante.
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| 35. |
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| 36. |
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| 37. |
- Sjögren, Thomas, et al.
(author)
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Suppression of Clutter in Multichannel SAR GMTI
- 2014
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In: IEEE Transactions on Geoscience and Remote Sensing. - : IEEE. - 0196-2892 .- 1558-0644. ; 52:7, s. 4005-4013
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Journal article (peer-reviewed)abstract
- In this paper, results of moving target detection in multichannel UHF-band Synthetic Aperture Radar (SAR) data are shown. The clutter suppression is done using Finite Impulse Response (FIR) filtering of multichannel SAR in combination with a 2-stage Fast Backprojection (FBP) algorithm to focus the moving target using relative speed. The FIR filter coefficients are chosen with the use of STAP filtering. Two parameters are used for target focusing, target speed in range and in azimuth. When the target is focused, both speed parameters of the target are found. In the experimental results, two channels were used in order to suppress clutter. In the resulting SAR images it is obvious that very strong scatterers and the forest areas have been suppressed in comparison to the moving target in the image scene. The gain obtained can be measured using SCNR gain, which is about 19dB. Another way to measure signal processing gain is the ability to suppress the strongest reflecting object in the SAR scene. The gain of target in relation to this object is 25dB. This shows that using UHF-band SAR GMTI for suppressing forest and increasing the target signal can work.
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| 38. |
- Smith, Gustav, et al.
(author)
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Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure
- 2016
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
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Journal article (peer-reviewed)abstract
- Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
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| 39. |
- Svensson, Daniel, et al.
(author)
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doepipeline : a systematic approach to optimizing multi-level and multi-step data processing workflows
- 2019
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In: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Selecting the proper parameter settings for bioinformatic software tools is challenging. Not only will each parameter have an individual effect on the outcome, but there are also potential interaction effects between parameters. Both of these effects may be difficult to predict. To make the situation even more complex, multiple tools may be run in a sequential pipeline where the final output depends on the parameter configuration for each tool in the pipeline. Because of the complexity and difficulty of predicting outcomes, in practice parameters are often left at default settings or set based on personal or peer experience obtained in a trial and error fashion. To allow for the reliable and efficient selection of parameters for bioinformatic pipelines, a systematic approach is needed.Results: We present doepipeline, a novel approach to optimizing bioinformatic software parameters, based on core concepts of the Design of Experiments methodology and recent advances in subset designs. Optimal parameter settings are first approximated in a screening phase using a subset design that efficiently spans the entire search space, then optimized in the subsequent phase using response surface designs and OLS modeling. Doepipeline was used to optimize parameters in four use cases; 1) de-novo assembly, 2) scaffolding of a fragmented genome assembly, 3) k-mer taxonomic classification of Oxford Nanopore Technologies MinION reads, and 4) genetic variant calling. In all four cases, doepipeline found parameter settings that produced a better outcome with respect to the characteristic measured when compared to using default values. Our approach is implemented and available in the Python package doepipeline.Conclusions: Our proposed methodology provides a systematic and robust framework for optimizing software parameter settings, in contrast to labor- and time-intensive manual parameter tweaking. Implementation in doepipeline makes our methodology accessible and user-friendly, and allows for automatic optimization of tools in a wide range of cases. The source code of doepipeline is available at https://github.com/clicumu/doepipeline and it can be installed through conda-forge.
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| 40. |
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