SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Jørgensen Thomas) "

Sökning: WFRF:(Jørgensen Thomas)

  • Resultat 1-50 av 84
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
  •  
2.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
  •  
3.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
  •  
4.
  • Saxena, Richa, et al. (författare)
  • Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
  •  
5.
  • Sønderby, Ida E., et al. (författare)
  • 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
  • 2021
  • Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
  •  
6.
  • Allentoft, Morten E., et al. (författare)
  • 100 ancient genomes show repeated population turnovers in Neolithic Denmark
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
  • Tidskriftsartikel (refereegranskat)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.
  •  
7.
  • Allentoft, Morten E., et al. (författare)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Tidskriftsartikel (refereegranskat)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.
  •  
8.
  • Cortes, Dina, et al. (författare)
  • A new model of paired clinical teaching of international and Danish medical students
  • 2016
  • Ingår i: Danish Medical Journal. - 2245-1919. ; 63:7, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Since 2006, one hospital has offered two clinical courses in obstetrics/gynaecology and paediatrics to international (I) students. However, as I-student enrolment increased, the hospital faced cut-backs. As from 2010, I-team course evaluations therefore dropped to unacceptable levels and more I- than Danish (DK) students failed exams. Therefore, in 2012 we started a three-year internationalisation project (I-project) at two hospitals. The primary intervention was to pair training for I- and DK-students at clinical contact, and to offer an exclusive daily lecturer for I-teams.METHODS: We compared the course evaluations and exam grades of I-teams and DK-teams for two years prior to (107 from I-teams - 211 participants from DK-teams) and during the I-project (245 participants from I-teams - 575 from DK-teams).RESULTS: During the I-project, the I-teams' course evaluations increased to acceptable values and to levels comparable to the evaluation scores of DK-teams. Furthermore, I-students now considered that their communication with the patients was acceptable. Before the I-project, I-students had lower exam grades (median = 10 (range: 0-12)) than DK-students (10 (4-12)) (p = 0.03), but during the I-project, exam grades increased to the levels achieved by DK-students (10 (2-12) - 10 (0-12) (p = 0.22), and no more I- than DK-students failed exams (p = 0.51).CONCLUSIONS: Pairing students for clinical training and allocating an exclusive lecturer for I-teams produced improved courses for internationalisation. Allocating an exclusive lecturer was associated with a cost of about 615 EUR per student per course when the team consisted of ten students.FUNDING: The Capital Region of Denmark and the University of Copenhagen.TRIAL REGISTRATION: not relevant.
  •  
9.
  • Flannick, Jason, et al. (författare)
  • Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:4, s. 357-357
  • Tidskriftsartikel (refereegranskat)abstract
    • Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
  •  
10.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
  •  
11.
  • Kim, Dae-Kyum, et al. (författare)
  • EVpedia: A Community Web Portal for Extracellular Vesicles Research
  • 2015
  • Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 31:6, s. 933-939
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
  •  
12.
  • Laursen, Peter Nørkjær, et al. (författare)
  • Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study
  • 2018
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 204, s. 128-138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.
  •  
13.
  • Laursen, Peter Nørkjær, et al. (författare)
  • Unreported exclusion and sampling bias in interpretation of randomized controlled trials in patients with STEMI
  • 2019
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 289, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT)of ST-elevation myocardial infarction (STEMI). Methods and Results: We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%)and 617 contemporary non-participants (22%)had died (Log-Rank: P < 0.001)after a median follow-up of 1333 days (range: 1–2021 days). In an unadjusted Cox regression model all groups of non-participants had a higher hazard ratio to predict mortality compared to participants: eligible excluded (n = 144)(hazard ratio: 3.41 (95% CI: (2.69–4.32)), ineligible excluded (n = 472)(hazard ratio: 3.42 (95% CI: (2.44–4.80), eligible non-screened (n = 154)(hazard ratio: 3.37 (95% CI: (2.36–4.82)), ineligible non-screened (n = 154)(hazard ratio: 6.48 (95% CI: (4.77–8.80). Conclusion: Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias.
  •  
14.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
  •  
15.
  •  
16.
  • Alzuhairi, Karam Sadoon, et al. (författare)
  • Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction : A DANAMI-3 sub-study
  • 2020
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 301, s. 215-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). Methods and results: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Conclusion: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.
  •  
17.
  •  
18.
  •  
19.
  • Andrén, Thomas, 1954-, et al. (författare)
  • IODP expedition 347 : Baltic Sea basin paleoenvironment and biosphere
  • 2015
  • Ingår i: Scientific Drilling. - : Copernicus GmbH. - 1816-8957 .- 1816-3459. ; 20, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The Integrated Ocean Drilling Program (IODP) expedition 347 cored sediments from different settings of the Baltic Sea covering the last glacial–interglacial cycle. The main aim was to study the geological development of the Baltic Sea in relation to the extreme climate variability of the region with changing ice cover and major shifts in temperature, salinity, and biological communities. Using the Greatship Manisha as a European Consortium for Ocean Research Drilling (ECORD) mission-specific platform, we recovered 1.6 km of core from nine sites of which four were additionally cored for microbiology. The sites covered the gateway to the North Sea and Atlantic Ocean, several sub-basins in the southern Baltic Sea, a deep basin in the central Baltic Sea, and a river estuary in the north.The waxing and waning of the Scandinavian ice sheet has profoundly affected the Baltic Sea sediments. During theWeichselian, progressing glaciers reshaped the submarine landscape and displaced sedimentary deposits from earlier Quaternary time. As the glaciers retreated they left a complex pattern of till, sand, and lacustrine clay, which in the basins has since been covered by a thick deposit of Holocene, organic-rich clay. Due to the stratified water column of the brackish Baltic Sea and the recurrent and widespread anoxia, the deeper basins harbor laminated sediments that provide a unique opportunity for high-resolution chronological studies.The Baltic Sea is a eutrophic intra-continental sea that is strongly impacted by terrestrial runoff and nutrient fluxes. The Holocene deposits are recorded today to be up to 50m deep and geochemically affected by diagenetic alterations driven by organic matter degradation. Many of the cored sequences were highly supersaturated with respect to methane, which caused strong degassing upon core recovery. The depth distributions of conservative sea water ions still reflected the transition at the end of the last glaciation from fresh-water clays to Holocene brackish mud. High-resolution sampling and analyses of interstitial water chemistry revealed the intensive mineralization and zonation of the predominant biogeochemical processes. Quantification of microbial cells in the sediments yielded some of the highest cell densities yet recorded by scientific drilling.
  •  
20.
  •  
21.
  • Beck, Halfdan, et al. (författare)
  • Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase
  • 2010
  • Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 188:5, s. 629-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Maintenance of genome integrity is of critical importance to cells. To identify key regulators of genomic integrity, we screened a human cell line with a kinome small interfering RNA library. WEE1, a major regulator of mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative regulators of CDK1 and -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA, which was accompanied by a marked increase in single-stranded DNA. This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. Furthermore, the inferior proliferation of CHK1-depleted cells is improved substantially by codepletion of CDC25A. We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication.
  •  
22.
  • Bennesved, Peter, 1986- (författare)
  • Sheltered Society : Civilian Air raid shelters in Sweden — from idea to materiality, 1918-1940 and beyond
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In 2002, Sweden finally stopped producing air raid shelters for its population after over sixty years of continuous production since 1938. Judging from the Swedish Civil Contingencies Agency, MSB, the Swedish Air raid shelter registry contain about 65,000 air raid shelters registered as being in use. This figure reflect a huge security infrastructure which, today, is said to provide shelter for around 70% of the Swedish population. By studying the interwar period and the origins of civil defence in Swedish history, this dissertation sets out to explain the origins of the Swedish air raid shelter and provide an explanation of how Sweden eventually became a “Sheltered Society”.In order to achieve this, this dissertation will study the interwar period up until the first year of the Second World War, 1918 to 1940, which can be said to be the formative years for aerial protection politics and air raid shelters. As a theoretical inspiration, the dissertation uses LTS theory, intertwined with a Multi-Level Perspective on technological transitions. Through the close reading of reports and articles, newspapers and archival materials, written by fortification officers, engineers, architects, politicians and journalists during these years, the study shows how the originally military bunkers and air raid shelters were conceptually transferred to civilian use during the interwar years by authors concerned about the technological and strategic developments in aerial warfare.This process was enabled by a careful navigation between militaristic notions of aerial protection and the politically neutral civilian use of air raid shelters. Key factors for the successful implementation was framing the shelters as a simple technical matter through the concept of “Construction-Technical Aerial Protection”, as well as removing all military involvement in building and organizing them, making them seem “civilian” rather than military. This eventually led to the ratification of the Air raid shelter statute of 1940, which could be said to be the origin of the Swedish air raid shelter system. While politicians, engineers and fortification officers launched this image of the air raid shelter, the contemporary press discourse also provided a means of interpreting the10newly introduced shelters as being culturally compatible with Swedish urban modernity, thus making the radical urban change appear less frightening and a natural part of the development of the burgeoning Swedish welfare state.
  •  
23.
  •  
24.
  • Björkman, Anne, 1981, et al. (författare)
  • Plant functional trait change across a warming tundra biome
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
  •  
25.
  •  
26.
  • Bomholt, Tobias, et al. (författare)
  • The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis
  • 2022
  • Ingår i: Blood Purification. - : S. Karger. - 0253-5068 .- 1421-9735. ; 51:7, s. 608-616
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD.METHODS: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (μmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM.FINDINGS: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0-1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: -0.1-[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (-7.3 mmol/mol, 95% CI: -10.0-[-4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64).DISCUSSION: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.
  •  
27.
  • Botteri, Edoardo, et al. (författare)
  • Characteristics of non-participants in a randomized colorectal cancer screening trial comparing sigmoidoscopy and faecal immunochemical testing.
  • 2022
  • Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 151:3, s. 361-371
  • Tidskriftsartikel (refereegranskat)abstract
    • Public health systems should guarantee universal access to health care services, including cancer screening. We assessed whether certain population subgroups were underrepresented among participants in colorectal cancer screening with sigmoidoscopy and faecal immunochemical testing (FIT). Between 2012 and 2019, about 140,000 individuals aged 50-74years were randomly invited to once-only sigmoidoscopy or first round of FIT screening. This study included 46,919 individuals invited to sigmoidoscopy and 70,019 to FIT between 2012 and 2017. We used logistic regression models to evaluate if demographic and socioeconomic factors and use of certain drugs were associated with participation. 24,159 (51.5%) individuals attended sigmoidoscopy and 40,931 (58.5%) FIT screening. Male gender, young age, low education and income, being retired or unemployed, living alone, being an immigrant, long driving time to screening centre, and use of antidiabetic and psychotropic drugs were associated with low participation in both screening groups. Many of these factors also predicted low acceptance of colonoscopy after positive FIT. While male gender, young age and living alone were more strongly associated with non-participation in FIT than sigmoidoscopy, low education and income, being retired or immigrant and long driving time were more strongly associated with non-participation in sigmoidoscopy than FIT. In conclusion, participation was lower in sigmoidoscopy than FIT. Predictors of non-participation were similar between arms. However, low socioeconomic status, being an immigrant and long driving time affected participation more in sigmoidoscopy screening, suggesting that FIT may guarantee more equal access to screening services than sigmoidoscopy.
  •  
28.
  • Bro-Jørgensen, Maiken Hemme, et al. (författare)
  • Ancient DNA analysis of Scandinavian medieval drinking horns and the horn of the last aurochs bull
  • 2018
  • Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 99, s. 47-54
  • Tidskriftsartikel (refereegranskat)abstract
    • The aurochs (Bos primigenius) was once widespread in Europe, Asia and North Africa. The aurochs was both the ancestor of domestic cattle, and co-existed alongside them for millennia post domestication, before going extinct in 1627. Several studies have suggested that admixture occurred between wild aurochs populations and domestic cattle. To contribute towards our understanding of this process, we generated near complete mitochondrial genomes (between 15063 and 16338 nucleotides) from material derived from the horn of the last aurochs bull (died in 1620) as well as five medieval period Scandinavian drinking horns that have been attributed to aurochs based on their size. Phylogenetic analysis on the data shows that three drinking horns carry European aurochs haplotype P, while two of the drinking horns and the horn of the last aurochs bull carry modern domestic taurine cattle T haplotypes. Our results therefore demonstrate that drinking horns may represent a unique source of material with which to study aurochs genetics, and that the last European aurochs likely underwent a degree of admixture with domestic cattle. We anticipate that future analysis of the nuclear DNA content of such horns will be able to shed further light into the specifics of these admixture events.
  •  
29.
  • Buch-Rasmussen, Thomas (creator_code:cre_t)
  • A device for the administration of a liquid medicament suspension
  • 1998
  • Patent (övrigt vetenskapligt/konstnärligt)abstract
    • In an ampoule for a medicament the space accommodating the medicament is defined by an ampoule wall (1) a pierceable seal (5) closing one end of the ampoule and a piston (7) closing the other end of the ampoule. A metal containing fixation element (8) is secured to one of the parts defining the medicament accommodating space. A mixing element (9, 10) also containing a metal and having a density larger than 1,0 g/cm<3> is movable in medicament accommodating space. At least one of the elements, the fixation element (8) and the mixing element (9, 10), can be attracted by a magnet, and at least one of these elements is a magnetic element, the magnetic strength being so that the mixing element (9, 10) can during normal handling of the ampoule be fixed relative to this ampoule by the magnetic attraction between the fixation element (8) and the mixing element (9, 10) but may be released from its fixed position by manual operation.
  •  
30.
  • Buch-Rasmussen, Thomas (creator_code:cre_t)
  • Coating system providing low friction
  • 1999
  • Patent (övrigt vetenskapligt/konstnärligt)abstract
    • The present invention relates to a coating system, in particular to a coating system for articles where plastic materials slide against flexible rubber materials. The coating system is a silicone oil based coating having a viscosity of at least 200,000 centistokes, i.e. a high viscosity coating. The coating comprises in a preferred embodiment a silicone oil based block or graft copolymer, or segmented copolymer. Further the invention relates to a process of producing a component of an article coated as described above, comprising adding the coating material to the component material prior to molding and subsequently molding the component from the mixture, or molding the component from the component material and subsequently applying the coating material to the at least one surface of the component, as well as an article coated with a silicone oil based coating as defined above. Such an article is preferably a medical article, such as a container or an injection cylinder and a stopper. The coatings according to the present invention are especially suited to use for permanently coating internal surfaces of containers equipped with stoppers for storage and administration of liquid protein preparations. The coatings providing low friction between the two components, such as a container wall and a rubber stopper, result in high-precision dosing. The described coatings are particularly useful for coating containers for storage and administration of liquid protein solutions, such as insulin formulations.
  •  
31.
  •  
32.
  • Chen, Wei-Min, et al. (författare)
  • Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
  • 2008
  • Ingår i: Journal of Clinical Investigation. - 0021-9738. ; Jun 2, s. 2620-2628
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.
  •  
33.
  • Currie, Thomas E., et al. (författare)
  • Integrating evolutionary theory and social–ecological systems research to address the sustainability challenges of the Anthropocene
  • 2024
  • Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - 0962-8436 .- 1471-2970. ; 379:1893
  • Forskningsöversikt (refereegranskat)abstract
    • The rapid, human-induced changes in the Earth system during the Anthropocene present humanity with critical sustainability challenges. Social–ecological systems (SES) research provides multiple approaches for understanding the complex interactions between humans, social systems, and environments and how we might direct them towards healthier and more resilient futures. However, general theories of SES change have yet to be fully developed. Formal evolutionary theory has been applied as a dynamic theory of change of complex phenomena in biology and the social sciences, but rarely in SES research. In this paper, we explore the connections between both fields, hoping to foster collaboration. After sketching out the distinct intellectual traditions of SES research and evolutionary theory, we map some of their terminological and theoretical connections. We then provide examples of how evolutionary theory might be incorporated into SES research through the use of systems mapping to identify evolutionary processes in SES, the application of concepts from evolutionary developmental biology to understand the connections between systems changes and evolutionary changes, and how evolutionary thinking may help design interventions for beneficial change. Integrating evolutionary theory and SES research can lead to a better understanding of SES changes and positive interventions for a more sustainable Anthropocene.
  •  
34.
  • Dantoft, Thomas Meinertz, et al. (författare)
  • Multiple chemical sensitivity described in the Danish general population : Cohort characteristics and the importance of screening for functional somatic syndrome comorbidity-The DanFunD study
  • 2021
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Multiple chemical sensitivity (MCS) is characterized by widespread symptoms attributed to exposure to airborne chemicals. MCS is categorized as a functional somatic syndrome (FSS), and MCS cases often meet the criteria for other types of FSS, e.g. fibromyalgia. The primary aim was to characterize MCS regarding symptom triggers, symptoms, lifestyle and describe demographics, socioeconomics and lifestyle factors associated with MCS. A secondary aim was to examine the implication of FSS comorbidity.Methods: Data were derived from a random sample of the Danish adult population enrolled in the Danish Study of Functional Disorders (DanFunD; n = 9,656). Questionnaire data comprised information used to delimit MCS and four additional types of FSS, as well as data on demographics, socioeconomics and lifestyle. MCS cases (n = 188) was stratified into subgroups; MCS only (n = 109) and MCS with comorbid FSS (n = 73). Information regarding FSS comorbidities were missing for six MCS cases. MCS subgroups and controls without FSS comorbidities (n = 7,791) were compared by means of logistic regression analyses, adjusted for age and sex.Results: MCS was associated with female sex, not being in occupation and low social status, but not with age or education. MCS cases reported normal dietary intake and smoking habits and lower alcohol consumption. Additional associations were found between MCS and low rate of cohabitation, sedentarism, daily physically limitations, and poor quality of sleep. However, subgroup analysis revealed that these findings were primarily associated with MCS with comorbid FSS.Conclusions: MCS was associated with lower socioeconomic status, physically inactivity and poor quality of sleep. Subgroup analysis revealed that several associations was explained by FSS comorbidity, i.e. MCS cases with no comorbid FSS showed normal rate of cohabitation and did not report physical limitations or difficulties sleeping. Overall, our findings emphasise the importance of screening MCS cases for FSS comorbidity both in epidemiological and clinical settings.
  •  
35.
  • Engstrøm, Thomas, et al. (författare)
  • Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients : A phase 2 randomised clinical trial
  • 2018
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 104:19, s. 1593-1599
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods: In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results: From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions: Administration of danegaptide to patients with STEMI did not improve myocardial salvage. Trial registration number: NCT01977755; Pre-results.
  •  
36.
  • Fenton, Thomas M., et al. (författare)
  • Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity
  • 2020
  • Ingår i: Immunity. - : Elsevier BV. - 1074-7613. ; 52:3, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a method for isolating human gut-associated lymphoid tissues (GALTs) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILFs and M-ILFs, respectively) as well as in GALT-free intestinal lamina propria (LP). SM-ILF and M-ILF showed distinct patterns of distribution along the length of the intestine, were linked to the systemic circulation through MAdCAM-1+ high endothelial venules and efferent lymphatics, and had immune profiles consistent with immune-inductive sites. IgA sequencing analysis indicated that human ILFs are sites where intestinal adaptive immune responses are initiated in an anatomically restricted manner. Our findings position ILFs as key inductive hubs for regional immunity in the human intestine, and the methods presented will allow future assessment of these compartments in health and disease.
  •  
37.
  • Forslund, Sofia K., et al. (författare)
  • Combinatorial, additive and dose-dependent drug–microbiome associations
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
  • Tidskriftsartikel (refereegranskat)abstract
    • During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
  •  
38.
  • Frederiksen, Line Elmerdahl, et al. (författare)
  • Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden : a register-based cohort study from the SALiCCS research programme
  • 2022
  • Ingår i: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 69
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. Methods: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. Findings: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3–16·5) for childhood cancer survivors, 14·0% (13·5–14·5) for siblings, and 12·7% (12·4–12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31–1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28–1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. Interpretation: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. Funding: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.
  •  
39.
  • Fredrik, Jörgensen, 1971-, et al. (författare)
  • Legal Rights Matter : Evidence from Panel Data on Creditor Protection and Debt
  • 2008
  • Ingår i: International Finance Review. - Bingley : Emerald Group Publishing Limited. - 1569-3767. ; 9, s. 303-336, s. 303-336
  • Tidskriftsartikel (refereegranskat)abstract
    • Using panel data derived from recent financial statements, we examine the relationship between changing creditor protection and leverage (and debt maturity) in a number of emerging market countries located in Central and Eastern Europe. We examine unlisted firms, which are more likely than listed companies to face credit constraints. Our main hypothesis is whether unlisted firms change their leverage and debt maturity as creditor rights increase. We confirm this to be the case at both the country- and firm-level; our findings are robust to alternative econometric specifications and inclusion of countrylevel and firm-level controls. We also find that legal origin is related to the level of debt and its maturity.
  •  
40.
  •  
41.
  • Gonzalez-Franquesa, Alba, et al. (författare)
  • Discovery of thymosin β4 as a human exerkine and growth factor
  • 2021
  • Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 321:5, s. 770-778
  • Tidskriftsartikel (refereegranskat)abstract
    • Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin b4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in the plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.
  •  
42.
  • Haddaway, Neal R., et al. (författare)
  • How does tillage intensity affect soil organic carbon? A systematic review
  • 2017
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 6:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: The loss of carbon (C) from agricultural soils has been, in part, attributed to tillage, a common practice providing a number of benefits to farmers. The promotion of less intensive tillage practices and no tillage (NT) (the absence of mechanical soil disturbance) aims to mitigate negative impacts on soil quality and to preserve soil organic carbon (SOC). Several reviews and meta-analyses have shown both beneficial and null effects on SOC due to no tillage relative to conventional tillage, hence there is a need for a comprehensive systematic review to answer the question: what is the impact of reduced tillage intensity on SOC? Methods: We systematically reviewed relevant research in boreoerate regions using, as a basis, evidence identified within a recently completed systematic map on the impacts of farming on SOC. We performed an update of the original searches to include studies published since the map search. We screened all evidence for relevance according to predetermined inclusion criteria. Studies were appraised and subject to data extraction. Meta-analyses were performed to investigate the impact of reducing tillage [from high (HT) to intermediate intensity (IT), HT to NT, and from IT to NT] for SOC concentration and SOC stock in the upper soil and at lower depths. Results: A total of 351 studies were included in the systematic review: 18% from an update of research published in the 2 years since the systematic map. SOC concentration was significantly higher in NT relative to both IT [1.18 g/kg ± 0.34 (SE)] and HT [2.09 g/kg ± 0.34 (SE)] in the upper soil layer (0-15 cm). IT was also found to be significant higher [1.30 g/kg ± 0.22 (SE)] in SOC concentration than HT for the upper soil layer (0-15 cm). At lower depths, only IT SOC compared with HT at 15-30 cm showed a significant difference; being 0.89 g/kg [± 0.20 (SE)] lower in intermediate intensity tillage. For stock data NT had significantly higher SOC stocks down to 30 cm than either HT [4.61 Mg/ha ± 1.95 (SE)] or IT [3.85 Mg/ha ± 1.64 (SE)]. No other comparisons were significant. Conclusions: The transition of tilled croplands to NT and conservation tillage has been credited with substantial potential to mitigate climate change via C storage. Based on our results, C stock increase under NT compared to HT was in the upper soil (0-30 cm) around 4.6 Mg/ha (0.78-8.43 Mg/ha, 95% CI) over ≥ 10 years, while no effect was detected in the full soil profile. The results support those from several previous studies and reviews that NT and IT increase SOC in the topsoil. Higher SOC stocks or concentrations in the upper soil not only promote a more productive soil with higher biological activity but also provide resilience to extreme weather conditions. The effect of tillage practices on total SOC stocks will be further evaluated in a forthcoming project accounting for soil bulk densities and crop yields. Our findings can hopefully be used to guide policies for sustainable management of agricultural soils.
  •  
43.
  • Haddaway, Neal Robert, et al. (författare)
  • How does tillage intensity affect soil organic carbon? A systematic review protocol
  • 2016
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Soils contain the greatest terrestrial carbon (C) pool on the planet. Since approximately 12 % of soil C is held in cultivated soils, management of these agricultural areas has a huge potential to affect global carbon cycling; acting sometimes as a sink but also as a source. Tillage is one of the most important agricultural practices for soil management and has been traditionally undertaken to mechanically prepare soils for seeding and minimize effects of weeds. It has been associated with many negative impacts on soil quality, most notably a reduction in soil organic carbon (SOC), although still a matter of considerable debate, depending on factors such as depth of measurement, soil type, and tillage method. No tillage or reduced intensity tillage are frequently proposed mitigation measures for preservation of SOC and improvement of soil quality, for example for reducing erosion. Whilst several reviews have demonstrated benefits to C conservation of no till agriculture over intensive tillage, the general picture for reduced tillage intensity is unclear. This systematic review proposes to synthesise an extensive body of evidence, previously identified through a systematic map. Methods: This systematic review is based on studies concerning tillage collated in a recently completed systematic map on the impact of agricultural management on SOC restricted to the warm temperate climate zone (i.e. boreo-temperate). These 311 studies were identified and selected systematically according to CEE guidelines. An update of the original search will be undertaken to identify newly published academic and grey literature in the time since the original search was performed in September 2013. Studies will be critically appraised for their internal and external validity, followed by full data extraction (meta-data describing study settings and quantitative study results). Where possible, studies will be included in meta-analyses examining the effect of tillage reduction ('moderate' (i.e. shallow) and no tillage relative to 'intensive' tillage methods such as mouldboard ploughing, where soil is turned over throughout the soil profile). The implications of the findings will be discussed in terms of policy, practice and research along with a discussion of the nature of the evidence base.
  •  
44.
  • Haddaway, Neal R., et al. (författare)
  • What are the effects of agricultural management on soil organic carbon in boreo-temperate systems?
  • 2015
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 4
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Soils contain the largest stock of organic carbon (C) in terrestrial ecosystems and changes in soil C stocks may significantly affect atmospheric CO2. A significant part of soil C is present in cultivated soils that occupy about 35 % of the global land surface. Agricultural intensification has led to practices that may decrease soil organic carbon (SOC), and agricultural management has the potential to be a powerful tool for climate change mitigation and increased soil fertility through SOC sequestration. Here, we systematically map evidence relating to the impacts of agricultural management on SOC in arable systems of the warm temperate and snow climate zones (subset of temperate and continental climates: Köppen–Geiger Classification). Methods: Seventeen academic citation databases, 3 search engines and 25 organisational websites were searched for literature (academic and grey) using search strings translated into a range of languages relevant to the included geographical scope of the topic. Stakeholders were also contacted with requests for evidence. Bibliographic checking of 127 relevant reviews was undertaken to check for missing articles. Screening for relevance against predefined inclusion criteria was undertaken at title, abstract and full text levels according to a published protocol. All relevant studies were coded in a meta-database describing the citation, study settings, methods and quantitative data available (without extraction of the study findings). A basic critical appraisal of included studies was also performed. A geographical information system (GIS) presenting the map database on a physical, online map was also produced. Results: A total of 735 studies from 553 articles was included in the systematic map database. Studies investigated one or more of five broad categories of interventions: amendments (286 studies), crop rotations (238), fertilisers (307), tillage (306), and multiple interventions (55). Studies were identified from across the includible climate zones, with the notable underrepresentation from Russia. The majority of studies employed only point sampling of SOC, low levels of true spatial replication and moderate study periods (i.e. 10–20 years). Missing key methodological information was found in 28 % of studies. Conclusions: Long-term study sites identified in this map provide a useful addition to existing databases of longterm experiments (LTEs). The identification of knowledge gaps, such as studies from Russia, also identify a need for improved cataloguing or reporting of existing and on-going research. This systematic map database represents a useful resource for decision-makers wishing to identify knowledge gaps warranting further primary research, knowledge gluts warranting further secondary research, and deficiencies and best practice in research methodology. In addition to the systematic map database, we have also produced two further resources: (1) a database of LTE sites investigating agricultural management and SOC, and (2) a database of reviews and meta-analyses. To our knowledge, this is the first systematic review or map that utilises a GIS for presentation of an evidence base, which we believe substantially increases the utility of the map outputs.
  •  
45.
  • Haddaway, Neal Robert, et al. (författare)
  • Which agricultural management interventions are most influential on soil organic carbon (using time series data)?
  • 2016
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 5:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Loss of soil organic carbon (SOC) from agricultural land is identified as one of the major threats to soils, as it influences both fertility and the production of ecosystem services from agriculture. Losses of SOC across regions are often determined by monitoring in different land use systems. Results from agricultural field experiments can reveal increasing SOC stocks after implementation of specific management practices compared to a control, though in time series experiments the relative rate of change is often negative and implying an overall loss. Long-term agricultural field experiments are indispensable for quantifying absolute changes in SOC stocks under different management regimes. Since SOC responses are seldom linear over time, time series data from these experiments are particularly valuable. Methods: This systematic review is based on studies reporting time series data collated in a recently completed systematic map on the topic restricted to the warm temperate climate zone and the snow climate zone. These 53 studies were identified and selected systematically according to CEE guidelines. An update of the original search for studies will be repeated using Web of Science and Google Scholar to include newly published academic and grey literature in the time since the original search was performed in September 2013. Studies will be subject to critical appraisal of the internal and external validity, followed by full data extraction (meta-data describing study settings and quantitative study results). Where possible, studies will be included in a quantitative synthesis using time series meta-analytical approaches. The implications of the meta-analytical findings will be discussed in terms of policy, practice and research along with a discussion of the nature of the evidence base.
  •  
46.
  • Hall, Thomas, et al. (författare)
  • Legal variation and capital structure : Comparing listed and non-listed companies
  • 2015
  • Ingår i: European Journal of Law and Economics. - : Springer Science and Business Media LLC. - 0929-1261 .- 1572-9990. ; 40:3, s. 511-543
  • Tidskriftsartikel (refereegranskat)abstract
    • We exploit the natural institutional variation in Western Europe to examine leverage (and debt maturity) for listed and non-listed companies (NLCs). We find that the legal efficiency measure (Djankov et al. 2008) is more closely related to the amount of leverage and debt maturity than is the creditor rights score of La Porta et al. (Law and Finance, NBER working paper 5661, 1996; J Financ 52:1131–1151, 1997). One component of the standard measure of creditor rights was consistently and positively associated with leverage: whether secured creditors are paid first in the event of distress. Firms located in French and German legal family countries have less leverage than companies in common law setting, but Scandinavian firms have more. Asset specificity has a negative impact on leverage, but a positive impact on debt maturity. Finally, using a matched sample of otherwise similar privately held companies, we find that listed firms have less debt, consistent with a corporate governance interpretation that presumably more dispersed publicly traded firms are more likely to avoid the disciplining device of leverage. The findings are robust to use of industry-level fixed effects.
  •  
47.
  • Hall, Thomas, et al. (författare)
  • Ownership and Performance in Europe
  • 2013
  • Ingår i: Review of Business. - 0034-6454. ; 33:2, s. 39-54
  • Tidskriftsartikel (refereegranskat)abstract
    • The article reflects on a cross-country study to explore the relationship between ownership concentration and corporate performance and shareholder's legal investor protection for both private and public firms in five European economies including Ireland, Austria, and Austria. It mentions that regression analysis of almost 37,000 firms from the period 1996 - 2005 was conducted and the study found that legal investor protection was least in Ukraine.
  •  
48.
  • Hallman, David, 1979-, et al. (författare)
  • Symposium: Arbete, individ och nacksmärta : Forskning vid Forte-centret “Kroppen i arbete – från problem till potential”
  • 2018
  • Ingår i: FALF KONFERENS 2018 Arbetet - problem eller potential för en hållbar livsmiljö? 10-12 juni 2018 i Gävle. - Gävle : Gävle University Press. - 9789188145284 ; , s. 102-
  • Konferensbidrag (refereegranskat)abstract
    • Besvär ifrån kroppens muskler och leder såsom nack- och ryggbesvär är fortfarande ett stort problem inom arbetslivet. Muskuloskeletal diagnos är den vanligaste orsaken till lång sjukfrånvaro inom privat sektor och näst vanligast inom kommuner och landsting. Orsakerna till dessa besvär kan vara relaterade till exponering både under arbete och på fritid, men även till individfaktorer. Vår forskargrupp har en bred ansats för att fylla kunskapsluckor inom detta område och kommer att presentera resultat från flera forskningsprojekt i symposiet Arbete, individ och nacksmärta.Långvarigt sittande har blivit alltmer vanligt förekommande i många yrkesgrupper. Långvarigt sittande och låg fysisk aktivitet har också uppmärksammats som ett betydande hälsoproblem i dagens arbetsliv och även som en möjlig riskfaktor för smärta i nacke-skuldra. Men forskningen om betydelsen av långvarigt sittande för smärta i nacke-skuldra är fortfarande begränsad. Likaså är det oklart om huvudets hållning vid sittandet och nackens funktion, exempelvis nackens rörelsefunktion och styrka, har betydelse för besvärsutveckling. Statiskt arbete med nacken i vridna och böjda positioner misstänks vara en riskfaktor för nack-skuldersmärta i yrken såsom tandläkare, men det är oklart varför vissa exponerade individer drabbas medan andra inte får ont. För de med långvarig smärta krävs ofta rehabiliterande åtgärder, och hur väl dessa åtgärder lyckas kan även det vara beroende av individens fysiska och psykosociala arbetsmiljö. Individens arbetsmiljö påverkar således inte bara risken för om man får besvär utan kan också ha betydelse för hur rehabiliteringen av besvären lyckas.Syftet med detta symposium är att presentera studier från Centrum för belastningsskadeforskning som handlar om nacksmärta i arbetslivet, sammanfatta kunskapsläget inom området och diskutera hur arbetet kan utformas för att bli hållbart och inkluderande. De forskningsexempel som presenteras berör stillasittande och hållning i arbetslivet och dess tänkbara konsekvenser för nacksmärta och hälsa, riskfaktorer för nacksmärta i tandläkaryrket och arbetsmiljöns betydelse för resultatet av rehabilitering vid nacksmärta. Symposiet avslutas med en frågestund och gemensam diskussion.
  •  
49.
  • Harborg, Sixten, et al. (författare)
  • Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors : a Danish population-based cohort study
  • 2020
  • Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 183:1, s. 153-160
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting. Patients and methods: We enrolled all postmenopausal patients diagnosed with stage I–III estrogen receptor positive breast cancer during the years 2007–2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥ 1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure. Results: We enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92–14.28] and 13.40 [95% CI 12.36–14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50–1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48–1.02]). Conclusions: Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy.
  •  
50.
  • Hauge, Camilla, et al. (författare)
  • Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation.
  • 2007
  • Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 26:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth factor/insulin-stimulated AGC kinases share an activation mechanism based on three phosphorylation sites. Of these, only the role of the activation loop phosphate in the kinase domain and the hydrophobic motif (HM) phosphate in a C-terminal tail region are well characterized. We investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within the kinase domain, promoting zipper-like association of the tail with the kinase domain, serving to stabilize the HM in its kinase-activating binding site. We present a molecular model for allosteric activation of AGC kinases by the turn motif phosphate via HM-mediated stabilization of the alphaC helix. In S6K and MSK, the turn motif phosphate thereby also protects the HM from dephosphorylation. Our results suggest that the mechanism described is a key feature in activation of upto 26 human AGC kinases.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 84
Typ av publikation
tidskriftsartikel (61)
forskningsöversikt (8)
samlingsverk (redaktörskap) (4)
patent (3)
rapport (2)
annan publikation (2)
visa fler...
konferensbidrag (2)
doktorsavhandling (1)
bokkapitel (1)
visa färre...
Typ av innehåll
refereegranskat (71)
övrigt vetenskapligt/konstnärligt (13)
Författare/redaktör
Hansen, Torben (9)
Jørgensen, Torben (9)
Engstrøm, Thomas (9)
Pedersen, Oluf (8)
Lønborg, Jacob (8)
Køber, Lars (8)
visa fler...
Laakso, Markku (7)
Boehnke, Michael (7)
Mohlke, Karen L (7)
Tuomilehto, Jaakko (7)
Stefansson, Kari (7)
Luan, Jian'an (7)
Jørgensen, Erik (7)
Pedersen, Frants (7)
Groop, Leif (6)
Wareham, Nicholas J. (6)
Kuusisto, Johanna (6)
McCarthy, Mark I (6)
Grarup, Niels (6)
Ingelsson, Erik (6)
Thorleifsson, Gudmar (6)
Thorsteinsdottir, Un ... (6)
Hedlund, Katarina (6)
Holmvang, Lene (6)
Kelbæk, Henning (6)
Kätterer, Thomas (6)
Loos, Ruth J F (6)
Jackson, Anne U. (6)
Bonnycastle, Lori L. (6)
Lyssenko, Valeriya (5)
Tuomi, Tiinamaija (5)
Salomaa, Veikko (5)
Hu, Frank B. (5)
Langenberg, Claudia (5)
Qi, Lu (5)
Hunter, David J (5)
Abecasis, Goncalo R. (5)
Barroso, Ines (5)
Nepper-Christensen, ... (5)
Helqvist, Steffen (5)
Eriksson, Johan G. (5)
Kovacs, Peter (5)
Altshuler, David (5)
Illig, Thomas (5)
Boerwinkle, Eric (5)
Voight, Benjamin F. (5)
Hveem, Kristian (5)
Prokopenko, Inga (5)
Frayling, Timothy M (5)
Vollenweider, Peter (5)
visa färre...
Lärosäte
Lunds universitet (42)
Uppsala universitet (17)
Umeå universitet (15)
Stockholms universitet (12)
Karolinska Institutet (12)
Göteborgs universitet (10)
visa fler...
Södertörns högskola (7)
Sveriges Lantbruksuniversitet (7)
Linköpings universitet (3)
Chalmers tekniska högskola (3)
Kungliga Tekniska Högskolan (1)
Högskolan i Gävle (1)
Försvarshögskolan (1)
visa färre...
Språk
Engelska (81)
Svenska (1)
Danska (1)
Norska (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (37)
Naturvetenskap (30)
Humaniora (9)
Samhällsvetenskap (8)
Lantbruksvetenskap (6)
Teknik (5)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy