| 1. |
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| 2. |
- Eriksson, Jan W., et al.
(författare)
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Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:9, s. 1923-1934
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The EFFECT-II study aimed to investigate the effects of dapagliflozin and omega-3 (n-3) carboxylic acids (OM-3CA). individually or combined, on liver fat content in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods This randomised placebo-controlled double-blind parallel-group study was performed at five clinical research centres at university hospitals in Sweden. 84 participants with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. Each group received oral doses of one of the following: 10 mg dapagliflozin (n = 21). 4 g OM3-CA (n = 20), a combination of both (n = 22) or placebo (n = 21). The primary endpoint was liver fat content assessed by MRI (proton density fat fraction [PDFF]) and, in addition, total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were assessed at baseline and after 12 weeks of treatment (completion of the trial). Results Participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m(2) (3.5) and liver PDFF 18% (9.3). All active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, -15%; dapagliflozin, -13%; OM-3CA + dapagliflozin, -21%. Only the combination treatment reduced liver PDFF (p = 0.046) and total liver fat volume (relative change, -24%,p = 0.037) in comparison with placebo. There was an interaction between the PNPLA31148M polymorphism and change in liver PDFF in the active treatment groups (p = 0.03). Dapagliflozin monotherapy, but not the combination with OM-3CA, reduced the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transfcrase (gamma-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21). Changes in gamma-GT correlated with changes in liver PDFF (rho = 0.53, p = 0.02). Dapagliflozin alone and in combination with OM-3CA improved glucose control and reduced body weight and abdominal fat volumes. Fatty acid oxidative stress biomarkers were not affected by treatments. There were no new or unexpected adverse events compared with previous studies with these treatments. Conclusions/interpretation Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content. Dapagliflozin monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.
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| 3. |
- Fryk, Emanuel, et al.
(författare)
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Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients
- 2016
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Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:7, s. 998-1006
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p < 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p < 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p < 0.05) and increased by overfeeding (p < 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p < 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.
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| 4. |
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| 5. |
- Paul-Visse, Gesine, et al.
(författare)
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Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients
- 2015
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:3, s. 1339-1346
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 mu g rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD.
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| 6. |
- Sjögren, Lovisa, et al.
(författare)
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Postprandial effects of the phosphodiesterase-5 inhibitor tadalafil in people with well-controlled Type 2 diabetes mellitus: a randomized controlled trial.
- 2016
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Ingår i: Diabetic medicine : a journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 33:9, s. 1299-1301
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus is a serious global health problem that is hard to treat in the long term, prompting great efforts to find new drug targets. Little attention has been paid, however, to the metabolic significance of the microcirculation in insulin-sensitive tissues, despite the fact that microvascular insulin resistance and endothelial dysfunction are closely associated and have been shown to precede Type 2 diabetes [1]. Endothelial nitric oxide plays a major role in mediating the beneficial effects of insulin on capillary recruitment and muscle glucose uptake [2] and in suppression of inflammatory pathways, including those activated by a high-fat diet [3]. This article is protected by copyright. All rights reserved.
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| 7. |
- Volkov, Petr, et al.
(författare)
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A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs) in cis and 5,342 SNP-CpG pairs in trans showing significant associations between genotype and DNA methylation in adipose tissue after correction for multiple testing, where cis is defined as distance less than 500 kb between a SNP and CpG site. These mQTLs include reported obesity, lipid and type 2 diabetes loci, e.g. ADCY3/POMC, APOA5, CETP, FADS2, GCKR, SORT1 and LEPR. Significant mQTLs were overrepresented in intergenic regions meanwhile underrepresented in promoter regions and CpG islands. We further identified 635 SNPs in significant cis-mQTLs associated with expression of 86 genes in adipose tissue including CHRNA5, G6PC2, GPX7, RPL27A, THNSL2 and ZFP57. SNPs in significant mQTLs were also associated with body mass index (BMI), lipid traits and glucose and insulin levels in our study cohort and public available consortia data. Importantly, the Causal Inference Test (CIT) demonstrates how genetic variants mediate their effects on metabolic traits (e.g. BMI, cholesterol, highdensity lipoprotein (HDL), hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR)) via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dys) metabolic traits associated with the development of obesity and diabetes.
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| 8. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 9. |
- Daka, Bledar, 1976, et al.
(författare)
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Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: A longitudinal observational study in the Vara-Skövde Cohort
- 2015
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 Daka et al.Background: The vasoconstricting peptide endothelin-1 has been proposed to be a marker of cardiovascular disease. Our aim was to investigate whether circulating endothelin-1 levels predict coronary heart disease (CHD) in Sweden. Methods: In 2002-2005, 2816 adult participants (30-74 years) were randomly selected from two municipalities in south-western Sweden. Cardiovascular risk factors and endothelin-1 levels were assessed at baseline, and incident CHD was followed-up in all participants through 2011. After exclusion of 50 participants due to known CHD at baseline and 21 participants because of unsuccessful analysis of endothelin-1, 2745 participants were included in the study. In total, 72 CHD events (52 in men and 20 in women) were registered during the follow-up time. Results: We showed that baseline circulating endothelin-1 levels were higher in women with incident CHD than in women without CHD (3.2 pg/ml, SE: 0.36 vs 2.4 pg/ml, SE: 0.03, p = 0.003) whereas this difference was not observed in men (2.3 pg/ml, SE: 0.16 vs 2.3 pg/ml, SE: 0.04, p = 0.828). An age-adjusted Cox proportional regression analysis showed an enhanced risk of CHD with increasing baseline endothelin-1 levels in women (hazard ratio (HR) = 1.51, 95 % CI = 1.1-2.1, p = 0.015) but not in men (HR = 0.98, 95 % CI = 0.8-1.2, p = 0.854). Furthermore, the predictive value of endothelin-1 for incident CHD in women was still significant after adjustments for age, HOMA-IR, apolipoprotein (apo)B/apoA1 and smoking (HR = 1.53, CI = 1.1-1.2, p = 0.024). Conclusion: Circulating endothelin-1 levels may predict CHD in women.
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| 10. |
- Daka, Bledar, 1976, et al.
(författare)
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Low concentrations of serum testosterone predict acute myocardial infarction in men with type 2 diabetes mellitus
- 2015
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Ingår i: Bmc Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to investigate the associations between endogenous testosterone concentrations and the incidence of acute myocardial infarction (AMI) in men and women with and without type 2 diabetes. Methods: The study comprised 1109 subjects >= 40 years of age (mean age 62 +/- 12 years) participating in a baseline survey in Sweden in 1993-94. Information about smoking habits and physical activity was obtained using validated questionnaires. Serum concentrations of testosterone and sex hormone-binding globulin (SHBG) were obtained using radioimmunoassay. Diagnosis of type 2 diabetes was based on WHO's 1985 criteria. Individual patient information on incident AMI was ascertained by record linkage with national inpatient and mortality registers from baseline through 2011. Results: The prevalence of type 2 diabetes at baseline was 10.0 % in men and 7.5 % in women. During a mean follow-up of 14.1 years (+/- 5.3), there were 74 events of AMI in men and 58 in women. In age-adjusted Cox models, a significant inverse association between concentrations of testosterone and AMI-morbidity was found in men with type 2 diabetes (HR = 0.86 CI (0.75-0.98)). In a final model also including waist-to-hip ratio, systolic blood pressure, total cholesterol and active smoking, the association still remained statistically significant (HR = 0.754 CI (0.61-0.92)). Conclusion: Low concentrations of testosterone predicted AMI in men with type 2 diabetes independent of other risk factors. Trials with testosterone investigating the effect regarding cardiovascular outcome are still lacking. Future trials in this field should take into account a modification effect of diabetes.
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| 11. |
- Dayeh, Tasnim, et al.
(författare)
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DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk
- 2016
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 11:7, s. 482-488
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Tidskriftsartikel (refereegranskat)abstract
- Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02–1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75–0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.
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| 12. |
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| 13. |
- Esbjörnsson, Joakim, et al.
(författare)
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Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau : a prospective open cohort study
- 2019
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Ingår i: The Lancet HIV. - : The Lancet Publishing Group. - 2405-4704 .- 2352-3018. ; 6:1, s. E25-E31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.
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| 14. |
- Forsström, David, 1981-
(författare)
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The use and experience of responsible gambling tools : An explorative analysis of user behavior regarding a responsible gambling tool and the consequences of use
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Responsible gambling tools are an intervention that is designed to decrease gambling among individuals with an at-risk gambling behavior. Studies have indicated that responsible gambling tools can decrease gambling behavior, but little is known about how this intervention is used by gamblers. The aim of the present thesis was to explore different facets of the use, experience and functions of these tools. Study I used descriptive statistics and latent class analysis (LCA) combined with multinomial regression to explore the use of the responsible gambling tool Playscan among 9528 gamblers (regular and at-risk gamblers). The participants had volunteered to use the tool. The functions of the tool had a high rate of initial use but a low rate of repeated use. The LCA identified five user classes. Two of the classes (self-testers and multifunctional users) were defined as high users of the tool and had a higher risk of developing gambling problems according to multinomial regression. The multifunctional users were characterized by an extensive use of all the functions while the other high usage class had an extensive use of the self-test. The three other classes were as follows: those who did not use the tool, those who visited the tool but did not engage in any of the functions, and those who only used the tool’s advice on how to decrease their gambling. Participants’ reasons for use and non-use of the tool were attributed to their degree of need of the tool and its functions. The tool’s most widely used function was the self-test that investigated the level of negative consequences faced by a user due to his or her gambling. Study II was a qualitative study investigating participants’ views, experiences and their reasons for using the tool. The study was conducted by interviewing 20 volunteer users of the tool. These semi-structured interviews were analyzed by thematic analysis. The results showed that the users had a positive attitude towards the tool and understood its purpose. The self-test was the most widely used function in this sample as well. However, the participants’ positive attitude toward the tool did not effectively encourage them to use it; they displayed low use of the tool’s functions. This paradox was explained by lack of feedback and the fact that some participants did not understand that they had registered to use the tool. Providing more feedback and tailoring the feedback to individual users were seen as ways of bridging the paradox. Study II also found that participants used the gambling website (which Playscan was linked to) in an analogue way, preparing their bets before placing them online. This limited the time they spent on the site and inhibited their use of Playscan. Study III was motivated by the extensive use of the self-test among users in Study I and Study II. The aim of Study III was to investigate the psychometric properties of the self-test (known as GamTest) to better understand how it could be used with Playscan in the most efficient way. Two thousand two hundred and thirty four respondents answered the questionnaire, along with instruments measuring depression, anxiety and another instrument measuring problems due to gambling. Factor analysis, parallel analysis, Cronbach’s alpha, and correlations were used to establish the tool’s psychometric properties. The results yielded a three-factor model, excellent reliability, and high correlation with the Problem Gambling Severity Index (PGSI), endorsing the validity of the self-test. The results also indicated that the questionnaire could be effectively shortened. Overall, the studies show that the tool has an initial high use, low repeated use and that the self-test is the most used feature. In addition, the self-test had good psychometric properties.
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| 15. |
- Hadrévi, Jenny, 1977-, et al.
(författare)
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Plasma metabolomic patterns in patients with exhaustion disorder
- 2019
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Ingår i: Stress. - : Taylor & Francis. - 1025-3890 .- 1607-8888. ; 22:1, s. 17-26
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Tidskriftsartikel (refereegranskat)abstract
- Exhaustion disorder (ED) is a stress-related disorder that often implies a great burden on the individual patient as well as on society. Previous studies have shown that ED is associated with metabolic deviations, such as lowered fasting glucose. Several mechanisms have been discussed as a plausible explanation of the lack of energy described by these patients. Metabolic processes and reduced ability to mobilize energy have been suggested as important factors. This study investigated metabolomics in 20 patients diagnosed with ED and compared them with 21 healthy controls. Plasma metabolic profiles were examined in both fasting and nonfasting (postprandial) conditions. Blood plasma samples were analyzed for metabolite content using gas chromatography mass spectrometry. A total of 62 different metabolites were simultaneously detected in each of the samples. Multivariate models indicated systematic differences between patients with ED and healthy controls in both their fasting and nonfasting plasma metabolite levels. Lysine and octadecenoic acid were more abundant and glutamine, glycine, serine and gluconic acid were less abundant in the patients across both conditions. In the present study, we comprehensively and simultaneously screen for changes in a large number of metabolites. Our results show a difference in systemic metabolites between patients with exhaustion disorder and healthy controls both in the fasting and in the postprandial states. Here, we present new potential biomarkers mirroring exhaustion disorder metabolism.
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| 16. |
- Hellgren, Margareta, 1955, et al.
(författare)
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A lifestyle intervention in primary care prevents deterioration of insulin resistance in patients with impaired glucose tolerance: A randomised controlled trial.
- 2016
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 44:7, s. 718-725
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesised that the expected increase in insulin resistance over three years' time in individuals with impaired glucose tolerance (IGT) and/or impaired fasting glucose could be attenuated by an intervention with focus on physical activity in ordinary primary care.We conducted a randomised controlled trial with 96 participants over three years. Examination of the participants included anthropometric measures, blood pressure, body weight and height, blood samples, an oral glucose tolerance test, and questionnaires about diet and lifestyle. The study subjects were randomised to either an intense intervention with information, group sessions, referral to physical activity and a step-counter (n = 31), a less intense intervention without the group sessions (n = 35), or care as usual group (CAUG) (n = 30). Differences between the groups were analysed with general linear models adjusted for age, gender, baseline values and time in the intervention.Individual insulin resistance increased in the CAUG. Due to having a similar effect, we combined the two intervention groups into a combined intervention group (CIG; n = 66) in the analyses. In individuals with IGT, the increase in the homeostatic model assessment-insulin resistance differed significantly between those in the CAUG and the CIG (Δ = 0.8; CI: 0.1-1.6; p = 0.034). Likewise, diastolic blood pressure decreased more in the CIG than in the CAUG (Δ = 5.1; CI: 0.1-10.0; p = 0.047). A total of 17 individuals developed Type 2 diabetes, 23% were in the CIG and 33% in the CAUG; so there was a 32% reduced risk in the intervention group. CONCLUSIONS A LIFESTYLE INTERVENTION FOCUSED ON PHYSICAL ACTIVITY IS FEASIBLE IN ORDINARY PRIMARY CARE AND PREVENTS DETERIORATION IN INSULIN SENSITIVITY IN INDIVIDUALS WITH IGT OVER A THREE-YEAR PERIOD.
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| 17. |
- Hellgren, Margareta, 1955, et al.
(författare)
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C-Reactive Protein Concentrations and Level of Physical Activity in Men and Women With Normal and Impaired Glucose Tolerance: A Cross-Sectional Population-Based Study in Sweden
- 2016
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Ingår i: Journal of Physical Activity & Health. - : Human Kinetics. - 1543-3080 .- 1543-5474. ; 13:6, s. 625-631
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to explore the association between self-reported leisure time physical activity (LTPA) and C-reactive protein (CRP) concentrations in men and women with and without impaired glucose tolerance (IGT). Methods: In a cross-sectional study, a random sample (n = 2,816) was examined with an oral glucose tolerance test, CRP and information about LTPA. Those with IGT or normal glucose tolerance (NGT) and CRP value <= 10 mg/L were selected (n = 2,367) for the study. Results: An inverse association between LTPA and CRP concentrations was observed in the population (P < .001), though, only in men with IGT (P = .023) and in women with NGT. Men with IGT, reporting slight physical activity up to 4 hours a week presented significantly higher CRP concentrations than normoglycemic men (Delta 0.6 mg/L, P = .004). However, this difference could not be found in men with IGT reporting more intense physical activity (Delta 0.01 mg/L, P = .944). Conclusions: Physical inactivity seems to have greater inflammatory consequences for men (vs. women) with IGT. More importantly, although 4 hours of physical activity per week is more than the usual minimum recommendation, an even greater intensity of LTPA appears to be required to limit subclinical inflammation in men with IGT.
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| 18. |
- Hellgren, Margareta, 1955, et al.
(författare)
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Insulin resistance predicts early cardiovascular morbidity in men without diabetes mellitus, with effect modification by physical activity
- 2015
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 22:7, s. 940-949
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Tidskriftsartikel (refereegranskat)abstract
- Aim: to assess how well insulin resistance predicts cardiovascular disease (CVD) in non-diabetic men and women and to explore the influence of physical activity. Methods: in this prospective study 2563 men and women without diabetes were examined with an oral glucose tolerance test, anthropometric measurements and blood pressure assessment. Questionnaires about lifestyle and physical activity were completed. Insulin resistance was estimated by fasting concentrations of plasma insulin and by HOMA index for insulin resistance. Participants were followed up for cardiovascular morbidity and mortality during an 8-year period, using information from the National Swedish Inpatient and Mortality registers. Results: at follow-up, HOMAir predicted CVD morbidity in males (50 events) and females (28 events) combined (HRage/sex-adj 1.4, 95% CI 1.1-1.7); however, when stratified by gender HOMAir was predictive solely in men (HRage-adj 1.8, 95% CI 1.3-2.4), whereas no association was found in women (HRage-adj 1.1, 95% CI 0.8-1.5). When stratifying the data for high and low physical activity, the predictive value of insulin resistance became stronger in sedentary men (HRage-adj 2.3, 95% CI 1.5-3.4) but was abolished in men performing moderate to vigorous physical activity (HRage-adj 1.0, 95% CI 0.6-1.6). The results remained when step-wise adjusted also for BMI, ApoB/ApoA1 and hypertension, as well as for smoking, alcohol consumption and education. Outcome for fasting plasma insulin was similar to HOMAir. Conclusions: insulin resistance predicts CVD in the general population; however, men may be more vulnerable to increased insulin resistance than women, and physically inactive men seem to be at high risk.
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| 19. |
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| 20. |
- Jansson, Per-Anders, 1961, et al.
(författare)
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Probiotic treatment using a mix of three Lactobacillus strains for lumbar spine bone loss in postmenopausal women: a randomised, double-blind, placebo-controlled, multicentre trial
- 2019
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Ingår i: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 1:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Postmenopausal bone loss in the spine is associated with an increased risk of vertebral fractures. Certain probiotic treatment protects rodents from ovariectomy-induced bone loss. The aim of the present study was to determine if treatment with a combination of three bacterial strains protects against the rapid spine bone loss occurring in healthy early postmenopausal women. Methods This randomised, double-blind, placebo-controlled, multicentre trial was done at four study centres in Sweden. Early postmenopausal women were randomly assigned in a 1:1 ratio to receive probiotic treatment consisting of three Lactobacillus strains (Lactobacillus paracasei DSM 13434, Lactobacillus plantarum DSM 15312, and Lactobacillus plantarum DSM 15313; 1 x 10(10 )colony-forming units per capsule) or placebo once daily for 12 months. The primary outcome was the percentage change from baseline in lumbar spine bone mineral density (LS-BMD) at 12 months. The primary analysis was done in all participants with BMD measurements available both at baseline and at 12 months. Analyses of adverse events and safety included all participants who had taken at least one capsule of placebo or Lactobacillus. This trial is registered with ClinicalTrials.gov, NCT02722980, and is completed. Findings Between April 18 and Nov 11,2016,249 participants were randomly assigned to receive probiotic product or placebo, and 234 (94%) completed the analyses required for the primary outcome. Lactobacillus treatment reduced the LS-BMD loss compared with placebo (mean difference 0.71%, 95% CI 0.06 to 1.35). The LS-BMD loss was significant in the placebo group (-0.72%, -1.22 to -0.22), whereas no bone loss was observed in the Lactobacillus-treated group (-0.01%, -0.50 to 0.48). The adverse events were similar between the two groups. Interpretation Probiotic treatment using a mix of three Lactobacillus strains protects against lumbar spine bone loss in healthy postmenopausal women. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 21. |
- Jarfors, Anders, 1963-, et al.
(författare)
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Influence of process parameters on surface appearance and roughness of a low Si containing Al-alloy, in semisolid casting
- 2015
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Ingår i: Solid State Phenomena. - Switzerland : Trans Tech Publications Inc.. - 1012-0394 .- 1662-9779. ; 217-218, s. 318-324
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Tidskriftsartikel (refereegranskat)abstract
- The visual appearance and surface roughness were experimentally investigated inindustrial scale for a low silicon containing aluminium alloy cast in semisolid state integrated withHPDC machine. A visual comparative technique and surface roughness in the form of the Rq valuewere used to evaluate the surface appearance and the surface roughness respectively. The resultswere investigated statistically to find significant models. It was shown that high quality appearance,following a comparative scale, was possible using high die temperature and high injection speed. Itwas also found that improving the surface roughness will deteriorate the visual appearance.
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| 22. |
- Mobini, Reza, 1965, et al.
(författare)
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Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial
- 2017
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 19:4, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy. Materials and methods: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (10(8) CFU/d) or high dose (10(10) CFU/d) of L. reuteri DSM 17938 for 12 weeks. The primary endpoint was the effect of supplementation on glycated haemoglobin (HbA1c). Secondary endpoints were insulin sensitivity (assessed by glucose clamp), liver fat content, body composition, body fat distribution, faecal microbiota composition and serum bile acids. Results: Supplementation with L. reuteri DSM 17938 for 12 weeks did not affect HbA1c, liver steatosis, adiposity or microbiota composition. Participants who received the highest dose of L. reuteri exhibited increases in insulin sensitivity index (ISI) and serum levels of the secondary bile acid deoxycholic acid (DCA) compared with baseline, but these differences were not significant in the between-group analyses. Post hoc analysis showed that participants who responded with increased ISI after L. reuteri supplementation had higher microbial diversity at baseline, and increased serum levels of DCA after supplementation. In addition, increases in DCA levels correlated with improvement in insulin sensitivity in the probiotic recipients. Conclusions: Intake of L. reuteri DSM 17938 for 12 weeks did not affect HbA1c in people with type 2 diabetes on insulin therapy; however, L. reuteri improved insulin sensitivity in a subset of participants and we propose that high diversity of the gut microbiota at baseline may be important.
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| 23. |
- Olausson, Josefin, 1983, et al.
(författare)
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Endothelin-1 as a predictor of impaired glucose tolerance and type 2 diabetes - A longitudinal study in the Vara-Skovde Cohort
- 2016
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 113, s. 33-37
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Tidskriftsartikel (refereegranskat)abstract
- We addressed whether endothelin-1, a marker of endothelial dysfunction, predicts impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in a population study in south-western Sweden. Follow-up after 9.7 years showed an association between circulating endothelin-1 levels at baseline and development of IGT/T2DM in women but not in men.
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| 24. |
- Oscarsson, Jan, et al.
(författare)
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Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease : A double-blind, randomized, placebo-controlled study
- 2018
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 12:6, s. 1390-1403
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. OBJECTIVE: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. METHODS: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. RESULTS: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs 3%, P = .04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P < .001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. CONCLUSIONS: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.
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| 25. |
- Rönn, Tina, et al.
(författare)
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Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:13, s. 3792-3813
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Tidskriftsartikel (refereegranskat)abstract
- Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed DNA methylation of ∼480,000 sites in human adipose tissue from 96 males and 94 females, and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1,050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of ageing in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2,825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with methylation of 711 sites, annotated to e.g. RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for metabolic diseases and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.
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| 26. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 27. |
- Zhang, Wenxin, et al.
(författare)
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Model-data fusion to assess year-round CO2 fluxes for an arctic heath ecosystem in West Greenland (69°N)
- 2019
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 1873-2240 .- 0168-1923. ; 272-273, s. 176-186
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying net CO2 exchange (NEE) of arctic terrestrial ecosystems in response to changes in climatic and environmental conditions is central to understanding ecosystem functioning and assessing potential feedbacks of the carbon cycle to future climate changes. However, annual CO2 budgets for arctic tundra are rare due to the difficulties of performing measurements during non-growing seasons. It is still unclear to what extent arctic tundra ecosystems currently act as a CO2 source, sink or are in balance. This study presents year-round eddy-covariance (EC) measurements of CO2 fluxes for an arctic heath ecosystem on Disko Island, West Greenland (69 °N) over five years. Based on a fusion of year-round EC-derived CO2 fluxes, soil temperature and moisture, the process-oriented model (CoupModel) has been constrained to quantify an annual budget and characterize seasonal patterns of CO2 fluxes. The results show that total photosynthesis corresponds to -202 ± 20 g C m−2 yr-1 with ecosystem respiration of 167 ± 28 g C m-2 yr-1, resulting in NEE of -35 ± 15 g C m-2 yr-1. The respiration loss is mainly described as decomposition of near-surface litter. A year with an anomalously deep snowpack shows a threefold increase in the rate of ecosystem respiration compared to other years. Due to the high CO2 emissions during that winter, the annual budget results in a marked reduction in the CO2 sink. The seasonal patterns of photosynthesis and soil respiration were described using response functions of the forcing atmosphere and soil conditions. Snow depth, topography-related soil moisture, and growing season warmth are identified as important environmental characteristics which most influence seasonal rates of gas exchange.
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