| 1. |
- Chu, Audrey Y, et al.
(författare)
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Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:1, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10(-8); false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.
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| 3. |
- Kullberg, R. F. J., et al.
(författare)
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Gut microbiota of adults with asthma is broadly similar to non-asthmatics in a large population with varied ethnic origins
- 2021
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Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial gut communities might predispose children to develop asthma. Yet, little is known about the role of these micro-organisms in adult asthmatics. We aimed to profile the relationship between fecal microbiota and asthma in a large-scale, ethnically diverse, observational cohort of adults. Fecal microbiota composition of 1632 adults (172 asthmatics and 1460 non-asthmatics) was analyzed using 16S ribosomal RNA gene sequencing. Using extremely randomized trees machine learning models, we assessed the discriminatory ability of gut bacterial features to identify asthmatics from non-asthmatics. Asthma contributed 0.019% to interindividual dissimilarities in intestinal microbiota composition, which was not significant (P = .97). Asthmatics could not be distinguished from non-asthmatics based on individual microbiota composition by an extremely randomized trees classifier model (area under the receiver operating characteristic curve = 0.54). In conclusion, there were no prominent differences in fecal microbiota composition in adult asthmatics when compared to non-asthmatics in an urban, large-sized and ethnically diverse cohort.
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| 4. |
- Weghuber, D., et al.
(författare)
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A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity
- 2020
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Ingår i: Pediatric Obesity. - 2047-6302 .- 2047-6310. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor agonist could be a treatment option for adolescent obesity.OBJECTIVE: To investigate the effect of exenatide extended release on body mass index (BMI)-SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity.METHODS: Six-month, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n = 44, 10-18 years, females n = 22) with BMI-SDS > 2.0 or age-adapted-BMI > 30 kg/m2 according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended release 2 mg (n = 22) or placebo (n = 22) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention.RESULTS: Exenatide reduced (P < .05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (-2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3 ; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5), and BMI (-0.83 kg/m2 ; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; P = .06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients.CONCLUSIONS: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI reduction for the patient group.
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| 5. |
- Axelsson, Robert, et al.
(författare)
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Evaluation of Multi-level Social Learning for Sustainable Landscapes : Perspective of a Development Initiative in Bergslagen, Sweden
- 2013
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Ingår i: Ambio. - : Springer Netherlands. - 0044-7447 .- 1654-7209. ; 42:2, s. 241-253
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Tidskriftsartikel (refereegranskat)abstract
- To implement policies about sustainable landscapes and rural development necessitates social learning about states and trends of sustainability indicators, norms that define sustainability, and adaptive multi-level governance. We evaluate the extent to which social learning at multiple governance levels for sustainable landscapes occur in 18 local development initiatives in the network of Sustainable Bergslagen in Sweden. We mapped activities over time, and interviewed key actors in the network about social learning. While activities resulted in exchange of experiences and some local solutions, a major challenge was to secure systematic social learning and make new knowledge explicit at multiple levels. None of the development initiatives used a systematic approach to secure social learning, and sustainability assessments were not made systematically. We discuss how social learning can be improved, and how a learning network of development initiatives could be realized.
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| 7. |
- Edholm, David, et al.
(författare)
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Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass
- 2015
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289 .- 1878-7533. ; 11:3, s. 602-606
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is desirable, because it can reduce liver volume and thereby facilitate the procedure. The optimal duration of a low-calorie diet (LCD) has not been established. The objective of this study was to assess changes in liver volume and body composition during 4 weeks of LCD.METHODS:Ten women (aged 43±8.9 years, 114±12.1 kg, and body mass index 42±2.6 kg/m2) were examined on days 0, 3, 7, 14, and 28 after commencing the LCD. At each evaluation, body composition was assessed through bioelectric impedance analysis, and liver volume and intrahepatic fat content were assessed by magnetic resonance imaging. Serum and urine samples were obtained. Questionnaires regarding quality of life and LCD-related symptoms were administered.RESULTS:In total, mean weight decreased by 7.4±1.2 kg (range 5.7-9.1 kg), and 71% of the weight loss consisted of fat mass according to bioelectric impedance analysis. From day 0 to day 3, the weight loss (2.0 kg) consisted mainly of water. Liver volume decreased by 18%±6.2%, from 2.1 to 1.7 liters (P<.01), during the first 2 weeks with no further change thereafter. A continuous 51%±16% decrease was seen in intrahepatic fat content. Systolic blood pressure, insulin, and lipids improved, while liver enzymes, glucose levels, and quality of life were unaffected.CONCLUSION:A significant decrease in liver volume (18%) occurred during the first 2 weeks of LCD treatment, and intrahepatic fat gradually decreased throughout the study period. A preoperative 2-week LCD treatment seems sufficient in similar patients.
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| 9. |
- Edholm, David, et al.
(författare)
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Preoperative 4-week low-calorie diet reduces liver volume and intrahepatic fat, and facilitates laparoscopic gastric bypass in morbidly obese
- 2011
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 21:3, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to explore changes in liver volume and intrahepatic fat in morbidly obese patients during 4 weeks of low-calorie diet (LCD) before surgery and to investigate if these changes would facilitate the following laparoscopic gastric bypass.METHODS: Fifteen female patients (121.3 kg, BMI 42.9) were treated preoperatively in an open study with LCD (800-1,100 kcal/day) during 4 weeks. Liver volume and fat content were assessed by magnetic resonance imaging and spectroscopy before and after the LCD treatment.RESULTS: Liver appearance and the complexity of the surgery were scored at the operation. Eighteen control patients (114.4 kg, BMI 40.8), without LCD were scored similarly. Average weight loss in the LCD group was 7.5 kg, giving a mean weight of 113.9 kg at surgery. Liver volume decreased by 12% (p < 0.001) and intrahepatic fat by 40% (p < 0.001). According to the preoperative scoring, the size of the left liver lobe, sharpness of the liver edge, and exposure of the hiatal region were improved in the LCD group compared to the controls (all p < 0.05).CONCLUSIONS: The overall complexity of the surgery was perceived lower in the LCD group (p < 0.05), due to improved exposure and reduced psychological stress (both p < 0.05). Four weeks of preoperative LCD resulted in a significant decrease in liver volume and intrahepatic fat content, and facilitated the subsequent laparoscopic gastric bypass as scored by the surgeon
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| 22. |
- Shahzad, Rahil, et al.
(författare)
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Automated extraction and labelling of the arterial tree from whole-body MRA data
- 2015
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Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 24:1, s. 28-40
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we present a fully automated algorithm for extraction of the 3D arterial tree and labelling the tree segments from whole-body magnetic resonance angiography (WB-MRA) sequences. The algorithm developed consists of two core parts (i) 3D volume reconstruction from different stations with simultaneous correction of different types of intensity inhomogeneity, and (ii) Extraction of the arterial tree and subsequent labelling of the pruned extracted tree. Extraction of the arterial tree is performed using the probability map of the "contrast" class, which is obtained as one of the results of the inhomogeneity correction scheme. We demonstrate that such approach is more robust than using the difference between the pre- and post-contrast channels traditionally used for this purpose. Labelling the extracted tree is performed by using a combination of graph-based and atlas-based approaches. Validation of our method with respect to the extracted tree was performed on the arterial tree subdivided into 32 segments, 82.4% of which were completely detected, 11.7% partially detected, and 5.9% were missed on a cohort of 35 subjects. With respect to automated labelling accuracy of the 32 segments, various registration strategies were investigated on a training set consisting of 10 scans. Further analysis on the test set consisting of 25 data sets indicates that 69% of the vessel centerline tree in the head and neck region, 80% in the thorax and abdomen region, and 84% in the legs was accurately labelled to the correct vessel segment. These results indicate clinical potential of our approach in enabling fully automated and accurate analysis of the entire arterial tree. This is the first study that not only automatically extracts the WB-MRA arterial tree, but also labels the vessel tree segments.
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| 23. |
- Stenlid, Rasmus, et al.
(författare)
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High DPP-4 concentrations in adolescents are associated with low intact GLP-1
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 103:8, s. 2958-2966
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Tidskriftsartikel (refereegranskat)abstract
- Context: Dipeptidyl Peptidase-4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1) and increased DPP4 levels are associated with obesity and visceral adiposity in adults.Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments.Design: Cross-sectional study, July 2012 to April 2015.Setting: Pediatric obesity clinic, Uppsala University Hospital.Patients and participants: Children and adolescents with obesity (n=59) and lean controls (n=21), age 8-18.Main outcome measures: BMI SDS, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and OGTT concentrations of glucose and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes and liver fat fraction.Results: Plasma DPP-4 decreased with age both in obese (41 ng/ml per year) and lean subjects (48 ng/ml per year). Plasma DPP-4 was higher in males both in the obesity and lean group. When adjusting for age and sex, plasma DPP-4 was negatively associated with intact GLP-1 at fasting, B=-12.3, 95% CI [-22.9, -1.8] and during OGTT, B=-12.1, 95% CI [-22.5, -1.7]. No associations were found between DPP-4 and plasma glucose measured at fasting or after a 2-hour OGTT. Plasma DPP-4 was 19% higher in the obese subjects. Among adipose tissue compartments the strongest association was with VAT, B=0.05, 95% CI [-0.02, 0.12].Conclusions: In adolescents, high plasma DPP-4 concentrations are associated with low proportion of intact GLP-1, high BMI, young age and male sex. The observed associations are compatible with an increased metabolism of GLP-1 in childhood obesity.
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| 24. |
- Ulker-Kaustell, Mahir, et al.
(författare)
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Modelling of Pot Bearings - A Preliminary Study
- 2018
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Ingår i: EXPERIMENTAL VIBRATION ANALYSIS FOR CIVIL STRUCTURES. - Cham : SPRINGER INTERNATIONAL PUBLISHING AG. - 9783319674438 - 9783319674421 ; , s. 343-353
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Konferensbidrag (refereegranskat)abstract
- Previous research indicates that roller and pot bearings may give rise to considerable non-linear effects in certain bridges. These effects appear as variations in natural frequency, mode shape and modal damping ratio, depending on the amplitude of vibration. At small amplitudes of vibration, it seems reasonable to assume that the rolling or sliding mechanism is inactive, thus yielding a stiffer structure and no additional dissipation of energy due to friction. At slightly larger amplitudes of vibration, although still remaining small with respect to geometrical non-linearity, the rolling or sliding mechanism activates, whereby the corresponding constraints are relieved. At the same time, because of the rolling or sliding friction, a certain amount of energy dissipates to the surroundings. In order to improve our understanding of these mechanisms and their practical implications, a preliminary experimental study has been performed with the aim of developing a simple model of these mechanisms, which can be included in theoretical models of bridges and other structures. In this paper, we give a short description of the outcome of our laboratory tests and the status of our model development process.
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| 25. |
- Wanhainen, Anders, et al.
(författare)
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The effect of ticagrelor on growth of small abdominal aortic aneurysms-a randomized controlled trial
- 2020
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 116:2, s. 450-456
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs). Methods and results: In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naive patients with AAA and with a maximum aortic diameter 35-49mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P=0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P=0.372). MRI diameter change was 2.5mm vs. 1.8mm (P=0.113), US diameter change 2.3mm vs. 2.2mm (P=0.778), and ILT volume change 12.9% vs. 10.4% (P=0.590). Conclusion: In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor.
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| 26. |
- Woksepp, Hanna, et al.
(författare)
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High target attainment for beta-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied
- 2017
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - Heidelberg : Springer. - 0934-9723 .- 1435-4373. ; 36:3, s. 553-563
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Tidskriftsartikel (refereegranskat)abstract
- Patients in the intensive care unit (ICU) are at risk for suboptimal levels of beta-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum beta-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ae18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT(> MIC)). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m(2). The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, > 77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of beta-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.
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