| 1. |
- Fridén, Michael, et al.
(author)
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Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease
- 2022
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In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
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Journal article (peer-reviewed)abstract
- Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited. Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions. Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis. Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.
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| 2. |
- Sennefelt Nyman, Sofi, et al.
(author)
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Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study : idarubicin dose selection, tissue response and survival
- 2022
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:11
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance.METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival.ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden.TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31.
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| 3. |
- Ahlström, Petter, et al.
(author)
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Why space is not enough : Service innovation and service delivery in senior housing
- 2022. - 1
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In: Management and Information Technology after Digital Transformation. - Abingdon and New York : Routledge. - 9780367612764 - 9780367628789 - 9781003111245 ; , s. 72-80
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Book chapter (peer-reviewed)abstract
- This chapter discusses senior housing to support the well-being of older individuals through the provision of physical and social resources. The authors show how digital services contribute to these developments by increasing the resources available and the capacity of older people to integrate resources and take advantage of the value-creating opportunities offered by senior housing solutions. They point out that senior users play a crucial role as active co-creators of their own well-being and contributors to both service innovation and service delivery. As digital services become essential for how older people manage their daily lives, they need to be more integrated in the physical spaces where the actions and memories that shape the lives of seniors take place. Digital services have the potential to both create and deliver new services that will enhance these experiences, which makes their integration with the physical space an important and inseparable component of service innovation and delivery in the context of senior housing.
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| 4. |
- Alsaqal, Salem, et al.
(author)
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The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.
- 2022
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In: Journal of Magnetic Resonance Imaging. - : John Wiley & Sons. - 1053-1807 .- 1522-2586. ; 56:2, s. -379
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL.PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability.STUDY TYPE: Prospective.SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability.FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence).ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified.STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05.RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively.DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH.LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
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| 5. |
- Bergström, Göran, 1964, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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In: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
-
Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 6. |
- Bergström, Göran, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
-
Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 7. |
- Fridén, Michael, et al.
(author)
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Associations between fatty acid composition in serum cholesteryl esters and liver fat, basal fat oxidation, and resting energy expenditure : a population-based study
- 2021
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In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 114:5, s. 1743-1751
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Journal article (peer-reviewed)abstract
- BACKGROUND: We have repeatedly shown in short-term feeding trials that a high intake of dietary n-6 PUFAs, i.e. linoleic acid, prevents liver fat accumulation compared with saturated fat. However, population-based data is lacking and the mechanisms behind such effects are unclear.OBJECTIVE: To investigate associations between serum cholesteryl ester (CE) fatty acids and liver fat, basal fat oxidation [respiratory quotient (RQ)], and resting energy expenditure (REE). We hypothesized that PUFA in particular is inversely associated with liver fat and that such a relation is partly explained by a PUFA-induced increase in basal fat oxidation or REE.METHODS: Cross-sectional analyses using linear regression models in a population-based cohort with data on serum CE fatty acid composition and liver fat (n = 308).RESULTS: Linoleic acid (18:2n-6) (β = -0.03, 95% CI: -0.06, -0.001) and Δ5 desaturase index were inversely associated, whereas, γ-linolenic acid (18:3n-6) (β = 0.59, 95% CI: 0.28, 0.90), dihomo-γ-linolenic acid (20:3n-6) (β = 1.20, 95% CI: 0.65, 1.75), arachidonic acid (20:4n-6) (β = 0.08, 95% CI: 0.002, 0.16), palmitoleic acid (16:1n-7) (β = 0.37, 95% CI: 0.04, 0.70), Δ6 desaturase, and stearoyl CoA desaturase-1 (SCD-1) index were directly associated with liver fat after adjustment for confounders. Several serum CE fatty acids were correlated with both liver fat and REE, but only the association between DHA (22:6n-3) and liver fat was clearly attenuated after adjustment for REE (from β = -0.63 95% CI: -1.24, -0.02 to β = -0.34, 95% CI: -0.95, 0.27). Palmitoleic acid and SCD-1 were weakly inversely correlated with RQ but could not explain a lower liver fat content.CONCLUSIONS: Several serum CE fatty acids are associated with liver fat, among them linoleic acid. Although we identified novel associations between individual fatty acids and RQ and REE, our findings imply that PUFAs might prevent liver fat accumulation through mechanisms other than enhanced whole-body energy metabolism.
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| 8. |
- Fridén, Michael, et al.
(author)
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Intake of Ultra-Processed Food and Ectopic-, Visceral- and Other Fat Depots : A Cross-Sectional Study.
- 2022
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In: Frontiers in nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
-
Journal article (peer-reviewed)abstract
- Introduction: The purpose of this study was to investigate associations between intake of ultra-processed food (UPF) and liver fat, pancreas fat and visceral adipose tissue (VAT) but also subcutaneous adipose tissue (SAT), VAT/SAT ratio and total fat mass.Materials and Methods: Cross-sectional analysis of n = 286 50-year old men and women. Energy percentage (%E) from UPF was calculated from a semi-quantitative food frequency questionnaire. Food items were categorized according to the NOVA-classification system and fat depots were assessed using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA). Associations were analyzed using linear regression, adjusted for sex, education, physical activity, smoking, dietary factors and BMI.Results: Mean intake of UPF was 37.8 ± 10.2 %E and the three largest contributors to this were crisp- and wholegrain breads and spreads, indicating overall healthy food choices. Consumption of UPF was associated with higher intake of energy, carbohydrates and fiber and lower intake of protein and polyunsaturated fat but no differences were observed for total fat, saturated fat (SFA), monounsaturated fat, sugar or alcohol between tertiles of UPF. Intake of UPF was positively associated with liver- and pancreas fat, VAT, VAT/SAT and inversely associated with total fat mass in crude models. The association for VAT remained after full adjustment (β = 0.01 (95% CI: 0.002, 0.02), P = 0.02) and was driven by women.Conclusion: Energy intake from UPF is not associated with ectopic fat, SAT or total fat after adjustment for multiple confounders in this population having overall healthy food habits. However, a positive association between UPF and VAT was observed which was driven by women.
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| 9. |
- Juhl, Carsten B., et al.
(author)
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TNF-alpha inhibitors for juvenile idiopathic arthritis
- 2020
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In: Cochrane Database of Systematic Reviews. - 1361-6137. ; 2020:8
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Research review (peer-reviewed)abstract
- Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and harms of TNFi in patients with JIA.
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| 10. |
- Langner, Taro, et al.
(author)
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Uncertainty-Aware Body Composition Analysis with Deep Regression Ensembles on UK Biobank MRI
- 2021
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In: Computerized Medical Imaging and Graphics. - : Elsevier BV. - 0895-6111 .- 1879-0771. ; 93
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Journal article (peer-reviewed)abstract
- Along with rich health-related metadata, an ongoing imaging study has acquired MRI of over 40,000 male and female UK Biobank participants aged 44-82 since 2014. Phenotypes derived from these images, such as measurements of body composition, can reveal new links between genetics, cardiovascular disease, and metabolic conditions. In this retrospective study, six measurements of body composition were automatically estimated by ResNet50 neural networks for image-based regression from neck-to-knee body MRI. Despite the potential for high speed and accuracy, these networks produce no output segmentations that could indicate the reliability of individual measurements. The presented experiments therefore examine mean-variance regression and ensembling for predictive uncertainty estimation, which can quantify individual measurement errors and thereby help to identify potential outliers, anomalies, and other failure cases automatically. In 10-fold cross-validation on data of about 8,500 subjects, mean-variance regression and ensembling showed complementary benefits, reducing the mean absolute error across all predictions by 12%. Both improved the calibration of uncertainties and their ability to identify high prediction errors. With intra-class correlation coefficients (ICC) above 0.97, all targets except the liver fat content yielded relative measurement errors below 5%. Testing on another 1,000 subjects showed consistent performance, and the method was finally deployed for inference to 30,000 subjects with missing reference values. The results indicate that deep regression ensembles could ultimately provide automated, uncertainty-aware measurements of body composition for more than 120,000 UK Biobank neck-to-knee body MRI that are to be acquired within the coming years.
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| 11. |
- Lind, Lars, et al.
(author)
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Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
- 2022
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In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
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Journal article (peer-reviewed)abstract
- Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
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| 12. |
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| 13. |
- Nilsson, Daniel, 1982-
(author)
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A ΔJ approach for nonlinear fatigue crack propagation : Experimental and numerical investigation of a ductile superalloy
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- This dissertation is a product of an academic-industrial collaboration between the Division of Solid Mechanics at Linköping University and Siemens Energy AB. The focus is on enhancing the design optimisation procedures for high-temperature components in industrial gas turbines (IGT). The research is centred around the behaviour of the nickelbased high-temperature superalloy Haynes 230 under service-like conditions with predominant thermal loads. The aim is to improve fatigue crack propagation life predictions for nonlinear conditions.The research findings validate the thermal ageing fatigue effects on Haynes 230 as seen in existing literature, especially on constitutive properties and crack initiation. Additionally, it was observed that thermal ageing has a minor effect on the crack growth rate up to 600 °C, which can be managed by updating the crack driving force with thermally aged properties.The project mainly focused on nonlinear crack propagation at isothermal and thermomechanical fatigue conditions. A new method for crack length description, using a modified compliance method, is introduced. This method simplifies and enhances the accuracy of crack length measurements and has become an established method for evaluating the single edge notch specimen used in the project under thermo-mechanical fatigue conditions.The nonlinear fatigue parameter ΔJ was incorporated into both Finite element method (FEM) computations and test evaluations, revealing linear trends with crack growth rates in loglog. The research highlights the crucial role of crack opening in establishing a correlation between ΔJ and crack growth rate. It was also concluded that the linear fatigue fracture parameter ΔK tends to underestimate the crack growth behaviour, resulting in non-conservative outcomes if the elasto-plastic stresses from the tests are considered.Lastly, a constitutive description of Haynes 230, based on the Ohno-Wang theory, under negligible viscoplastic effects, and an extension of the cycle jumping procedure that takes into account the significant hardening between the initial and midlife stages of the material, is presented. By this the notched geometry in 3D could be simulated with satisfying accuracy.
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| 14. |
- Omran, Meis, et al.
(author)
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Whole-Body MRI Surveillance : Baseline Findings in the Swedish Multicentre Hereditary TP53-Related Cancer Syndrome Study (SWEP53)
- 2022
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In: Cancers. - : MDPI. - 2072-6694. ; 14:2
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Journal article (peer-reviewed)abstract
- A surveillance strategy of the heritable TP53-related cancer syndrome (hTP53rc), commonly referred to as the Li–Fraumeni syndrome (LFS), is studied in a prospective observational nationwide multi-centre study in Sweden (SWEP53). The aim of this sub-study is to evaluate whole-body MRI (WB-MRI) regarding the rate of malignant, indeterminate, and benign imaging findings and the associated further workup generated by the baseline examination. Individuals with hTP53rc were enrolled in a surveillance program including annual whole-body MRI (WB-MRI), brain-MRI, and in female carriers, dedicated breast MRI. A total of 68 adults ≥18 years old have been enrolled to date. Of these, 61 fulfilled the inclusion criteria for the baseline MRI scan. In total, 42 showed a normal scan, while 19 (31%) needed further workup, of whom three individuals (3/19 = 16%) were diagnosed with asymptomatic malignant tumours (thyroid cancer, disseminated upper GI cancer, and liver metastasis from a previous breast cancer). Forty-three participants were women, of whom 21 had performed risk-reducing mastectomy prior to inclusion. The remaining were monitored with breast MRI, and no breast tumours were detected on baseline MRI. WB-MRI has the potential to identify asymptomatic tumours in individuals with hTP53rc syndrome. The challenge is to adequately and efficiently investigate all indeterminate findings. Thus, a multidisciplinary team should be considered in surveillance programs for individuals with hTP53rc syndrome.
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| 15. |
- Rosqvist, Fredrik, 1985-, et al.
(author)
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Abdominal Fat and Metabolic Health Markers but Not PNPLA3 Genotype Predicts Liver Fat Accumulation in Response to Excess Intake of Energy and Saturated Fat in Healthy Individuals
- 2020
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In: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7
-
Journal article (peer-reviewed)abstract
- Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA.Objective: To identify predictors of liver fat accumulation in response to an increased intake of SFA.Design: We pooled our two previously conducted double-blind randomized trials (LIPOGAIN and LIPOGAIN-2, clinicaltrials.gov NCT01427140 and NCT02211612) and used data from the n = 49 metabolically healthy men (n = 32) and women (n = 17) randomized to a hypercaloric diet through addition of SFA-rich muffins for 7-8 weeks. Associations between clinical and metabolic variables at baseline and changes in liver fat during the intervention were analyzed using Spearman rank correlation. Linear regression was used to generate a prediction model.Results: Liver fat increased by 33% (IQR 5.4-82.7%; P < 0.0001) in response to excess energy intake and this was not associated (r = 0.17, P = 0.23) with the increase in body weight (1.9 kg; IQR 1.1-2.9 kg). Liver fat accumulation was similar (P = 0.28) in carriers (33%, IQR 14-79%) and non-carriers (33%, IQR -11 to +87%) of the PNPLA3-I148M variant. Baseline visceral and liver fat content, as well as levels of the liver enzyme gamma-glutamyl transferase (GT), were the strongest positive predictors of liver fat accumulation-in contrast, adiponectin and the fatty acid 17:0 in adipose tissue were the only negative predictors in univariate analyses. A regression model based on eight clinical and metabolic variables could explain 81% of the variation in liver fat accumulation.Conclusion: Our results suggest there exists a highly inter-individual variation in the accumulation of liver fat in metabolically healthy men and women, in response to an increased energy intake from SFA and carbohydrates that occurs over circa 2 months. This marked variability in liver fat accumulation could largely be predicted by a set of clinical (e.g., GT and BMI) and metabolic (e.g., fatty acids, HOMA-IR, and adiponectin) variables assessed at baseline.
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| 16. |
- Rosqvist, Fredrik, 1985-, et al.
(author)
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Overfeeding polyunsaturated fat compared to saturated fat does not differentially influence lean tissue accumulation in overweight individuals : a randomized controlled trial
- 2024
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In: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 120:1, s. 121-128
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Journal article (peer-reviewed)abstract
- BACKGROUND: Fatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding polyunsaturated fat (PUFA) compared with saturated fat (SFA) induced greater lean tissue accumulation despite similar weight gain.OBJECTIVE: In a double-blind randomized controlled trial (RCT), we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight, and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA levels with lean tissue volume, in a large population-based sample (UK Biobank).METHODS: Sixty-one males and females with overweight (BMI 27.3 (interquartile range 25.4 to 29.3), age 43 (interquartile range 36 to 48)) were overfed SFA (palm oil) or n-6 PUFA (sunflower oil) for 8 weeks. Lean tissue was assessed by magnetic resonance imaging (MRI). We had access to n=13849 participants with data on diet, covariates and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids, in the UK Biobank.RESULTS: Body weight gain (mean±SD) was similar in PUFA (2.01±1.90 kg) and SFA (2.31±1.38 kg) groups. Lean tissue increased to a similar extent (0.54±0.93 L and 0.67±1.21 L for PUFA and SFA group, respectively, with a difference between groups of 0.07 (-0,21, 0,35)). We observed no differential effects on circulating amino acids, myostatin or interleukin-15 and no clear determinants of lean tissue accumulation. Similar non-significant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations.CONCLUSION: Overfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 weeks in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a large population-based cohort consuming their habitual diet.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02211612.
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