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Sökning: WFRF:(Ekstedt E.)

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21.
  • Franzén, Lennart E, et al. (författare)
  • Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies : a comparison to stereological point counting.
  • 2005
  • Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 18:7, s. 912-916
  • Tidskriftsartikel (refereegranskat)abstract
    • The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the histopathologist uses a four-graded scale: 0-3 or none, slight, moderate and severe. Scores 1-3 are considered to correspond to fat deposition in <33, 33-66 and >66% of the hepatocytes. There is a considerable inter- and intra-individual variation in such scoring methods and a more standardized and quantitative approach is preferable. In the present study, we compare the semiquantitative technique with the stereological point counting method in the assessment of hepatic steatosis. A total of 75 archived liver needle biopsies were used. They were selected according to the original routine diagnosis of slight, moderate or severe steatosis. In all, 10 randomly selected images from each biopsy were digitized into a computer, a point grid lattice was superimposed and the number of hits on fat globules was counted. A pathologist scored the specimens in a four-graded scale as described above. The mean liver biopsy area (volume) with fat in hepatocytes was 2.2% for grade 1, 9.2% for grade 2 and 23.1% for grade 3. The kappa value for the semiquantitative estimates was 0.71 for the unweigthed kappa and 0.87 for weighted kappa. The intraclass correlation coefficient (ICC) was 0.99 for images counted twice and 0.95 when two sets of images were captured from the same biopsy. These ICCs indicate excellent agreement and above that of the semiquantitative estimates. In conclusion, the area/volume of fat content of the hepatocytes is greatly overemphasized in semiquantitative estimation. Furthermore, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis in scientific studies and in clinical contexts when the amount of steatosis is important for treatment and prognosis, such as liver transplantation.
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22.
  • Hagstrom, Hannes, et al. (författare)
  • Serum levels of endotrophin are associated with nonalcoholic steatohepatitis
  • 2021
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:4, s. 437-442
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aimsThere are no currently available biomarkers that can accurately indicate the presence of non-alcoholic steatohepatitis (NASH). We investigated the association between endotrophin, a cleavage product of collagen type 6α3, and disease severity in patients with non-alcoholic fatty liver disease (NAFLD).MethodsWe measured serum endotrophin levels in 211 patients with NAFLD and nine healthy controls. Liver biopsy data was available for 141 (67%) of the patients. Associations between endotrophin and the presence of NASH and advanced fibrosis were investigated alone and in combination with standard clinical parameters using logistic regression.ResultsA total of 211 patients were enrolled in this study, consisting of 108 (51%) men and 103 (49%) women with a mean age of 55.6 years. 58 (27%) of the patients had advanced fibrosis. Of those with biopsy data, 87 (62%) had NASH. Serum levels of endotrophin were significantly higher in patients with NAFLD than those in healthy controls (37[±12] vs. 17[±7] ng/mL, p<.001). Serum levels of endotrophin were also significantly higher in patients with NASH than in those without NASH (40[±12] vs. 32[±13] ng/mL, p<.001). A model using age, sex, body mass index and levels of alanine aminotransferase (ALT), glucose and endotrophin effectively predicted the presence of NASH in a derivation (AUROC 0.83, 95%CI = 0.74–0.92) and validation cohort (AUROC 0.71, 95%CI = 0.54–0.88). There was no significant association between serum levels of endotrophin and advanced fibrosis.ConclusionsThese data suggest that serum endotrophin could be a valuable biomarker for diagnosing NASH, but not for detecting advanced fibrosis in NAFLD.
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24.
  • Lazarus, J.V., et al. (författare)
  • A cross-sectional study of the public health response to non-alcoholic fatty liver disease in Europe
  • 2020
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 72:1, s. 14-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & AimsNon-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and has become an important field of biomedical inquiry. We aimed to determine whether European countries have mounted an adequate public health response to NAFLD and non-alcoholic steatohepatitis (NASH).MethodsIn 2018 and 2019, NAFLD experts in 29 European countries completed an English-language survey on policies, guidelines, awareness, monitoring, diagnosis and clinical assessment in their country. The data were compiled, quality checked against existing official documents and reported descriptively.ResultsNone of the 29 participating countries had written strategies or action plans for NAFLD. Two countries (7%) had mentions of NAFLD or NASH in related existing strategies (obesity and alcohol). Ten (34%) reported having national clinical guidelines specifically addressing NAFLD and, upon diagnosis, all included recommendations for the assessment of diabetes and liver cirrhosis. Eleven countries (38%) recommended screening for NAFLD in all patients with either diabetes, obesity and/or metabolic syndrome. Five countries (17%) had referral algorithms for follow-up and specialist referral in primary care, and 7 (24%) reported structured lifestyle programmes aimed at NAFLD. Seven (24%) had funded awareness campaigns that specifically included prevention of liver disease. Four countries (14%) reported having civil society groups which address NAFLD and 3 countries (10%) had national registries that include NAFLD.ConclusionsWe found that a comprehensive public health response to NAFLD is lacking in the surveyed European countries. This includes policy in the form of a strategy, clinical guidelines, awareness campaigns, civil society involvement, and health systems organisation, including registries.Lay summaryWe conducted a survey on non-alcoholic fatty liver disease with experts in European countries, coupled with data extracted from official documents on policies, clinical guidelines, awareness, and monitoring. We found a general lack of national policies, awareness campaigns and civil society involvement, and few epidemiological registries.
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25.
  • Levandowski, Christoffer E, 1984, et al. (författare)
  • PLM Architecture for Optimization of Geometrical Interfaces in a Product Platform
  • 2011
  • Ingår i: Proceedings of the ASME 2011; International Design Engineering Technical Conferences & Computers and Information in Engineering Conference (Volume 2: 31st Computers and Information in Engineering Conference, Parts A and B ). - 9780791854792 ; :Paper no. DETC2011-47801, s. 1237-1244
  • Konferensbidrag (refereegranskat)abstract
    • Product platforms can be used as an enabler for offering a wide variety of products to the market, while keeping the development cost down. Reusing knowledge in new designs is a key concept of product platforms, whether it is about reusing entire parts, or reusing ideas and concepts. The Configurable Component (CC) concept is one way of describing a product platform, and is based on autonomous subsystems that are not fixed, but have a bandwidth within which they can vary. These systems are configured to fit the set of requirements resulting in product variants. Product Lifecycle Management (PLM) as a complementing business strategy deals with integrating processes, information, systems and people across the product lifecycle to support the development of complex products.This paper describes a case study where the CC concept is successfully implemented in a PLM environment to allow configuration of the systems in relation to each other. The focal point of this paper is configuration of the geometrical interfaces between sub systems. A car door from a Swedish car manufacturer, known for the tight fit in assembly, is used as an example. In this case, there are two requirements on the assembly. First, the assembly cannot be far from nominal, thus requiring robust interfaces between the ingoing parts. Second, the window must be mountable. The result is a PLM architecture with a Product Data Management (PDM) system, a Computer Aided Design (CAD) tool, two Computer Aided Engineering (CAE) tools and a configurator, all integrated.
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26.
  • Maaninen-Olsson, Eva, et al. (författare)
  • Knowledge renewal in project processes
  • 2006
  • Ingår i: Paper presented at the International Research Network on Organizing by Projects, October 11-13, 2006, Xi’an, China..
  • Konferensbidrag (populärvet., debatt m.m.)
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27.
  • Musso, G., et al. (författare)
  • Association of non-alcoholic fatty liver disease with chronic kidney disease : a systematic review and meta-analysis
  • 2014
  • Ingår i: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 11:7, s. e1001680-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.Methods and Findings:English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) andlt;60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.Conclusion:The presence and severity of NAFLD are associated with an increased risk and severity of CKD.Please see later in the article for the Editors Summary. © 2014 Musso et al.
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28.
  • Pavlides, Michael, et al. (författare)
  • Liver investigation: Testing marker utility in steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol
  • 2023
  • Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 134
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721
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30.
  • Xin, Zhao, et al. (författare)
  • A framework for optimization of hybrid aircraft
  • 2019
  • Ingår i: Proceedings of the ASME Turbo Expo. - : American Society of Mechanical Engineers (ASME). - 9780791858608 ; 3
  • Konferensbidrag (refereegranskat)abstract
    • To achieve the goals of substantial improvements in efficiency and emissions set by Flightpath 2050, fundamentally different concepts are required. As one of the most promising solutions, electrification of the aircraft primary propulsion is currently a prime focus of research and development. Unconventional propulsion sub-systems, mainly the electrical power system, associated thermal management system and transmission system, provide a variety of options for integration in the existing propulsion systems. Different combinations of the gas turbine and the unconventional propulsion sub-systems introduce different configurations and operation control strategies. The trade-off between the use of the two energy sources, jet fuel and electrical energy, is primarily a result of the trade-offs between efficiencies and sizing characteristics of these sub-systems. The aircraft structure and performance are the final carrier of these trade-offs. Hence, full design space exploration of various hybrid derivatives requires global investigation of the entire aircraft considering these key propulsion sub-systems and the aircraft structure and performance, as well as their interactions. This paper presents a recent contribution of the development for a physics-based simulation and optimization platform for hybrid electric aircraft conceptual design. Modeling of each subsystem and the aircraft structure are described as well as the aircraft performance modeling and integration technique. With a focus on the key propulsion sub-systems, aircraft structure and performance that interfaces with existing conceptual design frameworks, this platform aims at full design space exploration of various hybrid concepts at a low TRL level.
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