| 1. |
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| 2. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 3. |
- Eriksson, Olof, et al.
(författare)
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The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
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Tidskriftsartikel (refereegranskat)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
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| 4. |
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| 5. |
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| 6. |
- Ahlqvist, Emma, et al.
(författare)
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A common variant upstream of the PAX6 gene influences islet function in man.
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Impaired glucose tolerance and impaired insulin secretion have been reported in families with PAX6 mutations and it is suggested that they result from defective proinsulin processing due to lack of prohormone convertase 1/3, encoded by PCSK1. We investigated whether a common PAX6 variant would mimic these findings and explored in detail its effect on islet function in man. METHODS: A PAX6 candidate single nucleotide polymorphism (rs685428) was associated with fasting insulin levels in the Diabetes Genetics Initiative genome-wide association study. We explored its potential association with glucose tolerance and insulin processing and secretion in three Scandinavian cohorts (N = 8,897 individuals). In addition, insulin secretion and the expression of PAX6 and transcriptional target genes were studied in human pancreatic islets. RESULTS: rs685428 G allele carriers had lower islet mRNA expression of PAX6 (p = 0.01) and PCSK1 (p = 0.001) than AA homozygotes. The G allele was associated with increased fasting insulin (p (replication) = 0.02, p (all) = 0.0008) and HOMA-insulin resistance (p (replication) = 0.02, p (all) = 0.001) as well as a lower fasting proinsulin/insulin ratio (p (all) = 0.008) and lower fasting glucagon (p = 0.04) and gastric inhibitory peptide (GIP) (p = 0.05) concentrations. Arginine-stimulated (p = 0.02) insulin secretion was reduced in vivo, which was further reflected by a reduction of glucose- and potassium-stimulated insulin secretion (p = 0.002 and p = 0.04, respectively) in human islets in vitro. CONCLUSIONS/INTERPRETATION: A common variant in PAX6 is associated with reduced PAX6 and PCSK1 expression in human islets and reduced insulin response, as well as decreased glucagon and GIP concentrations and decreased insulin sensitivity. These findings emphasise the central role of PAX6 in the regulation of islet function and glucose metabolism in man.
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| 7. |
- Brukas, Vilis, et al.
(författare)
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How Sensitive Are Ecosystem Services in European Forest Landscapes to Silvicultural Treatment?
- 2015
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Ingår i: Forests. - : MDPI AG. - 1999-4907. ; 6, s. 1666-1695
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Tidskriftsartikel (refereegranskat)abstract
- While sustainable forestry in Europe is characterized by the provision of a multitude of forest ecosystem services, there exists no comprehensive study that scrutinizes their sensitivity to forest management on a pan-European scale, so far. We compile scenario runs from regionally tailored forest growth models and Decision Support Systems (DSS) from 20 case studies throughout Europe and analyze whether the ecosystem service provision depends on management intensity and other co-variables, comprising regional affiliation, social environment, and tree species composition. The simulation runs provide information about the case-specifically most important ecosystem services in terms of appropriate indicators. We found a strong positive correlation between management intensity and wood production, but only weak correlation with protective and socioeconomic forest functions. Interestingly, depending on the forest region, we found that biodiversity can react in both ways, positively and negatively, to increased management intensity. Thus, it may be in tradeoff or in synergy with wood production and forest resource maintenance. The covariables species composition and social environment are of punctual interest only, while the affiliation to a certain region often makes an important difference in terms of an ecosystem service's treatment sensitivity.
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| 8. |
- De Marinis, Yang, et al.
(författare)
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Serology assessment of antibody response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test
- 2020
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Ingår i: Infection Ecology and Epidemiology. - : Informa UK Limited. - 2000-8686. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019 (COVID-19) pandemic has created a global health- and economic crisis. Detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection. In this study, we applied a rapid COVID-19 IgM/IgG antibody test and performed serology assessment of antibody response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n = 45), the total antibody detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. The total IgM and IgG detection is 63% in patients with <2 weeks from disease onset; 85% in non-hospitalized patients with >2 weeks disease duration; and 91% in hospitalized patients with >2 weeks disease duration. We also compared different blood sample types and suggest a higher sensitivity by serum/plasma over whole blood. Test specificity was determined to be 97% on 69 sera/plasma samples collected between 2016-2018. Our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody detection patterns in association with disease progress and hospitalization. Our results support that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.
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| 9. |
- Ekström, Ola, et al.
(författare)
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Increasing circulating levels of Tenascin C in response to the Wingate Anaerobic test
- 2023
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 43:4, s. 271-277
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum.METHODS: Thirty-nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using ELISA.RESULTS: After the Wingate test, serum TNC increased on average by 23% [15-33], median [IQR]; P Wilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO 2max . TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue. CONCLUSION: TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO 2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation. This article is protected by copyright. All rights reserved.
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| 10. |
- Eriksson, Daniel, et al.
(författare)
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Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
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| 11. |
- Eriksson, Gabriella, et al.
(författare)
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Debiasing time saving judgements by manipulation of speed display
- 2014
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Ingår i: Proceedings of the Human Factors and Ergonomics Society Europe Chapter 2013 Annual Conference. - Groningen, NL : Human Factors and Ergonomics Society Europe chapter. ; , s. 161-168
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Konferensbidrag (refereegranskat)abstract
- The time saving bias predicts that when increasing speeding from a high speed (e.g. 100 kph) the time saved is overestimated and underestimated when increasing speed from a slow speed (e.g. 30 kph). An alternative meter indicating the inverted speed (min/km) was used to debias time saving judgements in an active driving task. The simulated driving task was to first drive a distance at a given speed and then drive the same distance again at the speed the driver judged was required in order to gain exactly three minutes in travel time compared to the first drive. A control group performed the same task with a speedometer and saved less than the targeted three minutes when increasing speed from a high speed and more than three minutes when increasing from a low speed, as predicted by the time saving bias. Participants in the alternative meter group were closer to the target. The study shows that biased intuitive judgements can be affected by changing information format.
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| 12. |
- Eriksson, Gabriella, et al.
(författare)
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Estimated Time of Arrival and Debiasing the Time Saving Bias
- 2015
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Ingår i: Ergonomics. - : Taylor & Francis. - 0014-0139 .- 1366-5847. ; 58:12, s. 1939-1946
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Tidskriftsartikel (refereegranskat)abstract
- The time saving bias predicts that the time saved when increasing speed from a high speed is overestimated, and underestimated when increasing speed from a slow speed. In a questionnaire, time saving judgements were investigated when information of estimated time to arrival was provided. In an active driving task, an alternative meter indicating the inverted speed was used to debias judgements. The simulated task was to first drive a distance at a given speed, and then drive the same distance again at the speed the driver judged was required to gain exactly three minutes in travel time compared to the first drive. A control group performed the same task with a speedometer and saved less than the targeted three minutes when increasing speed from a high speed, and more than three minutes when increasing from a low speed. Participants in the alternative meter condition were closer to the target. The two studies corroborate a time saving bias and show that biased intuitive judgements can be debiased by displaying the inverted speed.
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| 13. |
- Eriksson, Gabriella, 1983-, et al.
(författare)
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The time-saving bias : Judgements, cognition and perception
- 2013
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Ingår i: Judgment and Decision Making. - : Cambridge University Press (CUP). - 1930-2975. ; 8:4, s. 492-497
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Tidskriftsartikel (refereegranskat)abstract
- Biases in people's judgments of time saved by increasing the speed of an activity have been studied mainly with hypothetical scenarios (Svenson, 2008). The present study asked whether the classic time-saving bias persists as a perceptual bias when we control the speed of an activity and assess the perceived time elapsed at different speeds. Specifically, we investigated the time-saving bias in a driving simulator. Each participant was asked to first drive a distance at a given speed and then drive the same distance again at the speed she or he judged necessary to gain exactly three minutes in travel time compared to the first trip. We found that that the time-saving bias applies to active driving and that it affects the choice of driving speed. The drivers' time-saving judgements show that the perception of the time elapsed while driving does not eliminate the time-saving bias.
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| 14. |
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| 15. |
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| 16. |
- Eriksson, Jonas, et al.
(författare)
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Strategy to develop a MAO-A-resistant 5-hydroxy-L-[beta-C-11]tryptophan isotopologue based on deuterium kinetic isotope effects
- 2014
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe serotonin precursor 5-hydroxy-L-[β-11C]tryptophan ([11C]HTP) is in clinical use for localization of neuroendocrine tumors and has been suggested as a proxy marker for pancreatic islet cells. However, degradation by monoamine oxidase-A (MAO-A) reduces retention and the contrast to non-endocrine tissue.MethodsA synthesis method was developed for 5-hydroxy-L-[β-11C2H]tryptophan ([11C]DHTP), an isotopologue of [11C]HTP, labeled with 11C and 2H at the β-position adjacent to the carbon involved in MAO-A decarboxylation. MAO-A-mediated degradation of [11C]DHTP was evaluated and compared to non-deuterated [11C]HTP.Results[11C]DHTP was synthesized with a radiochemical purity of >98%, radioactivity of 620 ± 190 MBq, and deuterium (2H or 2H2) incorporation at the β-position of 22% ±5%. Retention and resistance to MAO-A-mediated degradation of [11C]DHTP were increased in cells but not in non-human primate pancreas.ConclusionsPartial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.
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| 17. |
- Eriksson, Mats-Ola, et al.
(författare)
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Morphologic Outcome after Endovascular Treatment of Complicated Type B Aortic Dissection
- 2013
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Ingår i: Journal of Vascular and Interventional Radiology. - : Elsevier BV. - 1051-0443 .- 1535-7732. ; 24:12, s. 1826-1833
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:To investigate the long-term morphologic changes of the aorta after thoracic endovascular aortic repair (TEVAR) for acute complicated type B aortic dissection and to analyze whether these changes differed between DeBakey class IIIa and IIIb dissections.MATERIALS AND METHODS:During the period 1999-2009, 58 patients with acute complicated type B aortic dissection were treated with TEVAR. Seven patients lacked follow-up data, leaving 51 patients-17 patients with DeBakey IIIa aortic dissection and 34 patients with DeBakey IIIa aortic dissection IIIb-for inclusion in the study. Computed tomography scans performed before and after TEVAR were evaluated. Maximum thoracic and abdominal aortic diameters and diameters of the true lumen and false lumen at the level of the maximum aortic diameter in the thorax and abdomen were analyzed as well as degree of thrombosis of the false lumen.RESULTS:There was an overall significant reduction of the thoracic aortic diameter, increased true lumen diameter, and reduced false lumen diameter (P < .05). Total thrombosis of the false lumen, with or without reintervention, was seen in 53% of all patients, in 41% primarily and in 12% after reintervention. The IIIa group had a higher degree of total false lumen thrombosis. All patients in the IIIb group had total thrombosis of the false lumen along the stent graft.CONCLUSIONS:Long-term follow-up showed favorable aortic remodeling after TEVAR for acute complicated type B aortic dissection. Total thrombosis of the false lumen occurred more often in patients with DeBakey IIIa aortic dissection compared with patients with DeBakey IIIb aortic dissection.
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| 18. |
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| 19. |
- Eriksson, Ola, 1967-, et al.
(författare)
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In vitro evaluation of brain lesioning electrodes (Leksell) using a computer-assisted video system
- 1999
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Ingår i: Neurological Research. - 0161-6412 .- 1743-1328. ; 21:1, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- Radiofrequency (RF) generated thermal brain lesions are widely used in functional neurosurgery. The size, shape and development of the lesions depends on system parameter settings and the electrode configuration. Difficulties in studying the effect of these factors in vivo stimulated us to develop an in vitro system for standardized comparison between different electrodes and physical parameters. A computer-assisted video system was set-up allowing continuous video recording of RF-generated coagulations in either a standard albumin solution or in the fresh white of a hen's egg as transparent test substrates. Ten lesions were made with each test electrode (two bipolar and three monopolar) in each of the two substrates at 70 degrees, 80 degrees and 90 degrees C (t = 60 sec). Due to the better homogeneity the lesions in the albumin solution were much more regular and reproducible. This made it possible to calculate the size (width 2.2 +/- 0.1 to 5.3 +/- 0.1 mm and length 3.0 +/- 0.1 to 8.7 +/- 0.3 mm) as well as the volume (8.5 +/- 1.4 mm3 to 133.5 +/- 26.8 mm3). It is concluded that this in vitro system offers a reproducible way to study and document the effect of different electrode configurations and RF-generator settings on the formation of a heat lesion. Even if the results are not directly applicable to the living human brain they give an estimate of the form and size of a coagulation lesion and can be of value for standardized comparisons between different electrodes.
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| 20. |
- Fagerberg, Nils, 1972-, et al.
(författare)
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Evaluation of individual-tree growth models for Picea abies based on a case study of an uneven-sized stand in southern Sweden
- 2022
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Ingår i: Scandinavian Journal of Forest Research. - : Taylor & Francis Group. - 0282-7581 .- 1651-1891. ; 37:1, s. 45-58
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Tidskriftsartikel (refereegranskat)abstract
- To develop recommendations for tree selection in Continuous Cover Forestry (CCF), access to valid tools for simulating growth at individual tree-level is necessary. To assist efforts to develop such tools, in this study, long-term observation data from two uneven-sized Norway spruce plots in southern Sweden are used to evaluate old and new individual-tree growth models (two established Swedish models, two new preliminary models and included as a reference, a Finnish model). The plots' historical management records and site conditions are the same, but their last thinning treatment differs. Observed diameter increment at tree-level is investigated in relation to treatment. Individual tree growth residuals of tested models are evaluated in relation to tree diameter, treatment, projection length and sensitivity to the predictor mean stand age. Furthermore, the relations between displayed residuals and basal area local competition are analysed. The analyses indicate that active thinning made annual diameter increment independent of tree diameter above a threshold level, while the absence of thinning supported a concave relationship. All tested models displayed a significant linear bias leading to overestimation of small trees' growth and increasing underestimations of larger trees' growth with tree diameter. All distance-independent models displayed residual trends related to local competition.
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| 21. |
- Fang, C.M., et al.
(författare)
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General trend of the mechanical properties of the ternary carbides M3SiC2 (M=transition metal)
- 2006
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 74:5, s. 054106-
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Tidskriftsartikel (refereegranskat)abstract
- We present results from first-principles calculations of ternary transition metal carbides in the M3SiC2 series (where M=early transition metal). We predict structural and mechanical properties of these new MN+1AXN phases. The bulk modulus of the ternary carbides, M3SiC2, are in the calculations found to be proportional to the bulk modulus of the corresponding binary carbides, MC. We have analyzed this behavior using a simple, nearest-neighbor bond model, as well as from first-principles total energy calculations and have found that it is caused by a considerably weaker M-Si bond compared to the M-C bond.
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| 22. |
- Ljungman, Christer, et al.
(författare)
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Propositions for refinement of the hybrid surgical technique for treatment of thoraco-abdominal aortic aneurysm
- 2008
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Ingår i: Scandinavian Journal of Surgery. - 1457-4969 .- 1799-7267. ; 97:2, s. 174-177
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Forskningsöversikt (refereegranskat)abstract
- Traditional open repair of thoraco-abdominal aortic aneurysms Crawford type II-IV carries a high perioperative risk and mortality. The hybrid technique for combined surgical and endovascular treatment offers an interesting alternative with reduced risk of paraparesis and possibly a reduced mortality rate. Propositions for refinement of this approach are outlined based on a single centre experience.
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| 23. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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| 24. |
- Oskolkov, Nikolay, et al.
(författare)
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High-throughput muscle fiber typing from RNA sequencing data
- 2022
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Ingår i: Skeletal Muscle. - : Springer Science and Business Media LLC. - 2044-5040. ; 12, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested. Methods: By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22). Results: The correlation between the sequencing-based method and the other two were rATPas = 0.44 [0.13–0.67], [95% CI], and rmyosin = 0.83 [0.61–0.93], with p = 5.70 × 10–3 and 2.00 × 10–6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads. Conclusions: This new method (https://github.com/OlaHanssonLab/PredictFiberType) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies.
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| 25. |
- Parikh, Hemang M, et al.
(författare)
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Relationship between insulin sensitivity and gene expression in human skeletal muscle
- 2021
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Ingår i: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin resistance (IR) in skeletal muscle is a key feature of the pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases and also predicts type 2 diabetes. However, the underlying molecular mechanisms are still poorly understood.METHODS: To explore these mechanisms, we related global skeletal muscle gene expression profiling of 38 non-diabetic men to a surrogate measure of insulin sensitivity, i.e. homeostatic model assessment of insulin resistance (HOMA-IR).RESULTS: We identified 70 genes positively and 110 genes inversely correlated with insulin sensitivity in human skeletal muscle, identifying autophagy-related genes as positively correlated with insulin sensitivity. Replication in an independent study of 9 non-diabetic men resulted in 10 overlapping genes that strongly correlated with insulin sensitivity, including SIRT2, involved in lipid metabolism, and FBXW5 that regulates mammalian target-of-rapamycin (mTOR) and autophagy. The expressions of SIRT2 and FBXW5 were also positively correlated with the expression of key genes promoting the phenotype of an insulin sensitive myocyte e.g. PPARGC1A.CONCLUSIONS: The muscle expression of 180 genes were correlated with insulin sensitivity. These data suggest that activation of genes involved in lipid metabolism, e.g. SIRT2, and genes regulating autophagy and mTOR signaling, e.g. FBXW5, are associated with increased insulin sensitivity in human skeletal muscle, reflecting a highly flexible nutrient sensing.
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