| 1. |
|
|
| 2. |
|
|
| 3. |
- del Risco Norrlid, Lilián, et al.
(författare)
-
Capabilities in the Nordic region for assessment of accidental uptake of radioiodine in emergency situations.
- 2014
-
Ingår i: The 4th European Regional IRPA Congress.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction The need for quantifying the uptake of radioiodine in thyroids has been repeatedly demonstrated following accidents. The aim of an early stage quick measurement is to identify the people who may have inhaled or ingested I-131 that imply the need for more extensive measurements and subsequent medical assessment. Objectives and methodology This work aims to evaluate the status of thyroid measurements capabilities in the Nordic region. The participating laboratories were offered the possibility of calibrating their systems with known and fully traceable activity of the I-131 simulator mock iodine (Ba133 + Cs137) in neck phantoms of three different sizes, adult, young and child. The laboratories have also received an unknown activity of mock iodine activity in a test neck phantom to measure and an emergency response scenario. The participants are required to report the result quickly, including an analysis regarding the committed organ dose due to the assumed intake and to describe the measurement procedure. Results The present in-vivo thyroid monitoring capabilities in the Nordic region are compiled. Given the variety of instruments calibrated, a guidance for the in-vivo determination of I-131 in thyroids is provided. This guidance is based on the measurement instructions that were circulated with the calibration phantoms and it includes the calibration factors for a list of the most frequent detectors. Among the variety of instruments are gamma cameras at hospitals, gamma spectrometers of different resolutions and handheld instruments of both spectrometric and count/dose rate capability. The detection limits for I131 attainable with the present resources are presented categorized per type of instrument. Also results of the intercomparison of measurements of I-131 activity, the estimated thyroid dose as well as compilation of dose assessment capacities are reported. Conclusions Prompt triage of many people regarding I-131 intake enable both the necessary early stage contamination control and the subsequent estimation of thyroid radiation doses. With proper calibration, many kinds of hand instruments can be used. Gamma cameras available in hospitals can also be an important resource in the context of I-131 measurements.
|
|
| 4. |
- Frankl, My, 1968-
(författare)
-
Psychotherapy for Substance Use Disorders – the importance of affects
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Substance use disorder (SUD) is a serious disorder with severe consequences for the individual, the family and for society. Comorbidity is common in the SUD population and the diversity of the disorder calls for a multiplicity of treatment options.The overall aim of this thesis was to explore the role of affects in psychotherapy for SUD. Further aims were to investigate affect-focused therapeutic orientations, demonstrate the importance of common factors and evaluate a measure of affect phobia.In Study I a naturalistic design was employed to examine how the discrepancy between patients' expectations and experience of psychotherapy related to alliance in 41 patients: 24 in individual therapy and 17 in group. An additional analysis concerned whether different dimensions of role expectations predicted retention in psychotherapy. Study II was the first psychometric evaluation of the Affect phobia test – a test developed to screen the ability to experience, express and regulate emotions. Data were collected from two samples: A clinical sample of 82 patients with depression and/or anxiety participating in a randomized controlled trial of Internet-based affect-focused treatment, and a university student sample of 197 students. Data analysed included internal consistency, test-retest reliability, factor analysis and calculation of an empirical cut-off. Study III focused on the feasibility of individual 10 week Affect Phobia Therapy (APT) for patients diagnosed with mild to moderate alcohol use disorder (AUD) and problematic affective avoidance in a nonconcurrent multiple baseline design. Study IV comprised an evaluation of the feasibility and preliminary effectiveness of APT adapted to a structured group format for patients (n=22) with comorbid substance use disorder and ADHD with core features of affective avoidance/emotion dysregulation in an open design.In Study I an overall discrepancy between role expectations and experiences was significantly related to a lower level of therapeutic alliance in group therapy. This relationship was not found in individual therapy. Expectations prior to psychotherapy characterized by defensiveness correlated negatively with therapy retention, even when controlling for waiting time for therapy. In Study II the internal consistency for the total score on the Affect phobia test was satisfactory but it was not for the affective domains, Anger/Assertion, Sadness/Grief, and Attachment/Closeness. Test retest reliability was satisfactory. The exploratory factor analysis resulted in a six-factor solution and only moderately matched the test´s original affective domains. An empirical cut-off between the clinical and the university student sample were calculated and yielded a cut-off of 72 points. In Study III patients reported no adverse events due to the treatment and finished the whole study period. The patients had different trajectories of alcohol consumption and craving and the hypothesis that heavy episodic drinking would subside during the time in therapy did not hold true. In Study IV patients reported significant pre-to post changes in increased self-compassion and decreased affect phobia but no change in psychological distress or emotion dysregulation. Craving fluctuated throughout the study period and patients’ drinking pattern changed in the direction of more social drinking.Main conclusions are the following: The Affect Phobia Test is a useful screening instrument for detecting emotional difficulties related to psychological malfunction. APT in both group and individual format are feasible treatments for the SUD population and has the potential to broaden the treatment options for some patients with SUD. Investigating expectations and fears prior to therapy may be means to prevent attrition.
|
|
| 5. |
- Ghiasi, S. M., et al.
(författare)
-
The Connexin 43 Regulator Rotigaptide Reduces Cytokine-Induced Cell Death in Human Islets
- 2020
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 21:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Intercellular communication mediated by cationic fluxes through the Connexin family of gap junctions regulates glucose-stimulated insulin secretion and beta cell defense against inflammatory stress. Rotigaptide (RG, ZP123) is a peptide analog that increases intercellular conductance in cardiac muscle cells by the prevention of dephosphorylation and thereby uncoupling of Connexin-43 (Cx43), possibly via action on unidentified protein phosphatases. For this reason, it is being studied in human arrhythmias. It is unknown if RG protects islet cell function and viability against inflammatory or metabolic stress, a question of considerable translational interest for the treatment of diabetes. Methods: Apoptosis was measured in human islets shown to express Cx43, treated with RG or the control peptide ZP119 and exposed to glucolipotoxicity or IL-1 beta + IFN gamma INS-1 cells shown to lack Cx43 were used to examine if RG protected human islet cells via Cx43 coupling. To study the mechanisms of action of Cx43-independent effects of RG, NO, IkB alpha degradation, mitochondrial activity, ROS, and insulin mRNA levels were determined. Results: RG reduced cytokine-induced apoptosis similar to 40% in human islets. In Cx43-deficient INS-1 cells, this protective effect was markedly blunted as expected, but unexpectedly, RG still modestly reduced apoptosis, and improved mitochondrial function, insulin-2 gene levels, and accumulated insulin release. RG reduced NO production in Cx43-deficient INS-1 cells associated with reduced iNOS expression, suggesting that RG blunts cytokine-induced NF-kappa B signaling in insulin-producing cells in a Cx43-independent manner. Conclusion: RG reduces cytokine-induced cell death in human islets. The protective action in Cx43-deficient INS-1 cells suggests a novel inhibitory mechanism of action of RG on NF-kappa B signaling.
|
|
| 6. |
- Hansen, Lea B.S., et al.
(författare)
-
A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
|
|
| 7. |
- Harms, Hendrik J., et al.
(författare)
-
Association of right ventricular myocardial blood flow with pulmonary pressures and outcome in cardiac amyloidosis
- 2023
-
Ingår i: JACC Cardiovascular Imaging. - : Elsevier. - 1936-878X .- 1876-7591.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied.Objectives: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA.Methods: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA.Results: MBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro–B-type natriuretic peptide levels, New York Heart Association functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with hazard ratio 9.0 (95% CI: 4.2-14.5), P < 0.0001).Conclusions: Measurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.
|
|
| 8. |
|
|
| 9. |
- Khilji, M. S., et al.
(författare)
-
The inducible β5i proteasome subunit contributes to proinsulin degradation in GRP94-deficient β-cells and is overexpressed in type 2 diabetes pancreatic islets
- 2020
-
Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - 0193-1849. ; 318:6
-
Tidskriftsartikel (refereegranskat)abstract
- Proinsulin is a misfolding-prone protein, and its efficient breakdown is critical when β-cells are confronted with high-insulin biosynthetic demands, to prevent endoplasmic reticulum stress, a key trigger of secretory dysfunction and, if uncompensated, apoptosis. Proinsulin degradation is thought to be performed by the constitutively expressed standard proteasome, while the roles of other proteasomes are unknown. We recently demonstrated that deficiency of the proinsulin chaperone glucoseregulated protein 94 (GRP94) causes impaired proinsulin handling and defective insulin secretion associated with a compensated endoplasmic reticulum stress response. Taking advantage of this model of restricted folding capacity, we investigated the role of different proteasomes in proinsulin degradation, reasoning that insulin secretory dynamics require an inducible protein degradation system. We show that the expression of only one enzymatically active proteasome subunit, namely, the inducible β5i-subunit, was increased in GRP94 CRISPR/Cas9 knockout (KO) cells. Additionally, the level of β5i-containing intermediate proteasomes was significantly increased in these cells, as was β5i-related chymotrypsin-like activity. Moreover, proinsulin levels were restored in GRP94 KO upon β5i small interfering RNA-mediated knockdown. Finally, the fraction of β-cells expressing the β5i subunit is increased in human islets from type 2 diabetes patients. We conclude that β5i is an inducible proteasome subunit dedicated to the degradation of mishandled proinsulin. Copyright © 2020 the American Physiological Society.
|
|
| 10. |
- Khilji, M. S., et al.
(författare)
-
The intermediate proteasome is constitutively expressed in pancreatic beta cells and upregulated by stimulatory, low concentrations of interleukin 1 beta
- 2020
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
-
Tidskriftsartikel (refereegranskat)abstract
- A central and still open question regarding the pathogenesis of autoimmune diseases, such as type 1 diabetes, concerns the processes that underlie the generation of MHC-presented autoantigenic epitopes that become targets of autoimmune attack. Proteasomal degradation is a key step in processing of proteins for MHC class I presentation. Different types of proteasomes can be expressed in cells dictating the repertoire of peptides presented by the MHC class I complex. Of particular interest for type 1 diabetes is the proteasomal configuration of pancreatic beta cells, as this might facilitate autoantigen presentation by beta cells and thereby their T-cell mediated destruction. Here we investigated whether so-called inducible subunits of the proteasome are constitutively expressed in beta cells, regulated by inflammatory signals and participate in the formation of active intermediate or immuno-proteasomes. We show that inducible proteasomal subunits are constitutively expressed in human and rodent islets and an insulin-secreting cell-line. Moreover, the beta 5i subunit is incorporated into active intermediate proteasomes that are bound to 19S or 11S regulatory particles. Finally, inducible subunit expression along with increase in total proteasome activities are further upregulated by low concentrations of IL-1 beta stimulating proinsulin biosynthesis. These findings suggest that the beta cell proteasomal repertoire is more diverse than assumed previously and may be highly responsive to a local inflammatory islet environment.
|
|
| 11. |
- Kuhre, Rune E., et al.
(författare)
-
No direct effect of SGLT2 activity on glucagon secretion
- 2019
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:6, s. 1011-1023
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Sodium–glucose cotransporter (SGLT) 2 inhibitors constitute a new class of glucose-lowering drugs, but they increase glucagon secretion, which may counteract their glucose-lowering effect. Previous studies using static incubation of isolated human islets or the glucagon-secreting cell line α-TC1 suggested that this results from direct inhibition of alpha cell SGLT1/2-activity. The aim of this study was to test whether the effects of SGLT2 on glucagon secretion demonstrated in vitro could be reproduced in a more physiological setting. Methods: We explored the effect of SGLT2 activity on glucagon secretion using isolated perfused rat pancreas, a physiological model for glucagon secretion. Furthermore, we investigated Slc5a2 (the gene encoding SGLT2) expression in rat islets as well as in mouse and human islets and in mouse and human alpha, beta and delta cells to test for potential inter-species variations. SGLT2 protein content was also investigated in mouse, rat and human islets. Results: Glucagon output decreased three- to fivefold within minutes of shifting from low (3.5 mmol/l) to high (10 mmol/l) glucose (4.0 ± 0.5 pmol/15 min vs 1.3 ± 0.3 pmol/15 min, p < 0.05). The output was unaffected by inhibition of SGLT1/2 with dapagliflozin or phloridzin or by addition of the SGLT1/2 substrate α-methylglucopyranoside, whether at low or high glucose concentrations (p = 0.29–0.99). Insulin and somatostatin secretion (potential paracrine regulators) was also unaffected. Slc5a2 expression and SGLT2 protein were marginal or below detection limit in rat, mouse and human islets and in mouse and human alpha, beta and delta cells. Conclusions/interpretation: Our combined data show that increased plasma glucagon during SGLT2 inhibitor treatment is unlikely to result from direct inhibition of SGLT2 in alpha cells, but instead may occur downstream of their blood glucose-lowering effects.
|
|
| 12. |
- Lacas, Benjamin, et al.
(författare)
-
Role of radiotherapy fractionation in head and neck cancers (MARCH) : an updated meta-analysis
- 2017
-
Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 18:9, s. 1221-1237
-
Tidskriftsartikel (refereegranskat)abstract
- Background The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. Methods For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Findings Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8). Interpretation This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. Funding Institut National du Cancer; and Ligue Nationale Contre le Cancer.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Mojtaba Ghiasi, Seyed, et al.
(författare)
-
The Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 is Essential for Proinsulin Handling
- 2019
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:4, s. 747-760
-
Tidskriftsartikel (refereegranskat)abstract
- Although endoplasmic reticulum (ER) chaperone binding to mutant proinsulin has been reported, the role of protein chaperones in the handling of wild-type proinsulin is under-investigated. Here, we have explored the importance of glucose regulated protein 94 (GRP94), a prominent ER chaperone known to fold insulin-like growth factors, in proinsulin handling within β-cells. We found that GRP94 co-immunoprecipitated with proinsulin and that inhibition of GRP94 function and/or expression reduced glucose-dependent insulin secretion, shortened proinsulin half-life and lowered intracellular proinsulin and insulin levels. This phenotype was accompanied by post-ER proinsulin misprocessing and higher numbers of enlarged insulin granules that contained amorphic material with reduced immunogold staining for mature insulin. Insulin granule exocytosis was two-fold accelerated but the secreted insulin had diminished bioactivity. Moreover, GRP94 knockdown or knockout in β-cells selectively activated Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK), without increasing apoptosis levels. Finally, GRP94 mRNA was overexpressed in islets from T2D patients. We conclude that GRP94 is a chaperone crucial for proinsulin handling and insulin secretion.
|
|
| 16. |
- Mortensen, Camilla Bekker, et al.
(författare)
-
Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium
- 2024
-
Ingår i: Intensive Care Medicine. - 0342-4642. ; 50:1, s. 103-113
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. Results: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of − 6.4%-points (95% confidence interval [CI] − 12.8%-points to − 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI − 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI − 9.3 to 17.5; P = 0.142) for EQ VAS. Conclusions: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.
|
|
| 17. |
- Mortensen, Camilla B., et al.
(författare)
-
Mortality and HRQoL in ICU patients with delirium : Protocol for 1-year follow-up of AID-ICU trial
- 2020
-
Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:10, s. 1519-1525
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Intensive care unit (ICU)-acquired delirium is frequent and associated with poor short- and long-term outcomes for patients in ICUs. It therefore constitutes a major healthcare problem. Despite limited evidence, haloperidol is the most frequently used pharmacological intervention against ICU-acquired delirium. Agents intervening against Delirium in the ICU (AID-ICU) is an international, multicentre, randomised, blinded, placebo-controlled trial investigates benefits and harms of treatment with haloperidol in patients with ICU-acquired delirium. The current pre-planned one-year follow-up study of the AID-ICU trial population aims to explore the effects of haloperidol on one-year mortality and health related quality of life (HRQoL). Methods : The AID-ICU trial will include 1000 participants. One-year mortality will be obtained from the trial sites; we will validate the vital status of Danish participants using the Danish National Health Data Registers. Mortality will be analysed by Cox-regression and visualized by Kaplan-Meier curves tested for significance using the log-rank test. We will obtain HRQoL data using the EQ-5D instrument. HRQoL analysis will be performed using a general linear model adjusted for stratification variables. Deceased participants will be designated the worst possible value. Results: We expect to publish results of this study in 2022. Conclusion: We expect that this one-year follow-up study of participants with ICU-acquired delirium allocated to haloperidol vs. placebo will provide important information on the long-term consequences of delirium including the effects of haloperidol. We expect that our results will improve the care of this vulnerable patient group.
|
|
| 18. |
- Nilsson, Emma A, et al.
(författare)
-
Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle.
- 2005
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 54:10, s. 3015-3020
-
Tidskriftsartikel (refereegranskat)abstract
- The gene encoding calpain-10 (CAPN10) has been identified as a candidate gene for type 2 diabetes. Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs. Muscle biopsies were obtained before and after hyperinsulinemic-euglycemic clamps from 166 young and elderly monozygotic and dizygotic twins as well as from 15 subjects with normal (NGT) or impaired glucose tolerance (IGT) exposed to an Intralipid infusion. We found hereditary effects on both basal and insulin-exposed CAPN10 mRNA expression. Carriers of the type 2 diabetes–associated single nucleotide polymorphism (SNP)-43 G/G genotype had reduced CAPN10 mRNA levels compared with subjects carrying the SNP-43 A-allele. Age had no significant influence on CAPN10 mRNA levels. Insulin had no significant effect on CAPN10 mRNA levels, neither in the twins nor in the basal state of the Intralipid study. However, after a 24-h infusion of Intralipid, we noted a significant increase in CAPN10 mRNA in response to insulin in subjects with NGT but not in subjects with IGT. In conclusion, we provide evidence that mRNA expression of CAPN10 in skeletal muscle is under genetic control. Glucose-tolerant but not glucose-intolerant individuals upregulate their CAPN10 mRNA levels in response to prolonged exposure to fat.
|
|
| 19. |
- Nyander Poulsen, Asser, et al.
(författare)
-
Assessment of accidental uptake of iodine-131 in emergency situations
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The need for quantifying the uptake of radioiodine (131I) in thyroids in emergency situations has repeatedly been demonstrated. With early stage measurements people who may have inhaled or ingested amounts of 131I can be identified and the need for more extensive measurements and/or subsequent medical assessment can be evaluated. The report presents the outcome from the activity THYROID in which calibrations of thyroid monitoring equipment in the Nordic countries were harmonized. A total of 38 sites in Scandinavia were identified holding equipment usable for screening for thyroid 131I contamination. Different instrument types can be used in an emergency situation as long as they are properly calibrated. The activity enabled to evaluate the regional preparedness regarding thyroid personal monitoring.
|
|
| 20. |
- Petit, Claire, et al.
(författare)
-
Chemotherapy and radiotherapy in locally advanced head and neck cancer : an individual patient data network meta-analysis
- 2021
-
Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:5, s. 727-736
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other.METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies).FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%).INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer.FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.
|
|
| 21. |
- Stalmokaitė, Ignė
(författare)
-
New Tides in Shipping : Studying incumbent firms in maritime energy transitions
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Shipping is a cornerstone of global transportation responsible for moving large volumes of traded goods. At the same time, negative environmental impacts of shipping operations have attracted growing concerns. Although recognised as the most energy-efficient mode of transportation compared to air and land-based transport, maritime transportation contributes significantly to air-borne emissions, alongside other types of pollutants. Hence, it is apparent that alternatives to highly polluting conventional marine fuels, i.e., crude oil or diesel, have to be found in shipping, just as in other sectors. Responding to calls for a greater attention to actors’ roles in transitions, as well as for broader sectoral coverage of empirical work in the field of sustainability transition studies, this doctoral thesis explores the role of incumbents (established shipping firms) in the early stages of maritime energy transitions. Focusing on incumbents is a relatively recent, yet rapidly evolving, stream of research in sustainability transitions studies, with increasing evidence showing heterogeneity and strategic variety in incumbent activities in various transition contexts. By drawing on a multi-level perspective from the socio-technical transition literature, the dynamic capabilities approach from the strategic management literature, and structuration theory, this thesis contributes new knowledge on “how” and “why” frontrunner incumbent shipping firms engage with maritime niche technologies and alternative energy solutions as well as what strategies they adopt to overcome increasing environmental sustainability pressures. These are the topics that have so far received scant attention in sustainability transitions studies. The thesis utilises a qualitative case study approach to study the selection of firms from passenger, vehicle carrier and container shipping business segments that are active in environmental work. The findings of this thesis indicate that the roles of shipping firms in the early stage of maritime energy transitions are diverse and more complex than often accounted for in sustainability transitions literature. It is demonstrated that due to increased regulatory, social and competitive pressures, firms’ activities with regards to engagement in maritime niche technologies and alternative energy have shifted from reactive to a mix of strategies where a portfolio of solutions are pursued at the same time across and within individual firms. While adoption of incremental end-of-pipe technologies reinforces dependence on the fossil fuel energy system, a parallel engagement and experimentation with alternative energy solutions indicates that incumbent firms can also adopt a central role in niche development activities.
|
|
| 22. |
-
Statsutviklingen i Skandinavia i middelalderen
- 2012
-
Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Framveksten av historie som vitenskap var i stor grad preget av spørsmålet om nasjonalstatens opprinnelse. Historiefaget ble brukt i nasjonens interesse. Et sentralt tema siden den tid har vært om vi kan bruke ordet "stat" om middelalderen. Hva kjennetegner denne staten og hvor sterk eller svak var den i middelalderen? Er det slik at den viktigste oppgaven var rettshåndhevelsen, der et fravær av stat ville vært mye verre. Eller er det slik at staten er et resultat av krig og vice versa? Denne boka er en bred gjennomgang av statsutviklingen i Skandinavia i middelalderen. Forfatterne konfronterer den tradisjonelle nasjonale fortellingen om statens utvikling med nyere synspunkter på europeisk statsdannelse. Hvor utbygget og organisert var statsapparatet i de tre skandinaviske kongerikene og Island i middelalderen? For å sirkle inn dette spørsmålet undersøker forfatterne utviklingen innenfor militærvesen, økonomi, rettshåndhevelse, ideologi, politisk kultur og sosial struktur. Samlet gir de ulike bidragene et utfyllende og oppdatert bilde av statsutviklingen og drivkreftene bak den i hele Skandinavia.
|
|
| 23. |
- Widenberg, Björn, et al.
(författare)
-
Thick screens perforated with a periodic array of apertures with arbitrary cross-section
- 2000
-
Ingår i: Journal Electromagnetic Waves and Applications. - 1569-3937. ; 14:9, s. 28-1303
-
Tidskriftsartikel (refereegranskat)abstract
- A plane wave impinges on a perfectly conducting thick screen perforated with a periodic array of apertures with arbitrary cross-section. The transmission and reflection coefficients are determined by a mode matching technique, earlier used by other authors for the case where the apertures have the geometry of a classical waveguide. The fields outside the screen are expanded in Floquet modes, while the fields inside the apertures are expanded in waveguide modes, obtained by the finite element method (FEM). Excellent agreement between computed and measured transmission is found for a thick screen at the X-band (8.2-12.4 GHz). Moreover, the present method and the spectral Galerkin method (which assumes that the thickness of the screen is zero) is compared for very thin screens, e.g., for a frequency selective surface (FSS). Investigation of the thickness dependence is also done, and it is found that the bandwidth decreases when the thickness dependence is also done, and it is found that the bandwidth decreases when the thickness of the screen is increased. Finally two complex geometries, hexagonal and tripole apertures, are studied.
|
|
| 24. |
- Widenberg, Björn, et al.
(författare)
-
Thick screens perforated with a periodic array of apertures with arbitrary cross-section
- 1999
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A plane wave impinges on a perfectly conducting thick screen perforated with a periodic array of apertures with arbitrary cross-section. The transmission and reflection coefficients are determined by a mode matching technique, earlier used by other authors for the case where the apertures have the geometry of a classical waveguide. The fields outside the screen are expanded in plane waves, while the fields inside the apertures are expanded in waveguide modes, obtained by the finite element method (FEM). Excellent agreement between computed and measured transmission is found for a thick screen at the X-band (8.2−12.4 GHz). Moreover, the present method and the spectral Galerkin method (which assumes that the thickness of the screen is zero) is compared for very thin screens, e.g., for a frequency selective surface (FSS). Investigation of the thickness dependence is also done, and it is found that the bandwidth decreases when the thickness of the screen is increased. Finally two complex geometries, hexagonal and tripole apertures, are studied.
|
|
| 25. |
- Åkerstedt, Henrik, et al.
(författare)
-
Operation and performance of the ATLAS Tile Calorimeter in Run 1
- 2018
-
Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 78:12
-
Tidskriftsartikel (refereegranskat)abstract
- The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter's performance during the years 2008-2012 using cosmic-ray muon events and proton-proton collision data at centre-of-mass energies of 7 and 8 TeV with a total integrated luminosity of nearly 30 fb(-1). The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton-proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report.
|
|
