| 1. |
- Lagedal, Rickard, et al.
(författare)
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Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.
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| 2. |
- Ekelund, Maria, 1970-
(författare)
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Psoriasis and Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis (JIA) : A Longitudinal Study of the Nordic JIA Cohort
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Juvenile idiopathic arthritis, JIA, is used as an umbrella term covering a heterogeneous group of chronic arthritis forms in children, many of which have important differences compared to adult arthritis, while others possibly represent similar diseases among children and adults. Classification aims to give a better understanding of the pathogenesis, patterns, disease trajectories and treatment responses. For the juvenile psoriatic arthritis, JPsA, the classification criteria are currently being debated. The distribution of affected joints in JIA differs greatly and it is unknown why some joints appear to be more affected than others. The temporomandibular joint (TMJ) can be affected early in the course of the disease and often the symptoms are mild and without obvious swelling.This thesis has its origin in the Nordic Study Group of Paediatric Rheumatology and the population-based prospective study of 510 children with newly diagnosed JIA included between 1997 and 1999. Totally 440 children were included in the eight-year follow-up, and in the TMJ study 265 patients were examined and underwent cone-beam computed tomography, CBCT, 17 years after onset.After eight years a considerable proportion of the children with definite psoriasis were classified as undifferentiated JIA based on the exclusion criteria in the ILAR classification. Our data also presents the heterogenicity of JPsA and the development over time of clinical variables supporting a psoriatic diathesis, as well as the overlap between JPsA and enthesitis-related arthritis in a group of patients. We found that extensive symptoms and dysfunctions of the TMJ are seen in JIA 17 years after disease onset, even in patients registered with inactive disease or remission. Individuals with substantial condylar damage on CBCT were found in all JIA categories. The deeper understanding of a chronic disease over time is crucial for research initiatives to improve care as well as for clinical decisions and planning of the health care.Our findings suggest a need for a more appropriate classification of JPsA and also that aspects of TMJ involvement should be included in the general health assessment in JIA.
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| 3. |
- Forsell, Johan, 1980-
(författare)
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Grupparbetsbedömning på individnivå : Gymnasielärares möjligheter och utmaningar
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Avhandlingens syfte är att öka kunskapen om och förståelsen av gymnasielärares möjligheter och utmaningar med att genomföra grupparbetsbedömning på individnivå av elevers kunskaper och förmågor utvecklade i samarbete. Fokus är på om och i så fall hur lärares perspektiv förändras i samband med genomförandet av en grupparbetsuppgift i klassrummet som inkluderar lärares grupparbetsbedömning på individnivå. Syftet med avhandlingen besvaras genom en kvalitativ forskningsansats. Avhandlingen omfattar fyra empiriska delstudier. Den första delstudien, en systematisk litteraturgenomgång omfattade 83 publikationer. Den andra och tredje delstudien baserades på 12 intervjuer med sex gymnasielärare. Den fjärde delstudien, baserad på 24 videoobservationer av sex gymnasielärare. Avhandlingens resultat visar att tidigare forskning om grupparbetsbedömning har fokuserat på att särskilja vem som bidragit med vad vid grupparbete. Fokus har legat på elevers sociala förmågor och grupprocesser snarare än bedömning av elevers kunskaper och förmågor. Utmaningar lärare beskriver med grupparbetsbedömning är att kunna särskilja enskilda prestationer från gruppens. Att kunna särskilja elevers individuella kunskaper och förmågor hänger också samman med att kunna skaffa ett underlag för grupparbetsbedömning, vilket är avgörande för att få både validitet och reliabilitet i bedömningen. En specifik utmaning med grupparbetsbedömning är att tillgodose dess tudelade syfte att både kunna genomföra bedömningar av god kvalitet och samtidigt stödja gruppers samarbete. Genom att använda en metod för individuell grupparbetsbedömning med muntliga tvärgruppspresentationer kan lärare samla underlag för elevers individuella kunskaper och förmågor och samtidigt stötta gruppers samarbete vid grupparbete. Vid muntliga tvärgruppspresentationer är interaktion mellan lärare och elever och mellan elever viktigt för att kunna möjliggöra ett underlag för bedömning av elevers individuella kunskaper och förmågor. För att interaktion ska uppstå krävs det att läraren tar en aktiv roll vid tvärgruppspresentationer och stimulerar med frågor och reflektioner.
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| 4. |
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| 5. |
- Langner, Taro, et al.
(författare)
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Fully convolutional networks for automated segmentation of abdominal adipose tissue depots in multicenter water–fat MRI
- 2019
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 81:4, s. 2736-2745
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: An approach for the automated segmentation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in multicenter water–fat MRI scans of the abdomen was investigated, using 2 different neural network architectures.Methods: The 2 fully convolutional network architectures U‐Net and V‐Net were trained, evaluated, and compared using the water–fat MRI data. Data of the study Tellus with 90 scans from a single center was used for a 10‐fold cross‐validation in which the most successful configuration for both networks was determined. These configurations were then tested on 20 scans of the multicenter study beta‐cell function in JUvenile Diabetes and Obesity (BetaJudo), which involved a different study population and scanning device.Results: The U‐Net outperformed the used implementation of the V‐Net in both cross‐validation and testing. In cross‐validation, the U‐Net reached average dice scores of 0.988 (VAT) and 0.992 (SAT). The average of the absolute quantification errors amount to 0.67% (VAT) and 0.39% (SAT). On the multicenter test data, the U‐Net performs only slightly worse, with average dice scores of 0.970 (VAT) and 0.987 (SAT) and quantification errors of 2.80% (VAT) and 1.65% (SAT).Conclusion: The segmentations generated by the U‐Net allow for reliable quantification and could therefore be viable for high‐quality automated measurements of VAT and SAT in large‐scale studies with minimal need for human intervention. The high performance on the multicenter test data furthermore shows the robustness of this approach for data of different patient demographics and imaging centers, as long as a consistent imaging protocol is used.
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| 6. |
- Weghuber, D., et al.
(författare)
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A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity
- 2020
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Ingår i: Pediatric Obesity. - 2047-6302 .- 2047-6310. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pharmacological treatment options for adolescents with obesity are very limited. Glucagon-like-peptide-1 (GLP-1) receptor agonist could be a treatment option for adolescent obesity.OBJECTIVE: To investigate the effect of exenatide extended release on body mass index (BMI)-SDS as primary outcome, and glucose metabolism, cardiometabolic risk factors, liver steatosis, and other BMI metrics as secondary outcomes, and its safety and tolerability in adolescents with obesity.METHODS: Six-month, randomized, double-blinded, parallel, placebo-controlled clinical trial in patients (n = 44, 10-18 years, females n = 22) with BMI-SDS > 2.0 or age-adapted-BMI > 30 kg/m2 according to WHO were included. Patients received lifestyle intervention and were randomized to exenatide extended release 2 mg (n = 22) or placebo (n = 22) subcutaneous injections given once weekly. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention.RESULTS: Exenatide reduced (P < .05) BMI-SDS (-0.09; -0.18, 0.00), % BMI 95th percentile (-2.9%; -5.4, -0.3), weight (-3 kg; -5.8, -0.1), waist circumference (-3.2 cm; -5.8, -0.7), subcutaneous adipose tissue (-552 cm3 ; -989, -114), 2-hour-glucose during OGTT (-15.3 mg/dL; -27.5, -3.1), total cholesterol (11.6 mg/dL; -21.7, -1.5), and BMI (-0.83 kg/m2 ; -1.68, 0.01) without significant change in liver fat content (-1.36; -3.12, 0.4; P = .06) in comparison to placebo. Safety and tolerability profiles were comparable to placebo with the exception of mild adverse events being more frequent in exenatide-treated patients.CONCLUSIONS: Treatment of adolescents with severe obesity with extended-release exenatide is generally well tolerated and leads to a modest reduction in BMI metrics and improvement in glucose tolerance and cholesterol. The study indicates that the treatment provides additional beneficial effects beyond BMI reduction for the patient group.
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| 7. |
- Ahlsson, Fredrik, 1967-, et al.
(författare)
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Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size
- 2013
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 168:1, s. 26-29
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.STUDY DESIGN:Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.RESULTS:Median (range) rate of glucose production was 805 (653-1337)μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576)μmol/min. HOMA insulin resistance averaged 1.5±0.75 and estimated fetal weights ranged between 2670 and 4175g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2±2.5mg/L and median level of leptin was 47.1 (9.9-58.0)μg/L. Adiponectin concentrations (7.2±2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.CONCLUSION:The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.
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| 8. |
- Aydin, Banu K., et al.
(författare)
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High levels of FSH before puberty are associated with increased risk of metabolic syndrome during pubertal transition
- 2022
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Ingår i: Pediatric Obesity. - : John Wiley & Sons. - 2047-6302 .- 2047-6310. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Background During perimenopause, the rise in serum follicle-stimulating hormone (FSH) is associated with increased adiposity, insulin resistance (IR), and metabolic syndrome (MetS). However, data for the pubertal period, which is characterized by increasing FSH levels and changing body composition, are limited. Objectives To investigate the relationships between FSH and anthropometric changes, IR markers, and development of MetS in the peripubertal period. Methods Uppsala Longitudinal Study of Childhood Obesity (ULSCO) is an ongoing study that aims to understand the factors contributing to childhood obesity and the development of obesity-related diseases. We analysed the subset of participants who were prepubertal at the first visit (n = 95, 77 with obesity). Mean follow-up time was 3.0 +/- 1.4 years. Results Higher serum FSH levels at the first visit were associated with an increased likelihood of elevation in body mass index (BMI SDS) (p = 0.025, OR = 16.10) and having MetS (p = 0.044, OR = 4.67) at the follow-up. We observed nonlinear relationships between varying serum FSH levels and markers of adiposity and IR, especially in girls. At the first visit, when girls were prepubertal, FSH was negatively associated with BMI (beta = -0.491, p = 0.005) and positively associated with sex hormone-binding globulin (SHBG) (beta = 0.625, p = 0.002). With the progression of puberty, negative associations between BMI and SHBG disappeared while FSH became positively associated with HOMA-IR (beta = 0.678, p = 0.025) and fasting insulin (beta = 0.668, p = 0.027). Conclusions Higher serum FSH levels in prepubertal children were associated with an increased risk of MetS development during pubertal transition. Along with nonlinear associations between varying serum FSH levels and IR markers, our results might imply a relationship between FSH and IR of puberty.
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| 9. |
- Bratteby Tollerz, Linda U, et al.
(författare)
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Reliability of energy cost calculations in children with cerebral palsy, cystic fibrosis and healthy controls
- 2011
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:12, s. 1616-1620
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study test-retest reliability of physiological cost index (PCI) and total cost index (TCI) in three groups of children. TCI modified PCI by excluding rest heart rate in calculation. Methods: Energy cost was evaluated from two consecutive walking tests, and results were compared between methods, tests and groups. Thirty-nine children, eight with cerebral palsy, 11 with cystic fibrosis and 20 healthy controls, aged 5-16 years participated in the study conducted at the Clinical Nutrition and Metabolism laboratory, University Hospital, Uppsala, Sweden. Heart rate was recorded during sitting and walking at self-selected speed. PCI and TCI were calculated using both non-steady-state and steady-state work heart rates. Test-retest reliability was analysed by mean of differences, pooled SD, coefficient of variation (CV%) and correlation coefficients. Results: Reliability was high for PCI and TCI. TCI showed consistently lower variation between tests than PCI for all groups. In the group with cerebral palsy, using non-steady-state showed highest reliability. Conclusion: Both PCI and TCI were reliable methods when calculating energy cost in children with cerebral palsy, cystic fibrosis and controls. TCI seemed to be a suitable alternative in the evaluation of gait efficiency in children.
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| 10. |
- Cadamuro, Janne, et al.
(författare)
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Deviating glucose results in an international dual-center study. A root cause investigation
- 2022
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Ingår i: Biochemia Medica. - : Croatian Society for Medical Biochemistry and Laboratory Medicine. - 1330-0962 .- 1846-7482. ; 32:1
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Tidskriftsartikel (refereegranskat)abstract
- During a dual-center study on obese and normal weight children and adolescents, focusing on glucose metabolism, we observed a marked difference in glucose results (N = 16,840) between the two sites, Salzburg, Austria and Uppsala, Sweden (P < 0.001). After excluding differences in patient characteristics between the two populations as cause of this finding, we investigated other preanalytic influences. Finally, only the tubes used for blood collection at the two sites were left to evaluate. While the Vacuette FC-Mix tube (Greiner Bio-One, Kremsmunster, Austria) was used in Uppsala, in Salzburg blood collections were performed with a lithium heparin tube (LH-Monovette, Sarstedt, Germany). To prove our hypothesis, we collected two blood samples in either of these tubes from 51 children (Salzburg N = 27, Uppsala N = 24) and compared the measured glucose results. Indeed, we found the suspected bias and calculated a correction formula, which significantly diminished the differences of glucose results between the two sites (P = 0.023). Our finding is in line with those of other studies and although this issue should be widely known, we feel that it is widely neglected, especially when comparing glucose concentrations across Europe, using large databases without any information on preanalytic sample handling.
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