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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 4. |
- Voight, Benjamin F., et al.
(författare)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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| 5. |
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| 6. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 7. |
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| 8. |
- Jokiranta, T S, et al.
(författare)
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Complement C3b interactions studied with surface plasmon resonance technique
- 2001
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Ingår i: International Immunopharmacology. - 1567-5769 .- 1878-1705. ; 1:3, s. 495-506
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Tidskriftsartikel (refereegranskat)abstract
- The surface plasmon resonance (SPR) phenomenon is utilized in a number of new real time biosensors. In this study, we have used this technique to study interactions between the central complement component C3b and its multiple ligands by using the Biacore equipment. The SPR technique is particularly suitable for analysis of the alternative complement pathway (AP) because the inherent nature of the latter is to amplify deposition of C3b on various surfaces. C3b was coupled onto the sensor surface and the coupling efficiency was compared under various conditions on both polystyrene and carboxymethylated dextran surfaces. After enzymatic C3b coupling or standard amine C3b coupling, we analyzed and compared the binding of four C3b ligands to the surface: factor B, factor H, C5 and the soluble complement receptor 1 (sCR1, CD35). Binding of each ligand to C3b was detected when C3b had been coupled either enzymatically or using the amine coupling, but the half-lives of the interactions were found to vary depending on the coupling procedure. Factor H binds to C3b via three interaction sites. The target sites are exposed on the C3b, C3c and C3d fragments of C3, respectively. Therefore, we also tested by using the Biacore whether factor B, C5 and sCR1 bind to C3c and/or C3d. It was found that factor B bound to C3d, but not to C3c. On the other hand, both C5 and sCR1 bound to C3c, but not to C3d. In conclusion, this study shows that SPR is a powerful tool in analyzing and mapping the interactions of C3b with its multiple ligands.
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| 9. |
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| 10. |
- Lavö, B, et al.
(författare)
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Fc receptor function and circulating immune complexes in gluten sensitive enteropathy - possible significance of serum IgA
- 1991
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 32, s. 876-880
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Tidskriftsartikel (refereegranskat)abstract
- The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy.
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| 11. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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An improved method to study complement receptor-mediated function of the fixed macrophage system in vivo
- 1991
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 61:1, s. 47-52
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Tidskriftsartikel (refereegranskat)abstract
- A method to coat unsensitized erythrocytes with fragments of C3 and C4 using autologous serum, in order to study complement receptor-dependent function of the fixed macrophage system, is presented. After incubation with serum under optimal conditions, at least 90% of the cells had C3b/iC3b deposited on the surface, with an average of 20 × 103 molecules per cell. Elimination of the coated cells by the fixed macrophage system was studied in 12 normal subjects. With a dose of 4.5 × 108 red cells injected, 75% of the cells were eliminated with a half-life of approximately 2.4 ± 0.3 min (n = 7). In subjects receiving ten times more cells, there was a rapid decrease in the amount of C3-coated cells, reaching a nadir with 85% remaining for 4–6 min, after which there was a gradual release of cells for another 20 min (n = 5). In absolute numbers, 3 × 108 of labeled cells were eliminated regardless of the dose injected. The coating procedure presented here is simple, does not introduce heterologous blood components and makes it possible to control the amount and the degree of fragmentation of the C3 and C4 deposited on the erythrocyte surface.
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| 12. |
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| 13. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Defective Fc receptor-mediated clearance in patients with primary biliary cirrhosis
- 1991
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 101:4, s. 1076-1082
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Tidskriftsartikel (refereegranskat)abstract
- Fc receptor-mediated clearance of immunoglobulin G-coated autologous erythrocytes was studied in patients with primary biliary cirrhosis (n = 14), alcoholic liver cirrhosis (n = 5) and healthy reference individuals (n = 14). The mean half-life of the sensitized erythrocytes was significantly prolonged in patients with primary biliary cirrhosis (85 +/- 25 minutes; P less than 0.001) compared with the corresponding value in patients with alcoholic cirrhosis (16 +/- 2 minutes) and healthy reference individuals (20 +/- 5 minutes), respectively. No correlation between clearance rate and age, liver histopathology, or serum levels of bilirubin, aminotransferases, immunoglobulin G, immunoglobulin A, and Clq binding or C3-containing immune complexes was found. The results presented here indicate a profound disturbance of Fc receptor-mediated immune clearance function in patients with primary biliary cirrhosis.
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| 14. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Development of an immunoassay for the detection of minute amounts of IgG-coated erythrocytes in whole blood: Its application for the assessment of Fc-mediated clearance of anti-D-coated erythrocytes in vivo
- 1989
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 57:3, s. 188-192
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Tidskriftsartikel (refereegranskat)abstract
- A rapid and sensitive immunoassay for the detection of minute quantities of IgG-coated erythrocytes in whole blood was developed. Washed red blood cells were incubated in two steps with anti-human IgG antiserum followed by 125I-labelled protein A. The assay was able to detect amounts of sensitized erythrocytes as small as 0.5 ml of packed erythrocytes in a total blood volume of 5 liters and hematocrit 40%. A linear relation between increasing amounts of IgG-coated red cells in whole blood and the binding of 125I-labelled protein A was obtained. We applied the technique on the assessment of the removal of IgG anti-D-coated erythrocytes from the circulation of test individuals. T1/2 for the elimination of approximately 4 ml packed red cells sensitized with 62 μg of anti-D in 14 normal subjects was 20±5 min (mean±SEM). A splenectomized person did not clear the injected cells from the circulation during the test period of 70 min. If a standard curve was constructed the total blood volume in the test subjects could be calculated. This value correlated well (r = 0.99) with the blood volume calculated from the height and weight of the test individuals.
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| 15. |
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| 16. |
- Ahrenstedt, Örjan, et al.
(författare)
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Enhanced local production of the complement components in the small intestine in Crohn's disease
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 322, s. 1345-1349
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum.The mean (±SEM) jejunal-fluid C4 concentration was 2.0±0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7±0.1 mg per liter; P<0.001). The mean C3 concentration was 1.0±0.1 mg per liter in the patients and 0.7±0.1 mg per liter in the controls (P<0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first-degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4).We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages.
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| 17. |
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| 18. |
- Bonde, J. P. E., et al.
(författare)
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Occupational risk of COVID-19 across pandemic waves: a two-year national follow-up study of hospital admissions
- 2022
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 48:8, s. 672-677
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Tidskriftsartikel (refereegranskat)abstract
- Objective Assuming that preventive measures to mitigate viral transmission of SARS-CoV-2 at the workplace may have been improved in the course of the COVID-19 pandemic, we examined the occupational risk of COVID-19 related hospital admission across the four pandemic waves in Denmark between week 8, 2020, and week 50, 2021. Methods The study included 4416 cases of COVID-19 related hospital admissions among 2.4 million Danish employees aged 20-69 with follow-up in 2020 through 2021. At-risk industrial sectors and a reference population were defined a priory by a job-exposure matrix on occupational risk for COVID-19. Incidence rate ratios (IRR) and potential effect modification by pandemic wave were computed with Poisson regression adjusted for demographic, social and health factors including completed COVID-19 vaccination. Results We observed an overall elevated relative risk in four of six at-risk industrial sectors, but the pandemic wave only modified the risk among healthcare employees, where the excess risk from a high initial level declined to background levels during the latest waves in models not adjusting for COVID-19 vaccination. In social care, education and transport, the elevated risk was not modified by pandemic wave. Conclusion Danish healthcare employees were to some extent protected against occupational transmission of SARS-CoV-2 during the two last pandemic waves even though the absolute risk conferred by occupation may not have been eliminated. Early vaccination of this group seems not to be the only explanation. The risk in other sectors remained elevated indicating a need to revisit preventive measures.
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| 19. |
- Bonde, J P E, et al.
(författare)
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Occupational risk of COVID-19 in foreign-born employees in Denmark
- 2023
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Ingår i: Occupational Medicine. - : Oxford University Press. - 0962-7480 .- 1471-8405.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.
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| 20. |
- Bondesson, Eva, et al.
(författare)
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Planar gamma scintigraphy - points to consider when quantifying pulmonary dry powder aerosol deposition
- 2003
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Ingår i: International Journal of Pharmaceutics. - 1873-3476. ; 251:1-2, s. 33-47
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Tidskriftsartikel (refereegranskat)abstract
- Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.
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| 21. |
- Cepeda, D., et al.
(författare)
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CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer
- 2013
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018
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Tidskriftsartikel (refereegranskat)abstract
- SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
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| 22. |
- Dewan, Ramita, et al.
(författare)
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Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
- 2021
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Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 109:3
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Tidskriftsartikel (refereegranskat)abstract
- We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
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| 23. |
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| 24. |
- Kozarcanin, Huda, et al.
(författare)
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The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
- 2016
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:3, s. 531-545
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Tidskriftsartikel (refereegranskat)abstract
- The lectin pathway's MASP-1/2 activates coagulation factors but the trigger of the activation is unknown. MASP-1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1-inhibitor. Activated platelets and fibrin were demonstrated to activate MASP-1 and MASP-2 both invitro and invivo. These findings may represent a crossroad between the complement and the coagulation systems. Summary Background The activated forms of the complement lectin pathway (LP) proteases MASP-1 and MASP-2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor invitro. In vivo studies also show that MASP-1 is involved in thrombogenesis. Objectives To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. Methods Novel sandwich-ELISAs for detection of complexes between MASP-1 or MASP-2 and the serpins C1 inhibitor (C1-INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP-1 and MASP-2. Results Activated platelets were shown by flow cytometry to bind Ficolin-1, -2 and -3 but not MBL, which was associated with activation of MASP-1 and MASP-2. We also demonstrated that fibrin and the plasmin-generated fibrin fragment DD in plasma, bind and activate MASP-1 and MASP-2. As demonstrated by the ELISA and SDS-PAGE/Western blotting, the fibrin-associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH were associated with markers of thrombotic disease and contact/coagulation system activation. Conclusions MASP-1 and MASP-2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions invitro and invivo, and may represent a novel activation/amplification mechanism in thromboinflammation.
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| 25. |
- Lindberg, Malin, Professor, 1978-, et al.
(författare)
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Co-Creative Place Innovation in an Arctic Town
- 2020
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Ingår i: Journal of Place Management and Development. - : Emerald Group Publishing Limited. - 1753-8335 .- 1753-8343. ; 13:4, s. 447-463
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The purpose of the study is to shed light on co-creative approaches for place innovation in an Arctic town, based on the relocation of Kiruna’s city center in northern Sweden. Three cases of co-creative innovation processes in Kiruna are investigated and compared: an R&D project about local perceptions and visions of attractive urban environments, an R&D project about norm-creative design principles for inclusive and attractive urban design, and an R&D project about cross-industrial synergies for city center attractiveness.Design/methodology/approach – The study’s research design encompasses a comparative and participatory approach. The comparative approach implies investigation and comparison of three cases of co-creative innovation processes in Kiruna. The participatory approach implies joint development of new knowledge by researchers and local actors. The data consists of participatory observations of workshops and qualitative interviews with local actors.Findings – The study reveals that the studied processes have harnessed the city center relocation as an opportunity to make Kiruna more attractive to residents and visitors, by employing the co-creative approaches of Living Lab, Now-Wow-How and Norm-creative design. These approaches have enabled experts and local actors to jointly identify excluding patterns and norms in the relocation process, and to envision inclusive and attractive (re-)configurations and (re-)conceptualizations of the future Kiruna.Research implications – The results add to the academic strand of inclusive urban transformation, by providing insights into co-creative approaches for re-imagining an Arctic town in times of industrial and social change. New insights are provided regarding how the geographical, industrial and cultural identity of an Arctic town can be harnessed to envision new configuration, content and communication that is attractive and accessible for a diversity of residents and visitors. Practical implications – The results highlight the potential to harness Arctic and rural characteristics in the promotion of urban attractiveness and public wellbeing, especially when combined with co-creative identification and transformation of excluding norms and patterns.Originality/value – The results provide new insights into how co-creative approaches may facilitate innovative and inclusive renewal of towns and cities in the Arctic and beyond.
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| 33. |
- Rönnelid, J, et al.
(författare)
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Immune complexes from SLE sera induce IL-10 production by a Fc-RII-dependent mechanism: A possible vicious circle maintaining B cell hyperactivity in SLE
- 2003
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 62, s. 37-42
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Tidskriftsartikel (refereegranskat)abstract
- Background: Raised interleukin (IL)6 and IL10 levels are thought to contribute to the pathogenesis of systemic lupus erythematosus (SLE) by enhancing autoantibody production and immune complex (IC) formation. These immune complexes can then stimulate cellular reactions through Fc and complement receptors.Objective: To investigate whether circulating SLE ICs stimulate type 2 cytokine production.Methods: Twenty serum samples from patients with active SLE were compared with sera from 18 healthy controls. Sera and polyethylene glycol (PEG) precipitates from sera were added to peripheral blood mononuclear cell (PBMC) cultures, and the production of IL10 and IL6 was investigated by enzyme linked immunospot assay (ELISPOT) and enzyme linked immunosorbent assay (ELISA). Fc gamma receptor (FcγR) antibodies were used in blocking experiments, and flow cytometry was used to assess the correlation between monocyte FcγR expression and IC-induced cytokine production.Results: Ten per cent dilutions of the SLE sera induced a significantly increased number of IL10-producing cells in comparison with control sera (median, 11.75 v 1.25 spot forming cells/50 000 PBMC; p<0.0001). PEG precipitates from SLE sera also induced significantly increased levels of IL10 (p=0.016) and IL6 (p=0.042) in comparison with control PEG precipitates. IL10 production induced by SLE PEG precipitates or by artificial ICs could be blocked by anti-FcγRII antibodies, and the FcγRII expression on CD14+ monocytes correlated with the IC-induced production of IL10 and IL6.Conclusions: SLE sera stimulate IL10 and IL6 production from PBMC, and this effect is at least partly explained by precipitable ICs acting through FcγRII. This effect provides a possible mechanism for the enhanced production of IL10 in SLE, whereby B cell activation, antibody production, IC stimulated monocytes/macrophages, and type 2 cytokines create a vicious cycle that may help to maintain B cell hyperactivity in SLE.
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| 36. |
- Wang, Hao, et al.
(författare)
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The amount of SARS-CoV-2 RNA in wastewater relates to the development of the pandemic and its burden on the health system
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Virus surveillance in wastewater can be a useful indicator of the development of the COVID-19 pandemic in communities. However, knowledge about how the amount of SARS-CoV-2 RNA in wastewater relates to different data on the burden on the health system is still limited. Herein, we monitored the amount of SARS-CoV-2 RNA and the spectrum of virus variants in weekly pooled wastewater samples for two years from mid-February 2020 and compared them with several clinical data. The two-year monitoring showed the weekly changes in the amount of viral RNA in wastewater preceded the hospital care needs for COVID-19 and the number of acute calls on adult acute respiratory distress by 1-2 weeks during the first three waves of COVID-19. Our study demonstrates that virus surveillance in wastewater can predict the development of a pandemic and its burden on the health system, regardless of society's test capacity and possibility of tracking infected cases.
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| 37. |
- Wikberg-Nilsson, Åsa, et al.
(författare)
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Tillgänglighetsdesign för stadens utveckling
- 2018
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Rapport (populärvet., debatt m.m.)abstract
- Det offentliga rummet: stadens gator, parker, byggnader och torg likväl som den kultur och sociala kontext som en viss stad har, skulle kunna utformas för att vara tillgängligt, användbart, inkluderande, attraktivt och välgörande för människan i betydligt större utsträckning än vad som görs idag. Troligtvis är det inte medveten diskriminering som ligger bakom mindre god design av det offentliga rummet, utan snarare okunskap om vad som kan och behöver göras. Fram tills dess människor befinner sig i en situation där de på något sätt själva är hindrade från att delta på lika villkor är det svårt att inse hur mycket det offentliga rummet påverkar oss. Det kan vara mindre hinder i form av ojämnt underlag som gör det svårt att ta sig fram för vissa, medan det omöjliggör framfart för andra. Det kan vara miljöer som vissa upplever som “vanliga” medan andra upplever sig djupt otrygga eller utestängda från desamma. Med andra ord är det offentliga rummets utrymmen där vi lever, jobbar och leker knutna till vart vi går och vad vi gör eller vart vi inte går eller gör. Av den anledningen anser vi att det finns behov av att utveckla konkreta metoder och handgripliga råd för att arbeta med mer medveten utformning av fysisk miljö: tillgänglighetsdesign. Tillgänglighetsdesign används här genomgående som ett brett begrepp för design av lösningar som upplevs trygga, användbara, inkluderande, attraktiva och välgörande. Vi utgår från en designpraktik som stödjer tanken att miljön måste vara tillgänglig för alla grupper i samhället. I det förstudieprojekt som beskrivs i kommande kapitel har av den anledningen en kartläggning skett med utgångspunkt i ett helhetsgrepp på tillgänglighetsdesign, det vill säga att motverka diskriminering och främja lika rättighter och möjligheter oavsett kön, könsöverskridande identitet eller uttryck, etnisk tillhörighet, religion eller annan trosuppfattning, funktionsnedsättning, sexuell läggning eller ålder. Förstudien har omfattat kartläggning av normkritiska perspektiv, lagar och riktlinjer kring fysisk tillgänglighet, social hållbarhet och tillgänglighet, universell och inkluderande design, samt inhämtning av inspiration från arkitektur, form och designområdet. Det har även omfattat identifiering av goda exempel från runt om i landet på vad tillgänglighetsdesign i bred bemärkelse kan omfatta och intervjuer med personer som arbetat med detta. Vi vill rikta ett stort tack till er som bidragit till arbetet. Vår avsikt är att de principer som utformats i förstudien för tillgänglighetsdesign ska diskuteras, användas och uppdateras vid all stadsutveckling. På så sätt kan vi åstadkomma ett helhetsgrepp på tillgänglighetsdesign och åstadkomma socialt hållbara, attraktiva och tillgängliga platser och miljöer runt om i landet.
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| 38. |
- Beijer, Kristina, et al.
(författare)
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Interaction between physical activity and television time on blood pressure level : cross-sectional data from 45000 individuals
- 2018
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 36:5, s. 1041-1050
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect.Methods:Linear regression analysis on cross-sectional data was performed in more than 45000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time.Results:High physical activity was associated with lower DBP (P=0.001), but not SBP. Active middle-aged men had lower DBP (-1.1mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P<0.001) and DBP (P=0.011) in both sexes and in most age groups. Watching 3h instead of 1h television per day was associated with higher SBP in middle-aged women (SBP: 1.1mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3h per day) in terms of DBP.Conclusion:Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.
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| 39. |
- Beijer, Kristina, et al.
(författare)
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Physical activity may compensate for prolonged TV time regarding pulse rate-a cross-sectional study
- 2018
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 123:4, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Background: Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate.Methods: Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18–45 years) and LifeGene (45–75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time.Results: A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1).Conclusions: A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.
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| 40. |
- Berglund, Lotta, et al.
(författare)
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Health on thin ice : methods of giving voice to Swedish citizens in urban planning and design to promote health in a cold climate
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the northern, sub-arctic, regions of the world the climate is cold a substantial part of the year which affecting people's health as low temperatures and darkness stress the body. At the same time the cold climate offers opportunities that can be utilized in an innovative manner, both technically and aesthetically, to develop the winter environment to be attractive and health promoting in outdoor activities.The aim of the study was to develop a methodology for giving voice to citizens to be used in the process of urban planning and design for good health in a cold climate. The qualitative investigations of citizen’s experiences of health promoting aspects included two workshops focused on the following questions; What are your experiences of health and well-being in a cold climate? How can this city be planned to promote health during the winter season? The 53 participants came from two cities in the northern part of Sweden. At Workshop 1 small groups of citizens (5-8) were asked to make a collective collage cutting and pasting images from magazines without talking to each other while soft music was playing in the background.When finished the silence was broken and the participants presented their contributions. At Workshop 2 small groups of citizens (5-8) were given maps of the city with different paths for walking tours aimed to pinpoint areas for improvement. After the walk the group presented their ideas for each other and a number of innovative ideas surfaced.Including citizens in the process of urban planning is not only a good source of ideas and information useful in the planning process but may be an opportunity to strengthen health literacy and healthy behavior. This study may serve as an example of an empowerment - based method including citizens in the process of urban planning and design.
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| 41. |
- Birse, Kenzie D., et al.
(författare)
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Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices
- 2017
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 215:4, s. 590-598
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Tidskriftsartikel (refereegranskat)abstract
- Background. Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods. Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results. We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P =.009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions. These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.
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| 42. |
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| 43. |
- Bonde, J. P. E., et al.
(författare)
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COVID-19-related hospital admission in spouses of partners in at-risk occupations
- 2023
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Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 49:3, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to quantify the risk of COVID-19-related hospital admission in spouses living with partners in at-risk occupations in Denmark during 2020-21.Methods Within a registry-based cohort of all Danish employees (N=2 451 542), we identified cohabiting couples, in which at least one member (spouse) held a job that according to a job exposure matrix entailed low risk of occupational exposure to SARS-CoV-2 (N=192 807 employees, 316 COVID-19 hospital admissions). Risk of COVID-19-related hospital admission in such spouses was assessed according to whether their partners were in jobs with low, intermediate or high risk for infection. Overall and sex-specific incidence rate ratios (IRR) of COVID-19-related hospital admission were computed by Poisson regression with adjustment for relevant covariates.Results The risk of COVID-19-related hospital admission was increased among spouses with partners in highrisk occupations [adjusted IRR (IRRadj)1.59, 95% confidence interval (CI) 1.1-2.2], but not intermediate-risk occupations (IRRadj 0.97 95% 0.8-1.3). IRR for having a partner in a high-risk job was elevated during the first three pandemic waves but not in the fourth (IRRadj 0.48 95% CI 0.2-1.5). Sex did not modify the risk of hospital admission.Conclusions SARS-CoV-2 transmission at the workplace may pose an increased risk of severe COVID-19 among spouses in low-risk jobs living with partners in high-risk jobs, which emphasizes the need for preventive measures at the workplace in future outbreaks of epidemic contagious disease. When available, effective vaccines seem essential.
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| 44. |
- Bonde, J. P. E., et al.
(författare)
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Occupational risk of SARS-CoV-2 infection: a nationwide register-based study of the Danish workforce during the COVID-19 pandemic, 2020-2021
- 2023
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 80:4, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveMost earlier studies on occupational risk of COVID-19 covering the entire workforce are based on relatively rare outcomes such as hospital admission and mortality. This study examines the incidence of SARS-CoV-2 infection by occupational group based on real-time PCR (RT-PCR) tests. MethodsThe cohort includes 2.4 million Danish employees, 20-69 years of age. All data were retrieved from public registries. The incidence rate ratios (IRRs) of first-occurring positive RT-PCR test from week 8 of 2020 to week 50 of 2021 were computed by Poisson regression for each four-digit Danish Version of the International Standard Classification of Occupations job code with more than 100 male and 100 female employees (n=205). Occupational groups with low risk of workplace infection according to a job exposure matrix constituted the reference group. Risk estimates were adjusted by demographic, social and health characteristics including household size, completed COVID-19 vaccination, pandemic wave and occupation-specific frequency of testing. ResultsIRRs of SARS-CoV-2 infection were elevated in seven healthcare occupations and 42 occupations in other sectors, mainly social work activities, residential care, education, defence and security, accommodation and transportation. No IRRs exceeded 2.0. The relative risk in healthcare, residential care and defence/security declined across pandemic waves. Decreased IRRs were observed in 12 occupations. DiscussionWe observed a modestly increased risk of SARS-CoV-2 infection among employees in numerous occupations, indicating a large potential for preventive actions. Cautious interpretation of observed risk in specific occupations is needed because of methodological issues inherent in analyses of RT-PCR test results and because of multiple statistical tests.
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| 45. |
- Cettner, Annicka, et al.
(författare)
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Stormwater management and urban planning : lessons from 40 years of innovation
- 2013
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Ingår i: Journal of Environmental Planning and Management. - : Informa UK Limited. - 0964-0568 .- 1360-0559. ; 56:6, s. 786-801
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Tidskriftsartikel (refereegranskat)abstract
- Urban planning is widely advocated as an important way to encourage the more sustainable management of urban stormwater using alternatives to piped systems. This paper explores the way in which Swedish water professionals have opportunities to influence stormwater planning and the barriers that limit their participation in this process. Empirical evidence has been obtained from in-depth semi-structured interviews with urban water professionals from nine Swedish municipalities. The paper shows that there is a perception of the legal requirements related to the provision of drainage services that inhibits the utilisation of non-piped solutions. There are also reservations about a dichotomy that inhibits actions - is stormwater an issue for the planning department or for the water department? It is concluded that water professionals have unique opportunities to integrate stormwater management approaches within wider urban planning practice and hence are able to encourage the use of alternative systems that are more sustainable than using traditional pipes or sewers.
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| 46. |
- Chapman, David, 1972-, et al.
(författare)
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Updating Winter: The Importance Of Climate-Sensitive Urban Design For Winter Settlements
- 2018
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Ingår i: Arctic Yearbook. - : Northern Research Forum ; University of the Arctic Thematic Network (TN) on Geopolitics and Security. - 2298-2418.
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Tidskriftsartikel (refereegranskat)abstract
- This study explores winter settlement urban design principles to begin to identify climate related conditions that are affecting soft mobility (walking and cycling) in these communities.Winter communities have evolved lifestyles and means that fit with working and living with local conditions and seasonal variations. With climate change, however, comes evolving weather’s that these communities need to adapt too. These changes may present new risks and unexpected challenges to outdoor soft mobility in the community.Public policy highlights physical inactivity as a major health concern. For these communities, winter has always limited outdoor soft-mobility. Here, we understand that in winter outdoor activity can be reduced by weather and fear of accidents.People’s understanding of the barriers and enablers to soft mobility are also often based on experience and ability to detect environmental clues. To help winter communities maximise the opportunities for outdoor soft mobility and the wellbeing benefits this can bring, built environments need to be designed with an understanding of climate change. This study explores barriers and enablers to soft mobility in winter and discusses them in light of climate change and human wellbeing. It is argued that established principles of urban design may require re-evaluation if we want to increase outdoor soft mobility in winter. Increases in physical activity could help reduce costs and pressures on health services by creating safer and more walkable communities. The paper concludes by suggesting that communities should focus on more context based winter urban design principles that account for ongoing climate change.
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| 47. |
- Chapman, David, 1972-, et al.
(författare)
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Winter City Urbanism : Enabling All Year Connectivity for Soft Mobility
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- This study explores connectivity for soft mobility in the winter season. Working with residents from the sub-arctic city of Luleå, Sweden, the research examines how the interaction between the built environment and winter season affects people’s use of the outdoor environment. The research questions for this study are, 1) how do residents perceive the effects of winter on an areas spatial structure and pattern of streets and pathways? and 2) what enablers and barriers impact resident soft mobility choices and use of the public realm in winter? Methods used were mental mapping and photo elicitation exercises. These were used to gain a better understanding of people’s perception of soft mobility in winter. The results were analysed to identify how soft mobility is influenced by the winter season. The discussion highlights that at the neighbourhood scale, residents perceive that the winter alters an areas spatial structure and pattern of streets and pathways. It was also seen to reduce ease of understanding of the public realm and townscape. In conclusion, it is argued that new and re-tooled town planning strategies, such as extending blue/ green infrastructure planning to include white space could help better enable all year outdoor activity in winter cities.
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| 48. |
- Ebrahimabadi, Saeed, et al.
(författare)
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The problems of addressing microclimate factors in urban planning of the subarctic regions
- 2015
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Ingår i: Environment and Planning, B. - : SAGE Publications. - 0265-8135 .- 1472-3417. ; 42:3, s. 415-430
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Tidskriftsartikel (refereegranskat)abstract
- Urban life in the towns of the subarctic regions is affected by the severity of the local climate, which must be taken into account in urban planning. Previous studies show that the use of climate knowledge in urban planning is hindered by different constraints. In this study we focus specifically on the problems of incorporating microclimate factors into the urban planning practices in northern Sweden. We rely on a literature study and focus on interviews as our study methods. Some of the major problems identified are the lack of design knowledge relevant to a cold climate, lack of user-friendly tools to analyze microclimate, overlooking the potential uses of local climate, and lack of support from politicians. The problems related to knowledge development and the lack of tools for microclimate analysis are discussed further. In terms of knowledge issues, the planners’ awareness of climate objectives achievable at different planning scales needs to be improved. There should be further research into the effect of urban form on the use of snow and on snow-removal activities. Tools for microclimate analysis should become more user friendly for planners. More importantly, planners need methods that combine different microclimate analyses and offer a complete assessment of a given design scheme.
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| 49. |
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| 50. |
- Efe, C., et al.
(författare)
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Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
- 2019
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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