| 1. |
- Leonard, Dag, et al.
(författare)
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Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants
- 2013
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Ingår i: Circulation: Cardiovascular Genetics. - : BMJ. - 1942-325X .- 1942-3268. ; 72:Suppl. 3, s. 270-270
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Tidskriftsartikel (refereegranskat)abstract
- Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9x10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.
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| 2. |
- Leonard, Dag, 1975-, et al.
(författare)
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Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis.
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:7, s. 1063-1069
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA.METHODS: Patients with SLE (n=1045) were genotyped using the 200K Immunochip SNP array (Illumina). The allele frequency was compared between patients with and without different manifestations of CVD. Results were replicated in a second SLE cohort (n=1043) and in an RA cohort (n=824). We analysed publicly available genetic data from general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of antiphospholipid antibodies (aPLs).RESULTS: We identified two new putative risk loci associated with increased risk for CVD in two SLE populations, which remained after adjustment for traditional CVD risk factors. An IL19 risk allele, rs17581834(T) was associated with stroke/myocardial infarction (MI) in SLE (OR 2.3 (1.5 to 3.4), P=8.5×10-5) and RA (OR 2.8 (1.4 to 5.6), P=3.8×10-3), meta-analysis (OR 2.5 (2.0 to 2.9), P=3.5×10-7), but not in population controls. The IL19 risk allele affected protein binding, and SLE patients with the risk allele had increased levels of plasma-IL10 (P=0.004) and aPL (P=0.01). An SRP54-AS1 risk allele, rs799454(G) was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3 to 2.2), P=2.5×10-5) but not in RA. The SRP54-AS1 risk allele is an expression quantitative trait locus for four genes.CONCLUSIONS: The IL19 risk allele was associated with stroke/MI in SLE and RA, but not in the general population, indicating that shared immune pathways may be involved in the CVD pathogenesis in inflammatory rheumatic diseases.
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| 3. |
- Sandling, Johanna K., et al.
(författare)
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Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80:1, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. Methods: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). Results: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. Conclusions: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.
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| 4. |
- Carlsson Almlöf, Jonas, et al.
(författare)
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Novel risk genes for systemic lupus erythematosus predicted by random forest classification
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.
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| 5. |
- Farias, Fabiana H. G., et al.
(författare)
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A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27, s. 432-441
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted re-sequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-U1-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.
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| 6. |
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| 7. |
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| 8. |
- Jansson, Sven-Arne, et al.
(författare)
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Health-related quality of life, assessed with a disease-specific questionnaire, in Swedish adults suffering from well-diagnosed food allergy to staple foods
- 2013
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 3:21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOur aim was to investigate the factors that affect health related quality of life (HRQL) in adult Swedish food allergic patients objectively diagnosed with allergy to at least one of the staple foods cow’s milk, hen’s egg or wheat. The number of foods involved, the type and severity of symptoms, as well as concomitant allergic disorders were assessed.MethodsThe disease-specific food allergy quality of life questionnaire (FAQLQ-AF), developed within EuroPrevall, was utilized. The questionnaire had four domains: Allergen Avoidance and Dietary Restrictions (AADR), Emotional Impact (EI), Risk of Accidental Exposure (RAE) and Food Allergy related Health (FAH). Comparisons were made with the outcome of the generic questionnaire EuroQol Health Questionnaire, 5 Dimensions (EQ-5D). The patients were recruited at an outpatient allergy clinic, based on a convincing history of food allergy supplemented by analysis of specific IgE to the foods in question. Seventy-nine patients participated (28 males, 51 females, mean-age 41 years).ResultsThe domain with the most negative impact on HRQL was AADR, assessing the patients’ experience of dietary restrictions. The domain with the least negative impact on HRQL was FAH, relating to health concerns due to the food allergy. One third of the patients had four concomitant allergic disorders, which had a negative impact on HRQL. Furthermore, asthma in combination with food allergy had a strong impact. Anaphylaxis, and particularly prescription of an epinephrine auto-injector, was associated with low HRQL. These effects were not seen using EQ-5D. Analyses of the symptoms revealed that oral allergy syndrome and cardiovascular symptoms had the greatest impact on HRQL. In contrast, no significant effect on HRQL was seen by the number of food allergies.ConclusionsThe FAQLQ-AF is a valid instrument, and more accurate among patients with allergy to staple foods in comparison to the commonly used generic EQ-5D. It adds important information on HRQL in food allergic adults. We found that the restrictions imposed on the patients due to the diet had the largest negative impact on HRQL. Both severity of the food allergy and the presence of concomitant allergic disorders had a profound impact on HRQL.
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| 9. |
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| 10. |
- Jönsen, Andreas, et al.
(författare)
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Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts
- 2016
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Ingår i: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 45:6, s. 684-690
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The main objectives of this study were to calculate total costs of illness and cost -driving disease features among patients with systemic lupus erythematosus (SLE) in Sweden. Methods: Five cohorts of well-defined SLE patients, located in different parts of the country were merged. Incident and prevalent cases from 2003 through 2010 were included. The American College of Rheumatology (ACR) classification criteria was used. From the local cohorts, data on demographics, disease activity (SLEDAI 2K), and organ damage (SDI) were collected. Costs for inpatient care, specialist outpatient care and drugs were retrieved from national registries at the National Board of Health and Welfare. Indirect costs were calculated based on sickness leave and disability pensions from the Swedish Social Insurance Agency. Results: In total, 1029 SLE patients, 88% females, were included, and approximately 75% were below 65 years at the end of follow-up, and thus in working age. The mean number of annual specialist physician visits varied from six to seven; mean annual inpatient days were 3.1-3.6, and mean annual sick leave was 123-148 days, all per patient. The total annual cost was 208,555 SEK ($33,369 = 22,941(sic)), of which direct cost was 63,672kr ($10,188 = 7004(sic)) and the indirect cost was 144,883 SEK ($23,181 = 15,937(sic)), all per patient. The costs for patients with short disease duration were higher. Higher disease activity as measured by a SLEDAI 2K score > 3 was associated with approximately 50% increase in both indirect and direct costs. Damage in the neuropsychiatric and musculoskeletal domains were also linked to higher direct and indirect costs, while organ damage in the renal and ocular systems increased direct costs. Conclusion: Based on this study and an estimate of slightly more than 6000 SLE patients in Sweden, the total annual cost for SLE in the country is estimated at $188 million (= 129.5 million (sic)). Both direct (30%) and indirect costs (70%) are substantial. Medication accounts for less than 10% of the total cost. The tax paid national systems for health care and social security in Sweden ensure equal access to health care, sick leave reimbursements, and disability pensions nationwide. Our extrapolated annual costs for SLE in Sweden are therefore the best supported estimations thus far, and they clearly underline the importance of improved management, especially to reduce the indirect costs. (C) 2016 Elsevier Inc. All rights reserved.
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| 11. |
- Lundström, Emeli, et al.
(författare)
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HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72:6, s. 1018-1025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES:Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients.METHODS:665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR.RESULTS: HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL—cardiolipin IgG and IgM, β2-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04—while HLA-DRB1*13 was associated with IgG antibodies (β2-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD.CONCLUSIONS:The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.
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| 12. |
- Protudjer, Jennifer L. P., et al.
(författare)
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Household Costs Associated with Objectively Diagnosed Allergy to Staple Foods in Children and Adolescents
- 2015
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Ingår i: Journal of Allergy and Clinical Immunology-In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 3:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported that indirect and intangible costs burden households with a food allergic adult. We now extend our investigation to households with food allergic children and adolescents. OBJECTIVE: The objective of this study was to estimate direct, indirect, and intangible costs of food allergy in households with a child and/or adolescent with objectively diagnosed allergy to staple foods (cow's milk, hen's egg, and/or wheat), and to compare these costs with age-and sex-matched controls. METHODS: Direct and indirect cost parent-reported data collected via the Food Allergy Socio-Economic Questionnaire of 84 children (0-12 years) and 60 adolescents (13-17 years) with objectively diagnosed allergy to staple foods ("cases") and age- and sex-matched controls (n = 94 children; n = 56 adolescents) were compared. Annual household costs were calculated. Total household costs included direct plus indirect costs. Intangible costs included parent-reported health of their child and/or adolescent, standard of living, and perceptions of well-being. RESULTS: Amongst cases, total household costs were higher by (sic)3961 for children and (sic)4792 for adolescents versus controls (P < .05), and were driven by direct (eg, medications) and indirect (eg, time with health care professionals) costs. For children only, a history of anaphylaxis was associated with higher direct costs than no anaphylaxis ((sic)13,016 vs (sic)10,044, P < .05). Intangible costs (eg, parent-reported health of a child and/or adolescent) were significantly impacted amongst cases versus controls (P < .01). CONCLUSION: Households with a child and/or adolescent with objectively diagnosed allergy to staple foods have higher total household costs than controls. Direct and indirect costs were significantly higher for cases versus controls amongst children only. Amongst both age groups, such allergy adversely impacted intangible costs. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
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| 13. |
- Protudjer, Jennifer Lisa Penner, et al.
(författare)
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Impaired health-related quality of life in adolescents with allergy to staple foods
- 2016
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cow's milk, hen's egg and wheat are staple foods in a typical western diet. Despite the ubiquity of these foods, the impact of staple food allergy on health-related quality of life (HRQL) amongst adolescents is incompletely understood. The aims of this study were to make use of the Swedish version of EuroPrevall's disease-specific food allergy quality of life questionnaire-teenager form (FAQLQ-TF) and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents. Methods: In this cross-sectional study, 58 adolescents aged 13-17 years [n = 40 (69 %) boys] with objectively-diagnosed allergy to the staple foods cow's milk, hen's egg and/or wheat and living in Stockholm, Sweden were included. Adolescents completed the FAQLQ-TF, which has a corresponding scale of 1 = best HRQL, and 7 = worst HRQL. Overall HRQL and domain-specific HRQL were established. Adolescents also reported symptoms, adrenaline auto injector (AAI) prescription and presence of other food allergies. A history of anaphylaxis was defined among those reporting difficulty breathing, inability to stand/collapse, and/or loss of consciousness. Clinically different HRQL was set at a mean difference of >= 0.5. Results: Overall mean HRQL was poorer than average [mean: 4.70/7.00 (95 % CI 4.30-5.01)]. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions (mean difference = 0.76; p < 0.001). Girls had clinically worse, but not statistically significantly different mean HRQL than boys (mean difference = 0.71; p < 0.07). HRQL tended to be worse amongst those with allergies to more than three foods or an AAI prescription. The number and types of symptoms, including a history of anaphylaxis were not associated with worse HRQL. Conclusions: As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL.
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| 14. |
- Reid, Sarah, et al.
(författare)
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High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79:3, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).METHODS: Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.RESULTS: SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10-86 and OR 7.48 (6.73 to 8.32), p=2.2×10-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10-2), anti-β2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10-2) in high to low quartile comparison.CONCLUSIONS: A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.
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| 15. |
- Reid, Sarah, et al.
(författare)
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High Genetic Risk Score Is Associated with Increased Organ Damage in SLE
- 2017
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 69
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with a complex genetic etiology. Over 80 risk genes for SLE have been identified and some genetic variants have demonstrated association with specific disease manifestations, such as STAT4 and nephritis. The overall effect of a patient’s hereditary risk factors on disease severity has so far not been studied. We therefore assessed the relationship between high genetic risk and development of organ damage in SLE.Methods: Patients with SLE, who met at least 4 ACR criteria (n = 1012), were genotyped using a 200K Immunochip SNP Array (Illumina). A genetic risk score (GRS) was assigned to each patient based on the single nucleotide polymorphisms (SNPs) which in previous studies have shown association (p<5×10-8) with SLE according to Morris, et al (Nat Genet, 2016. 48(8): p. 940-6). For 32 loci the SLE GWAS SNP was available on the ImmunoChip. For each SNP, the natural logarithm of the odds ratio (OR) for SLE susceptibility was multiplied by the number of risk alleles in each individual. The sum of all products for each patient was defined as the GRS. Information regarding organ damage according to Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SLICC-DI), disease manifestations, antibody profile, medication, current disease activity, age at diagnosis and sex was retrieved from medical records. Statistical analyzes were performed using Statistica 13.2 (Statsoft).Results: In an ordinal regression model, with SLICC-DI (0, 1, 2, 3, 4 and >4 points) as outcome and age and GRS as independent variables, an association was found between GRS and SLICC-DI (OR1.16 (1.03-1.31), p=0.015). The relationship was more pronounced for patients under 60 years of age (OR1.30 (1.11-1.52) p=7.1×10-4). Using a linear regression model, a negative relationship was observed between GRS and age at diagnosis (β = -0.13, p=1.5×10-5).When analyzing the 11 SLE criteria (ACR-82) using a logistic regression model associations were observed between GRS and nephritis (OR 1.26 (1.09-1.45), p=0.0015), the immunological criteria (OR 1.31 (1.13-1.51), p = 3.2×10-4) and arthritis (OR 0.84 (0.71-1.00), p=0.044). A high GRS was also associated with presence of anti-dsDNA (OR 1.37 (1.15-1.62), p=9.4×10-7) and low complement levels (OR 1.32 (1.03-1.68), p=0.044). No association was observed between GRS and disease activity at the time of follow-up and there was no difference in GRS between men and women with SLE.Conclusion: In patients with SLE, there is an association between a high genetic risk score and early disease onset. In addition, patients with high genetic risk scores have a higher risk of developing permanent organ damage compared to individuals with fewer risk genes. Our findings indicate that genetic profiling of patients with SLE may provide a tool for predicting severity of the disease.
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| 16. |
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| 17. |
- Svenungsson, Elisabet, et al.
(författare)
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A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:5, s. 834-840
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. Methods Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. Results The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (ORc)=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (ORc=2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (ORc=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p≤0.02 for all). Conclusion Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism.
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| 18. |
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| 19. |
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| 20. |
- Ahnström, Johan, et al.
(författare)
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Farmers' Interest in Nature and Its Relation to Biodiversity in Arable Fields
- 2013
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Ingår i: International Journal of Ecology. - : Hindawi Publishing Corporation. - 1687-9708 .- 1687-9716.
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity declines in farmland have been attributed to intensification of farming at the field level and loss of heterogeneity at the landscape level. However, farmers are not solely optimizing production; their actions are also influenced by social factors, tradition and interest in nature, which indirectly influence biodiversity but rarely are incorporated in studies of farmland biodiversity. We used social science methods to quantify farmers’ interest in nature on 16 farms with winter wheat fields in central Sweden, and combined this with biodiversity inventories of five organism groups (weeds, carabid beetles, bumblebees, solitary bees, and birds) and estimates of landscape composition andmanagement intensity at the field level.Agricultural intensity,measured as crop density, and farmers’ interest in nature explained variation in biodiversity, measured as the proportion of the regional species richness found on single fields. Interest in nature seemed to incorporate many actions taken by farmers and appeared to be influenced by both physical factors, for example, the surrounding landscape, and social factors, for example, social motivations.This study indicates that conservation of biodiversity in farmland, and design of new agri-environmental subsidy systems, would profit from taking farmers’ interest in nature and its relation to agricultural practices into account.
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| 21. |
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| 22. |
- Almlöf, Jonas Carlsson, et al.
(författare)
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Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus
- 2019
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Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 138:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare (0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported.
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| 23. |
- Andersson, Peter, Universitetslektor, 1959-, et al.
(författare)
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The Danish Problem: Soon Everybody’s? : A Comparative Analysis of Digitalization Effects on Letter Volumes
- 2019
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Ingår i: New Business and Regulatory Strategies in the Postal Sector. - Cham : Springer London. - 9783030029364 - 9783030029371 ; , s. 285-297
-
Bokkapitel (refereegranskat)abstract
- Letter volumes in Denmark dropped with 75 percent between 2000 and 2016, whereas Sweden’s declined with 34 percent. We make a comparative analysis of Denmark and Sweden by analyzing the effects of digitalization and the strategies from the common USO-provider Postnord. Denmark had a national digitalization strategy already from 2001 and a law in 2012 required everybody to have a digital mailbox. In response to falling demand, prices were increased sharply and service reduced. Sweden has a fragmented market for digital messages and with large postal volumes, competitive prices, a well-functioning market for second class mail and better ability to adjust costs, digital substitution was limited.
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| 24. |
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| 25. |
- Bengtsson, Fredrik, et al.
(författare)
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Knowledge Management - kunskapsbeskrivning och representation
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med projektet är att undersöka kunskapshantering inom museer för att få en klarare och mer strukturerad bild av det arbete som görs kring föremålen på ett museum. Vårt arbete grundar sig på material från ett antal intervjuer med anställda vid Museum Gustavianum i Uppsala samt skriftliga arbetsbeskrivningar som ligger till stöd för de anställda där. Vi har inte för avsikt att analysera den organisatoriska aspekten av museiarbetet.För att uppnå syftet har vi valt att utgå från tanken att arbetet med föremålen kan beskrivas som ett antal händelser som kretsar kring föremålet i olika situationer. Dessa händelser kan sedan relateras till varandra och på så sätt beskriva ett flöde som hänger logiskt samman för att nå ett givet mål.Genom denna ansats kan vi beskriva olika situationer som en logisk händelsekedja som låter sig analyseras för vidare arbete. Vi har för avsikt att utifrån detta material göra en skriftlig beskrivning, samt beskriva dessa händelsekedjor grafisk i form av ”flöden” för att slutligen ge exempel på modelleringar enligt CIDOC CRM. CIDOC CRM är en ontologisk referensmodell för att modellera kulturarvs-information.
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| 26. |
- Bengtsson, Hanna, et al.
(författare)
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PHYSICOCHEMICAL CHARACTERIZATION OF FRUIT AND VEGETABLE FIBER SUSPENSIONS. II: EFFECT OF VARIATIONS IN HEAT TREATMENT
- 2011
-
Ingår i: Journal of Texture Studies. - : Wiley. - 0022-4901. ; 42:4, s. 281-290
-
Tidskriftsartikel (refereegranskat)abstract
- The pectin content in the soluble and insoluble fractions of fiber suspensions from carrot, potato pulp and apple heat treated in four different ways was determined together with the particle size distribution, water-holding capacity (WHC), morphology and rheological properties of the fiber suspensions. In the carrot and apple suspensions, where beta-elimination was favored, the soluble pectin increased, whereas a significant but small decrease of the mean particle size of the insoluble material was obtained together with a significant decrease in WHC. For the potato pulp suspensions, however, only minor pectin solubilization was observed by heat treatment. Instead remaining starch in the cell matrix swelled on prolonged heating, leading to a different particle size distribution and a significant increase in WHC However, only minor effects on heating were seen on the elastic modulus for all fiber sources studied. But the source of fiber seems to be more important for the elastic modulus of the suspension, where the order of firmness in heated tissues (not the suspensions) seems to be the determining factor, being in the order of apple > potato > carrot.
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| 27. |
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| 28. |
- Bengtsson, Johan, et al.
(författare)
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Autonomic modulation networks in schizophrenia : The relationship between heart rate variability and functional and structural connectivity in the brain
- 2020
-
Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 300
-
Tidskriftsartikel (refereegranskat)abstract
- Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.
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| 29. |
- Bengtsson, Johanna, 1974, et al.
(författare)
-
Evaluations of effects due to low-frequency noise in a low demanding work situation
- 2004
-
Ingår i: Journal of Sound and Vibration. - : Elsevier BV. - 0022-460X .- 1095-8568. ; 278:1-2, s. 83-99
-
Tidskriftsartikel (refereegranskat)abstract
- Noise sources with a dominating content of low frequencies (20-200 Hz) are found in many occupational environments. This study aimed to evaluate effects of moderate levels of low-frequency noise on attention, tiredness and motivation in a low demanding work situation. Two ventilation noises at the same A-weighted sound pressure level of 45 dB were used: one of a low-frequency character and one of a flat frequency character (reference noise). Thirty-eight female subjects worked with six performance tasks for 4 h in the noises in a between-subject design. Most of the tasks were monotonous and routine in character. Subjective reports were collected using questionnaires and cortisol levels were measured in saliva. The major finding in this study was that low-frequency noise negatively influenced performance on two tasks sensitive to reduced attention and on a proof-reading task. Performances of tasks aimed at evaluating motivation were not significantly affected. The difference in work performance was not reflected by the subjective reports. No effect of noise was found on subjective stress or cortisol levels.
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| 30. |
- Bengtsson, Johanna, 1985-, et al.
(författare)
-
Ketoconazole, omeprazole, and primaquine prolong and enhance the aryl hydrocarbonreceptor signaling induced by the endogenous ligand FICZ
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Several compounds that inhibit cytochrome P4501 (CYP1) enzymes have been shown to actas aryl hydrocarbon receptor (AHR) agonists by reducing the metabolic turnover of the endogenous receptor ligand 6-formylindolo[3,2-b]carbazole (FICZ). In this study we aimed at investigating whether a group of widely prescribed drugs, namely ketoconazole (KTZ),omeprazole (OME) and primaquine (PQ), can act as indirect AHR activators via this mechanism. Inhibitory effects of KTZ, PQ, and OME were measured in CYP1A1 expressing supersomes and all three drugs inhibited CYP1A1 activity. KTZ was the most efficient inhibitor and HPLC analysis revealed that KTZ slowed down the metabolic turnover of intracellular FICZ. All three drugs induced the catalytic activity of CYP1A1 (7-ethoxyresorufin-O-deethylase, EROD) in HaCaT cells as well as increased the expression of CYP1A1 mRNA. Co-exposure to the drugs with FICZ prolonged and enhanced FICZ-induced AHR activation in a synergistic manner. Our findings indicate that KTZ activate AHR by inhibiting the metabolic turnover of FICZ. Interestingly, PQ and OME seem to act by other mechanisms that sensitize the cells to FICZ-dependent transcriptional activation of the AHR.To the author’s knowledge, this is the first publication indicating that KTZ, OME, and PQ can superinduce AHR signaling by increasing the responses to an endogenous receptor ligand.
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| 31. |
- Bengtsson, Johanna, 1974
(författare)
-
Low frequency noise during work. Effects on performance and annoyance
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims. Low frequency noise (LFN) is defined as "a noise with a dominant frequency content of 20 to 200 Hz". Common sources of LFN in occupational environments are ventilation, heating and air-conditioning systems, computer network installations and compressors. The aims were to evaluate the influence of LFN on performance, annoyance, other subjective effects, cortisol levels and subjective stress. A further aim was to evaluate whether the frequency balance and modulation frequency in a LFN influenced a subject's perception of pleasantness. Methods. All studies were laboratory experiments. The experiment reported in papers I and II comprised 32 subjects who worked for 2 h with four performance tasks under high workload during exposure to LFN and a reference noise at an A-weighted sound pressure level of 40 dB. The experiment reported in paper III comprised 38 subjects who worked for 4 h with six performance tasks under low workload during exposure to LFN or reference noise at an A-weighted sound pressure level of 45 dB. The experiment reported in paper IV comprised 30 subjects who varied the level of the sound characteristic's frequency balance and modulation frequency in the LFN to make the noise more pleasant.Results. LFN impaired performance in tasks with high and moderate demands on cognitive processing when carried out under high workload and in tasks with moderate and low demands when these were performed under low workload. No difference between noise conditions was found in low demand tasks performed under high workload and tasks evaluating motivation performed under low workload. LFN was rated to have a greater impairment on the work capacity and be more annoying than reference noise; the difference between noises was significant under high workload. No difference between noise conditions was found in subjective symptoms, but annoyance and reported impairment of the work capacity due to LFN was related to several symptoms. This was less frequently found for reference noise. Subjects high-sensitive to LFN or to noise in general performed less well and reported higher annoyance due to LFN. The effects caused by LFN were most pronounced for subjects high-sensitive to LFN. Exposure to LFN during high workload resulted in elevated cortisol levels among subjects high-sensitive to noise in general, and a tendency towards the same result was found for subjects high-sensitive to LFN. No clear relationships between cortisol levels and subjective stress were found. The resulting pleasant LFN comprised less perceivable modulations and a lower content of frequencies below 500 Hz. The effect was less marked when the original LFN did not comprise modulations and, when the A-weighted sound pressure level could be altered, a steeper slope was preferred to a higher level. Conclusions. The experiments showed that exposure to LFN during work can impair performance, lead to subjective annoyance and increase cortisol levels, even at moderate sound pressure levels. The effects were influenced by workload and noise sensitivity. The performance effects are hypothesised to be mediated by impaired learning and reduced attention. To achieve a more pleasant LFN, the noise should contain no or little perceivable modulations and a lower relative content of low frequencies.
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| 32. |
- Bengtsson, Johanna, 1974, et al.
(författare)
-
Sound characteristics in low frequency noise and their relevance for the perception of pleasantness
- 2004
-
Ingår i: Acta Acoustica. ; 90:1, s. 171-180
-
Tidskriftsartikel (refereegranskat)abstract
- Noise sources with a dominant content of low frequencies (20-200 Hz) are found in many occupational environments. Work efficiency has been found in two earlier studies to be impaired to a larger degree when working in a low frequency ventilation noise than when working in a flat frequency ventilation noise at the same A-weighted sound pressure level. Other previous studies indicate that different sound characteristics found in low frequency noise are important for the way in which low frequency noise affects humans, and better knowledge of these characteristics could lead to better methods for assessing low frequency noise in occupational environments. The aim of this study was to evaluate the influence of frequency balance between low and high frequencies, which affects the slope of the frequency spectra, and the modulation frequency on subjects´ perception of a pleasant low frequency noise. The results showed that the subjects preferred either a higher or a lower modulation frequency as compared to that of the original low frequency noise, both choices leading to less perceivable modulations. Furthermore, the subjects preferred a lower relative content of frequencies below 500 Hz, but only as long as the original low frequency noise contained modulations and the variations were made within a constant A-weighted sound pressure level. The results are discussed in relation to improved guidelines and to the previously suggested theory of slope of the frequency spectra and problems involved with the implementation of that theory.
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| 33. |
- Bengtsson, Johanna, 1985-
(författare)
-
The impact of cytochrome P4501-inhibitors on aryl hydrocarbon receptor signaling
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aryl hydrocarbon receptor (AHR) best known as a ligand-activated transcription factor that mediates toxic responses to xenobiotics such as dioxins, is also activated by certain endogenous compounds. Activation of the AHR up-regulates transcription of a large number of genes, including those encoding members of the cytochrome P450 1 family of enzymes (CYP1s). Although the AHR has been shown to be involved in several normal processes, its physiological role remains elusive. The endogenous ligand 6-formylindolo[3,2-b]carbazole (FICZ), formed from tryptophan, is present in cell culture media and biological specimens. FICZ is an excellent substrate for CYP1 enzymes and together FICZ/AHR/CYP1A1 interactions constitute an auto regulatory feedback loop that controls AHR signaling. A vast number of compounds that inhibit CYP1 enzymes have been reported to be AHR activators, even though they have little or no affinity for the receptor. We hypothesized, that their agonistic effects are dependent on the presence of background levels of FICZ. To test this, AHR signaling in different cell systems exposed to FICZ and/or inhibitors was assessed by measuring EROD activity and CYP1A1 transcription. In addition to a commercial culture medium, a medium free of background levels of FICZ was used. Activation of AHR by of a diverse set of CYP1A1 inhibitors did require FICZ in the culture medium. Furthermore, the compounds tested both prolonged and potentiated FICZ-induced receptor signaling. On the basis of these observations we propose that a compound may activate AHR signaling indirectly by inhibiting CYP1A1 and thereby attenuating the metabolism of FICZ. This mechanism was confirmed for certain polyphenols and pharmaceuticals. Surprisingly, the activating capacity and potentiating effect of two pharmaceuticals on AHR signaling could not be explained by the mechanism proposed, and we speculated that in these cases the agonistic effect might involve interactions of the cellular antioxidant response with the basic transcription machinery. Together, our observations provide a mechanistic explanation as to how compounds that inhibit CYP1A1 can activate AHR signaling. They also indicate that the general perception of the binding pocket of AHR as promiscuous, is probably wrong. The fact that indirect activation of AHR may cause sustained signaling requires further studies in vivo not least, in order to prevent toxicity.
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| 34. |
- Bengtsson, Mathilda, et al.
(författare)
-
Metoden ByggF-PST : Tillämpning av ByggaF på tillverkning av prefabricerade småhus i trä. Version 1.0
- 2018
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Metoden som presenteras i detta dokument är en tillämpning av ByggaF påprefabricerad småhustillverkning av hus med träbaserad stomme kallad:”ByggaF för Prefabricerade småhus med trästomme”, hädanefter omnämnd somByggaF-PST. ByggaF-PST är en metod som säkerställer, dokumenterar ochkommunicerar fuktsäkerheten i hela byggprocessen, från planering tillbruksskede. Metoden innebär ett arbetssätt för att uppfylla samhällets krav påfuktsäkerhet och innehåller rutiner och hjälpmedel för alla aktörer, frånsmåhustillverkare, konsulter, materialleverantörer och entreprenörer.
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| 35. |
- Bengtsson Ryberg, Johanna, 1974, et al.
(författare)
-
Low frequency noise in a paper mill control room
- 2007
-
Ingår i: Journal of Low Frequency Noise, Vibration and Active Control. - : SAGE Publications. - 0263-0923 .- 1461-3484 .- 2048-4046. ; 26:3, s. 165-176
-
Tidskriftsartikel (refereegranskat)abstract
- This field study aimed to evaluate the prevalence of annoyance and disturbance and the subjective perception of the sound environment due to noise, in an old and a new control room at a large paper mill. Working in a control room requires sustained attention and concentration and, in the case of error messages, rapid and correct decisions. In this study, the personnel's responses were collected by questionnaire, and detailed sound measurements were taken in both control rooms. The A-weighted sound pressure level in the new control room was 54.9 dB, a reduction from the 63.5 dB measured in the old room, and the C-weighted sound pressure level was 66.8 dB, a reduction from the 75.2 dB measured in the old room. The new control room was rated as being a less noisy environment; however, the personnel did complain about noise from other computers/equipment, radios, and the new laboratory.
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| 36. |
- Bengtsson Ryberg, Johanna, 1974, et al.
(författare)
-
Low frequency noise in a paper mill control room
- 2004
-
Ingår i: The 11th International Meeting on Low Frequency Noise and Vibration and its Control, 2004 30 August-1 September, Maastricht, The Netherlands. ; , s. 15-25
-
Konferensbidrag (refereegranskat)
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| 37. |
- Bengtsson Ryberg, Johanna, et al.
(författare)
-
The Effects of Wind Power on Human Interests : A Synthesis
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- PrefaceThere is a great need for knowledge concerning the impacts of wind power on humans, landscapes, the marine environment, birds, bats and other mammals.Previous studies of these environmental impacts have lacked an overall view of the effects. This has led to deficiencies in the processes surrounding the establishment of new wind farms. Vindval is a knowledge programme undertaken as a collaboration between the Swedish Energy Agency and the Swedish Environmental Protection Agency. Its aim is to gather and communicate scientific knowledge about the impacts of wind power on people and the natural environment. The programme continues until 2013.Vindval comprises some 30 individual research projects, together with four synthesis projects. Syntheses are prepared by experts, who compile and assess overall research results and experience regarding the effects of wind power in four different areas – humans, birds/bats, marine life and terrestrial mammals.The results of this research and synthesis work will provide a basis for environmental impact assessments and for the planning and permitting processes associated with wind power installations. Vindval requires high standards in the review and approval of research proposals, in order to ensure high-quality reports. The same high standards apply to the reporting, approval and publication of research results from the projects.This report was written by Johanna Bengtsson Ryberg, Gösta Bluhm, Karl Bolin, Bosse Bodén, Kristina Ek, Karin Hammarlund, Marianne Henningsson, Inga-Lena Hannukka, Carina Johansson, Sofia Jönsson, Sanna Mels, Tom Mels, Mats Nilsson, Erik Skärbäck, Patrik Söderholm, Åsa Waldo, Ingegärd Widerström, Niklas Åkerman.This report is a translation of the previous report in Swedish “Vindkraftens påverkan på människors intressen” (Naturvårdsverket report no 6497). Translated by Sofia Jönsson.The contents of the report are the responsibility of the authors.
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| 38. |
- Bengtsson, Therese, et al.
(författare)
-
Activation of defence responses to Phytophthora infestans in potato by BABA
- 2014
-
Ingår i: Plant Pathology. - : Wiley. - 0032-0862 .- 1365-3059. ; 63, s. 193-202
-
Tidskriftsartikel (refereegranskat)abstract
- Late blight caused by Phytophthora infestans is one of the most devastating diseases of the potato crop. Resistance breeding and current fungicides are unable to control the rapidly evolving P. infestans and new control strategies are urgently needed. This study examined mechanisms of dl-β-aminobutyric acid (BABA)-induced resistance (IR) in the potato-P. infestans system. Leaves from two cultivars that differ in their degree of resistance, Bintje and Ovatio, were analysed after foliar treatment with BABA. Rapid activation of various defence responses and a significant reduction in P. infestans growth were observed in leaves treated with BABA. In the more resistant cultivar, Ovatio, the activation was both faster and stronger than in Bintje. Microscopic analysis of leaves treated with BABA revealed induction of small hypersensitive response (HR)-like lesions surrounded by callose, as well as production of hydrogen peroxide (H2O2). Molecular and chemical analyses revealed soluble phenols such as arbutin and chlorogenic acid and activation of PR-1. These results show a direct activation of defence responses in potato, rather than priming as reported for other plant species. They also show that the efficiency of BABA-IR differs between cultivars, which highlights the importance of taking all aspects into consideration when establishing new methods for disease management.
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| 39. |
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| 40. |
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| 41. |
- Bengtsson, Torbjörn, 1955-, et al.
(författare)
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Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics
- 2020
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 αβ were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 α and β were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 αβ caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, β1-22, β7-34 and β1-20 retained an inhibitory activity. The peptides diffused rapidly (2 min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 αβ substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 αβ is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.
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| 42. |
- Bengtsson, Torbjörn, 1955-, et al.
(författare)
-
The lantibiotic gallidermin acts bactericidal against Staphylococcus epidermidis and Staphylococcus aureus and antagonizes the bacteria-induced proinflammatory responses in dermal fibroblasts
- 2018
-
Ingår i: MicrobiologyOpen. - : John Wiley & Sons. - 2045-8827. ; 7:6
-
Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance needs to be tackled from new angles, and antimicrobial peptides could be future candidates for combating bacterial infections. This study aims to investigate in vitro the bactericidal effects of the lantibiotic gallidermin on Staphylococcus epidermidis and Staphylococcus aureus, possible cytotoxic effects and its impact on host-microbe interactions. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of gallidermin were determined, and cytotoxicity and proinflammatory effects of gallidermin on fibroblasts, red blood cells (RBCs) and in whole blood were investigated. Both MIC and MBC for all four tested strains of S. epidermidis was 6.25 μg/ml. Both MIC and MBC for methicillin-sensitive S. aureus was 12.5 μg/ml and for methicillin-resistant S. aureus (MRSA) 1.56 μg/ml. Gallidermin displayed no cytotoxic effects on fibroblasts, only a high dose of gallidermin induced low levels of CXCL8 and interleukin-6. Gallidermin hemolyzed less than 1% of human RBCs, and did not induce reactive oxygen species production or cell aggregation in whole blood. In cell culture, gallidermin inhibited the cytotoxic effects of the bacteria and totally suppressed the bacteria-induced release of CXCL8 and interleukin-6 from fibroblasts. We demonstrate that gallidermin, expressing low cell cytotoxicity, is a promising candidate for treating bacterial infections caused by S. epidermidis and S. aureus, especially MRSA.
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| 43. |
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| 44. |
- Berkhout, Maria (Marjo) Johanna, 1976, et al.
(författare)
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Hypertension treatment in the oldest-old: focus group interviews with Swedish general practitioners.
- 2022
-
Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 1502-7724 .- 0281-3432. ; 40:3, s. 395-404
-
Tidskriftsartikel (refereegranskat)abstract
- This study explored the considerations and experiences of Swedish General Practitioners (GPs) of hypertension treatment in patients 80years and above.Qualitative design with focus group interviews. Data were analysed by qualitative content analysis.Primary health care centres (PHCCs), both rural and urban, in the Region of Västra Götaland, Sweden.GPs and GP trainees working at PHCCs in 2019 and 2020. Five focus group interviews with 24 physicians were performed.Considerations and experiences of hypertension treatment in the oldest-old.Eighteen GPs and six GP trainees participated in the study. The latent content was formulated in a theme: 'The physician's decision-making in the treatment of hypertension in the oldest-old implies the inclusion of both medical and humanistic considerations.' The manifest content constituted three main categories: 'The patient characteristics' included medical condition, behavioural factors and daily life. 'The physician's role' described the GP as a professional and her/his experienced support. 'The treatment decision' considered these categories and involved risk-benefit balancing and communication. For the future, the participants proposed better guidelines for the oldest-old multimorbid patients, increased teamwork, continuous cooperation with nurses and better cooperation with hospital physicians.Hypertension care for the oldest-old was experienced as complicated by GPs, due to the need of balancing medical and humanistic considerations. The GP's clinical experience and the received support were of importance when making the treatment decision based on risk-benefit balancing and communication with the patient.Key pointsGPs experienced the task of caring for the oldest-old patients with hypertension as complicated.Patient factors like multimorbidity, polypharmacy, behavioural factors and the patient's condition of daily life were identified.Clinical experience and the experienced support at the PHCC were discussed as important for the GPs' treatment decision.Treatment decisions for the oldest-old patients with hypertension were based on risk-benefit balancing and communication with the patients.
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| 45. |
- Bingerud, Mattias, 1986, et al.
(författare)
-
Tracks: Impactful Reform for Flexible Adaptable Education
- 2023
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Ingår i: Transforming Engineering Education 2023. - 2446-3833. - 9788775730230 ; , s. 23-27
-
Konferensbidrag (refereegranskat)abstract
- In this contribution we discuss the progress and achievements of the first three and half years of the Tracks initiative for reformed education at Chalmers University of Technology. In Tracks, the education is designed to give students opportunities to develop inter-disciplinary competencies and to follow individualized study tracks. The purpose of Tracks is also that Chalmers, in collaboration with strategic external partners, shorten the lead times for changing the education to embrace new technologies, emerging materials and concepts and to offer a meeting place for education, research, industry, and society. Three and a half years into the initiative, we conclude that the initial intentions have been achieved. In addition, the project brought unexpected positive effects in, e.g., terms of opportunities for newly recruited faculty and collaboration with sports associations and athletes.
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| 46. |
- Bolin, Karin, et al.
(författare)
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Association of STAT4 Polymorphism with Severe Renal Insufficiency in Lupus Nephritis
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. 84450-
-
Tidskriftsartikel (refereegranskat)abstract
- Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE) and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs) for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n = 512 controls) was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls) was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK. Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7x10(-9), OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (pless than0.0001). An additional six genes showed an association with lupus nephritis with pless than0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1). In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p = 1.6x10(-3) and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency.
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| 47. |
- Bolin, Karin, 1982-, et al.
(författare)
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Variants in BANK1 are associated with lupus nephritis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Lupus nephritis (LN) is a cause of significant morbidity in SLE. While the genetic background to SLE has been well characterized, less is known about genes predisposing to LN.Methods: The study consisted of 2886 SLE patients, including 947 (33%) with LN. The discovery cohort (Sweden, n=1091) and replication cohort 1 (US, n=962) were genotyped on the Immunochip and replication cohort 2 (Norway/Denmark, n=833) on a custom array chip. Allele frequencies were compared between patients with LN, proliferative nephritis, end-stage renal disease and LN negative patients. SNPs with p-value <0.001 in the discovery cohort were analyzed in replication cohort 1. Ten SNPs associated with LN in the discovery cohort (p<0.0002) were genotyped in replication cohort 2. DNA methylation data were available for 180 LN patients from the discovery cohort.Results: In the discovery cohort, six gene loci were associated with LN (p<1x10-4, NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y and PHCA). SNPs in BANK1 showed the strongest association with LN in replication cohort 1 (p=9.5x10-4), with a tendency for an association in replication cohort 2 (p=0.052). In a meta-analysis of all three cohorts the association between LN and BANK1 rs4699259, was strengthened (p=1.7x10‑7). There were no associations to proliferative nephritis or ESRD in the meta-analysis. Methylation quantitative trait loci (MeQTL) effects between a CpG site and several SNPs in BANK1 were identified.Conclusion: Genetic variations in BANK1 are associated with LN. There is evidence for genetic regulation of DNA methylation within the BANK1 locus, however, the exact role of BANK1 in LN pathogenesis remains to be elucidated.
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| 48. |
- Bolin, Karin, et al.
(författare)
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Variants in BANK1 are associated with lupus nephritis of European ancestry
- 2021
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Ingår i: Genes and Immunity. - : Springer Nature. - 1466-4879 .- 1476-5470. ; 22:3, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of lupus nephritis (LN) has not been completely elucidated. We performed a case-only study of 2886 SLE patients, including 947 (33%) with LN. Renal biopsies were available from 396 patients. The discovery cohort (Sweden, n = 1091) and replication cohort 1 (US, n = 962) were genotyped on the Immunochip and replication cohort 2 (Denmark/Norway, n = 833) on a custom array. Patients with LN, proliferative nephritis, or LN with end-stage renal disease were compared with SLE without nephritis. Six loci were associated with LN (p < 1 × 10−4, NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y, and ACER3) in the discovery cohort. Variants in BANK1 showed the strongest association with LN in replication cohort 1 (p = 9.5 × 10−4) and proliferative nephritis in a meta-analysis of discovery and replication cohort 1. There was a weak association between BANK1 and LN in replication cohort 2 (p = 0.052), and in the meta-analysis of all three cohorts the association was strengthened (p = 2.2 × 10−7). DNA methylation data in 180 LN patients demonstrated methylation quantitative trait loci (meQTL) effects between a CpG site and BANK1 variants. To conclude, we describe genetic variations in BANK1 associated with LN and evidence for genetic regulation of DNA methylation within the BANK1 locus. This indicates a role for BANK1 in LN pathogenesis.
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| 49. |
- Börgeson, Emma, et al.
(författare)
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Lipoxin A(4) inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression
- 2011
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Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 79:4, s. 1489-1497
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Tidskriftsartikel (refereegranskat)abstract
- Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A(4) (LXA(4)) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA(4) on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA(4). Furthermore, we found that LXA(4) significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA(4) was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA(4) antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.
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| 50. |
- Carlsson Almlöf, Jonas, et al.
(författare)
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Contributions of de novo variants to systemic lupus erythematosus
- 2021
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Ingår i: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 29:1, s. 184-193
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Tidskriftsartikel (refereegranskat)abstract
- By performing whole-genome sequencing in a Swedish cohort of 71 parent-offspring trios, in which the child in each family is affected by systemic lupus erythematosus (SLE, OMIM 152700), we investigated the contribution of de novo variants to risk of SLE. We found de novo single nucleotide variants (SNVs) to be significantly enriched in gene promoters in SLE patients compared with healthy controls at a level corresponding to 26 de novo promoter SNVs more in each patient than expected. We identified 12 de novo SNVs in promoter regions of genes that have been previously implicated in SLE, or that have functions that could be of relevance to SLE. Furthermore, we detected three missense de novo SNVs, five de novo insertion-deletions, and three de novo structural variants with potential to affect the expression of genes that are relevant for SLE. Based on enrichment analysis, disease-affecting de novo SNVs are expected to occur in one-third of SLE patients. This study shows that de novo variants in promoters commonly contribute to the genetic risk of SLE. The fact that de novo SNVs in SLE were enriched to promoter regions highlights the importance of using whole-genome sequencing for identification of de novo variants.
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