| 1. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 2. |
- Lundtoft, Christian, et al.
(författare)
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The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
- 2024
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Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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| 3. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 4. |
- Thorlacius, Guðný Ella, et al.
(författare)
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Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
- 2021
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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| 5. |
- Bergkvist, B, et al.
(författare)
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Sågverkens kostnader analys och modellbeskrivning typsågverk 100.000 m3 år 1986
- 1988
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten presenterar en modell för att analysera kostnaderna i ett sågverk för sågat, skeppningstorrt virke. Modellen har testats i fyra verk med en produktion kring 100.000 m3 per år. I modellen bryts kostnader ner på varje funktion i verket, t ex timmersortering, kantverk, torkning och orderanskaffning, samt på viktiga kostnadsslag, t ex kapital, personal, underhåll, elektricitet m m. Modellen är värdefull för bl a budgetering, efterkalkyl och prisstrategi.
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| 6. |
- Bergkvist, B, et al.
(författare)
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Sågverkens kostnader typsågverk 40.000 m3 år 1987 jämförelse mellan typsågverk 40.000 m3 och 100.000 m3 år 1987
- 1989
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten redovisar och analyserar detaljerat de kostnader ett sågverk i 40.000 m3-klassen har. Dessutom görs en intressant jämförelse av kostnaderna i sågverk i storleksklasserna 40.000 m3 och 100.000 m3, där anläggningarna utnyttjas i ett respektive två skift. Fyra företag av varje storlek har välvilligt ställt sitt material till vårt förfogande. Träteks modell för kostnadsanalysen redovisas i Träteks tidigare rapport I 8806039.
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| 7. |
- Capel, Pierre, et al.
(författare)
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Effective field theory analysis of the Coulomb breakup of the one-neutron halo nucleus 19 C
- 2023
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Ingår i: European Physical Journal A. - 1434-601X .- 1434-6001. ; 59:11
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Tidskriftsartikel (refereegranskat)abstract
- We analyse the Coulomb breakup of 19 C measured at 67A MeV at RIKEN. We use the Coulomb-Corrected Eikonal (CCE) approximation to model the reaction and describe the one-neutron halo nucleus 19 C within Halo Effective Field Theory (Halo EFT). At leading order we obtain a fair reproduction of the measured cross section as a function of energy and angle. The description is insensitive to the choice of optical potential, as long as it accurately represents the size of 18 C. It is also insensitive to the interior of the 19 C wave function. Comparison between theory and experiment thus enables us to infer asymptotic properties of the ground state of 19 C: these data put constraints on the one-neutron separation energy of this nucleus and, for a given binding energy, can be used to extract an asymptotic normalisation coefficient (ANC). These results are confirmed by CCE calculations employing next-to-leading order Halo EFT descriptions of 19 C: at this order the results for the Coulomb breakup cross section are completely insensitive to the choice of the regulator. Accordingly, this reaction can be used to constrain the one-neutron separation energy and ANC of 19 C.
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| 8. |
- Hansell, Peter, et al.
(författare)
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Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension
- 2013
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Ingår i: Clinical and experimental pharmacology & physiology. - : Blackwell Publishing. - 0305-1870 .- 1440-1681. ; 40:2, s. 123-137
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Forskningsöversikt (refereegranskat)abstract
- The high renal oxygen (O2) demand is associated primarily with tubular O2 consumption (Qo2) necessary for solute reabsorption. Increasing O2 delivery relative to demand via increased blood flow results in augmented tubular electrolyte load following elevated glomerular filtration, which, in turn, increases metabolic demand. Consequently, elevated kidney metabolism results in decreased tissue oxygen tension. The metabolic efficiency for solute transport (Qo2/TNa) varies not only between different nephron sites, but also under different conditions of fluid homeostasis and disease. Contributing mechanisms include the presence of different Na+ transporters, different levels of oxidative stress and segmental tubular dysfunction. Sustained hyperglycaemia results in increased kidney Qo2, partly due to mitochondrial dysfunction and reduced electrolyte transport efficiency. This results in intrarenal tissue hypoxia because the increased Qo2 is not matched by a similar increase in O2 delivery. Hypertension leads to renal hypoxia, mediated by increased angiotensin receptor tonus and oxidative stress. Reduced uptake in the proximal tubule increases load to the thick ascending limb. There, the increased load is reabsorbed, but at greater O2 cost. The combination of hypertension, angiotensin II and oxidative stress initiates events leading to renal damage and reduced function. Tissue hypoxia is now recognized as a unifying pathway to chronic kidney disease. We have gained good knowledge about major changes in O2 metabolism occurring in diabetic and hypertensive kidneys. However, further efforts are needed to elucidate how these alterations can be prevented or reversed before translation into clinical practice.
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| 9. |
- Hanson, Lars, et al.
(författare)
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ANNIE, a Tool for Integrating Ergonomics in the Design of Car Interiors
- 2000
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Ingår i: SAE Transactions – Journal of Materials and Manufacturing. Technical Paper 1999-01-3372. Reprinted From: Proceedings of the 1999 SAE Southern Automotive Manufacturing.. ; , s. 1-11
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Konferensbidrag (refereegranskat)abstract
- An example of a result from a long-term cooperation with Lund University (together with professor Roland Akselsson at the Department for Work Environment) there some of the authors (Engström) gained extensive grants (Wallenberg Stifelsen regarding equipment as well as other founding from e.g. the Swedish Work Environment Found). In this case the just mentioned EU-financing.
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| 10. |
- Hanson, Lars, et al.
(författare)
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ANNIE, a Tool for Integrating Ergonomics in the Design of Car Interiors
- 1999
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Ingår i: SAE technical paper series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191. ; 108:5, s. 1114-1124
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Tidskriftsartikel (refereegranskat)abstract
- In the ANNIE project - Applications of Neural Networks to Integrated Ergonomics - BE96-3433, a tool for integrating ergonomics into the design process is developed. This paper presents some features in the current ANNIE as applied to the design of car interiors. A variant of the ERGOMan mannequin with vision is controlled by a hybrid system for neuro-fuzzy simulation. It is trained by using an Elite system for registration of movements. An example of a trajectory generated by the system is shown. A fuzzy model is used for comfort evaluation. An experiment was performed to test its feasibility and it showed very promising results.
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