| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 4. |
- Demidov, V. V., et al.
(författare)
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Magnetic anisotropy in strained manganite films and bicrystal junctions
- 2013
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 113:16
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Tidskriftsartikel (refereegranskat)abstract
- Transport and magnetic properties of La0.67Sr0.33MnO3 (LSMO) manganite thin films and bicrystal junctions were investigated. Epitaxial manganite films were grown on SrTiO3, LaAlO3, NdGaO3 (NGO), and (LaAlO3)(0.3) + (Sr2AlTaO6)(0.7) substrates, and their magnetic anisotropy were determined by two independent techniques of magnetic resonance spectroscopy. It was demonstrated that by using these techniques, a small (0.3%) anisotropy of crystal structure at the (110) surface plane of the orthorhombic NGO substrate leads to uniaxial magnetic anisotropy of the films in the plane of the substrate at least at the room temperature. It was found that on vicinal NGO substrates, the value of magnetic anisotropy strength can be varied in the range 100-200 Oe at T = 295 K by changing the substrate vicinal angle from 0 degrees to 25 degrees. Measurement of the magnetic anisotropy of manganite bicrystal junction demonstrated the presence of two ferromagnetic spin subsystems for both types of bicrystal boundaries with tilting of basal plane of manganite tilted bicrystal (TB-junction) and with rotation of crystallographic axes (RB-junction) used for comparison. The magnetoresistance of TB-junctions increases with decreasing temperature and the misorientation angle. Variation of bicrystal misorientation angle does not lead to change of misorientation of easy magnetic axes in the film parts forming TB-junction. Analysis of the voltage dependencies of bicrystal junction conductivity show that the low value of the magnetoresistance for the LSMO bicrystal junctions can be caused by two scattering mechanisms. The first one is the spin-flip of spin-polarized carriers due to the strong electron-electron interactions in a disordered layer at the bicrystal boundary at low temperatures and the second one is spin-flip by antiferromagnetic magnons at high temperatures.
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| 5. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 6. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 7. |
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| 8. |
- Kozyrev, Sergey V, et al.
(författare)
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Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance(1-3). In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta 2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease.
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| 13. |
- Stepantsov, E.A., et al.
(författare)
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Investigation into the growth and structure of thin-film solid solutions of iron-based superconductors in the FeSe0.92-FeSe0.5Te0.5 system
- 2013
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Ingår i: Crystallography reports (Print). - 1063-7745 .- 1562-689X. ; 58:5, s. 735-738
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Tidskriftsartikel (refereegranskat)abstract
- Thin films of FeSe0.92 and FeSe0.5Te0.5 iron chalcogenide superconductors and solid solutions containing these components in different ratios have been grown on the surface of LaAlO3 (10 1¯ 2) crystals by pulsed laser deposition. Films of solid solutions have been deposited by simultaneous laser ablation from two targets of the FeSe0.92 and FeSe0.5Te0.5 stoichiometric compositions onto one substrate. An X-ray diffraction study of the film structure shows that the films grown are epitaxial and their lattice parameters regularly vary with the ratio of the deposited components, which was controllably varied by changing the ablation intensities from the targets.
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| 14. |
- Stepantsov, Evgeny, et al.
(författare)
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Ablation replacement of iron with Co, Mn, Ni, and Cu during growth of iron-based superconductor films in the Fe0.9M0.1Se0.92 system
- 2014
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Ingår i: Crystallography reports (Print). - 1063-7745 .- 1562-689X. ; 59:5, s. 739-743
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Tidskriftsartikel (refereegranskat)abstract
- Thin films of ironbased chalcogenide superconductors FeSe0.92, with iron partially replaced (atleast up to 10 at %) by elements such as cobalt, nickel, manganese, or copper, have been grown on the surfaceof (10 2) LaAlO3 crystals. Growth is performed by the laser ablation of a target prepared in the form of aceramic pellet by hightemperature synthesis and the sintering of preliminarily pressed stoichiometric mixture of powders. Iron in these ceramics is replaced with an alloying metal by no more than 3 at %. The rest(7 at %) of the metal is in the form of precipitates of other phases. Xray diffraction analysis of the grown filmshas shown that they are singlecrystal and free of any precipitates of other crystallographic orientations andphases. This is evidence of the complete (10 at %) replacement of iron with a doping metal in the film structure. This circumstance indicates that the synthesis of components occurs more actively and completely during laser ablation (than in solidphase chemical reactions) as a result of the transformation of multicomponent target material into plasma. Thus, one can fabricate film materials in a wider range of chemical compositions than in the form of solidphase synthesized ceramics.
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| 15. |
- Stepantsov, Evgeni, 1951, et al.
(författare)
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Investigation into the growth and structure of thin-film solid solutions of iron-based superconductors in the FeSe0.92-FeSe0.5Te0.5 system
- 2013
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Ingår i: Crystallography Reports. - : Pleiades Publishing Ltd. - 1562-689X .- 1063-7745. ; 58:5, s. 735-738
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Tidskriftsartikel (refereegranskat)abstract
- Thin films of FeSe0.92 and FeSe0.5Te0.5 iron chalcogenide superconductors and solid solutions containing these components in different ratios have been grown on the surface of LaAlO3 (102) crystals by pulsed laser deposition. Films of solid solutions have been deposited by simultaneous laser ablation from two targets of the FeSe0.92 and FeSe0.5Te0.5 stoichiometric compositions onto one substrate. An X-ray diffraction study of the film structure shows that the films grown are epitaxial and their lattice parameters regularly vary with the ratio of the deposited components, which was controllably varied by changing the ablation intensities from the targets.
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| 16. |
- Tai, F, et al.
(författare)
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Abdominal Wall Miscellaneous
- 2015
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Ingår i: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S5-S12
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Tidskriftsartikel (refereegranskat)
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| 17. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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| 18. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 19. |
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| 20. |
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| 22. |
- Alkaissi, Aidah, et al.
(författare)
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Disturbing postoperative symptoms are not reduced by prophylactic antiemetric treatment in patients at high risk for post-operative nausea and vomiting
- 2004
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 48:6, s. 761-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To give prophylactics or timely treatment for post-operative nausea and vomiting (PONV) is the question. We compared the intensity and number of disturbing post-operative symptoms (i.e. pain, PONV, headache, fatigue, etc.) after prophylactic antiemetic treatment in a group of patients with >30% risk for post-operative vomiting. METHODS: Four hundred and ninety-five patients, from three hospitals, planned for gynaecological surgery were randomized double blind. They were given granisetron 3 mg, droperidol 1.25 mg or no prophylactic antiemetic. Post-operative symptoms were followed for 24 h using a questionnaire. Symptoms were analyzed both according to their intensity and in a dichotomous fashion. RESULTS: The intensity of different symptoms differed depending on whether droperidol, granisetron or no antiemetic had been given (P = 0.005) but the overall incidence of moderate to very severe symptoms was similar in all groups. No group fared better in general. The total number of symptoms was higher in the groups given prophylactic treatment (P < 0.05). The relative risk reduction for PONV with granisetron or droperidol prophylaxis was 27%[95% confidence interval (CI) 8-43] and 22% (2-38), respectively. The NNT (number needed to treat) for granisetron (0-24 h) was 7 and for droperidol 8. The NNH (number needed to harm) (0-24 h) for headache and visual disturbances was 6 and 13 (NS) for granisteron and, 50 (NS) and 6 for droperidol. CONCLUSION: The intensity of symptoms or the total number of disturbing symptoms did not decrease after prophylactic antiemetic treatment in a group of patients, but the profile of disturbing symptoms changed. The relevance of post-operative symptoms in terms of patients' well-being needs to be addressed.
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| 23. |
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| 24. |
- Behravesh, Masoud, et al.
(författare)
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A prospective study of the relationships between movement and glycemic control during day and night in pregnancy
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore continuous glucose monitors and triaxial accelerometers from February through June 2018 in Sweden. The relationships between physical activity and sleep disturbance with blood glucose rate of change were assessed. An interaction term was fitted to determine difference in the relationship between movement and glucose variation, conditional on waking/sleeping. Total movement was inversely related to glucose rate of change (p < 0.001, 95% CI (− 0.037, − 0.026)). Stratified analyses showed total physical activity was inversely related to glucose rate of change (p < 0.001, 95% CI (− 0.040, − 0.028)), whereas sleep disturbance was not related to glucose rate of change (p = 0.07, 95% CI (< − 0.001, 0.013)). The interaction term was positively related to glucose rate of change (p < 0.001, 95% CI (0.029, 0.047)). This study provides temporal evidence of a relationship between total movement and glycemic control in pregnancy, which is conditional on time of day. Movement is beneficially related with glycemic control while awake, but not during sleep.
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| 25. |
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| 26. |
- Braganca, F. M. Serra, et al.
(författare)
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Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms.
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| 27. |
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| 28. |
- Cao, D., et al.
(författare)
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FOXP3 identifies regulatory CD25bright CD4+ T cells in rheumatic joints
- 2006
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Ingår i: Scand J Immunol. ; 63:6, s. 444-52
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells have recently been implicated in a number of human diseases, including rheumatoid arthritis. To investigate whether the presence of CD25+CD4+ regulatory T cells is a general finding in arthritic joints, synovial fluid of patients with different rheumatic diseases such as undifferentiated arthritides, systemic rheumatic diseases and reactive arthritis were investigated for the presence of such cells. In 95% of the patients, a higher frequency of CD25(bright)CD4+ T cells was found in synovial fluid as compared with peripheral blood. Both in vitro suppression experiments and FOXP3 mRNA analysis confirmed these cells to be natural regulatory T cells. Together with our previous data, we conclude that arthritic joints, irrespective of precise diagnosis and disease duration, are enriched with natural regulatory T cells. These results suggest that suppressor cells migrate to and/or multiply at the sites of inflammation as part of the immune responses' effort to combat injurious inflammation.
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| 29. |
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| 30. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 36. |
- Ekström, E., et al.
(författare)
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A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 616-617
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Alemtuzumab (ALZ) is a modulatory drug for patients with relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long-term safety and effectiveness in a real-world setting where ALZ was included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study 3” (IMSE 3) upon launch in Sweden (March 2014).Objective: To follow up the effectiveness and long-term safety of ALZ in a real-world setting.Methods: Swedish MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg).IMSE 3 includes patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS). The Wilcoxon signed-rank test was used to assess changes in effectiveness.Results: 118 patients (59% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2021. Mean age at treatment start was 34 years. At cut-off date 85 patients had been treated with ALZ with at least 48 months of follow-up. Mean values at baseline compared to 48 months showed significant improvements for MSSS and SDMT while EQ-5D, EDSS, MSIS-29 and VAS scores showed tendencies of improvement.The largest proportion of the entire cohort switched from natalizumab (39%) or were treatment naïve (14%) prior ALZ. The number of relapses per 1,000 patient years decreased from 441 before ALZ initiation to 84 during ALZ treatment (16% missing data). 36 adverse events (AEs) were reported to the Swedish Medical Products Agency. 23 were classified as serious and the most common AEs categories were infections and infestations and blood and lymphatic system disorders (23% respectively). For non-serious events endocrine disorders (43%) was the most common category. Two patients died during ALZ treatment, one of which was associated to ALZ treatment, and died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.Conclusions: Patients treated with ALZ for at least 48 months improved or remained stable across all effectiveness measures. Continued follow-up is needed to evaluate the real-world effectiveness and safety of ALZ.
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| 37. |
- Ekström, E., et al.
(författare)
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Real-world longitudinal data of peginterferon beta-1a from the Swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 626-627
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. Phase II and III studies have shown that PegIFN reduces relapse rate and disability progression. PegIFN were included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 6) due to the importance of studying the long-term safety and effectiveness.Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting.Methods: Data was obtained from the Swedish Neuro Registry (NeuroReg). All clinical measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.Results: 393 patients (78% female; 86% RRMS) were included in IMSE 6 between June 2015 and April 2021. Mean age at treatment start was 42 years, mean treatment duration was 23 months. 25% were treatment naïve and 47% switched from other injectables prior PegIFN. The one- and two-year drug survival rate was 58% and 41% respectively, and 31% overall. In total, 271 patients discontinued their PegIFN treatment at some time point, mainly due to adverse events (51%) and lack of effect (26%). Most patients switched to rituximab (37%). During the entire treatment period 54% were relapse-free and 8% had only one relapse (36% missing data). In patients treated at least 24 months tendencies of improve-ments were seen for SDMT and EQ-5D. MSIS-PSYCH showed significantly worsened results (21.2 ± 18.6 to 24.3 ± 19.3, n=46). EDSS, MSSS, MSIS-PHYS and VAS scores remained stable. 25 adverse events (AEs) have been reported to Swedish Medical Product Agency (MPA). 6 of these were classified as serious where general disorders and administration site, and skin (33% respectively) were the most common categories. General disorders and administration site were also the most common for non-serious AEs (68%).Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform. All clinical effectiveness measures, except MSIS-PHYS, remained stable in patients treated for at least 24 months in this nationwide population-based real-world study. Longer follow up is needed to address the long-term effectiveness.
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| 38. |
- Ekström, E., et al.
(författare)
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The long-term safety and effectiveness of natalizumab (IMSE 1) - Real-world data from a Swedish nationwide pharmaco-epidemiological study
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 618-619
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. The “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (August 2006).Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.Methods: IMSE 1 includes patients starting NTZ treatment. Data is collected from the nationwide Swedish Neuroregistry. Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT) are registered prospectively.Results: 3476 patients (75% female; 81% RRMS) were included from August 2006 until April 2021. Mean age at treatment start was 36 years and mean treatment duration was 51.3 months. 1190 patients were currently treated with NTZ at cut-off and 13% of these were JCV positive (JCV+) with a mean JCV index at 1.07 ± 0.97. 2470 patients (71%) discontinued their NTZ treatment at some time point where the main reason was JCV+ (40%). Most of these patients switched to rituximab (39%). The number of relapses per 1,000 patient years were reduced from 380 before treatment start to 73 during treatment (25% missing data). 61% were relapse-free and 12% had only one relapse during the entire treatment period. All clinical measures showed improvement in mean between baseline and 132 months. Improvements on MSSS, MSIS-29 and SDMT were statistically significant. 117 Serious AEs had been reported to the Swedish Medical Product Agency and included nine cases (2 fatal) of progressive multifocal leukoencephalopathy (PML). Eight of these nine cases had been reported between year 2008 and 2012, and one in 2018. 17 patients died within 6 months of last NTZ infusion. The most common category for non-serious AEs was infections and infestations (21%). For serious AEs neoplasms benign, malignant and unspecified were the most common (16%).Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding clinical cognitive, physical and psychological measures.
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| 42. |
- 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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- Faustini, F, et al.
(författare)
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Rituximab in Systemic Lupus Erythematosus: Transient Effects on Autoimmunity Associated Lymphocyte Phenotypes and Implications for Immunogenicity
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 826152-
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Tidskriftsartikel (refereegranskat)abstract
- B cell abnormalities are common in systemic lupus erythematosus (SLE), and include expansion of double negative (DN) and age-associated-like B cells (ABC-like). We aimed to investigate rituximab (RTX) effects on DN and ABC-like B-cell subsets and, when possible, also secondary effects on T cells. Fifteen SLE patients, fulfilling the ACR 1982 criteria, starting RTX and followed longitudinally up to two years, were analyzed for B- and T- lymphocyte subsets using multicolor flow cytometry. DN were defined as IgD-CD27- and ABC-like as CD11c+CD21- within the DN gate. Additional phenotyping was performed adding CXCR5 in the B-cell panel. Cellular changes were further analyzed in the context of the generation of anti-drug antibodies (ADA) against RTX and clinical information. The SLE patients were mainly females (86.6%), of median age 36.7 (29.8-49.4) years and disease duration of 6.1 (1.6-11.8) years. Within the DN subset, ABC-like (IgD-CD27-CD11c+CD21-) B cell frequency reduced from baseline median level of 20.4% to 11.3% (p=0.03), at early follow-up. The DN B cells were further subdivided based on CXCR5 expression. Significant shifts were observed at the early follow-up in the DN2 sub-cluster (CD11c+CXCR5-), which reduced significantly (-15.4 percentage points, p=0.02) and in the recently described DN3 (CD11c-CXCR5-) which increased (+13 percentage points, p=0.03). SLE patients treated with RTX are at high risk of developing ADA. In our cohort, the presence of ADA at 6 months was associated with lower frequencies of DN cells and to a more pronounced expansion of plasmablasts at early follow-up. The frequency of follicular helper T cells (TFH, CD4+PD-1+CXCR5+) and of peripheral helper T cells (TPH, CD4+PD-1+CXCR5-) did not change after RTX. A sub-cluster of PD-1highCD4+ T cells showed a significant decrease at later follow-up compared to early follow-up (p=0.0039). It is well appreciated that RTX transiently influences B cells. Here, we extend these observations to cell phenotypes which are believed to directly contribute to autoimmunity in SLE. We show early transient effects of RTX on ABC-like memory B cells, later effects on PD-1high CD4+ cells, and possible implications for RTX immunogenicity. Further insight in such effects and their monitoring may be of clinical relevance.
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- Faustini, F, et al.
(författare)
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RITUXIMAB THERAPY IN SYSTEMIC LUPUS ERYTHEMATOSUS - TRANSIENT EFFECTS ON AGE ASSOCIATED B-CELLS
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 203-204
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Immune system’s abnormalities in SLE involve several subsets of the B-cell compartment, including double negative B-cells (DN) and CD11c+CD21- B cells (also referred to as ABC-age associated B cells), which are expanded in the disease. ABC cells are also known to interact with T helper cells, T follicular and peripheral helper cells (1). Rituximab, a chimeric anti- CD20 antibody, depleting B cells, is commonly used off-label as treatment for SLE patients, especially in lupus nephritis. Little is known on the impact of B-cell depletion on such B-cell subsets and on B-T-cell interactions.Objectives:to investigate the effects of rituximab (RTX) on the frequencies of double negative B-cell subsets and CD11c+CD21- ABC cells and as well as T follicular helper (TFH, CXCR5+ PD-1+) and T peripheral helper (TPH, PD-1high) CD4+ T-cell subsets.Methods:15 SLE patients, starting RTX and followed longitudinally up to two years, were analyzed for lymphocyte subsets using multicolor flow cytometry. Cryopreserved PBMC were thawed and stained at the same time together with one buffy coat. Around 1 x 106 PBMC for each panel were labeled and further stained with fluorescent antibodies for B and T-cell markers. For the B-cell panel, PBMC were stained with anti-CD3, CD14, CD16, CD19, IgD, CD27, CD38, CD11c, CD21 and in some samples with anti-CXCR5 antibodies. For the T-cell panel, PBMC were labeled with anti-CD16, CD14, CD19 and CD3, CD4, CD8, PD-1, CCR7, CXCR5, CD45RA antibodies. All patients fulfilled the ACR 1982 classification criteria for SLE. Cellular changes were analyzed in the context of clinical information.Results:in the present cohort, the SLE patients were mainly female (86.6%) and of median age of 36.7 (29.8-49.4) with a disease duration of 6.1(1.6-11.8) years, and active disease with SLEDAI-2K at baseline 12.0 (8.0-16.0). The frequency of age-associated B cells (ABCs; CD27-IgD-CD11c+ CD21-) decreased by 13% (p=0.03) in the first two to four months after rituximab start, while globally the DN (IgD-CD27-) B cells transiently increased by around 3% (p=0.15) at the first follow-up. This increase could not be attributed to the DN1 (CXCR5+CD11c-) or DN2 (CXCR5-CD11c+) subsets but to the CD11c-CXCR5- DN (DN3) B cells (increase= 6.7%, p=0.03). In parallel, T effector cells (CCR7- CD45RA+) and TEMRA (CD45RA+ CCR7-) frequencies increased after first follow up in both CD4+ and CD8+ T cells. The frequency of TFH (CXCR5+ PD-1+) cells did not change after rituximab, however a decrease of PD-1high CD4+ cells was observed in most patients, although not significant, after 2-4 month of treatment. In most patients the frequency of PD-1high CD4+ cells either reduce or stay the same after RTX treatment (reduction= 0.53, p=0.28). After 11-15 months of RTX treatment the frequency of PD-1high CD4+ T cell reduces by a -0.5% in comparison to 2-4 months (p=0.039). The SLEDAI at baseline did not correlate with the frequency of PD-1high CD4+ T cells (r=0.03, p=0.9).Conclusion:the importance of T cell - B cell interactions in SLE pathogenesis was recently strengthened by the identification of the lymphocyte subsets TFH/TPH and ABCs respectively. Here, in the context of rituximab treated SLE, we could detect a reduction in the frequencies of both ABCs and PD-1high T cells after treatment with rituximab, while the DN3 and effector memory T cells frequencies increased. Our data suggests that anti-CD20 mediated B-cell depletion affects both B-cell and T-cell subsets frequencies, and that monitoring these specific cell subsets may be clinically relevant.References:[1]Bocharnikov AV, Keegan J, Wacleche VS, Cao Y, Fonseka CY, Wang G, et al. PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI insight. 2019;4(20)Disclosure of Interests:Francesca Faustini Speakers bureau: More than two years ago and not in relation to any aspect of the present research, Natalie Sippl: None declared, Ragnhild Stålesen: None declared, Karine Chemin: None declared, Iva Gunnarsson: None declared, Vivianne Malmström: None declared.
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- Ghosh, Sourav, et al.
(författare)
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Investigating the stable operating voltage for the MnFe2O4 Li-ion battery anode
- 2021
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Ingår i: Sustainable Energy & Fuels. - : Royal Society of Chemistry. - 2398-4902. ; 5:6, s. 1904-1913
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Tidskriftsartikel (refereegranskat)abstract
- Template-free synthesis of MnFe2O4 nanopowder is carried out by co-precipitation in a basic medium, evaluating the effects of cation ratio and reaction temperature on the phase composition crystallinity of the resulting powder. Single-phase samples of the target spinel are obtained at the stoichiometric Mn : Fe = 1 : 2 ratio under reflux conditions (100 degrees C), as confirmed by X-ray diffraction (XRD) and Fourier Transformed Infrared (FTIR) spectroscopy. Transmission electron microscopy (TEM) images confirmed that nanostructured MnFe2O4 particles are obtained, which is further supported by Debye-Scherrer calculations from XRD data and by AFM measurements. The produced oxide demonstrated considerable thermal stability according to TGA data. Magnetic characteristics are strongly dependent on the content of magnetic phase and phase composition, achieving a maximum of 54 emu g(-1) for single-phase stoichiometric MnFe2O4. Further, the electrochemical stability of this material as the anode is investigated in Li-ion batteries (LIBs). When the MnFe2O4 electrode is operated in the potential window of 0.01-3.0 V, the reversible capacity is enhanced by almost 45% (802 mA h g(-1)) after the 100(th) cycle with reference to the 2(nd) cycle reversible capacity (548 mA h g(-1)). Methodically dQ/dV plots are analyzed and compared to understand processes behind the evolution of extra capacity beyond its theoretical limit. Further, the upper cut-off potential is tuned to identify a stable operating potential window for the MnFe2O4 anode in LIBs.
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