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| 6. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 7. |
- Semb, G, et al.
(författare)
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Erratum
- 2017
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 9. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 10. |
- Hartley, Philippa, et al.
(författare)
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SKA Science Data Challenge 2: analysis and results
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 1967-1993
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Tidskriftsartikel (refereegranskat)abstract
- The Square Kilometre Array Observatory (SKAO) will explore the radio sky to new depths in order to conduct transformational science. SKAO data products made available to astronomers will be correspondingly large and complex, requiring the application of advanced analysis techniques to extract key science findings. To this end, SKAO is conducting a series of Science Data Challenges, each designed to familiarize the scientific community with SKAO data and to drive the development of new analysis techniques. We present the results from Science Data Challenge 2 (SDC2), which invited participants to find and characterize 233 245 neutral hydrogen (H i) sources in a simulated data product representing a 2000 h SKA-Mid spectral line observation from redshifts 0.25-0.5. Through the generous support of eight international supercomputing facilities, participants were able to undertake the Challenge using dedicated computational resources. Alongside the main challenge, 'reproducibility awards' were made in recognition of those pipelines which demonstrated Open Science best practice. The Challenge saw over 100 participants develop a range of new and existing techniques, with results that highlight the strengths of multidisciplinary and collaborative effort. The winning strategy - which combined predictions from two independent machine learning techniques to yield a 20 per cent improvement in overall performance - underscores one of the main Challenge outcomes: that of method complementarity. It is likely that the combination of methods in a so-called ensemble approach will be key to exploiting very large astronomical data sets.
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| 11. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
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| 12. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 13. |
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| 14. |
- Ledoux, X., et al.
(författare)
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The Neutrons for Science Facility at SPIRAL-2
- 2014
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Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752 .- 1095-9904. ; 119, s. 353-356
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Tidskriftsartikel (refereegranskat)abstract
- The Neutrons For Science (NFS) facility is a component of SPIRAL-2 laboratory under construction at Caen (France). SPIRAL-2 is dedicated to the production of high intensity Radioactive Ions Beams (RIB). It is based on a high-power linear accelerator (LINAG) to accelerate deuterons beams in order to produce neutrons by breakup reactions on a C converter. These neutrons will induce fission in U-238 for production of radioactive isotopes. Additionally to the RIB production, the proton and deuteron beams delivered by the accelerator will be used in the NFS facility. NFS is composed of a pulsed neutron beam and irradiation stations for cross-section measurements and material studies. The beams delivered by the LINAG will allow producing intense neutron beams in the 100 keV-40 MeV energy range with either a continuous or quasi-mono-energetic spectrum. At NFS available average fluxes will be up to 2 orders of magnitude higher than those of other existing time-of-flight facilities in the 1 MeV - 40 MeV range. NFS will be a very powerful tool for fundamental physics and application related research in support of the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. The facility and its characteristics are described, and several examples of the first potential experiments are presented.
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| 15. |
- Berthomier, M., et al.
(författare)
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Alfven : magnetosphere-ionosphere connection explorers
- 2012
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Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
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Tidskriftsartikel (refereegranskat)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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| 16. |
- Sanjeevi, Carani B., et al.
(författare)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 17. |
- Heggebo, L. C., et al.
(författare)
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Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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| 18. |
- Ledoux, X., et al.
(författare)
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The Neutrons for Science Facility at SPIRAL-2
- 2018
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Ingår i: Radiation Protection Dosimetry. - : OXFORD UNIV PRESS. - 0144-8420 .- 1742-3406. ; 180:1-4, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the Li-7(p, n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.
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| 19. |
- Ledoux, X., et al.
(författare)
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The neutrons for science facility at SPIRAL-2
- 2017
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Ingår i: ND 2016. - Les Ulis : EDP Sciences.
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Konferensbidrag (refereegranskat)abstract
- Numerous domains, in fundamental research as well as in applications, require the study of reactions induced by neutrons with energies from few MeV up to few tens of MeV. Reliable measurements also are necessary to improve the evaluated databases used by nuclear transport codes. This energy range covers a large number of topics like transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors. A new facility called Neutrons For Science (NFS) is being built for this purpose on the GANIL site at Caen (France). NFS is composed of a pulsed neutron beam for time-of-flight facility as well as irradiation stations for cross-section measurements. Neutrons will be produced by the interaction of deuteron and proton beams, delivered by the SPIRAL-2 linear accelerator, with thick or thin converters made of beryllium or lithium. Continuous and quasi-mono-energetic spectra will be available at NFS up to 40 MeV. In this fast energy region, the neutron flux is expected to be up to 2 orders of magnitude higher than at other existing time-of-flight facilities. In addition, irradiation stations for neutron-, proton- and deuteron-induced reactions will allow performing cross-section measurements by the activation technique. After a description of the facility and its characteristics, the experiments to be performed in the short and medium term will be presented.
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