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- 2019
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Tidskriftsartikel (refereegranskat)
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- Bybrant, M. C., et al.
(författare)
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Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p=.00001) and those with DQX/X (p.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p=.018).Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.
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- Hu, Xiping, et al.
(författare)
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SAfeDJ : A crowd-cloud codesign approach to situation-aware music delivery for drivers
- 2015
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Ingår i: ACM Transactions on Multimedia Computing, Communications, and Applications (TOMCCAP). - : Association for Computing Machinery (ACM). - 1551-6857 .- 1551-6865. ; 12:1s, s. 21:1-24
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Tidskriftsartikel (refereegranskat)abstract
- Driving is an integral part of our everyday lives, but it is also a time when people are uniquely vulnerable. Previous research has demonstrated that not only does listening to suitable music while driving not impair driving performance, but it could lead to an improved mood and a more relaxed body state, which could improve driving performance and promote safe driving significantly. In this article, we propose SAfeDJ, a smartphone-based situation-aware music recommendation system, which is designed to turn driving into a safe and enjoyable experience. SAfeDJ aims at helping drivers to diminish fatigue and negative emotion. Its design is based on novel interactive methods, which enable in-car smartphones to orchestrate multiple sources of sensing data and the drivers' social context, in collaboration with cloud computing to form a seamless crowdsensing solution. This solution enables different smartphones to collaboratively recommend preferable music to drivers according to each driver's specific situations in an automated and intelligent manner. Practical experiments of SAfeDJ have proved its effectiveness in music-mood analysis, and mood-fatigue detections of drivers with reasonable computation and communication overheads on smartphones. Also, our user studies have demonstrated that SAfeDJ helps to decrease fatigue degree and negative mood degree of drivers by 49.09% and 36.35%, respectively, compared to traditional smartphone-based music player under similar driving situations.
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- Onengut-Gumuscu, Suna, et al.
(författare)
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Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:4, s. 381-386
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.
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| 6. |
- Persson, M., et al.
(författare)
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The Better Diabetes Diagnosis (BDD) study – A review of a nationwide prospective cohort study in Sweden
- 2018
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 140, s. 236-244
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Forskningsöversikt (refereegranskat)abstract
- The incidence of type 1 diabetes (T1D) in Sweden is one of the highest in the world. However, the possibility of other types of diabetes must also be considered. In addition, individuals with T1D constitute a heterogeneous group. A precise classification of diabetes is a prerequisite for optimal outcome. For precise classification, knowledge on the distribution of genetic factors, biochemical markers and clinical features in individuals with new onset of diabetes is needed. The Better Diabetes Diagnosis (BDD), is a nationwide study in Sweden with the primary aim to facilitate a more precise classification and diagnosis of diabetes in order to enable the most adequate treatment for each patient. Secondary aims include identification of risk factors for diabetes-related co-morbidities. Since 2005, data on almost all children and adolescents with newly diagnosed diabetes in Sweden are prospectively collected and including heredity of diabetes, clinical symptoms, levels of C peptide, genetic analyses and detection of autoantibodies. Since 2011, analyses of HLA profile, autoantibodies and C peptide levels are part of clinical routine in Sweden for all pediatric patients with suspected diagnosis of diabetes. In this review, we present the methods and main results of the BDD study so far and discuss future aspects.
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| 7. |
- Aydemir, O, et al.
(författare)
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Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:7, s. 1523-1527
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control subjects (N = 668) homozygous for the HLA-DR3 high-risk haplotype were selected from multiple large T1D studies and examined to identify new T1D susceptibility loci using molecular inversion probe sequencing technology. We report that risk for T1D in HLA-DR3 homozygotes is increased significantly by a previously unreported haplotype of three single nucleotide polymorphisms (SNPs) within the first intron of HLA-DRA1. The homozygous risk haplotype has an odds ratio of 4.65 relative to the protective homozygous haplotype in our sample. Individually, these SNPs reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. From our analysis of available data, we conclude that the tri-SNP haplotype within HLA-DRA1 may modulate class II expression, suggesting that increased T1D risk could be attributable to regulated expression of class II genes. These findings could help clarify the role of HLA in T1D susceptibility and improve diabetes risk assessment, particularly in high-risk HLA-DR3 homozygous individuals.
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- Beam, Craig A., et al.
(författare)
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GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis
- 2017
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Ingår i: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 60:1, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.
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- Besser, Rachel E. J., et al.
(författare)
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Exploring C-peptide loss in type 1 diabetes using growth curve analysis
- 2018
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods Between 1976 and 2011, 442 T1D patients initially aged amp;lt; 18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9,18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (Superlmposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curves mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results The square root (root) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and root AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p amp;lt; 0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies.
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