SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Lundgren Markus) "

Sökning: WFRF:(Lundgren Markus)

  • Resultat 1-50 av 91
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Lundgren, Tobias, et al. (författare)
  • Acceptance and Commitment Training for Ice Hockey Players : A Randomized Controlled Trial
  • 2021
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent systematic reviews on the topic of mindfulness- and acceptance-based approaches in sport psychology conclude that there is a need for further trials using a more robust research methodology with direct performance as outcome. Acceptance and Commitment Training (ACT) is a contextual behavioral change method that focuses on facilitating psychological processes such as values, committed action, acceptance and mindfulness. In the present study designed as a randomized controlled trial, 34 junior elite ice hockey players were allocated into either an ACT group intervention or a wait list control group. Results showed significant effects on both objective performance outcomes (goals, assists, and taken shots) and blinded coach ratings of players' performance, focus and commitment to their development in favor of the ACT group. Effects lasted at 3-month follow-up for the coach ratings, but not for the objective performance measures. All ACT trained players recommended ACT to other players and considered the training as important for their development as ice hockey players. The results add to the growing body of evidence on ACT interventions for athletes and its effect on performance. Future studies should investigate the maintenance of effects from the psychological training over time, using robust research methodology and investigate theoretical coherent potential mediating variables.
  •  
2.
  • Ahlén Bergman, Emma, et al. (författare)
  • Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
  • 2018
  • Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
  •  
3.
  • Anand, Vibha, et al. (författare)
  • Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes : Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S
  • 2021
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44, s. 2269-2276
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes.RESEARCH DESIGN AND METHODS: For prospective cohorts in Finland, Germany, Sweden, and the U.S., 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes have been followed. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years.RESULTS: In the infant-toddler cohort, 1,413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two, or three autoantibodies at seroconversion: 45% (95% CI 40-52), 85% (78-90), and 92% (85-97), respectively. Among those with a single autoantibody, status 2 years after seroconversion predicted diabetes risk: 12% (10-25) if reverting to autoantibody negative, 30% (20-40) if retaining a single autoantibody, and 82% (80-95) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single-autoantibody status. Their 15-year diabetes incidence for higher- versus lower-risk genotypes was 40% (28-50) vs. 12% (5-38). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies, ranging from 20% per year to 6% per year in children developing multipositivity in ≤2 years or >7.4 years, respectively.CONCLUSIONS: The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining a single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.
  •  
4.
  • Andersson Svärd, Agnes, et al. (författare)
  • Decreased HLA-DQ expression on peripheral blood cells in children with varying number of beta cell autoantibodies
  • 2020
  • Ingår i: Journal of Translational Autoimmunity. - : Elsevier BV. - 2589-9090. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The risk for type 1 diabetes is strongly associated with HLA-DQ and the appearance of beta cell autoantibodies against either insulin, glutamate decarboxylase (GAD65), insulinoma-associated protein-2 (IA-2), or zinc transporter 8 (ZnT8). Prolonged exposure to autoantibodies may be related to T cell exhaustion known to occur in chronic infections or autoimmune disorders. It was hypothesized that autoantibody exposure may affect HLA-DQ expression on peripheral blood cells and thereby contribute to T cell exhaustion thought to be associated with the pathogenesis of type 1 diabetes. The aim of this study was to determine whether autoantibody exposure as an expression of autoimmunity burden was related to peripheral blood cell HLA-DQ cell surface expression in either 1) a cross-sectional analysis or 2) cumulative as area under the trajectory of autoantibodies during long term follow-up in the Diabetes Prediction in Skåne (DiPiS) study. Children (n = 67), aged 10-15 years were analyzed for complete blood count, HLA-DQ cell surface median fluorescence intensity (MFI), autoantibody frequency, and HLA genotypes by Next Generation Sequencing. Decreased HLA-DQ cell surface MFI with an increasing number of autoantibodies was observed in CD16+, CD14+CD16-, CD4+ and CD8+ cells but not in CD19+ cells and neutrophils. HLA-DQ cell surface MFI was associated with HLA-DQ2/8 in CD4+ T cells, marginally in CD14+CD16- monocytes and CD8+ T cells. These associations appeared to be related to autoimmunity burden. The results suggest that HLA-DQ cell surface expression was related to HLA and autoimmunity burden.
  •  
5.
  • Andersson Svärd, Agnes, et al. (författare)
  • Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes
  • 2022
  • Ingår i: ImmunoHorizons. - : The American Association of Immunologists. - 2573-7732. ; 6:8, s. 614-629
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction in Skåne study. Among four tri-SNPs, AGG (n = 67), GCA (n = 47), ACG (n = 11), and ACA (n = 9), HLA-DQ cell-surface MFI on CD4+ T cells was lower in AGG than GCA (p = 0.030) subjects. Cumulative autoimmunity burden was associated with reduced HLA-DQ cell-surface MFI in AGG compared with GCA in CD16+ cells (p = 0.0013), CD4+ T cells (p = 0.0018), and CD8+ T cells (p = 0.016). The results suggest that HLA-DRA1 tri-SNPs may be related to HLA-DQ cell-surface expression and autoimmunity burden.
  •  
6.
  • Backåker, Lars, 1984- (författare)
  • The Influence of Customer Agreements and Planning Principles on Rail Freight Performance
  • 2012
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rail freight transportation is recognized worldwide as a suitable transportation mode when it comes to long haul transportation of heavy commodities. The industry is also known to be capital intensive, highly dependent on infrastructural developments and requires thorough planning of operations. Despite intensive planning of operations, great challenges remain in how to make best use of existing resources. Especially uncertainties related to up-coming daily freight volumes stand as central causes behind such planning challenges. This thesis focuses on rail freight carload transportation and concerns how customer commitments influence operational performance as well as potentials for improvements of operational planning principles. Problem statements are addressed using three separate studies and all experiments involve quantitative approaches. The first study investigates effects of a potential Volume Variation Allowance (VVA) policy through simulation. The policy dictates how much freight volumes are allowed to vary by day of week. Results indicate that effects of the policy are relatively small, but an overall decrease in transportation times is observed. The study also identifies improvement potentials with respect to the current operational planning principles used within Swedish railways. The second study proposes a new optimization-based approach for trip plan generation. The approach, including a number of extensions, is evaluated against the current industry practice. Results confirm the potentials for reduced transportation times, shunting activities as well as service frequencies. All experiments satisfy existing customer commitments. The third study explores effects of a Fixed Carload Capacity (FCC) concept which partially allows capacity reservation on services. The study adopts an extension of the previously developed optimization approach. Results confirm the hypothetical trade-off between customer groups and the dependency on capacity reservation levels, but indicate that the concept has relatively small effects with respect to regular carload customers. On the other hand, benefits in terms of guarantee of service and reliability in transportation times can be observed for the customer under the agreement.
  •  
7.
  • Badinlou, Farzaneh, et al. (författare)
  • Trajectories of mental health outcomes following COVID-19 infection: a prospective longitudinal study
  • 2024
  • Ingår i: BMC PUBLIC HEALTH. - : BioMed Central Ltd. - 1471-2458. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe COVID-19 pandemic has triggered a global mental health crisis. Yet, we know little about the lasting effects of COVID-19 infection on mental health. This prospective longitudinal study aimed to investigate the trajectories of mental health changes in individuals infected with COVID-19 and to identify potential predictors that may influence these changes.MethodsA web-survey that targeted individuals that had been infected with COVID-19 was used at three time-points: T0 (baseline), T1 (six months), and T2 (twelve months). The survey included demographics, questions related to COVID-19 status, previous psychiatric diagnosis, post-COVID impairments, fatigue, and standardized measures of depression, anxiety, insomnia. Linear mixed models were used to examine changes in depression, anxiety, and insomnia over time and identify factors that impacted trajectories of mental health outcomes.ResultsA total of 236 individuals completed assessments and was included in the longitudinal sample. The participants' age ranged between 19 and 81 years old (M = 48.71, SD = 10.74). The results revealed notable changes in mental health outcomes over time. The trajectory of depression showed significant improvement over time while the trends in anxiety and insomnia did not exhibit significant changes over time. Younger participants and individuals who experienced severe COVID-19 infection in the acute phase were identified as high-risk groups with worst mental ill-health. The main predictors of the changes in the mental health outcomes were fatigue and post-COVID impairments.ConclusionsThe findings of our study suggest that mental health outcomes following COVID-19 infection exhibit a dynamic pattern over time. The study provides valuable insights into the mental health trajectory following COVID-19 infection, emphasizing the need for ongoing assessment, support, and interventions tailored to the evolving mental health needs of this population.
  •  
8.
  • Battaglia, Manuela, et al. (författare)
  • Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
  • 2020
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:1, s. 5-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
  •  
9.
  • Choque Olsson, Nora, et al. (författare)
  • Treatment satisfaction with cognitive-behavioral therapy among children and adolescents with anxiety and depression : A systematic review and meta-synthesis
  • 2021
  • Ingår i: Journal of Behavioral and Cognitive Therapy. - : Elsevier BV. - 2589-9791. ; 31:2, s. 147-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent reviews estimated that the worldwide prevalence of anxiety and depression in children and adolescents is increasing, which has led to rising demands for treatment. Studies on clinical outcomes have shown positive effects of cognitive-behavioral therapy (CBT) in children and adolescents with anxiety and depression. However, there is a limited body of studies on the perspectives and experiences of the treatment participants. The objective of this review was to investigate treatment satisfaction with CBT among children and adolescents with anxiety and depression. We focused on the reporting quality of the treatment satisfaction and experiences of participants in the selected studies. From 1379 identified studies, 35 were selected based on inclusion and exclusion criteria. The results of a meta-synthesis and proportional meta-analysis suggest moderate to high treatment satisfaction with CBT in depressed and anxious children and adolescents. The included studies showed moderate to good reporting quality on treatment satisfaction. The measurements used varied, indicating a risk of different evaluations under the concept of “treatment satisfaction”. The common topics measured for treatment satisfaction were acceptability, treatment usefulness, alliance, barriers, recommendation, and others, leading to uncertainty concerning generalization. A wide variety of measures were used, indicating the need for standardized measures for treatment satisfaction in future research.
  •  
10.
  • Cirenajwis, Helena, et al. (författare)
  • Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
  • 2015
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
  • Tidskriftsartikel (refereegranskat)abstract
    • Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
  •  
11.
  •  
12.
  •  
13.
  • Elding Larsson, Helena, et al. (författare)
  • Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes : A randomized clinical trial
  • 2018
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 19:3, s. 410-419
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Treatments have failed to delay or stop the autoimmune process, preceding onset of type 1 diabetes. We investigated if autoantigen-specific treatment with alum-formulated glutamate decarboxylase (GAD-Alum) was safe and affected progression to type 1 diabetes in children with islet autoimmunity.METHODS: In an investigator-initiated, double-blind, placebo-controlled clinical trial, non-diabetic children aged 4 to 17.9 years with autoantibodies to glutamate decarboxylase (GADA) and at least one of insulinoma-associated protein 2, insulin or zinc-transporter 8, were randomized, stratified by 2 or ≥3 islet autoantibodies, to 2 injections of 20 μg GAD-Alum or placebo, 30 days apart. Main outcome was safety, investigated by adverse events, hematology, chemistry, thyroid and celiac autoimmunity and titers of islet autoantibodies, and efficacy, investigated by cumulative incidence of diabetes onset over 5-year follow-up. Secondary variables: change in first-phase insulin release (FPIR) after intravenous glucose tolerance tests, fasting, 120 minutes and Area under the curve (AUC) C-peptide and p-glucose after oral glucose tolerance tests and HbA1c.RESULTS: Fifty children (median age: 5.2) were assigned 1:1 to GAD-Alum or placebo, all receiving full treatment and included in the analyses. GAD-Alum did not affect any safety parameter, while GADA titers increased (P = .001). Time to clinical diagnosis was not affected by treatment (hazard ratio, HR = 0.77, P = .574) in the full population or in the separate stratum groups. Treatment did not affect any of the secondary variables.CONCLUSIONS: GAD-Alum as a subcutaneous prime and boost injection was safe in prediabetic young children but did not affect progression to type 1 diabetes. The safety of GAD-Alum should prove useful in future prevention studies.
  •  
14.
  • Evertsson, Jonas, et al. (författare)
  • The thickness of native oxides on aluminum alloys and single crystals
  • 2015
  • Ingår i: Applied Surface Science. - : Elsevier BV. - 1873-5584 .- 0169-4332. ; 349, s. 826-832
  • Tidskriftsartikel (refereegranskat)abstract
    • We present results from measurements of the native oxide film thickness on four different industrial aluminum alloys and three different aluminum single crystals. The thicknesses were determined using X-ray reflectivity, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. In addition, atomic force microscopy was used for micro-structural studies of the oxide surfaces. The reflectivity measurements were performed in ultra-high vacuum, vacuum, ambient, nitrogen and liquid water conditions. The results obtained using X-ray reflectivity and X-ray photoelectron spectroscopy demonstrate good agreement. However, the oxide thicknesses determined from the electrochemical impedance spectroscopy show a larger discrepancy from the above two methods. In the present contribution the reasons for this discrepancy are discussed. We also address the effect of the substrate type and the presence of water on the resultant oxide thickness.
  •  
15.
  • Frohnert, Brigitte I., et al. (författare)
  • Refining the Definition of Stage 1 Type 1 Diabetes : An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity
  • 2023
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:10, s. 1753-1761
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA). RESEARCH DESIGN AND METHODS Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S. who have an increased genetic risk for type 1 diabetes. Analysis included 16,709 infants-toddlers enrolled by age 2.5 years and comparison between groups using Kaplan-Meier survival analysis. RESULTS Of 865 (5%) children with mIA, 537 (62%) progressed to type 1 diabetes. The 15-year cumulative incidence of diabetes varied from the most stringent definition (mIA/ Persistent/2: two or more islet autoantibodies positive at the same visit with two or more antibodies persistent at next visit; 88% [95% CI 85–92%]) to the least stringent (mIA/Any: positivity for two islet autoantibodies without co-occurring positivity or persistence; 18% [5–40%]). Progression in mIA/Persistent/2 was significantly higher than all other groups (P < 0.0001). Intermediate stringency definitions showed intermediate risk and were significantly different than mIA/Any (P < 0.05); however, differences waned over the 2-year follow-up among those who did not subsequently reach higher stringency. Among mIA/Persistent/2 individuals with three autoantibodies, loss of one autoantibody by the 2-year follow-up was associated with accelerated progression. Age was significantly associated with time from seroconversion to mIA/ Persistent/2 status and mIA to stage 3 type 1 diabetes. CONCLUSIONS The 15-year risk of progression to type 1 diabetes risk varies markedly from 18 to 88% based on the stringency of mIA definition. While initial categorization identifies highest-risk individuals, short-term follow-up over 2 years may help stratify evolving risk, especially for those with less stringent definitions of mIA.
  •  
16.
  • Ghadami Yazdi, Milad, et al. (författare)
  • Structure dependent effect of silicon on the oxidation of Al(111) and Al(100)
  • 2019
  • Ingår i: Surface Science. - : Elsevier. - 0039-6028 .- 1879-2758. ; 684, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of sub-monolayer silicon on the oxidation of Al(111) and Al(100) surfaces was investigated using X-ray Photoelectron Spectroscopy (XPS) and density functional theory (DFT) calculations. On both surfaces the adatom site is preferred over substituting Si into the Al-lattice; on Al(100) the four fold hollow site is vastly favored whereas on Al(111) bridge and hollow sites are almost equal in energy. Upon O 2 exposure, Si is not oxidized but buried at the metal/oxide interface under the growing aluminum oxide. On Al(111), Si has a catalytic effect on both the initial oxidation by aiding in creating a higher local oxygen coverage in the early stages of oxidation and, in particular, at higher oxide coverages by facilitating lifting Al from the metal into the oxide. The final oxide, as measured from the Al2p intensity, is 25–30% thicker with Si than without. This observation is valid for both 0.1 monolayer (ML) and 0.3 ML Si coverage. On Al(100), on the other hand, at 0.16 ML Si coverage, the initial oxidation is faster than for the bare surface due to Si island edges being active in the oxide growth. At 0.5 ML Si coverage the oxidation is slower, as the islands coalesce and he amount of edges reduces. Upon oxide formation the effect of Si vanishes as it is overgrown by Al 2 O 3 , and the oxide thickness is only 6% higher than on bare Al(100), for both Si coverages studied. Our findings indicate that, in addition to a vanishing oxygen adsorption energy and Mott potential, a detailed picture of atom exchange and transport at the metal/oxide interface has to be taken into account to explain the limiting oxide thickness.
  •  
17.
  • Ghalwash, Mohamed, et al. (författare)
  • Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood : a prospective cohort study
  • 2023
  • Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 7:4, s. 261-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10−18 years with an increased risk of developing type 1 diabetes. Methods: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. Findings: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5–20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34–0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50–0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1–1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6–9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86–95) sensitive, with a positive predictive value of 66% (60–72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89–97) but lowered the positive predictive value to 55% (49–60). Interpretation: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Funding: JDRF International.
  •  
18.
  • Ghalwash, Mohamed, et al. (författare)
  • Two-age islet-autoantibody screening for childhood type 1 diabetes : a prospective cohort study
  • 2022
  • Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587. ; 10:8, s. 589-596
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early prediction of childhood type 1 diabetes reduces ketoacidosis at diagnosis and provides opportunities for disease prevention. However, only highly efficient approaches are likely to succeed in public health settings. We sought to identify efficient strategies for initial islet autoantibody screening in children younger than 15 years. Methods: We harmonised data from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the USA (DAISY and DEW-IT) into the Type 1 Diabetes Intelligence (T1DI) cohort. 24 662 children at high risk of diabetes enrolled before age 2 years were included and followed up for islet autoantibodies and diabetes until age 15 years, or type 1 diabetes onset, whichever occurred first. Islet autoantibodies measured included those against glutamic acid decarboxylase, insulinoma antigen 2, and insulin. Main outcomes were sensitivity and positive predictive value (PPV) of detected islet autoantibodies, tested at one or two fixed ages, for diagnosis of clinical type 1 diabetes. Findings: Of the 24 662 participants enrolled in the Type 1 Diabetes Intelligence cohort, 6722 total were followed up to age 15 years or until onset of type 1 diabetes. Type 1 diabetes developed by age 15 years in 672 children, but did not develop in 6050 children. Optimal screening ages for two measurements were 2 years and 6 years, yielding sensitivity of 82% (95% CI 79–86) and PPV of 79% (95% CI 75–80) for diabetes by age 15 years. Autoantibody positivity at the beginning of each test age was highly predictive of diagnosis in the subsequent 2–5·99 year or 6–15-year age intervals. Autoantibodies usually appeared before age 6 years even in children diagnosed with diabetes much later in childhood. Interpretation: Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics. Funding: Juvenile Diabetes Research Foundation.
  •  
19.
  • Hagleitner, Daniel R., et al. (författare)
  • Bulk and surface characterization of In2O3(001) single crystals
  • 2012
  • Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 85:11
  • Tidskriftsartikel (refereegranskat)abstract
    • A comprehensive bulk and surface investigation of high-quality In2O3(001) single crystals is reported. The transparent-yellow, cube-shaped single crystals were grown using the flux method. Inductively coupled plasma mass spectrometry (ICP-MS) reveals small residues of Pb, Mg, and Pt in the crystals. Four-point-probe measurements show a resistivity of 2.0 +/- 0.5 x 10(5) Omega cm, which translates into a carrier concentration of approximate to 10(12) cm(-3). The results from x-ray diffraction (XRD) measurements revise the lattice constant to 10.1150(5) angstrom from the previously accepted value of 10.117 angstrom. Scanning tunneling microscopy (STM) images of a reduced (sputtered/annealed) and oxidized (exposure to atomic oxygen at 300 degrees C) surface show a step height of 5 angstrom, which indicates a preference for one type of surface termination. The surfaces stay flat without any evidence for macroscopic faceting under any of these preparation conditions. A combination of low-energy ion scattering (LEIS) and atomically resolved STM indicates an indium-terminated surface with small islands of 2.5 angstrom height under reducing conditions, with a surface structure corresponding to a strongly distorted indium lattice. Scanning tunneling spectroscopy (STS) reveals a pronounced surface state at the Fermi level (E-F). Photoelectron spectroscopy (PES) shows additional, deep-lying band gap states, which can be removed by exposure of the surface to atomic oxygen. Oxidation also results in a shoulder at the O 1s core level at a higher binding energy, possibly indicative of a surface peroxide species. A downward band bending of 0.4 eV is observed for the reduced surface, while the band bending of the oxidized surface is of the order of 0.1 eV or less.
  •  
20.
  • Harbst, Katja, et al. (författare)
  • Molecular profiling reveals low- and high-grade forms of primary melanoma.
  • 2012
  • Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
  • Tidskriftsartikel (refereegranskat)abstract
    • For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
  •  
21.
  •  
22.
  •  
23.
  • Hendriks, A. Emile J., et al. (författare)
  • Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes
  • 2024
  • Ingår i: Diabetes/Metabolism Research and Reviews. - 1520-7552. ; 40:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody-positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods: Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow-up strategies. Results: The guidance outlines recommended monitoring approaches based on age, disease stage and clinical setting. Individuals with presymptomatic type 1 diabetes are best followed up in specialist care. For stage 1, biannual assessments of random plasma glucose and HbA1c are suggested for children, while annual assessments are recommended for adolescents and adults. For stage 2, 3-monthly clinic visits with additional home monitoring are advised. The value of repeat OGTT in stage 1 and the use of continuous glucose monitoring in stage 2 are discussed. Primary care is encouraged to monitor individuals who decline specialist care, following the guidance presented. Conclusions: As type 1 diabetes screening programs become more prevalent, effective monitoring strategies are essential to mitigate the risk of complications such as DKA. This guidance serves as a valuable resource for clinicians, providing practical recommendations tailored to an individual's age and disease stage, both within specialist and primary care settings.
  •  
24.
  • Houben, Janne, et al. (författare)
  • The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study
  • 2022
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 23:8, s. 1707-1716
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents. Methods: Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study. Parents were asked to complete this questionnaire after they were told their child had an increased risk for T1D (Freder1k-study) and at several time points during an intervention study (POInT-study), where oral insulin was administered daily. Results: Data were collected from 2595 parents of 1371 children across five countries. Panic-related anxiety symptoms were reported by only 4.9% after hearing about their child having an increased risk. Symptoms of depression were limited to 19.4% of the parents at the result-communication visit and declined over time during the intervention study. When thinking about their child's risk for developing T1D (disease-specific anxiety), 47.2% worried, felt nervous and tense. Mothers and parents with a first-degree relative (FDR) with T1D reported more symptoms of depression and disease-specific anxiety (p < 0.001) than fathers and parents without a FDR. Conclusion: Overall, symptoms of depression and panic-related anxiety are comparable with the German population. When asked about their child's risk for T1D during the intervention study, some parents reported disease-specific anxiety, which should be kept in mind when considering population-based screening. As certain subgroups are more prone, it will be important to continue psychological screening and, when necessary, to provide support by an experienced, multidisciplinary team.
  •  
25.
  • Hummel, Sandra, et al. (författare)
  • Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes
  • Ingår i: Diabetologia. - 0012-186X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity. Methods: Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk. Results: The COVID-19 pandemic was associated with increased time-varying BMI (β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively). Conclusions/interpretation: Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes. Graphical Abstract: [Figure not available: see fulltext.]
  •  
26.
  • Jacobs, An, et al. (författare)
  • Vitamin D insufficiency in infants with increased risk of developing type 1 diabetes : A secondary analysis of the POInT Study
  • 2024
  • Ingår i: BMJ Paediatrics Open. - 2399-9772. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in light of the differences in local supplementation guidelines. Methods In the POInT Study, a multicentre primary prevention study between February 2018 and March 2021 in Germany, Poland, Belgium, England and Sweden, including infants aged 4-7 months at high genetic risk of developing β-cell autoantibodies, vitamin D levels were analysed at each study visit from inclusion (4-7 months) until 3 years, with an interval of 2 months (first three visits) or 4-6 months (visits 4-8). The protocol actively promotes vitamin D sufficiency to optimise immune tolerance. VDI was defined as a concentration below 30 ng/mL and was treated according to local guidelines of participating centres. Recovery from VDI was defined as a concentration above or equal to 30 ng/mL on the subsequent visit after VDI. Results 1050 infants were included, of which 5937 vitamin D levels were available for analyses. VDI was observed in 1464 (24.7%) visits and 507 (46.1%) of these were not resolved at the next visit. The risk of having VDI was independently associated with season (higher in winter), weight (higher with increased weight), age (higher with increased age) and country (higher in England). The risk of not recovering from VDI was independently associated with the season of the previously determined VDI, which was higher if VDI was identified in winter. Conclusions VDI is frequent in infants with increased risk of developing T1D. Treatment guidelines for VDI do not seem effective. Increasing supplementation dosages in this patient population seems warranted, especially during winter, and increasing dosages more aggressively after VDI should be considered.
  •  
27.
  • Jacobsen, Laura M., et al. (författare)
  • Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study
  • 2022
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992. ; 45:3, s. 624-633
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0–4, 5–9, and 10–14 years; n = 142, 151, and 86, respectively) with com-parisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes. RESULTS Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04–1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42–1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83–0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16–1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Twenty-three children (6.1%) had DKA at onset, only 1 (0.97%) of 103 with and 22 (8.0%) of 276 children without a first-degree relative (FDR) with type 1 diabetes (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001). CONCLUSIONS DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.
  •  
28.
  • Johles, Lis, et al. (författare)
  • Psychological Flexibility Among Competitive Athletes : A Psychometric Investigation of a New Scale
  • 2020
  • Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media S.A.. - 2624-9367. ; 2:110
  • Tidskriftsartikel (refereegranskat)abstract
    • There is increasing interest in applying acceptance and mindfulness interventions amongathletes. However, there is a lack of sport-specific psychometrically evaluated scales tomeasure the impact of these interventions. The present study describes the developmentof a measure: the Psychological Flexibility in Sport Scale (PFSS). Its validity was testedin two studies. In the first study, with 152 elite athletes from various sports, explorativefactor analysis was used to evaluate the scale’s validity, and one factor emerged withseven items. Significant correlations between psychological flexibility, performance, andquality of life were found. Moreover, the PFSS was significantly negatively associated withage, number of years in sport, and number of years as an elite athlete. In the secondstudy, the confirmatory factor analysis with a new population (252 athletes) supportedthe one-factor solution. Further, positive associations were found with anxiety (BAI) anddepression (BDI-I), indicating construct validity. In conclusion, this study presents a scalefor measuring psychological flexibility in a broad range of athletes, with satisfactorypsychometric properties and the potential to be a useful instrument for both researchersand clinicians in the sport field
  •  
29.
  • Johnson, Randi K., et al. (författare)
  • Metabolite-related dietary patterns and the development of islet autoimmunity
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
  •  
30.
  • Johnson, Suzanne Bennett, et al. (författare)
  • First-appearing islet autoantibodies for type 1 diabetes in young children : maternal life events during pregnancy and the child's genetic risk
  • 2021
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 64:3, s. 591-602
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Psychological stress has long been considered a possible trigger of type 1 diabetes, although prospective studies examining the link between psychological stress or life events during pregnancy and the child's type 1 diabetes risk are rare. The objective of this study was to examine the association between life events during pregnancy and first-appearing islet autoantibodies (IA) in young children, conditioned by the child's type 1 diabetes-related genetic risk.METHODS: The IA status of 7317 genetically at-risk The Environmental Determinants of Diabetes in the Young (TEDDY) participants was assessed every 3 months from 3 months to 4 years, and bi-annually thereafter. Reports of major life events during pregnancy were collected at study inception when the child was 3 months of age and placed into one of six categories. Life events during pregnancy were examined for association with first-appearing insulin (IAA) (N = 222) or GAD (GADA) (N = 209) autoantibodies in the child until 6 years of age using proportional hazard models. Relative excess risk due to interaction (RERI) by the child's HLA-DR and SNP profile was estimated.RESULTS: Overall, 65% of mothers reported a life event during pregnancy; disease/injury (25%), serious interpersonal (28%) and job-related (25%) life events were most common. The association of life events during pregnancy differed between IAA and GADA as the first-appearing autoantibody. Serious interpersonal life events correlated with increased risk of GADA-first only in HLA-DR3 children with the BACH2-T allele (HR 2.28, p < 0.0001), an additive interaction (RERI 1.87, p = 0.0004). Job-related life events were also associated with increased risk of GADA-first among HLA-DR3/4 children (HR 1.53, p = 0.04) independent of serious interpersonal life events (HR 1.90, p = 0.002), an additive interaction (RERI 1.19, p = 0.004). Job-related life events correlated with reduced risk of IAA-first (HR 0.55, p = 0.004), particularly in children with the BTNL2-GG allele (HR 0.48; 95% CI 0.31, 0.76).CONCLUSIONS/INTERPRETATION: Specific life events during pregnancy are differentially related to IAA vs GADA as first-appearing IA and interact with different HLA and non-HLA genetic factors, supporting the concept of different endotypes underlying type 1 diabetes. However, the mechanisms underlying these associations remain to be discovered. Life events may be markers for other yet-to-be-identified factors important to the development of first-appearing IA.
  •  
31.
  • Jonsdottir, Berglind, et al. (författare)
  • Are Perinatal Events Risk Factors for Childhood Thyroid Autoimmunity?
  • 2017
  • Ingår i: European Thyroid Journal. - : Bioscientifica. - 2235-0640 .- 2235-0802. ; 6:6, s. 298-306
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Environmental and genetic factors possibly trigger thyroid autoimmunity. Studies on perinatal risk factors for childhood thyroid autoimmunity are sparse.Objectives: The aim was to investigate if perinatal factors, family history of autoimmune diseases, and HLA-DQ genotypes contribute to thyroid autoimmunity in the Diabetes Prediction in Skåne (DiPiS) study.Methods: Samples from 1,874 ten-year-old children were analyzed for autoantibodies to thyroid peroxidase (TPOAb), thyroglobulin (TGAb), and HLA-DQ genotypes. Information on perinatal events and family history of autoimmunity was gathered prospectively in questionnaires.Results: Thyroid autoimmunity was found in 6.9% of the children (TPOAb 4.4%, TGAb 5.8%, both autoantibodies 3.3%) and was overrepresented in girls. Prematurity was positively related to TGAb (OR: 2.4, p = 0.003, p c = 0.021). Autoimmune diseases in the family increased the risk of thyroid autoimmunity: TPOAb (OR: 2.2, p = 0.012), any autoantibody (OR: 1.7, p = 0.04), and both autoantibodies (OR: 2.2, p = 0.024). A first-degree relative (FDR) with thyroid disease increased the risk for TPOAb (OR: 2.4, p = 0.03) and both autoantibodies (OR: 2.6, p = 0.03), a FDR or sibling with celiac disease increased the risk for both autoantibodies (OR: 3.7, p = 0.03, and OR: 4.8, p = 0.003), a FDR or sibling with diabetes increased the risk for thyroid autoantibody (OR: 3.0, p = 0.01, and OR: 5.4, p = 0.032), and a father with rheumatic disease increased the risk for TPOAb (OR: 15.2, p = 0.017), TGAb (OR: 11.3, p = 0.029), any autoantibody (OR: 9.6, p = 0.038), and both autoantibodies (OR: 20, p = 0.01).Conclusions: Thyroid autoimmunity was found in 6.9% of the 10-year-old children who were being followed for their risk of type 1 diabetes. No relation to perinatal factors was found, with the exception of a possible association between prematurity and TGAb. Family history of autoimmune diseases increased the risk of thyroid autoimmunity.
  •  
32.
  • Jonsdottir, Berglind, et al. (författare)
  • Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study
  • 2018
  • Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 228-237
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p <.001) also having higher TPOAb levels at 10 years (p =.049). TPOAb was associated with GADA (p =.002), ZnT8R/W/QA (p =.001) and IA-2A (p =.001) while TGAb were associated with ZnT8R/W/QA (p =.021). In boys only, TPOAb were associated with GADA (p =.002), IA-2A (p =.001), ZnT8R/W/QA (p =.001) and IAA (p =.009), and TGAb with GADA (p =.013), IA-2A (p =.005) and ZnT8R/W/QA (p =.003). Levels of IA-2A correlated to both TPOAb (p =.021) and to TGAb (p =.011). In boys only, levels of GADA and TGAb correlated (p =.009 as did levels of IA-2A and TPOAb (p =.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine. Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.
  •  
33.
  • Jonsdottir, Berglind, et al. (författare)
  • Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197.
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes.METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease.RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76).MAIN CONCLUSION: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.
  •  
34.
  • Krischer, Jeffrey P, et al. (författare)
  • Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
  • 2019
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
  •  
35.
  • Kwon, Bum Chul, et al. (författare)
  • DPVis : Visual Analytics with Hidden Markov Models for Disease Progression Pathways
  • 2021
  • Ingår i: IEEE Transactions on Visualization and Computer Graphics. - 1077-2626. ; 27:9, s. 3685-3700
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical researchers use disease progression models to understand patient status and characterize progression patterns from longitudinal health records. One approach for disease progression modeling is to describe patient status using a small number of states that represent distinctive distributions over a set of observed measures. Hidden Markov models (HMMs) and its variants are a class of models that both discover these states and make inferences of health states for patients. Despite the advantages of using the algorithms for discovering interesting patterns, it still remains challenging for medical experts to interpret model outputs, understand complex modeling parameters, and clinically make sense of the patterns. To tackle these problems, we conducted a design study with clinical scientists, statisticians, and visualization experts, with the goal to investigate disease progression pathways of chronic diseases, namely type 1 diabetes (T1D), Huntington's disease, Parkinson's disease, and chronic obstructive pulmonary disease (COPD). As a result, we introduce DPVis which seamlessly integrates model parameters and outcomes of HMMs into interpretable and interactive visualizations. In this study, we demonstrate that DPVis is successful in evaluating disease progression models, visually summarizing disease states, interactively exploring disease progression patterns, and building, analyzing, and comparing clinically relevant patient subgroups.
  •  
36.
  • Kwon, Bum Chul, et al. (författare)
  • Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict. Here we show, by longitudinal sampling of islet autoantibodies (IAb) to insulin, glutamic acid decarboxylase and islet antigen-2 that disease progression follows distinct trajectories. Of the combined Type 1 Data Intelligence cohort of 24662 participants, 2172 individuals fulfill the criteria of two or more follow-up visits and IAb positivity at least once, with 652 progressing to type 1 diabetes during the 15 years course of the study. Our Continuous-Time Hidden Markov Models, that are developed to discover and visualize latent states based on the collected data and clinical characteristics of the patients, show that the health state of participants progresses from 11 distinct latent states as per three trajectories (TR1, TR2 and TR3), with associated 5-year cumulative diabetes-free survival of 40% (95% confidence interval [CI], 35% to 47%), 62% (95% CI, 57% to 67%), and 88% (95% CI, 85% to 91%), respectively (p < 0.0001). Age, sex, and HLA-DR status further refine the progression rates within trajectories, enabling clinically useful prediction of disease onset.
  •  
37.
  • Lernmark, Åke, et al. (författare)
  • Immunology of β-Cell Destruction
  • 2015. - 2nd
  • Ingår i: Islets of Langerhans. - 9789400766853 ; , s. 1047-1080
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
38.
  • Li, Ying, et al. (författare)
  • Predicting Type 1 Diabetes Onset using Novel Survival Analysis with Biomarker Ontology
  • 2020
  • Ingår i: AMIA ... Annual Symposium proceedings. AMIA Symposium. - 1942-597X. ; 2020, s. 727-736
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes (T1D) is a chronic autoimmune disease that affects about 1 in 300 children and up to 1 in 100 adults during their life-time1. Improvements in early prediction of T1D onset may help prevent diagnosis for diabetic ketoacidosis, a serious complication often associated with a missed or delayed T1D diagnosis. In addition to genetic factors, progression to T1D is strongly associated with immunologic factors that can be measured during clinical visits. We developed a T1D-specific ontology that captures the dynamic patterns of these biomarkers and used it together with a survival model, RankSvx, proposed in our prior work2. We applied this approach to a T1D dataset harmonized from three birth cohort studies from the United States, Finland, and Sweden. Results show that the dynamic biomarker patterns captured in the proposed ontology are able to improve prediction performance (in concordance index) by 5.3%, 3.3%, 2.8%, and 1.0% over baseline for 3, 6, 9, and 12 month duration windows, respectively.
  •  
39.
  • Li, Zhiguo, et al. (författare)
  • Childhood Height Growth Rate Association With the Risk of Islet Autoimmunity and Development of Type 1 Diabetes
  • 2022
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:6, s. 1520-1528
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Rapid growth has been suggested to promote islet autoimmunity and progression to type 1 diabetes (T1D). Childhood growth has not been analyzed separately from the infant growth period in most previous studies, but it may have distinct features due to differences between the stages of development. Objective: We aimed to analyze the association of childhood growth with development of islet autoimmunity and progression to T1D diagnosis in children 1 to 8 years of age. Methods: Longitudinal data of childhood growth and development of islet autoimmunity and T1D were analyzed in a prospective cohort study including 10 145 children from Finland, Germany, Sweden, and the United States, 1-8 years of age with at least 3 height and weight measurements and at least 1 measurement of islet autoantibodies. The primary outcome was the appearance of islet autoimmunity and progression from islet autoimmunity to T1D. Results: Rapid increase in height (cm/year) was associated with increased risk of seroconversion to glutamic acid decarboxylase autoantibody, insulin autoantibody, or insulinoma-like antigen-2 autoantibody (hazard ratio [HR] = 1.26 [95% CI = 1.05, 1.51] for 1-3 years of age and HR = 1.48 [95% CI = 1.28, 1.73] for >3 years of age). Furthermore, height rate was positively associated with development of T1D (HR = 1.80 [95% CI = 1.15, 2.81]) in the analyses from seroconversion with insulin autoantibody to diabetes. Conclusion: Rapid height growth rate in childhood is associated with increased risk of islet autoimmunity and progression to T1D. Further work is needed to investigate the biological mechanism that may explain this association.
  •  
40.
  • Li, Zhiguo, et al. (författare)
  • Imputing Longitudinal Growth Data in International Pediatric Studies : Does CDC Reference Suffice?
  • 2021
  • Ingår i: AMIA ... Annual Symposium proceedings. AMIA Symposium. - 1942-597X. ; 2021, s. 754-762
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates a missing value imputation approach for longitudinal growth data in pediatric studies from multiple countries. We analyzed a combined cohort from five natural history studies of type 1 diabetes (T1D) in the US and EU with longitudinal growth measurements for 23,201 subjects. We developed a multiple imputation methodology using LMS parameters of CDC reference data. We measured imputation errors on both combined and individual cohorts using mean absolute percentage error (MAPE) and normalized root-mean-square error (NRMSE). Our results show low imputation errors using CDC reference. Overall height imputation errors were lower than for weight. The largest MAPE for weight and height among all age groups was 4.8% and 1.7%, respectively. When comparing performance between CDC reference and country-specific growth charts, we found no significant differences for height (CDC vs. German: p =0.993, CDC vs. Swedish: p=0.368) and for weight (CDC vs. Swedish: p=0.513) for all ages.
  •  
41.
  • Lind, Alexander, et al. (författare)
  • Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays
  • 2024
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 104
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTwo or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.MethodsIAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1–10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.FindingsThe ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.InterpretationADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.
  •  
42.
  • Lind, Alexander, et al. (författare)
  • First trimester enterovirus IgM and beta cell autoantibodies in mothers to children affected by type 1 diabetes autoimmunity before 7 years of age
  • 2018
  • Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 0165-0378. ; 127, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Autoimmune (type 1) diabetes (T1D) is a frequent chronic disease in children and adolescents globally. Gestational enterovirus (EV) infections have been associated with an increased risk for T1D in the offspring. We test the hypothesis that EV infections during the first trimester were associated with beta cell autoantibodies in mothers of children who developed islet autoantibodies before 7 years of age. Materials and methods: Local registries were used to identify mothers to children born 2000–2007 who developed either beta cell autoantibodies or T1D during follow up. Serum samples from the first trimester were located in the Biobank. A total of 448 index mothers were identified and compared to 891 matched control mothers. EV-IgM was determined in a capture enzyme immunoassay. Beta cell autoantibodies were analyzed in standard radio binding assays. Results: The frequency of EV-IgM in index mothers was 20% (89/448), which did not differ from the control mothers 20% (175/891) (p = 0.922). Index mothers had multiple beta cell autoantibodies more often than control mothers (p = 0.037). Beta cell autoantibodies were increased during the November–April winter months in index compared to control mothers (p = 0.022). The observed difference was possibly explained by the months of February-April (p = 0.014). Concomitant EV-IgM and beta cell autoantibodies tended to be more common among index compared to control mothers (p = 0.039). Conclusion: EV-IgM during the first trimester may be associated with beta cell autoantibodies in mothers to children who developed either beta cell autoantibodies or T1D before 7 years of age.
  •  
43.
  • Lind, Alexander, et al. (författare)
  • Multiplex agglutination-PCR (ADAP) autoantibody assays compared to radiobinding autoantibodies in type 1 diabetes and celiac disease
  • 2022
  • Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 506
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiplex Antibody-Detection by Agglutination-PCR (ADAP) assay was compared to singleplex standard radiobinding assays (RBA) to detect autoantibodies against insulin (IAA), GAD65 (GADA), islet antigen-2 (IA-2A), ZnT8 (ZnT8A) and tissue transglutaminase (TGA). Serum samples from 272 (114F/158M), 15-73 years of age healthy controls and 227 (109F/118M) newly diagnosed type 1 diabetes children, 1-11 years of age, were analyzed in both assay systems.The original WHO standard 97/550 and in-house reference standards for RBA were compared to ADAP. The ADAP and RBA generated parallel reference standards in all assays except TGA. Lower detection limits were observed in the ADAP assay for GADA,IAA and ZnT8A, markedly for TGA, but not for IA-2A. The Receiver Operating Characteristics (ROC) curve AUC analyses for pairwise comparison of ADAP with RBA showed no difference for GADA (n.s.), ADAP greater AUC for IAA (p = 0.005), RBA greater AUC for IA-2A (p = 0.0004) and ZnT8A (p < 0.0001) while ADAP TGA had a greater AUC compared to both RBA TGA-IgG (p < 0.0001) and TGA-IgA (p < 0.0001) . These data suggest that the ADAP and RBA assays are comparable with equal performance for GADA, better ADAP performance for IAA while the RBA showed better performance in both IA-2A and ZnT8A associated with greater heterogeneity in autoantibody levels. The simultaneous analysis of 5 different autoantibodies by ADAP in sample volume reduced to only 4 μL and at an increased lower detection limit in all assays except IA-2A makes the ADAP automated autoantibody assay a distinct advantage for high throughput screening.
  •  
44.
  • Lugar, Marija, et al. (författare)
  • SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood
  • 2023
  • Ingår i: JAMA. - 0098-7484. ; 330:12
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.OBJECTIVE: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.DESIGN, SETTING, AND PARTICIPANTS: Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022.EXPOSURE: SARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022.MAIN OUTCOMES AND MEASURES: The development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed.RESULTS: Consent was obtained for 885 (441 girls) children who were included in follow-up antibody measurements from age 6 months. SARS-CoV-2 antibodies developed in 170 children at a median age of 18 months (range, 6-25 months). Islet autoantibodies developed in 60 children. Six of these children tested positive for islet autoantibodies at the same time as they tested positive for SARS-CoV-2 antibodies and 6 at the visit after having tested positive for SARS-CoV-2 antibodies. The sex-, age-, and country-adjusted hazard ratio for developing islet autoantibodies when the children tested positive for SARS-CoV-2 antibodies was 3.5 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (<18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009).CONCLUSION AND RELEVANCE: In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.
  •  
45.
  • Lundgren, Markus, et al. (författare)
  • Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
  • 2017
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
  •  
46.
  •  
47.
  • Lundgren, Markus, et al. (författare)
  • Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skane study
  • 2015
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:1, s. 75-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis The aim of this study was to examine the effect of cord blood autoantibodies on the risk for type 1 diabetes in children followed prospectively from birth. Methods The Diabetes Prediction in Skane (DiPiS) study consists of 35,853 children from the general population born during 2000-2004. Samples were collected at birth and analysed for HLA genotypes and autoantibodies to glutamate decarboxylase 65 (GAD65), insulin and insulinoma-associated protein 2 (IA-2). After adjusting for HLA, sex, maternal age and parental type 1 diabetes, independent associations with risk of diabetes were assessed using multivariate Cox proportional hazards models. Results In total, 151 children (0.4%) had developed type 1 diabetes by the end of 2013 at a median age of 5.8 years (0.8-12.2 years). In the multivariate analysis, the presence of IA-2 autoantibodies (IA-2A) in cord blood (HR 6.88, 95% CI 1.46,32.4; p = 0.003), but not maternal diabetes (HR 1.38, 95% CI 0.24,7.84; p = 0.71), was associated with risk of developing type 1 diabetes. No increased risk could be seen for the presence of autoantibodies to GAD65 or insulin. Conclusions/interpretation Our study indicates that the presence of cord blood IA-2A superimposes maternal diabetes and other cord blood islet autoantibodies as a predictor of type 1 diabetes development in the child. These findings may be of significance for future screening and study protocols on type 1 diabetes prediction.
  •  
48.
  •  
49.
  • Lundgren, Markus, et al. (författare)
  • Effect of screening for type 1 diabetes on early metabolic control : the DiPiS study
  • 2019
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:1, s. 53-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: It has been shown that children previously enrolled in follow-up studies have better glycaemic control during the early period after diabetes diagnosis. The aim of this study was to analyse glycaemic control over a longer period, past the period of partial remission, after diagnosis in children followed before diagnosis in the Swedish Diabetes Prediction in Skåne (DiPiS) study compared with children of equal age not enrolled in pre-diabetes follow-up, receiving equivalent diabetes care. Methods: HbA1c from diagnosis and for the following 5 years, as well as differences in insulin dosage, BMI, pump use, partial remission according to insulin dose-adjusted HbA1c and baseline demographics were compared between children who were enrolled in follow-up and had received information on diabetes risk (n = 51) and children not enrolled in follow-up (n = 78). Results: The group followed before diagnosis had a higher proportion of first-degree relatives (FDRs) with diabetes (28% vs 5.6%; p = 0.001) and a higher proportion of participants with mothers born in Sweden (100% vs 89%; p = 0.02). No significant differences in total daily insulin dose, pump use or other baseline sociodemographic factors were detected between the groups. Median HbA1c at diagnosis and at 1, 2, 3, 4 and 5 years after diabetes diagnosis was significantly lower in children followed before diagnosis (all p < 0.05), and was not related to FDR status. Conclusions/interpretation: Compared with controls not previously enrolled in follow-up, our study shows that children enrolled in longitudinal follow-up before the diagnosis of diabetes have better glycaemic control, measured by HbA1c, up to 5 years after diagnosis and during the initial period of partial remission. Improved glycaemic control in the initial years of living with type 1 diabetes could affect long-term outcome and complications and might also improve study enrolment in future longitudinal studies.
  •  
50.
  • Lundgren, Markus, et al. (författare)
  • Influence of early-life parental severe life events on the risk of type 1 diabetes in children : the DiPiS study
  • 2018
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 55:8, s. 797-804
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Stress and severe life events (SLEs) modify autoimmune disease susceptibility. Here, we aimed to establish if SLEs reported by parents during the first 2 years of life influence the risk of developing type 1 diabetes (T1D) using data from the prospective Diabetes Prediction in Skåne (DiPiS) study. Methods: Prospective questionnaire data recorded at 2 months (n = 23,187) and 2 years of age (n = 3784) from the DiPiS cohort of children were included in the analysis. SLEs were analyzed both by groups and as a combined variable. A Cox proportional hazards model was used to calculate hazard ratios (HRs) for T1D diagnosis for the total cohort and for the HLA-DQ2/8 high-risk population. Affected first-degree relatives, HLA-DQ risk group, paternal education level, and parents’ country of birth were included as covariates. Results: There was a significantly increased risk of T1D in children with SLEs occurring during the child’s first 2 years of life for both the total cohort (HR 1.67; 95% CI 1.1, 2.7; p = 0.03) and the DQ2/8 cohort (HR 2.2; 95% CI 1.1, 4.2; p = 0.018). Subgroup analysis of events related to unemployment, divorce, or family conflict showed a significant hazard for these events occurring both during and after pregnancy in the DQ2/8 cohort (HR 2.17; 95% CI 1.1, 4.3; p = 0.03 and HR 4.98; 95% CI 2.3, 11; p < 0.001, respectively) and after pregnancy in the total cohort (multiple regression HR 2.07; 95% CI 1.01, 4.2; p = 0.047). Conclusions: Children of parents experiencing an SLE during the child’s first 2 years of life were at increased risk of T1D. Further studies including those measuring immune and stress-related biomarkers are necessary to validate the findings.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 91
Typ av publikation
tidskriftsartikel (80)
rapport (3)
konferensbidrag (3)
forskningsöversikt (2)
doktorsavhandling (1)
bokkapitel (1)
visa fler...
licentiatavhandling (1)
visa färre...
Typ av innehåll
refereegranskat (80)
övrigt vetenskapligt/konstnärligt (9)
populärvet., debatt m.m. (2)
Författare/redaktör
Lundgren, Markus (60)
Elding Larsson, Hele ... (25)
Lernmark, Åke (22)
Toppari, Jorma (20)
Veijola, Riitta (19)
Maziarz, Marlena (12)
visa fler...
Hagopian, William (12)
Lundgren, Tobias (11)
Anand, Vibha (11)
Frohnert, Brigitte I (11)
Larsson, Helena Eldi ... (11)
Bonifacio, Ezio (11)
Achenbach, Peter (11)
Ramelius, Anita (10)
Rewers, Marian (10)
Jonsdottir, Berglind (10)
Törn, Carina (10)
Ziegler, Anette G. (10)
Ng, Kenney (9)
Ziegler, Anette-Gabr ... (9)
Salami, Falastin (9)
Agardh, Daniel (8)
Winkler, Christiane (8)
Akolkar, Beena (8)
Kordonouri, Olga (8)
Haller, Michael J. (7)
Steck, Andrea K. (7)
Lundgren, Edvin (6)
Parling, Thomas (6)
Knip, Mikael (6)
Krischer, Jeffrey (6)
Jansson-Fröjmark, Ma ... (6)
Ask, Maria (5)
Soldemo, Markus (5)
Weissenrieder, Jonas (5)
Ghalwash, Mohamed (5)
Dunne, Jessica L (5)
Larsson, Helena (5)
Hagopian, William A. (5)
Rewers, Marian J. (5)
She, Jin Xiong (5)
Krischer, Jeffrey P. (5)
Vehik, Kendra (5)
Todd, John A. (5)
Johnson, Suzanne Ben ... (5)
Besser, Rachel E. J. (5)
Bremer, Jenny (5)
Gard, Thomas (5)
Johansen, Fredrik (5)
Markan, Maria (5)
visa färre...
Lärosäte
Lunds universitet (68)
Karolinska Institutet (14)
Stockholms universitet (8)
Göteborgs universitet (5)
Umeå universitet (5)
Uppsala universitet (5)
visa fler...
Linköpings universitet (5)
Kungliga Tekniska Högskolan (4)
Karlstads universitet (4)
Luleå tekniska universitet (2)
Mälardalens universitet (2)
Mittuniversitetet (1)
Södertörns högskola (1)
RISE (1)
Högskolan Dalarna (1)
visa färre...
Språk
Engelska (85)
Svenska (6)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (68)
Samhällsvetenskap (15)
Naturvetenskap (9)
Teknik (2)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy