SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Liu Helena) srt2:(2020-2024)"

Sökning: WFRF:(Liu Helena) > (2020-2024)

  • Resultat 1-41 av 41
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
  •  
2.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
  •  
3.
  • Calabrese, Claudia, et al. (författare)
  • Genomic basis for RNA alterations in cancer
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
  •  
4.
  • Abdulla, N., et al. (författare)
  • Epidemiology of hip fracture in Qatar and development of a country specific FRAX model
  • 2022
  • Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A Summary Hip fracture data were retrieved from electronical medical records for the years 2017-2019 in the State of Qatar and used to create a FRAX (R) model to facilitate fracture risk assessment. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi, and Kuwait but fracture probabilities varied due to differences in mortality. Objective This paper describes the epidemiology of osteoporotic fractures in the State of Qatar that was used to develop the country-specific fracture prediction FRAX (R) tool. Methods Hip fracture data were retrieved from electronic medical records for the years 2017-2019 in the State of Qatar. The age and sex specific incidence of hip fracture in Qatari residents and national mortality rates were used to create a FRAX (R) model. Fracture probabilities were compared with those from neighboring countries having FRAX models. Results Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi and Kuwait. In contrast, probabilities of a major osteoporotic fracture or hip fracture were lower in Qatar than in Kuwait but higher than those in Abu Dhabi and Saudi Arabia due to differences in mortality. Conclusion The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.
  •  
5.
  • Al-Daghri, N. M., et al. (författare)
  • The application of FRAX in Saudi Arabia
  • 2021
  • Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A Summary Assessment and treatment pathways based on age-specific intervention thresholds in Saudi Arabi can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk. Purpose Intervention thresholds for the treatment of osteoporosis have historically been based on the measurement of bone mineral density. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Saudi Arabia based on fracture probabilities derived from FRAX (R). Methods The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Saudi Arabia. The methodology was applied to women age 40 years or more drawn from a tertiary referral population for skeletal assessment. Missing data for the calculation of FRAX was simulated using data from the referral and FRAX derivation cohorts. Results Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.0% at the age of 50 years increasing to 7.6% at the age of 70 years. A total of 163 of 1365 women (11.9%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 5 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended for 593 women (43.4%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. Of these, 220 individuals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test. Conclusion Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.
  •  
6.
  • Alvehus, Johan, et al. (författare)
  • Leadership, power, and politics
  • 2024
  • Ingår i: Routledge Critical Companion to Leadership Studies. - 9781032425153
  • Bokkapitel (refereegranskat)
  •  
7.
  • Axelsson, Kristian F, 1973, et al. (författare)
  • Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism
  • 2022
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. OBJECTIVE To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. MAIN OUTCOMES AND MEASURES The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). RESULTS A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pH PT group and 803 522 person-years for the control group. Compared with the control group, the pH PT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). CONCLUSIONS AND RELEVANCE Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.
  •  
8.
  • Bonagas, Nadilly, et al. (författare)
  • Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
  • 2022
  • Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
  • Tidskriftsartikel (refereegranskat)abstract
    • The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
  •  
9.
  • Dimai, H. P., et al. (författare)
  • Osteoporosis treatment in Austria-assessment of FRAX-based intervention thresholds for high and very high fracture risk
  • 2022
  • Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A Summary The adoption of the management pathway proposed by the National Osteoporosis Guideline Group (NOGG), UK applied using the Austrian FRAX (R) tool in a referral population of Austrian women categorises 22-29% of women age 40 years or more eligible for treatment of whom 28-34% are classified at very high risk. Purpose The aim of this study is to provide a reference document for the further development of existing guidelines for the management of osteoporosis in Austria, considering FRAX-based intervention thresholds for high and very high fracture risk. Methods The model development was based on two Austrian hospital referral cohorts. Baseline information was collected to compute the 10-year probability (using the Austrian FRAX model) of a major osteoporotic fracture (MOF) and hip fracture both with and without the inclusion of femoral neck bone mineral density (BMD). Assessment thresholds for BMD testing were defined, as well as intervention thresholds. In addition, thresholds that characterise men and women at high and very high fracture risk were established. The management pathway followed that currently recommended by the UK National Osteoporosis Guideline Group (NOGG). Results The two cohorts comprised a total of 1306 women and men with a mean age of 66.7 years. Slightly more than 50% were eligible for treatment by virtue of a prior fragility fracture. In those women without a prior fracture, 22% (n = 120) were eligible for treatment based on MOF probabilities. Of these, 28% (n = 33) were found to be at very high risk. When both MOF and hip fracture probabilities were used to characterise risk, 164 women without a prior fracture were eligible for treatment (29%). Of these, 34% (n = 56) were found to be at very high risk. Fewer men without prior fracture were eligible for treatment compared with women. Conclusion The management pathway as currently outlined is expected to reduce inequalities in patient management. The characterisation of very high risk may aid in the identification of patients suitable for treatment with osteoanabolic agents.
  •  
10.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
  •  
11.
  • Gavilanez, E. L., et al. (författare)
  • An assessment of intervention thresholds for high fracture risk in Chile
  • 2023
  • Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: Assessment and treatment pathways using FRAX-based intervention thresholds in Chile can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk. Purpose: The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Chile based on major osteoporotic fracture (MOF) probabilities derived from FRAX®. Methods: Intervention and assessment thresholds were derived using methods adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Chile. Age-dependent and hybrid assessment and intervention thresholds were applied to 1998 women and 1122 men age 50years or more drawn from participants in the National Health Survey 2016–2017. Results: Approximately 12% of men and women had a prior fragility fracture and would be eligible for treatment for this reason. Using age-dependent thresholds, an additional 2.6% of women (0.3% of men) were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended in 5% of men and 38% of women. With hybrid thresholds, an additional 13% of women (3.6% of men) were eligible for treatment and BMD recommended in 11% of men and 42% of women. Conclusion: The application of hybrid intervention thresholds ameliorates the disparity in fracture probabilities seen with age-dependent thresholds. Probability-based assessment of fracture risk, including the use of the hybrid intervention thresholds for Chile, is expected to help guide decisions about treatment.
  •  
12.
  • 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.
  •  
13.
  • Harvey, N. C., et al. (författare)
  • Greater pQCT Calf Muscle Density Is Associated with Lower Fracture Risk, Independent of FRAX, Falls and BMD: A Meta-Analysis in the Osteoporotic Fractures in Men (MrOS) Study
  • 2022
  • Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 6:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross-sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta-analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow-up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T-score, Fracture Risk Assessment Tool (FRAX) 10-year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean +/- SD age 77.0 +/- 5.1, 73.9 +/- 4.9, 80 +/- 3.4 years, followed for a mean +/- SD 7.8 +/- 2.2, 8.1 +/- 2.3, 5.3 +/- 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72-1.0 and 0.78; 95% CI, 0.66-0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T-score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88-1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59-0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. (C) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
  •  
14.
  • Harvey, Nicholas C., et al. (författare)
  • Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study : A Meta-Analysis
  • 2021
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:7, s. 1235-1244
  • Tidskriftsartikel (refereegranskat)abstract
    • Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.
  •  
15.
  • Johansson, Lena, 1972, et al. (författare)
  • Improved fracture risk prediction by adding VFA-identified vertebral fracture data to BMD by DXA and clinical risk factors used in FRAX
  • 2022
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 33:8, s. 1725-1738
  • Tidskriftsartikel (refereegranskat)abstract
    • Vertebral fracture (VF) is a strong predictor of subsequent fracture. In this study of older women, VF, identified by dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA), were associated with an increased risk of incident fractures and had a substantial impact on fracture probability, supporting the utility of VFA in clinical practice. Purpose Clinical and occult VF can be identified using VFA with dual-energy X-ray absorptiometry (DXA). The aim of this study was to investigate to what extent VFA-identified VF improve fracture risk prediction, independently of bone mineral density (BMD) and clinical risk factors used in FRAX. Methods A total of 2852 women, 75-80 years old, from the prospective population-based study SUPERB cohort, were included in this study. At baseline, BMD was measured by DXA, VF diagnosed by VFA, and questionnaires used to collect data on risk factors for fractures. Incident fractures were captured by X-ray records or by diagnosis codes. An extension of Poisson regression was used to estimate the association between VFA-identified VF and the risk of fracture and the 5- and 10-year probability of major osteoporotic fracture (MOF) was calculated from the hazard functions for fracture and death. Results During a median follow-up of 5.15 years (IQR 4.3-5.9 years), the number of women who died or suffered a MOF, clinical VF, or hip fracture was 229, 422, 160, and 124, respectively. A VFA-identified VF was associated with an increased risk of incident MOF (hazard ratio [HR] = 1.78; 95% confidence interval [CI] 1.46-2.18), clinical VF (HR = 2.88; 95% [CI] 2.11-3.93), and hip fracture (HR = 1.67; 95% [CI] 1.15-2.42), adjusted for age, height, and weight. For women at age 75 years, a VFA-identified VF was associated with 1.2-1.4-fold greater 10-year MOF probability compared with not taking VFA into account, depending on BMD. Conclusion Identifying an occult VF using VFA has a substantial impact on fracture probability, indicating that VFA is an efficient method to improve fracture prediction in older women.
  •  
16.
  • Kanis, J. A., et al. (författare)
  • Primary hyperparathyroidism and fracture probability
  • 2023
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 34, s. 489-499
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of hip and major osteoporotic fracture was increased in patients with primary hyperparathyroidism even in patients not referred for parathyroidectomy. The risk of death was also increased which attenuated an effect on fracture probabilities. The findings argue for widening the indications for parathyroidectomy in mild primary hyperparathyroidism.Introduction Primary hyperparathyroidism (PHPT) is associated with an increase in the risk of fracture. In FRAX, the increase in risk is assumed to be mediated by low bone mineral density (BMD). However, the risk of death is also increased and its effect on fracture probability is not known.Objective The aim of this study was to determine whether PHPT affects hip fracture and major osteoporotic fracture risk independently of bone mineral density (BMD) and whether this and any increase in mortality affects the assessment of fracture probability.Methods A register-based survey of patients with PHPT and matched controls in Denmark were identified from hospital registers. The incidence of death, hip fracture, and major osteoporotic fracture were determined for computing fracture probabilities excluding time after parathyroidectomy. The gradient of risk for fracture for differences in BMD was determined in a subset of patients and in BMD controls. The severity of disease was based on serum calcium and parathyroid hormone levels.Results We identified 6884 patients with biochemically confirmed PHPT and 68,665 matched population controls. On follow-up, excluding time after parathyroidectomy in those undergoing surgery, patients with PHPT had a higher risk of death (+52%), hip fracture (+48%), and major osteoporotic fracture (+36%) than population controls. At any given age, average 10-year probabilities of fracture were higher in patients with PHPT than population controls. The gradient of fracture risk with differences in BMD was similar in cases and controls. Results were similar when confined to patients not undergoing parathyroidectomy. Fracture probability decreased with the severity of disease due to an increase in mortality rather than fracture risk.Conclusion The risk of hip and other major osteoporotic fracture is increased in PHPT irrespective of the disease severity. Fracture probability was attenuated due to the competing effect of mortality. The increased fracture risk in patients treated conservatively argues for widening the indications for parathyroidectomy in mild PHPT.
  •  
17.
  • Kemppinen, Julia, et al. (författare)
  • Microclimate, an important part of ecology and biogeography
  • 2024
  • Ingår i: GLOBAL ECOLOGY AND BIOGEOGRAPHY. - 1466-822X .- 1466-8238. ; 33:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Brief introduction: What are microclimates and why are they important?Microclimate science has developed into a global discipline. Microclimate science is increasingly used to understand and mitigate climate and biodiversity shifts. Here, we provide an overview of the current status of microclimate ecology and biogeography in terrestrial ecosystems, and where this field is heading next.Microclimate investigations in ecology and biogeographyWe highlight the latest research on interactions between microclimates and organisms, including how microclimates influence individuals, and through them populations, communities and entire ecosystems and their processes. We also briefly discuss recent research on how organisms shape microclimates from the tropics to the poles.Microclimate applications in ecosystem managementMicroclimates are also important in ecosystem management under climate change. We showcase new research in microclimate management with examples from biodiversity conservation, forestry and urban ecology. We discuss the importance of microrefugia in conservation and how to promote microclimate heterogeneity.Methods for microclimate scienceWe showcase the recent advances in data acquisition, such as novel field sensors and remote sensing methods. We discuss microclimate modelling, mapping and data processing, including accessibility of modelling tools, advantages of mechanistic and statistical modelling and solutions for computational challenges that have pushed the state-of-the-art of the field.What's next?We identify major knowledge gaps that need to be filled for further advancing microclimate investigations, applications and methods. These gaps include spatiotemporal scaling of microclimate data, mismatches between macroclimate and microclimate in predicting responses of organisms to climate change, and the need for more evidence on the outcomes of microclimate management.
  •  
18.
  • Larsson, B. A. M., et al. (författare)
  • The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density
  • 2021
  • Ingår i: Osteoporosis International. - : SPRINGER LONDON LTD. - 0937-941X .- 1433-2965. ; 32, s. 75-84
  • Tidskriftsartikel (refereegranskat)abstract
    • The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.
  •  
19.
  • Li, Xiaofei, et al. (författare)
  • Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin
  • 2023
  • Ingår i: Nature Neuroscience. - : Springer Nature. - 1097-6256 .- 1546-1726. ; 26:5, s. 891-901
  • Tidskriftsartikel (refereegranskat)abstract
    • The authors created a comprehensive developmental cell atlas for spatiotemporal gene expression of the human spinal cord, revealed species-specific regulation during development and used the atlas to infer novel markers for pediatric ependymomas. The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5-12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.
  •  
20.
  • Lindgren, Helena, 1969-, et al. (författare)
  • Francisella tularensis-specific antibody levels in sera from Swedish patients with suspected tularemia during a 13-year period
  • 2024
  • Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: For a majority of tularemia patients, serology is the basis for the diagnosis. The aim of this study was to perform an analysis of the samples analyzed at a Swedish reference laboratory for the presence of Francisella tularensis-specific antibody levels in sera from individuals with suspected tularemia. Annual and monthly variations of the total number of samples and proportions of positive samples were analyzed, as well as the influence of age and gender.Methods: We performed a retrospective analysis of the presence of F. tularensis-specific antibodies in serological samples from patients with suspected tularemia analyzed during the period 2010 - 2022 at the University Hospital of Umeå in Sweden, a national reference laboratory, by use of various statistical methods. In total, some 15,100 serum samples had been analyzed for the presence of IgG and IgM antibodies by ELISA during the 13-year period.Results: Overall, there were higher number of samples with IgG positive or borderline titers, 2,522 and 921, respectively, than with IgM positive or borderline titers, 1,802 and 409, respectively. Repeated samples were obtained from some 1,930 individuals and approximately a third of the cases, which were initially seronegative, had seroconverted when resampled. Peak number of monthly samples were recorded in August and September, > 3,000. Annual numbers varied greatly and peak numbers were observed in 2015 and 2019, 1,832 and 2,250, respectively, whereas some other years the numbers were 700 – 800. There was also much variation in the annual and monthly percentages of positive samples and they varied between less than 10% to greater than 20%. The highest percentages of positive samples were recorded in September and October. IgG and IgM titers declined with age and these differences were highly significant for IgG titers, with decreasing average titers for each 20-year interval.Discussion: Collectively, the data demonstrate the marked annual and seasonal variations in tularemia sampling occurring in Sweden. Also, the proportion of positive samples increased during months and years with peak number of samples. Another notable finding was that average antibody titers decreased with increased age.
  •  
21.
  • Liu, Ju, et al. (författare)
  • A System Model and An Innovation Approach toward Sustainable Housing Renovation
  • 2020
  • Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Housing renovation is a common concern to owners, tenants and to society at large. In addition to the high economic costs, the implementation of housing renovation usually have a long-term impact on the society and the built environment. This is a theoretical paper that develops a system model for understanding sustainable housing renovation as a system phenomenon which has multiple sustainability goals, complicated dynamic processes, diverse actors, and a sophisticated institutional environment. It identifies the key challenges of a sustainable housing renovation system, namely the conflicting sustainability goals and the conflicting stakeholder interests. To address these two challenges, the paper suggests an innovation approach in which the process of innovation (linear versus organic) and the typology of innovation (product versus process and business versus social) toward sustainable housing renovation are discussed.
  •  
22.
  • Liu, Jianyang, et al. (författare)
  • Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis
  • 2024
  • Ingår i: ARTHRITIS RESEARCH & THERAPY. - 1478-6354 .- 1478-6362. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient's response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy. Methods: This study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-alpha blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B-2 (TXBM), 2,3-dinor-6-keto prostaglandin F-1a (PGIM), leukotriene E-4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography-mass spectrometry (LC-MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes. Results: Patients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24. Conclusions: Treatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.
  •  
23.
  • Liu, Xiang, et al. (författare)
  • Distinct growth phases in early life associated with the risk of type 1 diabetes : The teddy study
  • 2020
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:3, s. 556-562
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study followed 7,522 genetically high-risk children in Sweden, Finland, Germany, and the U.S. from birth for a median of 9.0 years (interquartile range 5.7–10.6) with available growth data. Of these, 761 (10.1%) children developed IA and 290 (3.9%) children were diagnosed with T1D. Bayesian two-phase piecewise linear mixed models with a random change point were used to estimate children’s individual growth trajectories. Cox proportional hazards models were used to assess the effects of associated growth parameters on the risks of IA and progression to T1D. RESULTS A higher rate of weight gain in infancy was associated with increased IA risk (hazard ratio [HR] 1.09 [95% CI 1.02, 1.17] per 1 kg/year). A height growth pattern with a lower rate in infancy (HR 0.79 [95% CI 0.70, 0.90] per 1 cm/year), higher rate in early childhood (HR 1.48 [95% CI 1.22, 1.79] per 1 cm/year), and younger age at the phase transition (HR 0.76 [95% CI 0.58, 0.99] per 1 month) was associated with increased risk of progression from IA to T1D. A higher rate of weight gain in early childhood was associated with increased risk of progression from IA to T1D (HR 2.57 [95% CI 1.34, 4.91] per 1 kg/year) in children with first-appearing GAD autoantibody only. CONCLUSIONS Growth patterns in early life better clarify how specific growth phases are associated with the development of T1D.
  •  
24.
  • Liu, Xijia, et al. (författare)
  • Utility of Borrelia-specific IgM and IgG antibody titer determinations during a 12-year period : results from a clinical laboratory in Northern Sweden
  • 2023
  • Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Interpretation of serological findings in suspected Lyme borreliosis (LB) is challenging and IgM reactivities may have low predictive value. Therefore, if used indiscriminately, there is a risk for incorrect diagnosis of LB. To evaluate the usefulness of IgM titer determination, we performed a study of the prevalence of Borrelia-specific antibodies in serological samples from patients with suspected LB analyzed during the period 2010 - 2021 at the University Hospital of Umeå in Sweden. In total, 19,335 samples had been analyzed for the presence of IgG and IgM antibodies. Overall, there were higher percentages of IgM positive or borderline titers, 1,847 (9.6%) and 905 (4.7%), respectively, than IgG positive or borderline titers, 959 (5.0%) and 406 (2.1%), respectively. Peak number of samples were recorded 2012 - 2013, exceeding 1,800, whereas there were around 1,200 during 2020 - 2021. The peak number of positive IgG and/or positive IgM samples were observed during the period 2015 - 2017 with close to, or above 400, and concomitantly, the proportion of IgG positive samples increased markedly. For IgG positive samples, the increase followed a positive linear time trend (P< 0.001). Peak monthly numbers were observed during August, September, and October. This seasonal increase was significant for the IgG positive group (P< 0.05), but not for the IgM positive/IgG negative group. Repeated samples were obtained from 3,188 individuals and of the initial samples 2,817 were (88%) IgG negative and 2,315 (72%) were IgM negative and of these, 130 (4%) showed IgG seroconversion and 300 (9%) IgM seroconversion. Collectively, the data demonstrate that IgG and/or IgM positive samples represented a minority of all samples, even when repeated sampling had occurred, and IgM positive samples were much more common than IgG positive samples. Thus, the accuracy of the clinical suspicion was low and this will lead to a low predictive value of the analysis, in particular of IgM. These findings question the use of IgM titer determination as a routine analysis.
  •  
25.
  • Liu, Yuchu, 1992, et al. (författare)
  • An architecture for enabling A/B experiments in automotive embedded software
  • 2021
  • Ingår i: Proceedings - 2021 IEEE 45th Annual Computers, Software, and Applications Conference, COMPSAC 2021. - : IEEE. ; , s. 992-997
  • Konferensbidrag (refereegranskat)abstract
    • A/B experimentation is a known technique for data-driven product development and has demonstrated its value in web-facing businesses. With the digitalisation of the automotive industry, the focus in the industry is shifting towards software. For automotive embedded software to continuously improve, A/B experimentation is considered an important technique. However, the adoption of such a technique is not without challenge. In this paper, we present an architecture to enable A/B testing in automotive embedded software. The design addresses challenges that are unique to the automotive industry in a systematic fashion. Going from hypothesis to practice, our architecture was also applied in practice for running online experiments on a considerable scale. Furthermore, a case study approach was used to compare our proposal with state-of-practice in the automotive industry. We found our architecture design to be relevant and applicable in the efforts of adopting continuous A/B experiments in automotive embedded software.
  •  
26.
  • Liu, Yuchu, 1992, et al. (författare)
  • Bayesian causal inference in automotive software engineering and online evaluation
  • 2022
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Randomised field experiments, such as A/B testing, have long been the gold standard for evaluating software changes. In the automotive domain, running randomised field experiments is not always desired, possible, or even ethical. In the face of such restrictions, we show how to utilise observational studies in combination with Bayesian causal inference to understand real-world impacts from complex automotive software updates and help development organisations arrive at causal conclusions. In this study, we present three causal inference models in the Bayesian framework and their corresponding cases to address three commonly experienced challenges of software evaluation in the automotive domain. We apply Bayesian propensity score matching for producing balanced control and treatment groups, Bayesian regression discontinuity for identifying covariate dependent treatment assignments, and Bayesian difference-in-differences for causal inference on treatment effect overtime. We demonstrate the potential of causal inference with our industry collaborators with studies conducted on a fleet of vehicles. The cases are presented in details as well as the related the theory of causal assumption to the practice of running observational studies. Finally, we discuss the potential and pitfalls of the Bayesian causal models.
  •  
27.
  • Liu, Yuchu, 1992, et al. (författare)
  • Bayesian propensity score matching in automotive embedded software engineering
  • 2021
  • Ingår i: Proceedings - Asia-Pacific Software Engineering Conference, APSEC. - 1530-1362. ; 2021-December, s. 233-242
  • Konferensbidrag (refereegranskat)abstract
    • Randomised field experiments, such as A/B testing, have long been the gold standard for evaluating the value that new software brings to customers. However, running randomised field experiments is not always desired, possible or even ethical in the development of automotive embedded software. In the face of such restrictions, we propose the use of the Bayesian propensity score matching technique for causal inference of observational studies in the automotive domain. In this paper, we present a method based on the Bayesian propensity score matching framework, applied in the unique setting of automotive software engineering. This method is used to generate balanced control and treatment groups from an observational online evaluation and estimate causal treatment effects from the software changes, even with limited samples in the treatment group. We exemplify the method with a proof-of-concept in the automotive domain. In the example, we have a larger control (Nc = 1100) fleet of cars using the current software and a small treatment fleet (Nt = 38), in which we introduce a new software variant. We demonstrate a scenario that shipping of a new software to all users is restricted, as a result, a fully randomised experiment could not be conducted. Therefore, we utilised the Bayesian propensity score matching method with 14 observed covariates as inputs. The results show more balanced groups, suitable for estimating causal treatment effects from the collected observational data. We describe the method in detail and share our configuration. Furthermore, we discuss how can such a method be used for online evaluation of new software utilising small groups of samples.
  •  
28.
  • Liu, Yuchu, et al. (författare)
  • Bayesian propensity score matching in automotive embedded software engineering
  • 2021
  • Ingår i: 2021 28th Asia-Pacific Software Engineering Conference (APSEC). - : IEEE. - 9781665437844 - 9781665437851
  • Konferensbidrag (refereegranskat)abstract
    • Randomised field experiments, such as A/B testing, have long been the gold standard for evaluating the value that new software brings to customers. However, running randomised field experiments is not always desired, possible or even ethical in the development of automotive embedded software. In the face of such restrictions, we propose the use of the Bayesian propensity score matching technique for causal inference of observational studies in the automotive domain. In this paper, we present a method based on the Bayesian propensity score matching framework, applied in the unique setting of automotive software engineering. This method is used to generate balanced control and treatment groups from an observational online evaluation and estimate causal treatment effects from the software changes, even with limited samples in the treatment group. We exemplify the method with a proof-of-concept in the automotive domain. In the example, we have a larger control (Nc = 1100) fleet of cars using the current software and a small treatment fleet (Nt = 38), in which we introduce a new software variant. We demonstrate a scenario that shipping of a new software to all users is restricted, as a result, a fully randomised experiment could not be conducted. Therefore, we utilised the Bayesian propensity score matching method with 14 observed covariates as inputs. The results show more balanced groups, suitable for estimating causal treatment effects from the collected observational data. We describe the method in detail and share our configuration. Furthermore, we discuss how can such a method be used for online evaluation of new software utilising small groups of samples.
  •  
29.
  • Liu, Yuchu, 1992, et al. (författare)
  • Size matters? Or not : A/B testing with limited sample in automotive embedded software
  • 2021
  • Ingår i: 2021 47TH EUROMICRO CONFERENCE ON SOFTWARE ENGINEERING AND ADVANCED APPLICATIONS (SEAA 2021). - : IEEE. - 9781665427050 ; , s. 300-307
  • Konferensbidrag (refereegranskat)abstract
    • A/B testing is gaining attention in the automotive sector as a promising tool to measure casual effects from software changes. Different from the web-facing businesses, where A/B testing has been well-established, the automotive domain often suffers from limited eligible users to participate in online experiments. To address this shortcoming, we present a method for designing balanced control and treatment groups so that sound conclusions can be drawn from experiments with considerably small sample sizes. While the Balance Match Weighted method has been used in other domains such as medicine, this is the first paper to apply and evaluate it in the context of software development. Furthermore, we describe the Balance Match Weighted method in detail and we conduct a case study together with an automotive manufacturer to apply the group design method in a fleet of vehicles. Finally, we present our case study in the automotive software engineering domain, as well as a discussion on the benefits and limitations of the A/B group design method.
  •  
30.
  • Lorentzon, Mattias, 1970, et al. (författare)
  • Osteoporosis and fractures in women: the burden of disease
  • 2022
  • Ingår i: Climacteric. - : Informa UK Limited. - 1369-7137 .- 1473-0804. ; 25:1, s. 4-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis is a disease characterized by impaired bone microarchitecture and reduced bone mineral density (BMD) resulting in bone fragility and increased risk of fracture. In western societies, one in three women and one in five men will sustain an osteoporotic fracture in their remaining lifetime from the age of 50 years. Fragility fractures, especially of the spine and hip, commonly give rise to increased morbidity and mortality. In the five largest European countries and Sweden, fragility fractures were the cause of 2.6 million disability-adjusted life years in 2016 and the fracture-related costs increased from euro29.6 billion in 2010 to euro37.5 billion in 2017. In the European Union and the USA, only a small proportion of women eligible for pharmacological treatment are being prescribed osteoporosis medication. Secondary fracture prevention, using Fracture Liaison Services, can be used to increase the rates of fracture risk assessment, BMD testing and use of osteoporosis medication in order to reduce fracture numbers. Additionally, established primary prevention strategies, based on case-finding methods utilizing fracture prediction tools, such as FRAX, to identify women without fracture but with elevated risk, are recommended in order to further reduce fracture numbers.
  •  
31.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
  •  
32.
  •  
33.
  • Pietilä, Riikka, et al. (författare)
  • Molecular anatomy of adult mouse leptomeninges
  • 2023
  • Ingår i: Neuron. - : Elsevier. - 0896-6273 .- 1097-4199. ; 111:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we iden-tify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arach-noid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
  •  
34.
  • Saleh, Y. A. L., et al. (författare)
  • Incidence of hip fracture in Saudi Arabia and the development of a FRAX model
  • 2022
  • Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A prospective hospital-based survey in representative regions of Saudi Arabia determined the incidence of fractures at the hip. The hip fracture rates were used to create a FRAX (R) model to facilitate fracture risk assessment in Saudi Arabia. Objective This paper describes the incidence of hip fracture in the Kingdom of Saudi Arabia that was used to characterize the current and future burden of hip fracture, to develop a country-specific FRAX (R) tool for fracture prediction and to compare fracture probabilities with neighbouring countries. Methods During a 2-year (2017/2018) prospective survey in 15 hospitals with a defined catchment population, hip fractures in Saudi citizens were prospectively identified from hospital registers. The number of hip fractures and future burden was determined from national demography. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Saudi Arabia. Fracture probabilities were compared with those from Kuwait and Abu Dhabi. Results The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 2,949 and is predicted to increase nearly sevenfold to 20,328 in 2050. Hip fracture rates were comparable with estimates from Abu Dhabi and Kuwait. By contrast, probabilities of a major osteoporotic fracture or hip fracture from the age of 70 years were much lower than those seen in Abu Dhabi and Kuwait due to higher mortality estimates for Saudi Arabia. Conclusion A country-specific FRAX tool for fracture prediction has been developed for Saudi Arabia which is expected to help guide decisions about treatment.
  •  
35.
  • Schweinsberg, Martin, et al. (författare)
  • Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
  • 2021
  • Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
  • Tidskriftsartikel (refereegranskat)abstract
    • In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
  •  
36.
  • Steck, Andrea K., et al. (författare)
  • Factors Associated With the Decline of C-Peptide in a Cohort of Young Children Diagnosed With Type 1 Diabetes
  • 2021
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:3, s. 1380-1388
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Understanding factors involved in the rate of C-peptide decline is needed to tailor therapies for type 1 diabetes (T1D). OBJECTIVE: Evaluate factors associated with rate of C-peptide decline after a T1D diagnosis in young children. DESIGN: Observational study. SETTING: Academic centers. PARTICIPANTS: A total of 57 participants from the Environmental Determinants of Diabetes in the Young (TEDDY) study who were enrolled at 3 months of age and followed until T1D, and 56 age-matched children diagnosed with T1D in the community. INTERVENTION: A mixed meal tolerance test was used to measure the area under the curve (AUC) C-peptide at 1, 3, 6, 12, and 24 months postdiagnosis. OUTCOME: Factors associated with rate of C-peptide decline during the first 2 years postdiagnosis were evaluated using mixed effects models, adjusting for age at diagnosis and baseline C-peptide. RESULTS: Adjusted slopes of AUC C-peptide decline did not differ between TEDDY subjects and community controls (P = 0.21), although the former had higher C-peptide baseline levels. In univariate analyses combining both groups (n = 113), younger age, higher weight and body mass index z-scores, female sex, an increased number increased number of islet autoantibodies, and IA-2A or ZnT8A positivity at baseline were associated with a higher rate of C-peptide loss. Younger age, female sex, and higher weight z-score remained significant in multivariate analysis (all P < 0.02). At 3 months after diagnosis, higher HbA1c became an additional independent factor associated with a higher rate of C-peptide decline (P < 0.01). CONCLUSION: Younger age at diagnosis, female sex, higher weight z-score, and HbA1c were associated with a higher rate of C-peptide decline after T1D diagnosis in young children.
  •  
37.
  • Thomas, E. A., et al. (författare)
  • Chiridota heheva-the cosmopolitan holothurian
  • 2020
  • Ingår i: Marine Biodiversity. - : Springer Science and Business Media LLC. - 1867-1616 .- 1867-1624. ; 50:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemosynthetic ecosystems have long been acknowledged as key areas of enrichment for deep-sea life, supporting hundreds of endemic species. Echinoderms are among the most common taxa inhabiting the periphery of chemosynthetic environments, and of these, chiridotid holothurians are often the most frequently observed. Yet, published records of chiridotids in these habitats are often noted only as supplemental information to larger ecological studies and several remain taxonomically unverified. This study therefore aimed to collate and review all known records attributed to Chiridota Eschscholtz, 1829, and to conduct the first phylogenetic analysis into the relationship of these chiridotid holothurians across global chemosynthetic habitats. We show that Chiridota heheva Pawson & Vance, 2004 is a globally widespread, cosmopolitan holothurian that occupies all three types of deep-sea chemosynthetic ecosystem-hydrothermal vents, cold seeps and organic falls-as an organic-enrichment opportunist. Furthermore, we hypothesise that C. heheva may be synonymous with another vent-endemic chiridotid, Chiridota hydrothermica Smirnov et al., 2000, owing to the strong morphological, ecological and biogeographical parallels between the two species, and predict that any chiridotid holothurians subsequently discovered at global reducing environments will belong to this novel species complex. This study highlights the importance of understudied, peripheral taxa, such as holothurians, to provide insights to biogeography, connectivity and speciation at insular deep-sea habitats.
  •  
38.
  • Ullgren, Helena, et al. (författare)
  • Clinical characteristics and factors associated with COVID-19-related death and morbidity among hospitalized patients with cancer : a Swedish cohort study
  • 2021
  • Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 60:11, s. 1459-1465
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Cancer patients are considered to have a higher risk of dying and developing severe Coronavirus Disease 2019 (COVID-19). To date, there are few studies including co-morbidities and sociodemographic factors when investigating the outcome of COVID-19 in a cohort of cancer patients. In this study, we analyzed cancer patients that have been hospitalized due to COVID-19 during the first wave of the pandemic in Sweden to investigate the impact of COVID-19 on mortality and morbidity.Patients and methods: We retrospectively collected data on all patients with cancer that were hospitalized due to COVID-19-related symptoms at Uppsala University Hospital and Karolinska University Hospital between 1 March and 31 August 2020. The primary endpoint was COVID-19-related death and the secondary endpoint was to describe COVID-19 severity, defined as symptom severity (grades 0–4) and length of stay (LOS) at the university hospitals.Results: In total, 193 patients were included among which 31% died due to COVID-19 and 8% died of other causes. In a multivariable analysis, older age >70 (OR 3.6; 95% CI [1.8–7.3], p < 0.001) and male gender (OR 2.8 [1.4–5.8], p = 0.005) were factors associated with higher likelihood of COVID-19-related death. Several comorbidities ≥2 (OR 5.4 [2.0–14.3], p = 0.001) was independently associated with COVID-19 severity. Treatment with chemotherapy within 90 days prior to COVID-19 diagnosis were not associated with COVID-19-related death or severity.Conclusion: Factors associated with higher likelihood of COVID-19-related death were older age and male gender. More severe COVID-19 symptoms were seen in patients with multiple comorbidities. We did not see any associations between COVID-19-related death or severity and recent treatment including chemotherapy. In summary, this supports a thorough assessment regarding potential risks with COVID-19 infection in patients with cancer, with a combination of individual risk factors in addition to cancer treatments.
  •  
39.
  • Vandenput, Liesbeth, et al. (författare)
  • A meta-analysis of previous falls and subsequent fracture risk in cohort studies
  • 2024
  • Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
  • Tidskriftsartikel (refereegranskat)abstract
    • SummaryThe relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.IntroductionPrevious falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).MethodsThe resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.ResultsFalls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.ConclusionsA previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
  •  
40.
  • Wangefelt Ström, Helena, 1968-, et al. (författare)
  • Heritage Politics and Identity
  • 2020
  • Ingår i: ANANKE Quadrimestrale di cultura, storia e techniche della conservazione. - Milano. - 1129-8219. ; :89, s. 121-127
  • Tidskriftsartikel (refereegranskat)abstract
    • Il contributo presenta il lavoro svolto dagli studenti del corso Heritage Politics and Identity presso Uppsala University Campus Gotland, riflettendo sul significato di heritage e i suoi legami con l'identità culturale e la politica. Dopo una breve introduzione sull'approccio verso la patrimonializzazione tenuto nel corso, si presentano le interessanti ricerche di alcuni studenti, con provenienza da tutto il mondo, che variano da riflessioni su le nomine UNESCO, post-colonialismo e diritti umani, accessibilità, turismo e gestione del patrimonio.
  •  
41.
  • Zheng, Z. A., et al. (författare)
  • Potential Adverse Effect of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate
  • 2022
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:6, s. 1117-1124
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN-BMD, 0.66 versus 0.64 g/cm(2), p < 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3-year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01-1.62; p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81-1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65-1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58-0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip -2.75% versus -1.27%, p = 0.078; femoral neck -3.06% versus -1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-41 av 41
Typ av publikation
tidskriftsartikel (36)
konferensbidrag (4)
bokkapitel (1)
Typ av innehåll
refereegranskat (40)
övrigt vetenskapligt/konstnärligt (1)
Författare/redaktör
Lorentzon, Mattias, ... (13)
Vandenput, Liesbeth, ... (12)
Kanis, J. A. (12)
Johansson, Helena, 1 ... (12)
Harvey, N. C. (11)
Liu, E. W. (8)
visa fler...
McCloskey, E. V. (7)
McCloskey, E. (5)
Liu, E. (4)
Bosch, Jan, 1967 (4)
Liu, Yang (3)
Mitchell, Philip B (3)
Ohlsson, Claes, 1965 (3)
Boehnke, Michael (3)
Toppari, Jorma (3)
Mellström, Dan, 1945 (3)
Martin, Nicholas G. (3)
Fernández-Aranda, Fe ... (2)
Jiménez-Murcia, Susa ... (2)
Jonsson, Lina, 1982 (2)
Agartz, Ingrid (2)
Alda, Martin (2)
Fullerton, Janice M (2)
Melle, Ingrid (2)
Roberts, Gloria (2)
Andreassen, Ole A (2)
Karlsson, Magnus K. (2)
van den Akker, Olmo ... (2)
Cooper, Cyrus (2)
Kogevinas, Manolis (2)
Breen, Gerome (2)
Veijola, Riitta (2)
Adolfsson, Rolf (2)
Molina, Esther (2)
Wareham, Nicholas J. (2)
Lissowska, Jolanta (2)
Alfredsson, Lars (2)
Rosengren, Björn E (2)
Treasure, Janet (2)
Rouleau, Guy A. (2)
Sjöstedt, Anders (2)
Liu, Xiang (2)
Werge, Thomas (2)
Appadurai, Vivek (2)
Djurovic, Srdjan (2)
Smeland, Olav B. (2)
Bellivier, Frank (2)
Chen, Hsi-Chung (2)
Jamain, Stéphane (2)
Forstner, Andreas J (2)
visa färre...
Lärosäte
Göteborgs universitet (19)
Lunds universitet (11)
Karolinska Institutet (11)
Uppsala universitet (10)
Umeå universitet (5)
Malmö universitet (4)
visa fler...
Chalmers tekniska högskola (4)
Kungliga Tekniska Högskolan (3)
Stockholms universitet (3)
Linköpings universitet (2)
Handelshögskolan i Stockholm (1)
Mittuniversitetet (1)
Högskolan Dalarna (1)
visa färre...
Språk
Engelska (41)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (29)
Naturvetenskap (10)
Teknik (3)
Samhällsvetenskap (3)

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