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1.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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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.
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3.
  • Andersson, Sofi A., 1970, et al. (författare)
  • Arm impairment and walking speed explain real-life activity of the affected Arm and leg after stroke
  • 2021
  • Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 53:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine to what extent accelerometer-based arm, leg and trunk activity is associated with sensorimotor impairments, walking capacity and other factors in subacute stroke. Design: Cross-sectional study. Patients: Twenty-six individuals with stroke (mean age 55.4 years, severe to mild motor impairment). Methods: Data on daytime activity were collected over a period of 4 days from accelerometers placed on the wrists, ankles and trunk. A forward stepwise linear regression was used to determine associations between free-living activity, clinical and demographic variables. Results: Arm motor impairment (Fugl-Meyer Assessment) and walking speed explained more than 60% of the variance in daytime activity of the more-affected arm, while walking speed alone explained 60% of the more-affected leg activity. Activity of the less-affected arm and leg was associated with arm motor impairment (R2=0.40) and independence in walking (R2=0.59). Arm activity ratio was associated with arm impairment (R2=0.63) and leg activity ratio with leg impairment (R2=0.38) and walking speed (R2=0.27). Walking-related variables explained approximately 30% of the variance in trunk activity. Conclusion: Accelerometer-based free-living activity is dependent on motor impairment and walking capacity. The most relevant activity data were obtained from more-affected limbs. Motor impairment and walking speed can provide some information about real-life daytime activity levels.
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4.
  • Brunkwall, Louise, et al. (författare)
  • The Malmö Offspring Study (MOS) : design, methods and first results.
  • 2021
  • Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 36, s. 103-116
  • Tidskriftsartikel (refereegranskat)abstract
    • As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
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5.
  • Calling, Susanna, et al. (författare)
  • Coronary heart disease in mothers and fathers of adult children with alcohol use disorders
  • 2021
  • Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 116:12, s. 3390-3397
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Having a family member with an alcohol use disorder (AUD) may negatively affect a person's health. Our aim was to study the long-term risk of coronary heart disease (CHD) in parents who have an offspring with AUD. Design: Cohort study with Cox regression models and co-sibling analyses. Setting: Sweden. Participants: From population registers, we selected all parent-offspring pairs in which the parent was born in Sweden between 1945 and 1965. Measurements: Baseline was set when the offspring was 15 years old and AUD was assessed from medical and criminal registers. The parents were followed for CHD during a mean follow-up of 18 years. Hazard ratios (HRs) in mothers and fathers were calculated and adjusted for potential confounders (year of birth, age at childbirth, sex of the child, parent' AUD, educational level, and marital status). Findings: In mothers, the adjusted HR for CHD was 1.24 (95% CI = 1.19–1.28) in relation to having a child with AUD. In fathers, the HR for CHD was lower than in mothers but still increased; the adjusted HR was 1.08 (95% CI = 1.05–1.12). In the co-sibling analyses, the HRs for mothers were similar to the HRs estimated from the population-based sample, but in fathers the association did not remain significant (HR = 0.98 [0.90–1.06]). Conclusions: In Sweden, there appears to be an association between having an offspring with alcohol use disorder and increased risk of developing coronary heart disease. For fathers, the association did not remain in co-sibling analyses.
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6.
  • Célind, Jimmy, et al. (författare)
  • Timing of the pubertal growth spurt and prostate cancer
  • 2021
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.
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7.
  • Chartier, Karen G., et al. (författare)
  • Triangulation of evidence on immigration and rates of alcohol use disorder in Sweden : Evidence of acculturation effects
  • 2023
  • Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 47:1, s. 104-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study aimed to determine the robustness of the impact of immigration on risk for alcohol use disorder (AUD) using different measures, designs, and immigrant regional cohorts. Methods: The analytic sample included all individuals born between 1950 and 1990 and registered in Sweden from 1973 to 2017. Using Cox regression models, we examined the risk for AUD from Swedish nationwide registries in immigrants to Sweden from seven geographical regions: Africa, Asia and Oceania, Eastern Europe, Finland, Latin America and the Caribbean, Middle East/North Africa, and Western countries. We assessed greater exposure to Swedish culture, which we interpreted as increasing acculturation, by (i) comparing first-generation immigrants and their children with no and one native Swedish parent and (ii) examining age at immigration. The baseline comparison group was the native Swedish population. We also examined AUD risk in first-generation sibling pairs discordant for their age at immigration. Results: In nearly all immigrant cohorts in Sweden, increasing degrees of acculturation, as assessed by both our variables, were associated with rates of AUD that approached those of the Swedish population. These findings occurred in both men and women and both regional cohorts whose first-generation immigrants had lower and higher levels of AUD than native-born Swedes. For most cohorts, the rates of change with acculturation were greater in women than in men. In sibling pairs from most regions, the sibling who was younger at immigration had a higher rate of AUD. Conclusions: An examination of both sexes and two different proxies for acculturation provides consistent support for socio-cultural influences on AUD risk. Our co-sibling analyses suggest that a meaningful proportion of this effect is likely to be causal in nature.
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8.
  • Dahlman, Disa, et al. (författare)
  • Socioeconomic correlates of incident and fatal opioid overdose among Swedish people with opioid use disorder
  • 2021
  • Ingår i: Substance Abuse: Treatment, Prevention, and Policy. - : Springer Science and Business Media LLC. - 1747-597X. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Opioid overdose (OD) and opioid OD death are major health threats to people with opioid use disorder (OUD). Socioeconomic factors are underexplored potential determinants of opioid OD. In this study, we assessed socioeconomic and other factors and their associations with incident and fatal opioid OD, in a cohort consisting of 22,079 individuals with OUD. Methods: We performed a retrospective, longitudinal study based on Swedish national register data for the period January 2005–December 2017. We used Cox proportional hazard models to investigate the risk of incident and fatal opioid OD as a function of several individual, parental and neighborhood covariates. Results: Univariate analysis showed that several covariates were associated with incident and fatal opioid OD. In the multivariate analysis, incident opioid OD was associated with educational attainment (Hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.94–0.97), having received social welfare (HR 1.31; 95% CI 1.22–1.39), and criminal conviction (HR 1.53; 95% CI 1.42–1.65). Fatal opioid OD was also associated with criminal conviction (HR 1.93; 95% CI 1.61–2.32). Conclusion: Individuals with low education and receipt of social welfare had higher risks of incident opioid OD and individuals with criminal conviction were identified as a risk group for both incident and fatal opioid OD. Our findings should raise attention among health prevention policy makers in general, and among decision-makers within the criminal justice system and social services in particular.
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9.
  • Edwards, Alexis C., et al. (författare)
  • Alcohol use disorder and non-fatal suicide attempt : findings from a Swedish National Cohort Study
  • 2022
  • Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 117:1, s. 96-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Alcohol use disorder (AUD) is associated with increased risk of non-fatal suicide attempt. We aimed to measure the strength and mechanistic nature of the association between AUD and increased suicide attempt and determine any causal pathways and/or shared risk factors. Design: We used Cox proportional hazards models in population-level and co-relative analyses to evaluate the risk of first non-fatal suicide attempt as a function of previous AUD. Setting and Participants: We used continuously updated longitudinal nationwide Swedish registry data on native Swedes born from 1950 to 1970 (n = 2 229 619) and followed from age 15 until 2012. Measurements: AUD and suicide attempt were identified using International Classification of Diseases (ICD)-8, ICD-9, and ICD-10 codes. AUD was also identified using pharmacy and criminal records. Genetic and family environmental risks were derived based on relatedness via the Multi-Generation Register and shared residency via the Population and Housing Census and the Total Population Register. Findings: AUD was robustly associated with suicide attempt in crude models (hazard ratio [HR] = 15.24 [95% CI: 14.92, 15.56]). In models adjusted for sociodemographic factors and psychiatric comorbidity, the association was attenuated: for women, HRs declined gradually across time, ranging from 5.55 (3.72, 8.29) during the observation period that ranged from age 15 to 19 years to 1.77 (1.65, 1.90) at age 40 or older. For men, the corresponding figures were 6.12 (4.07, 9.19) and 1.83 (1.72, 1.94); in contrast to women, risk of suicide attempt among men increased from age 15 to 29 before declining. In co-relative models, a residual association remained, consistent with a causal path from AUD to suicide attempt. Conclusions: In Sweden, alcohol use disorder appears to be an important predictor of suicide attempt even in the context of other psychiatric disorders. The observed association is likely the result of features that jointly impact risk of alcohol use disorder and suicide attempts (genetic liability, psychiatric illness, and childhood stressors) and a potentially causal pathway, acting independently or in conjunction with one another.
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10.
  • Edwards, Alexis C., et al. (författare)
  • Alcohol Use Disorder and Risk of Suicide in a Swedish Population-Based Cohort
  • 2020
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 177:7, s. 627-634
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The authors examined the association between alcohol use disorder (AUD) and risk of suicide, before and after accounting for psychiatric comorbidity, and assessed the extent to which the observed association is due to a potentially causal mechanism or genetic and familial environmental confounding factors that increase risk for both. METHODS: Longitudinal population-wide Swedish medical, criminal, and pharmacy registries were used to evaluate the risk of death by suicide as a function of AUD history. Analyses employed prospective cohort and co-relative designs, including data on 2,229,880 native Swedes born between 1950 and 1970 and observed from age 15 until 2012. RESULTS: The lifetime rate of suicide during the observation period was 3.54% for women and 3.94% for men with AUD, compared with 0.29% and 0.76% of women and men, respectively, without AUD. In adjusted analyses, AUD remained robustly associated with suicide: hazard ratios across observation periods ranged from 2.61 to 128.0 among women and from 2.44 to 28.0 among men. Co-relative analyses indicated that familial confounding accounted for some, but not all, of the observed association. A substantial and potentially causal relationship remained after accounting for a history of other psychiatric diagnoses. CONCLUSIONS: AUD is a potent risk factor for suicide, with a substantial association persisting after accounting for confounding factors. These findings underscore the impact of AUD on suicide risk, even in the context of other mental illness, and implicate the time frame shortly after a medical or criminal AUD registration as critical for efforts to reduce alcohol-related suicide.
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