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Sökning: WFRF:(Rasmussen Morten)

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  • Allentoft, M. E., et al. (författare)
  • Population genomics of Bronze Age Eurasia
  • 2015
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 522:7555, s. 167-
  • Tidskriftsartikel (refereegranskat)abstract
    • The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.
  • Covacu, Ruxandra, et al. (författare)
  • Nitric oxide exposure diverts neural stem cell fate from neurogenesis towards astrogliogenesis
  • 2006
  • Ingår i: Stem Cells. - : AlphaMed Press. - 1549-4918 .- 1066-5099. ; 24:12, s. 2792-2800
  • Tidskriftsartikel (refereegranskat)abstract
    • Regeneration of cells in the central nervous system is a process that might be affected during neurological disease and trauma. Because nitric oxide (NO) and its derivatives are powerful mediators in the inflammatory cascade, we have investigated the effects of pathophysiological concentrations of NO on neurogenesis, gliogenesis, and the expression of proneural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated, and this corresponded to decreased expression of the proneural gene neurogenin-2 and beta-III-tubulin. The decreased ability to generate neurons was also found to be transmitted to the progeny of the cells. NO exposure was instead beneficial for astroglial differentiation, which was confirmed by increased activation of the Janus tyrosine kinase/signal transducer and activator of transcription transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions, whereby its proastroglial fate-determining effect on neural stem cells might directly influence the neuroregenerative process.
  • Granholm, Anders, et al. (författare)
  • Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial
  • 2021
  • Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238.
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
  • Granholm, Anders, et al. (författare)
  • Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis
  • 2021
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
  • Holst, Mette, et al. (författare)
  • Nutritional screening and risk factors in elderly hospitalized patients : association to clinical outcome?
  • 2013
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley-Blackwell. - 0283-9318 .- 1471-6712. ; 27:4, s. 953-961
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to test the intervalidity of three different nutrition screening tools towards a broad population of elderly hospitalized patients. The association with risk factors and mortality was investigated. This is a prospective cohort study in three medical, surgical and geriatric settings, in Denmark and Sweden. Patients >65 years were consecutively included. Patients were screened by mini-nutritional assessment (MNA), malnutrition universal screening tool (MUST) and nutritional risk screening (NRS-2002). Anthropometrics, cognitive test (SPMSQ), as well as a questionnaire investigation regarding eating problems and life situation, were performed. Mortality within 12 months was investigated. In total, 233 patients mean (SD) age 81(7.64) years were included. A large variation in prevalence of nutritional risk was determined between the screening tools, MNA was 68% vs. MUST, 47% and NRS 54%, p < 0.0001. An overall agreement of 67% was seen (κ 0.52-0.55). Risk factors were associated with nutritional risk, including depressive mood. Only handgrip strength, fungus in mouth, serum albumin, CRP and cognitive function were associated with mortality. Fungus had the strongest association (OR 3.7; CI 1.19-11.30). The overall mortality rate was 27% during 12 months. However, none of the three screening tools predicted 12-month mortality. The findings show great variation in the prevalence of nutritional risk of under nutrition both between the tools and the settings. The level of agreement between the tools was moderate, and none of the three tools were capable of predicting 12-month mortality. A functional and psychological evaluation including oral health seems recommendable in elderly patients at nutritional risk.
  • Jelenkovic, Aline, et al. (författare)
  • Associations between birth size and later height from infancy through adulthood : An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project
  • 2018
  • Ingår i: Early Human Development. - : Elsevier. - 0378-3782 .- 1872-6232. ; 120, s. 53-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14–4.25 cm and 0.18–0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
  • Jelenkovic, Aline, et al. (författare)
  • Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
  • Margaryan, Ashot, et al. (författare)
  • Population genomics of the Viking world
  • 2020
  • Ingår i: Nature. - : Springer Nature. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
  • Tidskriftsartikel (refereegranskat)abstract
    • The maritime expansion of Scandinavian populations during the Viking Age (about ad 750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
  • Mowe, Morten, et al. (författare)
  • Insufficient nutritional knowledge among health care workers?
  • 2008
  • Ingår i: Clinical nutrition (Edinburgh, Scotland). - 1532-1983 .- 0261-5614. ; 27:2, s. 196-202
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Though a great interest and willingness to nutrition therapy, there is an insufficient practice compared to the proposed ESPEN guidelines for nutrition therapy. The aim of this questionnaire was to study doctors and nurses' self-reported knowledge in nutritional practice, with focus on ESPEN's guidelines in nutritional screening, assessment and treatment. METHODS: A questionnaire about different aspects of nutritional practice was answered by 4512 doctors and nurses in Denmark, Sweden and Norway. RESULTS: The most common cause for insufficient nutritional practice was lack of nutritional knowledge. Twenty-five percent found it difficult to identify patient in need of nutritional therapy, 39% lacked techniques for identifying malnourished patients, and 53% found it difficult to calculate the patients' energy requirement and 66% lacked national guidelines for clinical nutrition. Twenty-eight percent answered that insufficient nutrition practice could lead to complications and prolonged hospital stay. Those that answered that their nutritional knowledge was good had also a better nutritional practice. CONCLUSION: The self-reported nutritional knowledge was inadequate among Scandinavian doctors and nurses. Increased nutritional knowledge seems to improve the nutritional practice. A combination of an integrated nutrition curriculum during the education, together with post-graduated education for both physicians and nurses should be established.
  • Munch, Marie Warrer, et al. (författare)
  • Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial : Protocol and statistical analysis plan
  • 2021
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. Methods The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. Discussion The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.
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