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1.
  • Dahlerup, Jens Frederik, et al. (author)
  • High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23
  • 2016
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 51:11, s. 1332-1338
  • Journal article (peer-reviewed)abstract
    • Objective: Iron isomaltoside (Monofer®) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA. Materials and methods: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters. Results: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found. Conclusion: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.
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3.
  • Grövdal, Michael, et al. (author)
  • Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy
  • 2010
  • In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:3, s. 293-302
  • Journal article (peer-reviewed)abstract
    • This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction chemotherapy. Sixty patients were enrolled and treated by standard induction chemotherapy. Patients that reached CR started maintenance therapy with subcutaneous azacytidine, 5/28 d until relapse. Promoter-methylation status of CDKN2B (P15 ink4b), CDH1 and HIC1 was examined pre-induction, in CR and 6, 12 and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients.
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4.
  • Grövdal, Michael, et al. (author)
  • Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome
  • 2007
  • In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:23, s. 7107-7112
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard prognostic variables and methylation status of the P15(ink4b) (P15), E-cadherin (CDH), and hypermethylated in cancer 1 (HIC) genes were analyzed before treatment. RESULTS: Forty percent of the patients achieved complete remission (CR). CR rate was lower in patients with high WBC counts (P = 0.03) and high CD34 expression on bone marrow cells (P = 0.02). Whereas P15 status alone was not significantly associated with CR rate (P = 0.25), no patient with hypermethylation of all three genes achieved CR (P = 0.03). Moreover, patients with CDH methylation showed a significantly lower CR rate (P = 0.008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect of methylation status on the outcome of conventional chemotherapy in high-risk MDS and acute myelogenous leukemia following MDS. Provided confirmed in an independent study, our results should be used as a basis for therapeutic decision-making in this patient group.
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  • Kassebaum, Nicholas J., et al. (author)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Journal article (peer-reviewed)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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  • Madsen, Jasmine Melissa, et al. (author)
  • Clinical outcomes of no stenting in patients with ST-segment elevation myocardial infarction undergoing deferred primary percutaneous coronary intervention
  • 2022
  • In: EuroIntervention. - 1774-024X. ; 18:6, s. 482-491
  • Journal article (peer-reviewed)abstract
    • Background: ST-segment elevation myocardial infarction (STEMI) is treated with stenting, but the underlying stenosis is often not severe, and stenting may potentially be omitted. Aims: The aim of the study was to investigate outcomes of patients with STEMI treated with percutaneous coronary intervention (PCI) without stenting. Methods: Patients were identified through the DANAMI-3-DEFER study. Stenting was omitted in the patients with stable flow after initial PCI and no significant residual stenosis on the deferral procedure, who were randomised to deferred stenting. These patients were compared to patients randomised to conventional PCI treated with immediate stenting. The primary endpoint was a composite of all-cause mortality, recurrent myocardial infarction (MI), and target vessel revascularisation (TVR). Results: Of 603 patients randomised to deferred stenting, 84 were treated without stenting, and in patients randomised to conventional PCI (n=612), 590 were treated with immediate stenting. Patients treated with no stenting had a median stenosis of 40%, median vessel diameter of 2.9 mm, and median lesion length of 11.4 mm. During a median follow-up of 3.4 years, the composite endpoint occurred in 14% and 16% in the no and immediate stenting groups, respectively (unadjusted hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.48-1.60; p=0.66). The association remained non-significant after adjusting for confounders (adjusted HR 0.53, 95% CI: 0.22-1.24; p=0.14). The rates of TVR and recurrent MI were 2% vs 4% (p=0.70) and 4% vs 6% (p=0.43), respectively. Conclusions: Patients with STEMI, with no significant residual stenosis and stable flow after initial PCI, treated without stenting, had comparable event rates to patients treated with immediate stenting.
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  • Myrum, Craig, et al. (author)
  • Common variants in the ARC gene are not associated withcognitive abilities
  • 2015
  • In: Brain and Behavior. - : Wiley. - 2162-3279. ; 5:10
  • Journal article (peer-reviewed)abstract
    • Introduction: The Activity-Regulated Cytoskeleton-associated (ARC) gene encodes a protein that is critical for the consolidation of synaptic plasticity and long-term memory formation. Given ARC's key role in synaptic plasticity, we hypothesized that genetic variations in ARC may contribute to interindividual variability in human cognitive abilities or to attention-deficit hyperactivity disorder (ADHD) susceptibility, where cognitive impairment often accompanies the disorder. Methods: We tested whether ARC variants are associated with six measures of cognitive functioning in 670 healthy subjects in the Norwegian Cognitive NeuroGenetics (NCNG) by extracting data from its Genome-Wide Association Study (GWAS). In addition, the Swedish Betula sample of 1800 healthy subjects who underwent similar cognitive testing was also tested for association with 19 tag SNPs. Results: No ARC variants show association at the study-wide level, but several markers show a trend toward association with human cognitive functions. We also tested for association between ARCSNPs and ADHD in a Norwegian sample of cases and controls, but found no significant associations. Conclusion: This study suggests that common genetic variants located in ARC do not account for variance in human cognitive abilities, though small effects cannot be ruled out.
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  • Nilsson, Lars, et al. (author)
  • Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8.
  • 2002
  • In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 100:1, s. 259-267
  • Journal article (peer-reviewed)abstract
    • Clonality studies of mature cells suggest that the primary transformation event in myelodysplastic syndrome (MDS) most frequently occurs in a myeloid-restricted progenitor, a hypothesis supported by recent studies of purified CD34(+)Thy1(+) hematopoietic stem cells (HSCs) in cases with trisomy 8 (+8). In contrast, we recently demonstrated that a lymphomyeloid HSC is the target for transformation in MDS cases with del(5q), potentially reflecting heterogeneity within MDS. However, since +8 is known to frequently be a late event in the MDS transformation process, it remained a possibility that CD34(+)CD38(-)Thy1(+) HSC disomic for chromosome 8 might be part of the MDS clone. In the present studies, although a variable fraction of CD34(+)CD38(-)Thy1(+) cells were disomic for chromosome 8, they did not possess normal HSC activity in long-term cultures and nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Mixing experiments with normal CD34(+)CD38(-) cells suggested that this HSC deficiency was intrinsic and not mediated by indirect mechanisms. Furthermore, investigation of 4 MDS cases with combined del(5q) and +8 demonstrated that the +8 aberration was always secondary to del(5q). Whereas del(5q) invariably occurs in CD34(+)CD38(-)Thy-1(+) HSCs, the secondary +8 event might frequently arise in progeny of MDS HSCs. Thus, CD34(+)CD38(-)Thy1(+) HSCs are invariably part of the MDS clone also in +8 patients, and little HSC activity can be recovered from the CD34(+) CD38(-)Thy1(+) HSC. Finally, in advanced cases of MDS, the MDS reconstituting activity is exclusively derived from the minor CD34(+)CD38(-) HSC population, demonstrating that MDS stem cells have a similar phenotype as normal HSCs, potentially complicating the development of autologous transplantation for MDS.
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  • Oddsson, Asmundur, et al. (author)
  • Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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  • Petzold, Axel, et al. (author)
  • Neurofilament ELISA validation
  • 2010
  • In: JOURNAL OF IMMUNOLOGICAL METHODS. - 0022-1759. ; 352:1-2, s. 23-31
  • Journal article (peer-reviewed)
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  • Petzold, Axel, et al. (author)
  • Neurofilament ELISA validation
  • 2010
  • In: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 352:1-2, s. 23-31
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.
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  • Vos, Theo, et al. (author)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Journal article (peer-reviewed)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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  • Aartsen, M. G., et al. (author)
  • The IceCube Neutrino Observatory : instrumentation and online systems
  • 2017
  • In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
  • Journal article (peer-reviewed)abstract
    • The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
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  • Abrego, Nerea, et al. (author)
  • Airborne DNA reveals predictable spatial and seasonal dynamics of fungi
  • 2024
  • In: Nature. - 0028-0836 .- 1476-4687. ; 631, s. 835-842
  • Journal article (peer-reviewed)abstract
    • Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.
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  • Bjällmark, Anna, et al. (author)
  • Velocity tracking - a novel method for quantitative analysis of longitudinal myocardial function
  • 2007
  • In: Journal of the American Society of Echocardiography. - : Elsevier. - 0894-7317 .- 1097-6795. ; 20:7, s. 847-856
  • Journal article (peer-reviewed)abstract
    • Doppler tissue imaging is a method for quantitative analysis of longitudinal myocardial velocity. Commercially available ultrasound systems can only present velocity information using a color Dopplerbased overlapping continuous color scale. The analysis is time-consuming and does not allow for simultaneous analysis in different projections. We have developed a new method, velocity tracking, using a stepwise color coding of the regional longitudinal myocardial velocity. The velocity data from 3 apical projections are presented as static and dynamic bull's-eye plots to give a 3-dimensional understanding of the function of the left ventricle. The static bull's-eye plot can display peak systolic velocity, late diastofic tissue velocity, or the sum of peak systolic velocity and early diastolic tissue velocity. Conversely, the dynamic bull's-eye plot displays how the myocardial velocities change over one heart cycle. Velocity tracking allows for a fast, simple, and hituitive visual analysis of the regional longitudinal contraction pattern of the left ventricle with a great potential to identify characteristic pathologic patterns.
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  • Bolin, Karin, 1982-, et al. (author)
  • Variants in BANK1 are associated with lupus nephritis
  • Other publication (other academic/artistic)abstract
    • Background: Lupus nephritis (LN) is a cause of significant morbidity in SLE. While the genetic background to SLE has been well characterized, less is known about genes predisposing to LN.Methods: The study consisted of 2886 SLE patients, including 947 (33%) with LN. The discovery cohort (Sweden, n=1091) and replication cohort 1 (US, n=962) were genotyped on the Immunochip and replication cohort 2 (Norway/Denmark, n=833) on a custom array chip. Allele frequencies were compared between patients with LN, proliferative nephritis, end-stage renal disease and LN negative patients. SNPs with p-value <0.001 in the discovery cohort were analyzed in replication cohort 1. Ten SNPs associated with LN in the discovery cohort (p<0.0002) were genotyped in replication cohort 2. DNA methylation data were available for 180 LN patients from the discovery cohort.Results: In the discovery cohort, six gene loci were associated with LN (p<1x10-4, NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y and PHCA). SNPs in BANK1 showed the strongest association with LN in replication cohort 1 (p=9.5x10-4), with a tendency for an association in replication cohort 2 (p=0.052). In a meta-analysis of all three cohorts the association between LN and BANK1 rs4699259, was strengthened (p=1.7x10‑7). There were no associations to proliferative nephritis or ESRD in the meta-analysis. Methylation quantitative trait loci (MeQTL) effects between a CpG site and several SNPs in BANK1 were identified.Conclusion: Genetic variations in BANK1 are associated with LN. There is evidence for genetic regulation of DNA methylation within the BANK1 locus, however, the exact role of BANK1 in LN pathogenesis remains to be elucidated.
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21.
  • Bolin, Karin, et al. (author)
  • Variants in BANK1 are associated with lupus nephritis of European ancestry
  • 2021
  • In: Genes and Immunity. - : Springer Nature. - 1466-4879 .- 1476-5470. ; 22:3, s. 194-202
  • Journal article (peer-reviewed)abstract
    • The genetic background of lupus nephritis (LN) has not been completely elucidated. We performed a case-only study of 2886 SLE patients, including 947 (33%) with LN. Renal biopsies were available from 396 patients. The discovery cohort (Sweden, n = 1091) and replication cohort 1 (US, n = 962) were genotyped on the Immunochip and replication cohort 2 (Denmark/Norway, n = 833) on a custom array. Patients with LN, proliferative nephritis, or LN with end-stage renal disease were compared with SLE without nephritis. Six loci were associated with LN (p < 1 × 10−4, NFKBIA, CACNA1S, ITGA1, BANK1, OR2Y, and ACER3) in the discovery cohort. Variants in BANK1 showed the strongest association with LN in replication cohort 1 (p = 9.5 × 10−4) and proliferative nephritis in a meta-analysis of discovery and replication cohort 1. There was a weak association between BANK1 and LN in replication cohort 2 (p = 0.052), and in the meta-analysis of all three cohorts the association was strengthened (p = 2.2 × 10−7). DNA methylation data in 180 LN patients demonstrated methylation quantitative trait loci (meQTL) effects between a CpG site and BANK1 variants. To conclude, we describe genetic variations in BANK1 associated with LN and evidence for genetic regulation of DNA methylation within the BANK1 locus. This indicates a role for BANK1 in LN pathogenesis.
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  • Calderon, Moises A, et al. (author)
  • EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
  • 2012
  • In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
  • Journal article (peer-reviewed)abstract
    • Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
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23.
  • Castor, Anders, et al. (author)
  • Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
  • 2005
  • In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 11:6, s. 630-637
  • Journal article (peer-reviewed)abstract
    • The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.
  •  
24.
  • Christesen, Henrik B. T., et al. (author)
  • Rapid genetic analysis in congenital hyperinsulinism
  • 2007
  • In: Hormone Research. - : S. Karger AG. - 0301-0163. ; 67:4, s. 184-188
  • Journal article (peer-reviewed)abstract
    • Backgound: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. Methods: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. Results: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. Conclusion: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations. Copyright (c) 2007 S. Karger AG, Basel.
  •  
25.
  • Ekstrand, Carl, et al. (author)
  • Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis
  • 2019
  • In: Acta Veterinaria Scandinavica. - : BMC. - 0044-605X .- 1751-0147. ; 61
  • Journal article (peer-reviewed)abstract
    • Background: Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis.Results: Inflammation was induced in the radiocarpal joint of six horses by injection of 2ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3mg) and once with saline. Dexamethasone was quantified by means of UHPLC-MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0-5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration-time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration-response relation in an experimental model of synovitis.Conclusions: The quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.
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26.
  • Ferdousi, Hosne Ara, et al. (author)
  • Clinical characteristics of school children with birch and/or grass pollen hay-fever (The PAT-Study)
  • Other publication (other academic/artistic)abstract
    • Background: To describe the clinical characteristics of school children with hay-fever based on baseline data from the PAT-Study.Material: Two hundred and five children, 6-15 years, mean 10.7 years, with birch and or grass pollen hay-fever, without known asthma were recruited by six pediatric allergy centers in Northern and Central Europe.Methods: Bronchial hyperresponsiveness (BHR) to methacholine tested by methacholine bronchial provocation test (MBPT) expressed in PC20 was registered during the birch and grass pollen seasons. During the winter symptoms of conjunctivitis, rhinitis and asthma were graded by visual analogue scale (VAS), conjunctival provocation test with birch and or timothy pollen extracts, skin tests with a panel of allergen extracts and MBPT were done and a questionnaire was filled in. Differences of p <0.01 level or less were considered significant.Results: Despite the children were included because of seasonal hay-fever without known asthma, 42/205 children (21 %) got doctor diagnosed asthma (DDA) after the first season. During the three seasons, between 60 and 73 % of the children had a PC20 to methacholine ≤ 8 mg/ml, about 30 % to ≤ 2 mg/ml and 7-10% even to ≤ 0.5 mg/ml. Most children had both rhinitis and conjunctivitis. Furthermore, 119/201 children (59%) were regularly exposed to furred animals.There was an association between DDA and the sum of VAS for asthma during the pollen seasons.The BHR was significantly more pronounced in those with than those without DDA during all three seasons: Using the three cut offs, the difference was most pronounced during the winter season but reached also significance using the cut off limit 0.5 mg/ml during the birch pollen season.Doctor diagnosed asthma correlated to PC20 during the seasons for most of the cut off limits for PC20 and in general there was an association in PC20 between the seasons independent of cut off limits.Furthermore, DDA, but not BHR, correlated to exposure to traffic and there was an association between exposure to traffic and industrial pollution, but not to ETS or duration of breastfeeding.Conclusion: The most striking feature of school children with uncomplicated hay-fever was the high frequency of DDA and BHR, most pronounced during the winter, the high frequency of exposure to living animals and sensitization to indoor allergens. Hay-fever is a generalized disease. Even without obvious asthma, BHR is common and most children have symptoms from both the eyes and the airways. Diagnosis of asthma in children with hay-fever and early anti-inflammatory treatment may improve the prognosis.
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27.
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28.
  • Forouzanfar, Mohammad H, et al. (author)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
  •  
29.
  • Gakidou, E., et al. (author)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
  • 2017
  • In: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1345-1422
  • Journal article (peer-reviewed)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
  •  
30.
  • Glinge, Charlotte, et al. (author)
  • Familial clustering of unexplained heart failure – A Danish nationwide cohort study
  • In: International Journal of Cardiology. - 0167-5273.
  • Journal article (peer-reviewed)abstract
    • Aims: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. Methods and results: Using Danish nationwide registry data (1978–2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29–2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69–9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40–9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75–10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90–19.49]. Conclusion: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.
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31.
  • Glinge, Charlotte, et al. (author)
  • Seasonality of ventricular fibrillation at first myocardial infarction and association with viral exposure
  • 2020
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
  • Journal article (peer-reviewed)abstract
    • Aims To investigate seasonality and association of increased enterovirus and influenza activity in the community with ventricular fibrillation (VF) risk during first ST-elevation myocardial infarction (STEMI). Methods This study comprised all consecutive patients with first STEMI (n = 4,659; aged 18–80 years) admitted to the invasive catheterization laboratory between 2010–2016, at Copenhagen University Hospital, Rigshospitalet, covering eastern Denmark (2.6 million inhabitants, 45% of the Danish population). Hospital admission, prescription, and vital status data were assessed using Danish nationwide registries. We utilized monthly/weekly surveillance data for enterovirus and influenza from the Danish National Microbiology Database (2010–2016) that receives copies of laboratory tests from all Danish departments of clinical microbiology. Results Of the 4,659 consecutively enrolled STEMI patients, 581 (12%) had VF before primary percutaneous coronary intervention. In a subset (n = 807), we found that VF patients experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with the patients without VF (OR 3.39, 95% CI 1.76–6.54). During the study period, 2,704 individuals were diagnosed with enterovirus and 19,742 with influenza. No significant association between enterovirus and VF (OR 1.00, 95% CI 0.99–1.02), influenza and VF (OR 1.00, 95% CI 1.00–1.00), or week number and VF (p-value 0.94 for enterovirus and 0.89 for influenza) was found. Conclusion We found no clear seasonality of VF during first STEMI. Even though VF patients had experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with patients without VF, no relationship was found between enterovirus or influenza exposure and occurrence of VF.
  •  
32.
  • Hansen, Martin, et al. (author)
  • Animal manure separation technologies diminish the environmental burden of steroid hormones
  • 2015
  • In: Environmental Science and Technology Letters. - 2328-8930. ; 2:4, s. 133-137
  • Journal article (peer-reviewed)abstract
    • Newly developed treatment technologies are capable of separating livestock manure into a liquid fraction and a solid fraction using sedimentation, mechanical, and/or chemical methods. These technologies offer a potential means of distributing nutrients to agricultural lands without the unwanted environmental risks associated with the release of steroid hormones to adjacent waterways. To assess the potential benefit of these technologies in reducing the level of release of steroid hormones to adjacent waterways, distribution profiles of nine steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17α-estradiol, and 17β-estradiol) were determined in raw swine manure, and in solid and liquid fractions separated from ten full-scale manure separation systems. Steroid hormone concentrations, normalized for nitrogen content, were significantly higher in separated solids than in liquids. If separated liquids are applied instead of raw manure, steroid hormone loading can be reduced by a factor of 2 at a constant nitrogen fertilization level.
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33.
  • Hansen, Martin, et al. (author)
  • Animal manure separation technologies diminish the environmental burden of steroid hormones
  • 2015
  • In: Environmental Science and Technology Letters. - : American Chemical Society. - 2328-8930. ; 2:4, s. 133-137
  • Journal article (peer-reviewed)abstract
    • Newly developed treatment technologies are capable of separating livestock manure into a liquid fraction and a solid fraction using sedimentation, mechanical, and/or chemical methods. These technologies offer a potential means of distributing nutrients to agricultural lands without the unwanted environmental risks associated with the release of steroid hormones to adjacent waterways. To assess the potential benefit of these technologies in reducing the level of release of steroid hormones to adjacent waterways, distribution profiles of nine steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17α-estradiol, and 17β-estradiol) were determined in raw swine manure, and in solid and liquid fractions separated from ten full-scale manure separation systems. Steroid hormone concentrations, normalized for nitrogen content, were significantly higher in separated solids than in liquids. If separated liquids are applied instead of raw manure, steroid hormone loading can be reduced by a factor of 2 at a constant nitrogen fertilization level.
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34.
  • Hjorth Larsen, Ask, et al. (author)
  • The atomic simulation environment-a Python library for working with atoms
  • 2017
  • In: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 29:27
  • Research review (peer-reviewed)abstract
    • The atomic simulation environment (ASE) is a software package written in the Python programming language with the aim of setting up, steering, and analyzing atomistic simulations. In ASE, tasks are fully scripted in Python. The powerful syntax of Python combined with the NumPy array library make it possible to perform very complex simulation tasks. For example, a sequence of calculations may be performed with the use of a simple 'for-loop' construction. Calculations of energy, forces, stresses and other quantities are performed through interfaces to many external electronic structure codes or force fields using a uniform interface. On top of this calculator interface, ASE provides modules for performing many standard simulation tasks such as structure optimization, molecular dynamics, handling of constraints and performing nudged elastic band calculations.
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35.
  • Jacobsen, Carsten Suhr, et al. (author)
  • Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples
  • 2018
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.
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36.
  • Jacobsen, Kristin, 1982- (author)
  • Processing of the APP family by the α-secretases ADAM10 and TACE
  • 2010
  • Licentiate thesis (other academic/artistic)abstract
    • Alzheimer’s disease (AD) is a progressive neurodegenerative disease, which is characterized by formation of amyloid plaques in the brain. The major constituent of these plaques is the hydrophobic peptide Aβ. Aβ accumulation is considered to be the main cause of the pathology seen in AD brains. Aβ is produced through sequential cleavage of the amyloid precursor protein (APP). APP can be processed by two different enzymatic pathways. Formation of Aβ requires cleavage of APP by β- and γ-secretase. However, most proteolytic processing of APP does not result in Aβ formation. Instead, APP is mainly cleaved by α-secretase, which not only precludes formation of the toxic Aβ peptide but also generates the neuroprotective sAPPα fragment. Increasing the α-secretase processing of APP is thereby a potential therapeutic strategy for AD. APP is a member of a conserved gene family, also including the APP-like proteins-1 and -2 (APLP1 and APLP2). The APP family members have essential and overlapping functions and have been reported to be processed in a similar way by the same enzymes. The processing of all APP family members is increased in response to several stimuli, including retinoic acid (RA) and insulin-like growth factor-1 (IGF-1), which also induce a shift towards α-secretase processing. The aim of this thesis was to investigate the mechanisms and signaling involved in induced α-secretase processing of the APP family. The main α-secretase candidates are ADAM10 and TACE. In this thesis we wanted to study the effects on expression levels of ADAM10 and TACE during RA treatment. We also wanted to investigate the mechanism behind IGF-1-induced processing of APP and APLP2. We found that both ADAM10 and TACE are up-regulated in response to RA, but that the signaling pathways involved differed between the two enzymes. Similarly, we showed that IGF-1-induced processing of APLP2, but not of APP, is dependent on PKC. Furthermore, we showed that ADAM10 is the main α-secretase for APP, whereas TACE cleaves APLP2 in response to IGF-1. We conclude that although APP and APLP2 proteolytic processing are induced by the same stimuli, the processing is dependent on different signaling pathways and processing enzymes, which in turn are differentially regulated.
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37.
  • Jacobsen, Lars C, et al. (author)
  • The secretory leukocyte protease inhibitor (SLPI) and the secondary granule protein lactoferrin are synthesized in myelocytes, colocalize in subcellular fractions of neutrophils, and are coreleased by activated neutrophils.
  • 2008
  • In: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 83, s. 1155-1164
  • Journal article (peer-reviewed)abstract
    • The secretory leukocyte protease inhibitor (SLPI) re-establishes homeostasis at sites of infection by virtue of its ability to exert antimicrobial activity, to suppress LPS-induced cellular immune responses, and to reduce tissue damage through inhibition of serine proteases released by polymorphonuclear neutrophil granulocytes (PMNs). Microarray analysis of bone marrow (BM) populations highly enriched in promyelocytes, myelocytes/metamyelocytes (MYs), and BM neutrophils demonstrates a transient, high mRNA expression of SLPI and genuine secondary granule proteins (GPs) in MYs. Consistent with this finding, immunostaining of BM cells showed SLPI and the secondary GP lactoferrin (LF) to be present in cells from the myelocyte stage and throughout neutrophil differentiation. Subcellular fractionation studies demonstrated the colocalization of SLPI and LF in subcellular fractions highly enriched in secondary granules. Finally, exocytosis studies demonstrated a corelease of SLPI and LF within minutes of activation. Collectively, these findings strongly indicate that SLPI is localized in secondary granules of PMNs. However, the amount of SLPI detected in PMNs is low compared with primary keratinocytes stimulated by growth factors involved in wound healing. This implicates that neutrophil-derived SLPI might not contribute essentially to re-establishment of homeostasis at sites of infection but rather, exert physiologically relevant intracellular activities. These might include the protection of secondary GPs against proteolytic activation and/or degradation by proteases, which might be dislocated to secondary granules at minute amounts as a consequence of spillover.
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38.
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39.
  • Jacobsen, Mia Ravn, et al. (author)
  • Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction
  • 2021
  • In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 342, s. 15-22
  • Journal article (peer-reviewed)abstract
    • Background: To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials. Methods: All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models. Results: In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35–0.70) and prasugrel (HR 0.48, 95% CI 0.33–0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011–2015 showed similar results. Conclusions: Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.
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40.
  • Jensen, Jette Nygaard, et al. (author)
  • Comparison of antibiotic prescribing and antimicrobial resistance in urinary tract infections at the municipal level among women in two Nordic regions
  • 2018
  • In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 73:8, s. 2207-2214
  • Journal article (peer-reviewed)abstract
    • Objectives: To describe and compare the prescribing of antibiotics used for urinary tract infections and its correlation with resistance in Escherichia coli in urinary samples across two adjacent regions - the Capital Region and the Skaane Region - and their municipalities in Denmark and Sweden. Methods: The Capital Region consists of 29 municipalities and 725 960 female inhabitants aged ≥18 years and the Skaane Region consists of 33 municipalities and 515 668 female inhabitants aged ≥18 years. Aggregated data from outpatient care on the prescribing of pivmecillinam, trimethoprim and nitrofurantoin from both regions were analysed. The Department of Clinical Microbiology in both regions provided data on E. coli resistance in urinary samples from women aged ≥18 years. Data were measured as the number of prescriptions/1000 women/year, number of DDDs/1000 women/year and DDDs/prescription. Correlation analyses between antibiotic prescribing and antibiotic resistance rates were performed. Results: Antibiotic prescribing and resistance rates were significantly higher in the Capital Region compared with the Skaane Region. Large variations in prescription and resistance rates were found at the municipal level, but there were no correlations between the antibiotic prescription and resistance rates when each region was analysed separately. Conclusions: Although closely related, there are large differences in antibiotic prescribing and antibiotic resistance. It is suggested that the regional guidelines are an important driver and explanatory factor for the variations; however, further research is needed in this new field and factors such as the influence of cultural aspects should be the target of further research.
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41.
  • Kampmann, Freja Bach, et al. (author)
  • Study protocol of the InterVitaminK trial : A Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health
  • 2023
  • In: BMJ Open. - 2044-6055. ; 13:5
  • Journal article (peer-reviewed)abstract
    • Introduction Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification. Methods and analysis The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52-82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 μg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance. Ethics and dissemination Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported. Trial registration number NCT05259046.
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42.
  • Kharazi, Shabnam, et al. (author)
  • Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation
  • 2011
  • In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:13, s. 3613-3621
  • Journal article (peer-reviewed)abstract
    • Acquisition of homozygous activating growth factor receptor mutations might accelerate cancer progression through a simple gene-dosage effect. Internal tandem duplications (ITDs) of FLT3 occur in approximately 25% cases of acute myeloid leukemia and induce ligand-independent constitutive signaling. Homozygous FLT3-ITDs confer an adverse prognosis and are frequently detected at relapse. Using a mouse knockin model of Flt3-internal tandem duplication (Flt3-ITD)-induced myeloproliferation, we herein demonstrate that the enhanced myeloid phenotype and expansion of granulocyte-monocyte and primitive Lin(-)Sca1(+)c-Kit(+) progenitors in Flt3-ITD homozygous mice can in part be mediated through the loss of the second wild-type allele. Further, whereas autocrine FLT3 ligand production has been implicated in FLT3-ITD myeloid malignancies and resistance to FLT3 inhibitors, we demonstrate here that the mouse Flt3(ITD/ITD) myeloid phenotype is FLT3 ligand-independent. (Blood. 2011; 118(13):3613-3621)
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43.
  • Koch, Markus, et al. (author)
  • Frequency of breaks, amount of muscular rest, and sustained muscle activity related to neck pain in a pooled dataset
  • 2024
  • In: PLoS ONE. - 1932-6203. ; 19:6, s. 1-22
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Neck pain remains a persistent challenge in modern society and is frequently encountered across a wide range of occupations, particularly those involving repetitive and monotonous tasks. It might be expected that patterns of trapezius muscle activity at work, characterized by few breaks and prolonged periods of sustained muscle activity, are linked to neck pain. However, previous cross-sectional studies have generally failed to establish a definitive association. While some longitudinal studies have suggested that extended periods of heightened muscle activity could be a risk factor for neck pain, these findings often relied on limited participant numbers or specific professional groups. This study aimed to investigate the relationship between trapezius muscle activity and neck pain by pooling data from seven Scandinavian research institutes encompassing a diverse range of occupational backgrounds.METHODS: Electromyographic (EMG) data for the upper trapezius muscle, collected during working hours, were coupled with questionnaire responses pertaining to neck pain, individual characteristics, and potential confounding variables for a total of 731 subjects. Additionally, longitudinal data from 258 subjects were available. The various EMG datasets were consolidated into a standardized format, and efforts were made to harmonize inquiries about neck pain. Regression analyses, adjusting for sex and height, were conducted to explore the associations between muscle activity variables and neck pain. An exposure index was devised to quantify the cumulative neck load experienced during working hours and to differentiate between various occupational categories.RESULTS: The cross-sectional data displayed a distinct pattern characterized by positive associations for brief periods of sustained muscle activity (SUMA) and negative associations for prolonged SUMA-periods and neck pain. The longitudinal data exhibited a contrasting trend, although it was not as pronounced as the cross-sectional findings. When employing the exposure index, notable differences in cumulative muscle load emerged among occupational groups, and positive associations with longitudinal neck pain were identified.DISCUSSION: The results suggest that individuals with neck pain experience higher cumulative workloads and extended periods of muscle activity over the long term. In the short term, they appear to compensate by taking frequent short breaks, resulting in a lower cumulative workload. Regardless of their occupation, it is crucial to distribute work breaks throughout the workday to ensure that the cumulative load remains manageable.
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44.
  • Kyu, Hmwe H, et al. (author)
  • Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013 : Findings From the Global Burden of Disease 2013 Study.
  • 2016
  • In: JAMA pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 170:3, s. 267-287
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.
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45.
  • Lehmann-Jacobsen, Emilie (author)
  • Myanmar´s Media from an Audience Perspective
  • 2018
  • Reports (pop. science, debate, etc.)abstract
    • This publication presents the findings from an audience study carried out by International Media Support (IMS), its partner institution Fojo Media Institute and Enlightened Myanmar Research Foundation (EMRef) in May 2018. The report provides indications of the media habits of the population of Myanmar as well as people’s understanding of news and information flows.The study found that there is a widespread preference towards local media as people feel that these media outlets provide them with information relevant to their local communities and daily lives. Television is a preferred medium for consuming news but social media, and Facebook in particular, is catching up. A culture of sharing news and information ensures that even people without access to Facebook know of the platform and get updates through friends and family.People’s trust in media differs but with many preferring state-owned media to deliver trustworthy and reliable news and information. Some news consumers showcase a natural skepticism towards news and information, but limited access to reliable information makes it difficult for them to verify what they read, see or hear. Despite some people’s ability to critically reflect on the information they encounter, the level of media literacy in Myanmar remains low with many finding it difficult to decipher media content and grasp the role and purpose of media and news.Based on the findings, the report ends with 12 recommendations. Six are directed towards the Myanmar media industry, journalists and other content producers while the remaining six are targeted at media development organizations and learning institutions. IMS-Fojo hopes that these recommendations can serve as inspiration for the continuous development and professionalization of the media in Myanmar.IMS-Fojo would like to express gratitude towards the men and women who participated in the study. Without their willingness to share their views and media habits, this study could not have been carried out. IMS-Fojo is equally appreciative of EMReF’s professional approach and readiness to carry out an audience study in Myanmar without prior experience.
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46.
  • Leonard, Dag, 1975- (author)
  • Cardiovascular Disease and Immune Mechanisms in Systemic Lupus Erythematosus
  • 2014
  • Doctoral thesis (other academic/artistic)abstract
    • Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease characterized by autoantibody production and an activated type I interferon system. Cardiovascular disease (CVD) is as a major cause of morbidity and mortality. The aim of this thesis was to identify genetic risk factors for CVD in SLE. The role of T cells in regulation of the interferon-α (IFNα) production by plasmacytoid dendritic cells (pDCs) was also investigated.   In paper I, a thicker intima, thinner media and increased intima/media ratio was found in young premenopausal women with SLE compared to healthy controls indicating increased cardiovascular risk. As traditional ultrasound assessment of the common carotid intima-media thickness (CCA-IMT) in SLE has given conflicting results separate measurement of the intima and media can be a useful tool to identify SLE patients at increased risk of CVD.   In paper II, an association was demonstrated in SLE between a STAT4 risk allele and ischemic cerebrovascular disease and presence of anti-phospholipid antibodies (aPL). The association remained after adjustment for traditional CVD risk factors. A possible mechanism for this association is that the risk allele leads to increased production of aPL, which promotes thromboembolism.   In paper III, a genetic locus in IRF8 was identified to be associated to coronary heart disease (CHD) in SLE. The association remained after adjustment of other CHD risk factors.  Patients with the IRF8 risk variant had increased CCA-IMT, more carotid plaques and reduced frequency of circulating B cells. Weaker binding of nuclear protein to the risk allele was demonstrated, suggesting a regulatory function of the IRF8 risk variant.   In paper IV, activated T cells were found to strongly enhance the IFNα production by pDC stimulated with RNA-containing immune complexes via GM-CSF and IL-3. Activated SLE T cells enhanced the IFNα production to the same extent as T cells from healthy controls. This finding together with previous observations in SLE of increased levels of GM-CSF and IL-3 suggests that T cells contribute to the activated type I interferon system in SLE.   In conclusion, this thesis demonstrates that genetic predisposition is important for CVD in SLE and describes a new role for T cells in the pathogenesis of SLE.
  •  
47.
  • Madsen, Jasmine Melissa, et al. (author)
  • Long-term prognostic outcomes and implication of oral anticoagulants in patients with new-onset atrial fibrillation following st-segment elevation myocardial infarction
  • 2021
  • In: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 238, s. 89-99
  • Journal article (peer-reviewed)abstract
    • Background: New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted. Methods: A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes. Results: Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, P<.001) and risk of bleeding leading to hospitalization (adjusted HR 1.36, 95% CI 1.00-1.85, P=.050), and non-significant increased risk of ischemic stroke (adjusted HR 1.45, 95% CI 0.96-2.19, P=.08) and re-MI (adjusted HR 1.14, 95% CI 0.86-1.52, P=.35) with a median follow-up of 5.8 years. In NEW-AF patients, 38% received OAC therapy, which was associated with reduced long-term mortality (adjusted HR 0.69, 95% CI 0.47-1.00, P=.049). Conclusions: NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality.
  •  
48.
  • Mogelhoj, A., et al. (author)
  • Ab Initio van der Waals Interactions in Simulations of Water Alter Structure from Mainly Tetrahedral to High-Density-Like
  • 2011
  • In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 115:48, s. 14149-14160
  • Journal article (peer-reviewed)abstract
    • The structure of liquid water at ambient conditions is studied in ab initio molecular dynamics simulations in the NVE ensemble using van der Waals (vdW) density-functional theory, i.e., using the new exchange-correlation functionals optPBE-vdW and vdW-DF2, where the latter has softer nonlocal correlation terms. Inclusion of the more isotropic vdW interactions counteracts highly directional hydrogen bonds, which are enhanced by standard functionals. This brings about a softening of the microscopic structure of water, as seen from the broadening of angular distribution functions and, in particular, from the much lower and broader first peak in the oxygen-oxygen pair-correlation function (PCF) and loss of structure in the outer hydration shells. Inclusion of vdW interactions is shown to shift the balance of resulting structures from open tetrahedral to more close-packed. The resulting O-O PCF shows some resemblance with experiment for high-density water (Soper, A. K.; Ricci, M.A. Phys. Rev. Lett. 2000, 84, 2881), but not directly with experiment for ambient water. Considering the accuracy of the new functionals for interaction energies, we investigate whether the simulation protocol could cause the deviation. An O-O PCF consisting of a linear combination of 70% from vdW-DF2 and 30% from low-density liquid water, as extrapolated from experiments, reproduces near-quantitatively the experimental O-O PCF for ambient water. This suggests the possibility that the new functionals maybe reliable and that instead larger-scale simulations in the NPT ensemble, where the density is allowed to fluctuate in accordance with proposals for supercooled water, could resolve the apparent discrepancy with the measured PCF.
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49.
  • Moltke Sörensen, Ann-Dorit, et al. (author)
  • Interactions between Iron, Phenolic Compounds, Emulsifiers, and pH in Omega-3-Enriched Oil-in-Water Emulsions
  • 2008
  • In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 56:5, s. 1740-1750
  • Journal article (peer-reviewed)abstract
    • The behavior of antioxidants in emulsions is influenced by several factors such as pH and emulsifier type. This study aimed to evaluate the interaction between selected food emulsifiers, phenolic compounds, iron, and pH and their effect on the oxidative stability of n-3 polyunsaturated lipids in a 10% oil-in-water emulsion. The emulsifiers tested were Tween 80 and Citrem, and the phenolic compounds were naringenin, rutin, caffeic acid, and coumaric acid. Lipid oxidation was evaluated at all levels, that is, formation of radicals (ESR), hydroperoxides (PV), and secondary volatile oxidation products. When iron was present, the pH was crucial for the formation of lipid oxidation products. At pH 3 some phenolic compounds, especially caffeic acid, reduced Fe3+ to Fe2+, and Fe2+ increased lipid oxidation at this pH compared to pH 6. Among the evaluated phenols, caffeic acid had the most significant effects, as caffeic acid was found to be prooxidative irrespective of pH, emulsifier type, and presence of iron, although the degrees of lipid oxidation were different at the different experimental conditions. The other evaluated phenols were prooxidative at pH 3 in Citrem-stabilized emulsions and had no significant effect at pH 6 in Citrem- or Tween-stabilized emulsions on the basis of the formation of volatiles. The results indicated that phenol−iron complexes/nanoparticles were formed at pH 6.
  •  
50.
  • Mountjoy, Margo, et al. (author)
  • 2023 International Olympic Committee's (IOC) consensus statement on Relative Energy Deficiency in Sport (REDs)
  • 2023
  • In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 57:17, s. 1073-1097
  • Journal article (other academic/artistic)abstract
    • Relative Energy Deficiency in Sport (REDs) was first introduced in 2014 by the International Olympic Committee's expert writing panel, identifying a syndrome of deleterious health and performance outcomes experienced by female and male athletes exposed to low energy availability (LEA; inadequate energy intake in relation to exercise energy expenditure). Since the 2018 REDs consensus, there have been >170 original research publications advancing the field of REDs science, including emerging data demonstrating the growing role of low carbohydrate availability, further evidence of the interplay between mental health and REDs and more data elucidating the impact of LEA in males. Our knowledge of REDs signs and symptoms has resulted in updated Health and Performance Conceptual Models and the development of a novel Physiological Model. This Physiological Model is designed to demonstrate the complexity of either problematic or adaptable LEA exposure, coupled with individual moderating factors, leading to changes in health and performance outcomes. Guidelines for safe and effective body composition assessment to help prevent REDs are also outlined. A new REDs Clinical Assessment Tool-Version 2 is introduced to facilitate the detection and clinical diagnosis of REDs based on accumulated severity and risk stratification, with associated training and competition recommendations. Prevention and treatment principles of REDs are presented to encourage best practices for sports organisations and clinicians. Finally, methodological best practices for REDs research are outlined to stimulate future high-quality research to address important knowledge gaps.
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