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Sökning: WFRF:(Blomberg P)

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1.
  • Rajewsky, N., et al. (författare)
  • LifeTime and improving European healthcare through cell-based interceptive medicine
  • 2020
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
  • Tidskriftsartikel (refereegranskat)abstract
    • LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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  • Groenen, M. A., et al. (författare)
  • Analyses of pig genomes provide insight into porcine demography and evolution
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
  • Tidskriftsartikel (refereegranskat)abstract
    • For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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  • Auffray, C., et al. (författare)
  • COVID-19 and beyond : a call for action and audacious solidarity to all the citizens and nations, it is humanity’s fight
  • 2020
  • Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9, s. 1130-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 was facilitated by the increasing intensity of air travel, urban congestion and human contact during the past decades. Until therapies and vaccines are available, tests for virus exposure, confinement and distancing measures have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. Self-organizing initiatives by scientists and citizens are developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies. 
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  • Aarestrup, FM, et al. (författare)
  • Towards a European health research and innovation cloud (HRIC)
  • 2020
  • Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1, s. 18-
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.
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  • Ferwerda, Bart, et al. (författare)
  • Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock.
  • 2009
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:25, s. 10272-10277
  • Tidskriftsartikel (refereegranskat)abstract
    • Adequate responses by our innate immune system toward invading pathogens were of vital importance for surviving infections, especially before the antibiotic era. Recently, a polymorphism in Mal (Ser180Leu, TIRAP rs8177374), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, has been described to provide protection against a broad range of infectious pathogens. We assessed the functional effects of this polymorphism in human experimental endotoxemia, and we demonstrate that individuals bearing the TIRAP 180L allele display an increased, innate immune response to TLR4 and TLR2 ligands, but not to TLR9 stimulation. This phenotype has been related to an increased resistance to infection. However, an overshoot in the release of proinflammatory cytokines by TIRAP 180L homozygous individuals suggests a scenario of balanced evolution. We have also investigated the worldwide distribution of the Ser180Leu polymorphism in 14 populations around the globe to correlate the genetic makeup of TIRAP with the local infectious pressures. Based on the immunological, clinical, and genetic data, we propose that this mutation might have been selected in West Eurasia during the early settlement of this region after the out-of-Africa migration of modern Homo sapiens. This combination of functional and genetic data provides unique insights to our understanding of the pathogenesis of sepsis.
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  • Awah, Nancy, 1976-, et al. (författare)
  • Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian children
  • 2011
  • Ingår i: Parasite immunology (Print). - : Wiley. - 0141-9838 .- 1365-3024. ; 33:2, s. 104-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have implicated reactive antibodies to the low molecular weight rhoptry-associated proteins (RAP-1, RAP-2/RSP-2 and RAP-3) in erythroid cell destruction during Plasmodium falciparum infection. In this pilot study, the frequency, specificity and functional capacity of naturally acquired anti-RAP-2/RSP-2 antibodies were investigated in the sera of anaemic and nonanaemic malaria-infected Cameroonian children. All sera recognized RAP-2/RSP-2 by FACS, irrespective of the clinical status of the subjects. However, the anaemic children showed higher levels of IgG antibodies than the nonanaemic group, while both groups showed similar levels of IgM antibodies. Only few individuals had detectable levels of RAP-2/RSP-2-specific IgG1 and IgG3 subclass antibodies, while no IgG2 and IgG4 subclass antibodies were detected in these subjects. By ELISA, the anaemic group tended to show higher levels of antibodies to RAP-2/RSP-2 regarding all antibody classes tested, except for IgG4 and IgE. Unexpectedly, sera from the nonanaemic group activated complement to a greater extent than those from the anaemic group. These results need to be confirmed in extended studies but indicate that the effector functions of the RAP-2/RSP-2-reactive antibodies may be more important than their amounts. Such antibodies could play a role in both immunity and pathogenesis during P. falciparum infection.
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  • Horbury, T., et al. (författare)
  • Cross-scale : A multi-spacecraft mission to study cross-scale coupling in space plasmas
  • 2006
  • Ingår i: European Space Agency, (Special Publication) ESA SP. ; , s. 561-568
  • Konferensbidrag (refereegranskat)abstract
    • Collisionless astrophysical plasmas exhibit complexity on many scales: if we are to understand their properties and effects, we must measure this complexity. We can identify a small number of processes and phenomena, one of which is dominant in almost every space plasma region of interest: shocks, reconnection and turbulence. These processes act to transfer energy between locations, scales and modes. However, this transfer is characterised by variability and 3D structure on at least three scales: electron kinetic, ion kinetic and fluid. It is the nonlinear interaction between physical processes at these scales that is the key to understanding these phenomena and predicting their effects. However, current and planned multi-spacecraft missions such as Cluster and MMS only study variations on one scale in 3D at any given time - we must measure the three scales simultaneously fully to understand the energy transfer processes. We propose a mission, called Cross-Scale, to study these processes. Cross-Scale would comprise three nested groups, each consisting of up to four spacecraft. Each group would have a different spacecraft separation, at approximately the electron and ion gyroradii, and a larger MHD scale. We would therefore be able to measure variations on all three important physical scales, simultaneously, for the first time. The spacecraft would fly in formation through key regions of near-Earth space: The solar wind, bowshock, magnetosheath, magnetopause and magnetotail.
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  • Kulpraneet, M., et al. (författare)
  • Analysis of IL-4 promoter and VNTR polymorphisms in Thai patients with pulmonary tuberculosis
  • 2019
  • Ingår i: Tropical Biomedicine. - 0127-5720. ; 36:4, s. 874-882
  • Tidskriftsartikel (refereegranskat)abstract
    • Tuberculosis (TB) is a leading cause of morbidity and mortality in Thailand. Cytokines play important roles in defense against Mycobacterium tuberculosis infection. Interleukin (IL)-4 is one of the anti-inflammatory cytokines and has been found to be elevated in TB patients. The common polymorphisms in IL-4 gene, including IL-4-590C/T, IL-4-33C/T, and IL-4-variable number of tandem repeats (VNTR) intron 3 have been reported to be associated with risk for some diseases. The purpose of this study was to investigate possible associations between the above mentioned three common functional polymorphisms in the IL-4 gene in patients with pulmonary tuberculosis (PTB) in a Thai population. Forty three patients with PTB and 90 healthy control subjects were studied. The three common polymorphisms of the IL-4 gene were determined using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). The allele and genotype frequencies of IL-4-590 C/T, -33 C/T, VNTR intron 3 polymorphisms did not show significant differences between PTB patients and healthy controls ( genotype: p=0.88, p=0.92, p=0.40; allele: p=0.38, p=0.44, p=0.53, respectively). However, the allele distribution of the IL-4 -590 C, -33 C, and VNTR R3 was higher among PTB patients (25.58%, 25.58%, 25.58%, respectively) than among control subjects (20%, 20.48%, 19.44%, respectively). This may suggest that IL-4-590C/T, -33C/T and VNTR intron 3 might play a role in susceptibility to PTB. A larger cohort may possibly help conclude our findings.
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  • Nunez, J. C. B., et al. (författare)
  • From tides to nucleotides: Genomic signatures of adaptation to environmental heterogeneity in barnacles
  • 2021
  • Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:23, s. 6417-6433
  • Tidskriftsartikel (refereegranskat)abstract
    • The northern acorn barnacle (Semibalanus balanoides) is a robust system to study the genetic basis of adaptations to highly heterogeneous environments. Adult barnacles may be exposed to highly dissimilar levels of thermal stress depending on where they settle in the intertidal (i.e., closer to the upper or lower tidal boundary). For instance, barnacles near the upper tidal limit experience episodic summer temperatures above recorded heat coma levels. This differential stress at the microhabitat level is also dependent on the aspect of sun exposure. In the present study, we used pool-seq approaches to conduct a genome wide screen for loci responding to intertidal zonation across the North Atlantic basin (Maine, Rhode Island, and Norway). Our analysis discovered 382 genomic regions containing SNPs which are consistently zonated (i.e., SNPs whose frequencies vary depending on their position in the rocky intertidal) across all surveyed habitats. Notably, most zonated SNPs are young and private to the North Atlantic. These regions show high levels of genetic differentiation across ecologically extreme microhabitats concomitant with elevated levels of genetic variation and Tajima's D, suggesting the action of non-neutral processes. Overall, these findings support the hypothesis that spatially heterogeneous selection is a general and repeatable feature for this species, and that natural selection can maintain functional genetic variation in heterogeneous environments.
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  • Schafer, S., et al. (författare)
  • Spatio-temporal structure of a poloidal Alfven wave detected by Cluster adjacent to the dayside plasmapause
  • 2008
  • Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 26:7, s. 1805-1817
  • Tidskriftsartikel (refereegranskat)abstract
    • A case study of a poloidal ULF pulsation near the dayside plasmapause is presented based on Cluster observations of magnetic and electric fields. The pulsation is detected close to the magnetic equatorial plane at L shells L=[4.4, 4.6] and oscillates with a frequency of f=23 mHz. Investigating the wave energy flux reveals the standing wave nature of the observed pulsation. An estimation of the azimuthal wave number exposes a narrow azimuthal structure of the wave field with m approximate to 160. Spatial and temporal characteristics of the pulsation are analyzed in detail by representing data in a field line related coordinate system and a range-time-intensity representation. This allows an estimation of both the spatial extension of the wave field in the radial direction and its temporal decay rate. The analysis furthermore indicates that the same field lines are excited to a standing wave oscillation twice. Furthermore an accurate identification of a phase jump of the wave field across L shells is possible. Comparing the radial localization of the detected wave with theoretically expected field line eigenfrequencies reveals that the wave field is confined in the Alfven resonator at the outer edge of the plasmapause.
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  • Shamovsky, I., et al. (författare)
  • Theoretical studies of chemical reactivity of metabolically activated forms of aromatic amines towards DNA.
  • 2012
  • Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 25:10, s. 2236-2252
  • Tidskriftsartikel (refereegranskat)abstract
    • The metabolism of aromatic and heteroaromatic amines (ArNH2) results in nitrenium ions (ArNH+) that modify nucleobases of DNA, primarily deoxyguanosine (dG), by forming dG-C8 adducts. The activated amine nitrogen in ArNH+ reacts with the C8 of dG, which gives rise to mutations in DNA. For the most mutagenic ArNH2, including the majority of known genotoxic carcinogens, the stability of ArNH+ is of intermediate magnitude. To understand the origin of this observation as well as the specificity of reactions of ArNH+ with guanines in DNA, we investigated the chemical reactivity of the metabolically activated forms of ArNH2, that is, ArNHOH and ArNHOAc, toward 9-methylguanine by DFT calculations. The chemical reactivity of these forms is determined by the rate constants of two consecutive reactions leading to cationic guanine intermediates. The formation of ArNH+ accelerates with resonance stabilization of ArNH+, whereas the formed ArNH+ reacts with guanine derivatives with the constant diffusion-limited rate until the reaction slows down when ArNH+ is about 20 kcal/mol more stable than PhNH+. At this point, ArNHOH and ArNHOAc show maximum reactivity. The lowest activation energy of the reaction of ArNH+ with 9-methylguanine corresponds to the charge-transfer π-stacked transition state (π-TS) that leads to the direct formation of the C8 intermediate. The predicted activation barriers of this reaction match the observed absolute rate constants for a number of ArNH+. We demonstrate that the mutagenic potency of ArNH2 correlates with the rate of formation and the chemical reactivity of the metabolically activated forms toward the C8 atom of dG. On the basis of geometric consideration of the π-TS complex made of genotoxic compounds with long aromatic systems, we propose that precovalent intercalation in DNA is not an essential step in the genotoxicity pathway of ArNH2. The mechanism-based reasoning suggests rational design strategies to avoid genotoxicity of ArNH2 primarily by preventing N-hydroxylation of ArNH2.
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  • Smith, Annabel L., et al. (författare)
  • Global gene flow releases invasive plants from environmental constraints on genetic diversity
  • 2020
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:8, s. 4218-4227
  • Tidskriftsartikel (refereegranskat)abstract
    • When plants establish outside their native range, their ability to adapt to the new environment is influenced by both demography and dispersal. However, the relative importance of these two factors is poorly understood. To quantify the influence of demography and dispersal on patterns of genetic diversity underlying adaptation, we used data from a globally distributed demographic research network comprising 35 native and 18 nonnative populations of Plantago lanceolata. Species-specific simulation experiments showed that dispersal would dilute demographic influences on genetic diversity at local scales. Populations in the native European range had strong spatial genetic structure associated with geographic distance and precipitation seasonality. In contrast, nonnative populations had weaker spatial genetic structure that was not associated with environmental gradients but with higher within-population genetic diversity. Our findings show that dispersal caused by repeated, long-distance, human-mediated introductions has allowed invasive plant populations to overcome environmental constraints on genetic diversity, even without strong demographic changes. The impact of invasive plants may, therefore, increase with repeated introductions, highlighting the need to constrain future introductions of species even if they already exist in an area.
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  • Stenler, S., et al. (författare)
  • Micro-minicircle gene therapy : Implications of size on fermentation, complexation, shearing resistance, and expression
  • 2014
  • Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier BV. - 2162-2531. ; 3, s. e140-
  • Tidskriftsartikel (refereegranskat)abstract
    • The minicircle (MC), composed of eukaryotic sequences only, is an interesting approach to increase the safety and efficiency of plasmid-based vectors for gene therapy. In this paper, we investigate micro-MC (miMC) vectors encoding small regulatory RNA. We use a construct encoding a splice-correcting U7 small nuclear RNA, which results in a vector of 650 base pairs (bp), as compared to a conventional 3600 bp plasmid carrying the same expression cassette. Furthermore, we construct miMCs of varying sizes carrying different number of these cassettes. This allows us to evaluate how size influences production, supercoiling, stability and efficiency of the vector. We characterize coiling morphology by atomic force microscopy and measure the resistance to shearing forces caused by an injector device, the Biojector. We compare the behavior of miMCs and plasmids in vitro using lipofection and electroporation, as well as in vivo in mice. We here show that when the size of the miMC is reduced, the formation of dimers and trimers increases. There seems to be a lower size limit for efficient expression. We demonstrate that miMCs are more robust than plasmids when exposed to shearing forces, and that they show extended expression in vivo.
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  • Tjärnlund, Anna, et al. (författare)
  • Polymeric Ig receptor knockout mice are more susceptible to mycobacteria infection in the respiratory tract
  • 2006
  • Ingår i: International Immunology. - : Oxford university press. - 0953-8178 .- 1460-2377. ; 18:5, s. 807-816
  • Tidskriftsartikel (refereegranskat)abstract
    • It is generally accepted that cellular, and not humoral immunity, plays the crucial role in defense against intracellular bacteria. However, accumulating data indicate the importance of humoral immunity for the defense against a number of intracellular bacteria, including mycobacteria. We have investigated the role of secretory IgA, the main isotype found in mucosal tissues, in protection against mycobacterial infection, using polymeric IgR (pIgR)-deficient mice. Characterization of the humoral response induced after intra-nasal immunizations with the mycobacterial antigen PstS-1 revealed a loss of antigen-specific IgA response in saliva from the knockout mice. IgA level in the bronchoalveolar lavage of knockout mice was similar to wild-type level, although the IgA antibodies must have reached the lumen by other means than pIgR-mediated transport. Infection with Mycobacterium bovis bacillus Calmette–Guérin (BCG) demonstrated that the immunized pIgR−/− mice were more susceptible to BCG infection than immunized wild-type mice, based on higher bacterial loads in the lungs. This was accompanied by a reduced production of both IFN-γ and tumor necrosis factor-alpha (TNF-α) in the lungs. Additionally, the pIgR−/− mice displayed reduced natural resistance to mycobacterial infection proved by significantly higher bacterial growth in their lungs compared with wild-type mice after infection with virulent Mycobacterium tuberculosis. The knockout mice appeared to have a delayed mycobacteria-induced immune response with reduced expression of protective mediators, such as IFN-γ, TNF-α, inducible nitric oxide synthase and regulated upon activation normal T cell sequence, during early infection. Collectively, our results show that actively secreted IgA plays a role in protection against mycobacterial infections in the respiratory tract, by blocking entrance of bacilli into the lungs, in addition to modulation of the mycobacteria-induced pro-inflammatory response.
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  • Tornhammar, P., et al. (författare)
  • Association of cardiometabolic risk factors with hospitalisation or death due to COVID-19: Population-based cohort study in Sweden (SCAPIS)
  • 2021
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To assess the association of cardiometabolic risk factors with hospitalisation or death due to COVID-19 in the general population. Design, setting and participants Swedish population-based cohort including 29 955 participants. Exposures Cardiometabolic risk factors assessed between 2014 and 2018. Main outcome measures Hospitalisation or death due to COVID-19, as registered in nationwide registers from 31 January 2020 through 12 September 2020. Associations of cardiometabolic risk factors with the outcome were assessed using logistic regression adjusted for age, sex, birthplace and education. Results Mean (SD) age was 61.2 (4.5) and 51.5% were women. 69 participants experienced hospitalisation or death due to COVID-19. Examples of statistically significant associations between baseline factors and subsequent hospitalisation or death due to COVID-19 included overweight (adjusted OR (aOR) vs normal weight 2.73 (95% CI 1.25 to 5.94)), obesity (aOR vs normal weight 4.09 (95% CI 1.82 to 9.18)), pre-diabetes (aOR vs normoglycaemia 2.56 (95% CI 1.44 to 4.55)), diabetes (aOR vs normoglycaemia 3.96 (95% CI 2.13 to 7.36)), sedentary time (aOR per hour/day increase 1.10 (95% CI 1.02 to 1.17)), grade 2 hypertension (aOR vs normotension 2.44 (95% CI 1.10 to 5.44)) and high density lipoprotein cholesterol (aOR per mmol/L increase 0.33 (95% CI 0.17 to 0.65)). Statistically significant associations were not observed for grade 1 hypertension (aOR vs normotension 1.03 (95% CI 0.55 to 1.96)), current smoking (aOR 0.56 (95% CI 0.24 to 1.30)), total cholesterol (aOR per mmol/L increase 0.90 (95% CI 0.71 to 1.13)), low density lipoprotein cholesterol (aOR per mmol/L increase 0.90 (95% CI 0.69 to 1.15)) and coronary artery calcium score (aOR per 10 units increase 1.00 (95% CI 0.99 to 1.01)). Conclusions In a large population-based sample from the general population, several cardiometabolic risk factors were associated with hospitalisation or death due to COVID-19. © Authors 2021
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  • Abdeldaim, Guma, et al. (författare)
  • Is quantitative PCR for the pneumolysin (ply) gene useful for detection of pneumococcal lower respiratory tract infection?
  • 2009
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 15:6, s. 565-570
  • Tidskriftsartikel (refereegranskat)abstract
    • The pneumolysin (ply) gene is widely used as a target in PCR assays for Streptococcus pneumoniae in respiratory secretions. However, false-positive results with conventional ply-based PCR have been reported. The aim here was to study the performance of a quantitative ply-based PCR for the identification of pneumococcal lower respiratory tract infection (LRTI). In a prospective study, fibreoptic bronchoscopy was performed in 156 hospitalized adult patients with LRTI and 31 controls who underwent bronchoscopy because of suspicion of malignancy. Among the LRTI patients and controls, the quantitative ply-based PCR applied to bronchoalveolar lavage (BAL) fluid was positive at >/=10(3) genome copies/mL in 61% and 71% of the subjects, at >/=10(5) genome copies/mL in 40% and 58% of the subjects, and at >/=10(7) genome copies/mL in 15% and 3.2% of the subjects, respectively. Using BAL fluid culture, blood culture, and/or a urinary antigen test, S. pneumoniae was identified in 19 LRTI patients. As compared with these diagnostic methods used in combination, quantitative ply-based PCR showed sensitivities and specificities of 89% and 43% at a cut-off of 10(3) genome copies/mL, of 84% and 66% at a cut-off of 10(5) genome copies/mL, and of 53% and 90% at a cut-off of 10(7) genome copies/mL, respectively. In conclusion, a high cut-off with the quantitative ply-based PCR was required to reach acceptable specificity. However, as a high cut-off resulted in low sensitivity, quantitative ply-based PCR does not appear to be clinically useful. Quantitative PCR methods for S. pneumoniae using alternative gene targets should be evaluated.
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  • Amodu, O. K., et al. (författare)
  • Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria
  • 2012
  • Ingår i: Acta Tropica. - : Elsevier BV. - 0001-706X .- 1873-6254. ; 123:2, s. 72-77
  • Tidskriftsartikel (refereegranskat)abstract
    • In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI95%: 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group 0 was demonstrated with a decreased risk of severe malaria OR=0.743 (CI95%: 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI95%: 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children.
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  • Andre, M, et al. (författare)
  • Ion energization mechanisms at 1700 km in the auroral region
  • 1998
  • Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - 0148-0227. ; 103:A3, s. 4199-4222
  • Tidskriftsartikel (refereegranskat)abstract
    • Observations obtained by the Freja satellite at altitudes around 1700 km in the high-latitude magnetosphere are used to study ion energization perpendicular to the geomagnetic field. Investigations of ions, electrons, plasma densities, electric and magnetic wave fields, and field-aligned currents are used to study O+ heating mechanisms. Three ion heating events are studied in detail, and 20 events are used in a detailed statistical study. More than 200 events are classified as belonging to one of four major types of ion heating and are ordered as a function of magnetic local time. The most common types of ion heating are associated with broadband low-frequency electric wave fields occurring at all local times. These waves cover frequencies from below one up to several hundred hertz and correspond to the most intense O+ energization. Heating by these waves at frequencies of the order of the O+ gyrofrequency at 25 Hz seems to be the important energization mechanism, causing O+ ion mean energies up to hundreds of eV. The broadband waves are associated with Alfven waves with frequencies up to at least a few hertz and with field-aligned currents. Other types of O+ energization events are less common. During these events the ions are heated by waves near the lower hybrid frequency or near half the proton gyrofrequency. These waves are generated by auroral electrons or in a few cases by precipitating ions.
  •  
48.
  • Andre, M, et al. (författare)
  • Ion energization mechanisms at 1700 km in the auroral region
  • 1998
  • Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - : AMER GEOPHYSICAL UNION. ; 103:A3, s. 4199-4222
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Observations obtained by the Freja satellite at altitudes around 1700 km in the high-latitude magnetosphere are used to study ion energization perpendicular to the geomagnetic field. Investigations of ions, electrons, plasma densities, electric and magnet
  •  
49.
  •  
50.
  •  
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