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  • Dankiewicz, Josef, et al. (författare)
  • Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
  • 2021
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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  • Kurth, F, et al. (författare)
  • Large-scale analysis of structural brain asymmetries during neurodevelopment : Associations with age and sex in 4265 children and adolescents.
  • 2024
  • Ingår i: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 45:11, s. e26754-
  • Tidskriftsartikel (refereegranskat)abstract
    • Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.
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  • Wimberger, Sandra, 1987, et al. (författare)
  • Simultaneous inhibition of DNA-PK and Pol ϴ improves integration efficiency and precision of genome editing
  • 2023
  • Ingår i: Nature Communications. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Pol ϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing. Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Pol ϴ inhibition with potent compounds increases editing efficiency and precision.
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  • Jungebluth, P, et al. (författare)
  • Retraction Statement
  • 2023
  • Ingår i: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 102:5, s. 402-404
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Klein, P., et al. (författare)
  • Temporal, spatial and spectroscopic study of plasma emission on Cu target in bipolar HiPIMS
  • 2023
  • Ingår i: Plasma sources science & technology. - : IOP Publishing Ltd. - 0963-0252 .- 1361-6595. ; 32:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar high power impulse magnetron sputtering introduces new possibilities to affect positive ions created during the negative discharge pulse in order to tailor thin films with specific parameters. This paper studies plasma emission in different experimental conditions during different phases of the positive pulse with spectral, spatial and temporal resolution. It is found that predominantly the working gas gives rise to plasma emission during the positive pulse. The plasma emission is observed only in regions of low magnetic confinement, forming a mushroom-like shape in the middle of the target or a dome-like shape on the outer parts of the target. An explanation of the discharge kinetics is proposed based on the acquired data.
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  • Robba, C., et al. (författare)
  • Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial
  • 2022
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Mechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients. Methods and analysis This is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)-target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients' prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay. Ethics and dissemination The TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals.
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  • Walsh, Roddy, et al. (författare)
  • Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
  • 2021
  • Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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  • Bergquist, Filip, 1970, et al. (författare)
  • Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
  • 2022
  • Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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  • Lundin, M., et al. (författare)
  • Diffusely Increased Myocardial Extracellular Volume with or without Focal Late Gadolinium Enhancement: Prevalence and Associations with Left Ventricular Size and Function
  • 2022
  • Ingår i: Journal of Thoracic Imaging. - 0883-5993 .- 1536-0237. ; 37:1, s. 17-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Myocardial extracellular volume fraction (ECV) using cardiovascular magnetic resonance (CMR) can identify diffuse lesions not detected by late gadolinium enhancement (LGE). We aimed to determine the prevalence of increased ECV and its relation to other CMR findings. Materials and Methods: Consecutive patients (n=609, age median [interquartile range] 53 [39 to 66] y, 62% male) underwent CMR at 1.5 T. Focal lesions on LGE images were noted. ECV in regions without focal LGE findings defined diffuse changes. Pronounced increases in left ventricular (LV) end-diastolic volume index and LV mass index, and pronounced decreases in LV ejection fraction were defined as >3 SD from the sex-specific mean in healthy volunteers. Results: Of 609 patients without amyloidosis or hypertrophic cardiomyopathy, 8% had diffusely increased ECV and 5% of all patients had diffusely increased ECV without any focal LGE findings. Multivariate analysis showed that a pronounced increase in the LV end-diastolic volume index was associated with increased ECV (P=0.001), but not LGE (P=0.52). A pronounced decrease in LV ejection fraction was associated with the presence of LGE (P<0.001), but not with increased ECV (P=0.41). Conclusions: Eight percent of patients in this clinical cohort with known or suspected heart disease had diffusely increased ECV and 60% of these lacked focal LGE findings. LV size is independently associated with increased ECV, whereas systolic dysfunction is independently associated with LGE. This image-based clinical study demonstrates that ECV-CMR provides additional information negligibly related to the results of LGE imaging, and thereby increases the diagnostic yield of CMR. © 2020 Lippincott Williams and Wilkins. All rights reserved.
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  • Mzobe, P., et al. (författare)
  • Morphometric Control on Dissolved Organic Carbon in Subarctic Streams
  • 2020
  • Ingår i: Journal of Geophysical Research - Biogeosciences. - 2169-8953. ; 125:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate change has the potential to alter hydrological regimes and to expand saturated areas in permafrost environments, which are important sources of organic carbon. The sources, transfer zones, and delivery mechanisms of carbon into the stream network are controlled by the morphometric properties of the catchment; however, the utility and limitations of these properties as predictors of dissolved organic carbon concentrations have rarely been systematically evaluated. This study tested the relationships between 18 morphometric indicators and observed dissolved organic carbon (DOC) concentrations in the Stordalen catchment, Sweden. Geospatial and explorative statistics were combined to assess the topographical, areal, and linear indicators influencing the distribution of DOC in the catchment. The results suggest that catchment morphometric indicators can be used as proxies to predict DOC concentrations along a longitudinal continuum in subarctic climate regions (R2 up to 0.52). Morphometry indicators that best served as predictors of DOC concentration in the model were as follows: relief, slope length and steepness factor (LS‐factor), sediment transport capacity, and catchment area. Due to the influence that catchment form exerts in DOC spatial patterns and processing, a morphometric approach can serve as a first approximation of DOC spatial patterns within a catchment. The initial step in identifying carbon sources based on the catchment topography has the potential to allow for quick and multilevel comparison within and between catchments.
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  • Riggi, Laura, et al. (författare)
  • Early-season mass-flowering crop cover dilutes wild bee abundance and species richness in temperate regions : A quantitative synthesis
  • 2024
  • Ingår i: Journal of Applied Ecology. - 0021-8901 .- 1365-2664. ; 61:3, s. 452-464
  • Tidskriftsartikel (refereegranskat)abstract
    • Pollinators benefit from increasing floral resources in agricultural landscapes, which could be an underexplored co-benefit of mass-flowering crop cultivation. However, the impacts of mass-flowering crops on pollinator communities are complex and appear to be context-dependent, mediated by factors such as crop flowering time and the availability of other flower resources in the landscape. A synthesis of research is needed to develop management recommendations for effective pollinator conservation in agroecosystems. By combining 22 datasets from 13 publications conducted in nine temperate countries (20 European, 2 North American), we investigated if mass-flowering crop flowering time (early or late season), bloom state (during or after crop flowering) and extent of non-crop habitat cover in the landscape moderated the effect of mass-flowering crop cover on wild pollinator abundance and species richness in mass-flowering crop and non-crop habitats. During bloom, wild bee abundance and richness are negatively related to mass-flowering crop cover. Dilution effects were predominant in crop habitats and early in the season, except for bumblebees, which declined with mass-flowering crop cover irrespective of habitat or season. Late in the season and in non-crop habitats, several of these negative relationships were either absent or reversed. Late-season mass-flowering crop cover is positively related to honeybee abundance in crop habitats and to other bee abundance in non-crop habitats. These results indicate that crop-adapted species, like honeybees, move to forage and concentrate on late-season mass-flowering crops at a time when flower availability in the landscape is limited, potentially alleviating competition for flower resources in non-crop habitats. We found no evidence of pollinators moving from mass-flowering crop to non-crop habitats after crop bloom. Synthesis and applications: Our results confirm that increasing early-season mass-flowering crop cover dilutes wild pollinators in crop habitats during bloom. We find that dilution effects were absent late in the season. While mass-flowering crop cultivation alone is unlikely to be sufficient for maintaining pollinators, as part of carefully designed diverse crop rotations or mixtures combined with the preservation of permanent non-crop habitats, it might provide valuable supplementary food resources for pollinators in temperate agroecosystems, particularly later in the season when alternative flower resources are scarce.
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  • Bakker, F. T., et al. (författare)
  • The Global Museum: natural history collections and the future of evolutionary science and public education
  • 2020
  • Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Natural history museums are unique spaces for interdisciplinary research and educational innovation. Through extensive exhibits and public programming and by hosting rich communities of amateurs, students, and researchers at all stages of their careers, they can provide a place-based window to focus on integration of science and discovery, as well as a locus for community engagement. At the same time, like a synthesis radio telescope, when joined together through emerging digital resources, the global community of museums (the 'Global Museum') is more than the sum of its parts, allowing insights and answers to diverse biological, environmental, and societal questions at the global scale, across eons of time, and spanning vast diversity across the Tree of Life. We argue that, whereas natural history collections and museums began with a focus on describing the diversity and peculiarities of species on Earth, they are now increasingly leveraged in new ways that significantly expand their impact and relevance. These new directions include the possibility to ask new, often interdisciplinary questions in basic and applied science, such as in biomimetic design, and by contributing to solutions to climate change, global health and food security challenges. As institutions, they have long been incubators for cutting-edge research in biology while simultaneously providing core infrastructure for research on present and future societal needs. Here we explore how the intersection between pressing issues in environmental and human health and rapid technological innovation have reinforced the relevance of museum collections. We do this by providing examples as food for thought for both the broader academic community and museum scientists on the evolving role of museums. We also identify challenges to the realization of the full potential of natural history collections and the Global Museum to science and society and discuss the critical need to grow these collections. We then focus on mapping and modelling of museum data (including place-based approaches and discovery), and explore the main projects, platforms and databases enabling this growth. Finally, we aim to improve relevant protocols for the long-term storage of specimens and tissues, ensuring proper connection with tomorrow's technologies and hence further increasing the relevance of natural history museums.
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  • Bratt, E., et al. (författare)
  • The STEPSTONES transition program for adolescents with congenital heart disease is effective in improving patient empowerment : a randomized controlled trial
  • 2022
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:Suppl. 2, s. 2745-2745
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Congenital heart disease (CHD) is the most common birth defect, with a global birth prevalence of 8.2 per 1000 new-borns. Improvements in the diagnosis and treatment of children with CHD have resulted in increasing life prospects, with more than 90% surviving into adulthood today. To ensure expert lifetime care, patients need to transfer from paediatric-oriented care to adult-oriented care. At the same time, they need to transition from a dependent child with CHD to an independent adult who can manage living with CHD. Thus, during adolescence, patients with CHD need to acquire knowledge and skills to independently manage their health, while simultaneously experiencing a series of physical, cognitive and social changes. To facilitate this phase, transitional care is needed. However, high-level empirical evidence on the effectiveness of transitional care is scarce.Purpose: To investigate the empowering effect (primary outcome) of a structured person-centred transition programme for adolescents with CHD, and to study the effectiveness on transition readiness, patient-reported health, quality of life, health behaviours, disease-related knowledge, parental uncertainty, and parental perception of transition readiness (secondary outcomes).Methods: The STEPSTONES-CHD trial comprised a hybrid experimental design, in which a randomized controlled trial (RCT) was embedded in a longitudinal, observational study. The trial was conducted in seven CHD centres in Sweden. Two centres were allocated to the RCT-arm, randomising participants to intervention (IG) or control group (CG). The other five centres were intervention-naïve centres and served as contamination check control group (CCCG). Outcomes were measured at the age of 16 y (T0; baseline), 17y (T1) and 18.5y (T2).Results: The change in empowerment from T0 to T2 differed significantly between the IG and CG (mean difference=3.44; 95% CI: 0.27–6.65; p=0.036) in favour for IG. For the secondary outcomes, significant differences in change over time were found in parental involvement (p=0.008), CHD-specific knowledge (p=0.0002), and satisfaction with physical appearance (p=0.039). No differences in primary or secondary outcomes were detected between CG and CCCG, indicating that there was no contamination in the CG.Conclusion: The STEPSTONES-CHD trial demonstrated the effectiveness of a person-centred transition programme in empowering adolescents with CHD. Furthermore, parental involvement, satisfaction with physical appearance and CHD-related knowledge were positively influenced. This trial provides empirical underpinnings for the implementation of transition programmes for afflicted adolescents.
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  • Carvajal, Liliana, et al. (författare)
  • Measurement of Mental Health Among Adolescents at the Population Level: A Multicountry Protocol for Adaptation and Validation of Mental Health Measures
  • 2023
  • Ingår i: Journal of Adolescent Health. - : Elsevier. - 1054-139X .- 1879-1972. ; 72:1S, s. S27-S33
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Mental disorders are among the leading causes of disability among adolescents aged 10-19 years. However, data on prevalence of mental health conditions are extremely sparse across low- and middle-income countries, even though most adolescents live in these settings. This data gap is further exacerbated because few brief instruments for adolescent mental health are validated in these settings, making population-level measurement of adolescent mental health especially cumbersome to carry out. In response, the UNICEF has undertaken the Measurement of Mental Health Among Adolescents at the Population Level (MMAP) initiative, validating open-access brief measures and encouraging data collection in this area.Methods: This protocol presents the MMAP mixed-methods approach for cultural adaptation and clinical validation of adolescent mental health data collection tools across settings. Qualitative activities include an initial translation and adaptation, review by mental health experts, focus-group discussions with adolescents, cognitive interviews, synthesis of findings, and back-translation. An enriched sample of adolescents with mental health problems is then interviewed with the adapted tool, followed by gold-standard semistructured diagnostic interviews.Results: The study protocol is being implemented in Belize, Kenya, Nepal, and South Africa and includes measures for anxiety, depression, functional limitations, suicidality, care-seeking, and connectedness. Analyses, including psychometrics, will be conducted individually by country and combined across settings to assess the MMAP methodological process.Discussion:This protocol contributes to closing the data gap on adolescent mental health conditions by providing a rigorous process of cross-cultural adaptation and validation of data collection approaches.
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  • Foster, Rachel A., et al. (författare)
  • Richelia
  • 2022
  • Ingår i: Bergey's Manual of Systematics of Archaea and Bacteria. - : John Wiley & Sons. - 9781118960608 ; , s. 1-17
  • Bokkapitel (refereegranskat)abstract
    • Ri.che'li.a. N.L. fem. n. Richelia, named for the Danish admiral Andreas du Plessis de Richelieu (1852–1932).Cyanobacteria / Cyanobacteria / Cyanobacteriales / Nostocaceae / RicheliaFilamentous heterocyst-forming, Gram-stain-negative, aerobic, phototrophic, N2-fixing, and occurring either as free-living or most often associated with several marine diatom genera (Rhizosolenia, Hemiaulus, and Chaetoceros). Filaments (trichomes) contain variable numbers of sheathless vegetative cells and one terminal heterocyst. Filaments lack akinetes and have limited motility via gliding. Gas vesicles are absent. Cyanophycin granules can be present in vegetative cells and heterocysts. Glycogen appears as large deposits, and thylakoids are dispersed randomly. Reproduce by normal cell division and asynchronous with one host diatom Rhizosolenia. DNA G + C content (mol%) from draft genomes varies 33–39%; genome size varies 3.42–6.04 Mb. Reduces atmospheric N2 with nitrogenase. Known habitats are warm (24–27.5°C), marine, and oligotrophic seas with intermediate (32 PSU) to fully marine (36 PSU) salinities. Biogeochemically relevant as N2 fixers and drivers of carbon export. Have been reported in all major ocean basins (Atlantic, Pacific, and Indian) and smaller seas (Mediterranean Sea and Red Sea).DNA G + C content (mol%): 33–39 (genome sequence).Type species: Richelia intracellularis Schmidt in Ostenfeld and Schmidt 1901.
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  • Girardi, P., et al. (författare)
  • Anti-Toxin Responses to Natural Enterotoxigenic Escherichia coli (ETEC) Infection in Adults and Children in Bangladesh
  • 2023
  • Ingår i: Microorganisms. - 2076-2607. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic Escherichia coli infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts. (2) Methods: A total of 617 adult and 480 pediatric diarrheal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. The plasma samples were analyzed for antibody responses against the ETEC toxins. (3) Results: Heat-stable toxin (ST)-positive ETEC is the main cause of ETEC infection in adults, unlike in children in an endemic setting. We detected very low levels of anti-ST antibodies, and no ST-neutralizing activity. However, infection with ETEC strains expressing the heat-labile toxin (LT) induced systemic antibody responses in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralizing activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralizing activity. (4) Conclusions: Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralizing activity.
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  • Gudmundsson, Jon Tomas, 1965-, et al. (författare)
  • Ionization region model of high power impulse magnetron sputtering of copper
  • 2022
  • Ingår i: Surface & Coatings Technology. - : ELSEVIER SCIENCE SA. - 0257-8972 .- 1879-3347. ; 442
  • Tidskriftsartikel (refereegranskat)abstract
    • The ionization region model (IRM) is applied to model high power impulse magnetron sputtering (HiPIMS) discharges with a Cu target. We apply the model to three discharges that were experimentally explored in the past, or applied to deposit thin copper films, with the aim to quantify internal plasma process parameters and thereby understand how these discharges differ from each other. The temporal variation of the various neutral and ionic species, the electron density and temperature, as well as internal discharge parameters, such as the ionization probability, back attraction probability, and ionized flux fraction of the sputtered species, are determined. We demonstrate that the Cu+ ions dominate the total ion current to the target surface and that all the discharges are dominated by self-sputter recycling to reach high discharge currents. Furthermore, the ion flux into the diffusion region is dominated by Cu+ ions, which represents roughly 80% of the total ion flux onto the substrate, in agreement with experimental findings. For the discharges operated with peak discharge current densities in the range 0.9 - 1.3 A cm-2, the ion back-attraction probability of the Cu+ ion (beta t) is low compared to previously investigated HiPIMS discharges, or in the range 44 - 50%, while the ionization probability (alpha t) is in the range 61 - 69%, and the ionized flux fraction is in the range 32 - 40%. It is, furthermore, found that operating these Cu HiPIMS discharges at lower working gas pressures (in the present case around 0.5 Pa) is beneficial in terms of optimizing ionization of the sputtered species.
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  • Gupta, Dhanu, et al. (författare)
  • Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
  • 2021
  • Ingår i: Nature Biomedical Engineering. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 2157-846X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.
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40.
  • Hederström, Veronica, et al. (författare)
  • White clover pollinators and seed set in relation to local management and landscape context
  • 2024
  • Ingår i: Agriculture, Ecosystems and Environment. - 0167-8809. ; 365
  • Tidskriftsartikel (refereegranskat)abstract
    • Bees are declining, which is worrisome since they both have intrinsic conservation value and play a major role as pollinators in both natural and managed ecosystems. Land use change and lack of suitable habitats are often suggested as driving forces of bee decline. To propose mitigation measures to halt bee decline, it is important to understand how land use relates to bee abundance and diversity, and to explore consequences for their provision of pollination services. White clover, Trifolium repens, is an outcrossing mass-flowering crop, which could serve as an abundant, although ephemeral, food resource for bees. We investigated how the bee community in 39 fields of white clover grown for seed, related to local field management (organic, conventional without insecticides and conventional with insecticides) and landscape context (proportion semi-natural land), and how this pollinator community related to white clover seed set. The honey bee, Apis mellifera, was the most commonly observed bee species, and two generalist bumble bee species, Bombus terrestris and B. lapidarius, were the subsequently most common. We observed fewer non-Apis bees, and a lower bee species richness in organic white clover seed fields compared to conventional fields independent of insecticide treatment. Bee species richness in both conventional and organic fields were positively related to the proportion of semi-natural land in the landscape, likely because of a larger species pool in such landscapes. Initial seed set in immature inflorescences was positively related to bee abundance, whereas final seed set in mature inflorescences was unrelated to bee abundance, possibly as a consequence of seed-eating weevils consuming a large proportion of the seeds. We conclude that both bee visitation and seed set in white clover benefit from conventional management and that landscapes rich in semi-natural habitats will make future crop production more resilient. The observed positive relationship between bee abundance and initial seed set suggests that if we can mitigate pest impacts and increase bee abundance in clover seed fields, the final seed yield can be increased. Thus, bee decline should be considered and mitigated both to maintain biodiversity in general and for crop seed production specifically.
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41.
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42.
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43.
  • Laber, Christien P., et al. (författare)
  • Seasonal and Spatial Variations in Synechococcus Abundance and Diversity Throughout the Gullmar Fjord, Swedish Skagerrak
  • 2022
  • Ingår i: Frontiers in Microbiology. - Lausanne : Frontiers Media S.A.. - 1664-302X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • The picophytoplankton Synechococcus is a globally abundant autotroph that contributes significantly to primary production in the oceans and coastal areas. These cyanobacteria constitute a diverse genus of organisms that have developed independent niche spaces throughout aquatic environments. Here, we use the 16S V3-V4 rRNA gene region and flow cytometry to explore the diversity of Synechococcus within the picophytoplankton community in the Gullmar Fjord, on the west coast of Sweden. We conducted a station-based 1-year time series and two transect studies of the fjord. Our analysis revealed that within the large number of Synechococcus amplicon sequence variants (ASVs; 239 in total), prevalent ASVs phylogenetically clustered with clade representatives in both marine subcluster 5.1 and 5.2. The near-surface composition of ASVs shifted from spring to summer, when a 5.1 subcluster dominated community developed along with elevated Synechococcus abundances up to 9.3 x 10(4) cells ml(-1). This seasonal dominance by subcluster 5.1 was observed over the length of the fjord (25 km), where shifts in community composition were associated with increasing depth. Unexpectedly, the community shift was not associated with changes in salinity. Synechococcus abundance dynamics also differed from that of the photosynthetic picoeukaryote community. These results highlight how seasonal variations in environmental conditions influence the dynamics of Synechococcus clades in a high latitude threshold fjord.
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44.
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45.
  • Lundin, C., et al. (författare)
  • There is no association between combined oral hormonal contraceptives and depression : a Swedish register-based cohort study
  • 2022
  • Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 129:6, s. 917-925
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non-users. Design: Register-based cohort study.Setting: Sweden.Sample: Women aged 15–25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585).Methods: Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC-users compared with non-users were modelled by Poisson regression. Adjustments included age, medical indication for HC-use and parental history of mental disorders, among others.Main outcome measures: Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register.Results: Compared with non-users, women on combined oral contraceptives (COCs) and oral progestogen-only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87–0.91) and 1.03 (95% CI 0.99–1.06) after adjustments, respectively. Age-stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93–0.98), whereas use of progestogen-only pills (RR 1.13, 95% CI 1.07–1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30–1.58), implant (RR 1.38, 95% CI 1.30–1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46–1.73) were associated with increased risks.Conclusions: This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non-oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results. Tweetable abstract: There is no association between combined hormonal contraceptives and depression.
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46.
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47.
  • Neufeld, Janina, et al. (författare)
  • Global and local visual processing in autism - a co-twin-control study
  • 2020
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 61:4, s. 470-479
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Autism Spectrum Disorder (ASD) is associated with altered global and local visual processing. However, the nature of these alterations remains controversial, with contradictory findings and notions ranging from a reduced drive to integrate information into a coherent 'gestalt' ("weak central coherence" = WCC) to an enhanced perceptual functioning (EPF) in local processing.METHODS: This study assessed the association between autism and global/local visual processing, using a large sample of monozygotic (MZ) and dizygotic (DZ) twins (N = 290, 48% females, age = 8-31 years). The Fragmented Pictures Test (FPT) assessed global processing, whereas local processing was estimated with the Embedded Figures Test (EFT) and the Block Design Test (BDT). Autism was assessed both categorically (clinical diagnosis), and dimensionally (autistic traits). Associations between visual tasks and autism were estimated both across the cohort and within-twin pairs where all factors shared between twins are implicitly controlled.RESULTS: Clinical diagnosis and autistic traits predicted a need for more visual information for gestalt processing in the FPT across the cohort. For clinical diagnosis, this association remained within-pairs and at trend-level even within MZ twin pairs alone. ASD and higher autistic traits predicted lower EFT and BDT performance across the cohort, but these associations were lost within-pairs.CONCLUSIONS: In line with the WCC account, our findings indicate an association between autism and reduced global visual processing in children, adolescents and young adults (but no evidence for EPF). Observing a similar association within MZ twins suggests a non-shared environmental contribution.
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48.
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49.
  • Ovaskainen, Otso, et al. (författare)
  • Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA
  • 2024
  • Ingår i: Scientific Data. - 2052-4463. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
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