| 11. |
- Golden, Gregory J, et al.
(författare)
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Endothelial Heparan Sulfate Mediates Hepatic Neutrophil Trafficking and Injury during Staphylococcus aureus Sepsis
- 2021
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Ingår i: mBio. - 2161-2129. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic failure is an important risk factor for poor outcome in septic patients. Using a chemical tagging workflow and high-resolution mass spectrometry, we demonstrate that rapid proteome remodeling of the vascular surfaces precedes hepatic damage in a murine model of Staphylococcus aureus sepsis. These early changes include vascular deposition of neutrophil-derived proteins, shedding of vascular receptors, and altered levels of heparin/heparan sulfate-binding factors. Modification of endothelial heparan sulfate, a major component of the vascular glycocalyx, diminishes neutrophil trafficking to the liver and reduces hepatic coagulopathy and organ damage during the systemic inflammatory response to infection. Modifying endothelial heparan sulfate likewise reduces neutrophil trafficking in sterile hepatic injury, reflecting a more general role of heparan sulfate contribution to the modulation of leukocyte behavior during inflammation. IMPORTANCE Vascular glycocalyx remodeling is critical to sepsis pathology, but the glycocalyx components that contribute to this process remain poorly characterized. This article shows that during Staphylococcus aureus sepsis, the liver vascular glycocalyx undergoes dramatic changes in protein composition associated with neutrophilic activity and heparin/heparan sulfate binding, all before organ damage is detectable by standard circulating liver damage markers or histology. Targeted manipulation of endothelial heparan sulfate modulates S. aureus sepsis-induced hepatotoxicity by controlling the magnitude of neutrophilic infiltration into the liver in both nonsterile and sterile injury. These data identify an important vascular glycocalyx component that impacts hepatic failure during nonsterile and sterile injury.
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| 12. |
- Kaminski, Thomas, et al.
(författare)
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Assessing the constraint of atmospheric CO2 and NO2 measurements from space on city-scale fossil fuel CO2 emissions in a data assimilation system
- 2022
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Ingår i: Frontiers in Remote Sensing. - : Frontiers Media SA. - 2673-6187. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The European Copernicus programme plans to install a constellation of multiple polar orbiting satellites (Copernicus Anthropogenic CO2 Monitoring Mission, CO2M mission) for observing atmospheric CO2 content with the aim to estimate fossil fuel CO2 emissions. We explore the impact of potential CO2M observations of column-averaged CO2 (XCO2), nitrogen dioxide (NO2), and aerosols in a 200 × 200 km2 domain around Berlin. For the quantification of anticipated XCO2 random and systematic errors we developed and applied new error parameterisation formulae based on artificial neural networks. For the interpretation of these data, we further established a CCFFDAS modelling chain from parameters of emission models to XCO2 and NO2 observations to simulate the 24 h periods preceeding simulated CO2M overpasses over the study area. For one overpass in winter and one in summer, we present a number of assessments of observation impact in terms of the posterior uncertainty in fossil fuel emissions on scales ranging from 2 to 200 km. This means the assessments include temporal and spatial scales typically not covered by inventories. The assessments differentiate the fossil fuel CO2 emissions into two sectors, an energy generation sector (power plants) and the complement, which we call “other sector.” We find that combined measurements of XCO2 and aerosols provide a powerful constraint on emissions from larger power plants; the uncertainty in fossil fuel emissions from the largest three power plants in the domain was reduced by 60%–90% after assimilating the observations. Likewise, these measurements achieve an uncertainty reduction for the other sector that increases when aggregated to larger spatial scales. When aggregated over Berlin the uncertainty reduction for the other sector varies between 28% and 48%. Our assessments show a considerable contribution of aerosol observations onboard CO2M to the constraint of the XCO2 measurements on emissions from all power plants and for the other sector on all spatial scales. NO2 measurements onboard CO2M provide a powerful additional constraint on the emissions from power plants and from the other sector. We further apply a Jacobian representation of the CCFFDAS modelling chain to decompose a simulated CO2 column in terms of spatial emission impact. This analysis reveals the complex structure of the footprint of an observed CO2 column, which indicates the limits of simple mass balances approaches for interpretation of such observations.
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| 13. |
- Kaminski, Thomas, et al.
(författare)
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Assessing the Impact of Atmospheric CO2 and NO2 Measurements From Space on Estimating City-Scale Fossil Fuel CO2 Emissions in a Data Assimilation System
- 2022
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Ingår i: Frontiers in Remote Sensing. - : Frontiers Media SA. - 2673-6187. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The European Copernicus programme plans to install a constellation of multiple polar orbiting satellites (Copernicus Anthropogenic CO2 Monitoring Mission, CO2M mission) for observing atmospheric CO2 content with the aim to estimate fossil fuel CO2 emissions. We explore the impact of potential CO2M observations of column-averaged CO2 (XCO2), nitrogen dioxide (NO2), and aerosols in a 200 × 200 km2 domain around Berlin. For the quantification of anticipated XCO2 random and systematic errors we developed and applied new error parameterisation formulae based on artificial neural networks. For the interpretation of these data, we further established a CCFFDAS modelling chain from parameters of emission models to XCO2 and NO2 observations to simulate the 24 h periods preceeding simulated CO2M overpasses over the study area. For one overpass in winter and one in summer, we present a number of assessments of observation impact in terms of the posterior uncertainty in fossil fuel emissions on scales ranging from 2 to 200 km. This means the assessments include temporal and spatial scales typically not covered by inventories. The assessments differentiate the fossil fuel CO2 emissions into two sectors, an energy generation sector (power plants) and the complement, which we call “other sector.” We find that combined measurements of XCO2 and aerosols provide a powerful constraint on emissions from larger power plants; the uncertainty in fossil fuel emissions from the largest three power plants in the domain was reduced by 60%–90% after assimilating the observations. Likewise, these measurements achieve an uncertainty reduction for the other sector that increases when aggregated to larger spatial scales. When aggregated over Berlin the uncertainty reduction for the other sector varies between 28% and 48%. Our assessments show a considerable contribution of aerosol observations onboard CO2M to the constraint of the XCO2 measurements on emissions from all power plants and for the other sector on all spatial scales. NO2 measurements onboard CO2M provide a powerful additional constraint on the emissions from power plants and from the other sector. We further apply a Jacobian representation of the CCFFDAS modelling chain to decompose a simulated CO2 column in terms of spatial emission impact. This analysis reveals the complex structure of the footprint of an observed CO2 column, which indicates the limits of simple mass balances approaches for interpretation of such observations.
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| 14. |
- Kephart, George, et al.
(författare)
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Item selection, scaling and construct validation of the Patient-Reported Inventory of Self-Management of Chronic Conditions (PRISM-CC) measurement tool in adults
- 2022
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Ingår i: Quality of Life Research. - : Springer Nature. - 0962-9343 .- 1573-2649. ; 31:9, s. 2867-2880
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To select and scale items for the seven domains of the Patient-Reported Inventory of Self-Management of Chronic Conditions (PRISM-CC) and assess its construct validity.Methods: Using an online survey, data on 100 potential items, and other variables for assessing construct validity, were collected from 1055 adults with one or more chronic health conditions. Based on a validated conceptual model, confirmatory factor analysis (CFA) and item response models (IRT) were used to select and scale potential items and assess the internal consistency and structural validity of the PRISM-CC. To further assess construct validity, hypothesis testing of known relationships was conducted using structural equation models.Results: Of 100 potential items, 36 (4–8 per domain) were selected, providing excellent fit to our hypothesized correlated factors model and demonstrating internal consistency and structural validity of the PRISM-CC. Hypothesized associations between PRISM-CC domains and other measures and variables were confirmed, providing further evidence of construct validity.Conclusion: The PRISM-CC overcomes limitations of assessment tools currently available to measure patient self-management of chronic health conditions. This study provides strong evidence for the internal consistency and construct validity of the PRISM-CC as an instrument to assess patient-reported difficulty in self-managing different aspects of daily life with one or more chronic conditions. Further research is needed to assess its measurement equivalence across patient attributes, ability to measure clinically important change, and utility to inform self-management support.
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| 15. |
- Newby, Gretchen, et al.
(författare)
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Testing and treatment for malaria elimination : a systematic review
- 2023
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Ingår i: Malaria Journal. - : BioMed Central (BMC). - 1475-2875. ; 22:1
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Forskningsöversikt (refereegranskat)abstract
- Background Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies.Methods A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission.Results A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively.Conclusion Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.
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| 16. |
- Pecl, Gretta T., et al.
(författare)
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Climate-driven 'species-on-the-move' provide tangible anchors to engage the public on climate change
- 2023
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Ingår i: People and Nature. - : John Wiley & Sons. - 2575-8314. ; 5:5, s. 1384-1402
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Tidskriftsartikel (refereegranskat)abstract
- Over recent decades, our understanding of climate change has accelerated greatly, but unfortunately, observable impacts have increased in tandem. Both mitigation and adaptation have not progressed at the level or scale warranted by our collective knowledge on climate change. More effective approaches to engage people on current and future anthropogenic climate change effects are urgently needed. Here, we show how species whose distributions are shifting in response to climate change, that is, ‘species-on-the-move’, present an opportunity to engage people with climate change by linking to human values, and our deep connections with the places in which we live, in a locally relevant yet globally coherent narrative. Species-on-the-move can impact ecosystem structure and function, food security, human health, livelihoods, culture and even the climate itself through feedback to the climate system, presenting a wide variety of potential pathways for people to understand that climate change affects them personally as individuals. Citizen science focussed on documenting changes in biodiversity is one approach to foster a deeper engagement on climate change. However, other possible avenues, which may offer potential to engage people currently unconnected with nature, include arts, games or collaborations with rural agriculture (e.g. new occurrences of pest species) or fisheries organisations (e.g. shifting stocks) or healthcare providers (e.g. changing distributions of disease vectors). Through the importance we place on the aspects of life impacted by the redistribution of species around us, species-on-the-move offer emotional pathways to connect with people on the complex issue of climate change in profound ways that have the potential to engender interest and action on climate change. Read the free Plain Language Summary for this article on the Journal blog.
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| 17. |
- Schijven, Dick, et al.
(författare)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 18. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 19. |
- Stepniewska, Kasia, et al.
(författare)
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Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission : A WWARN individual patient meta-analysis.
- 2020
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:7, s. 1215-1226
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
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| 20. |
- Stepniewska, Kasia, et al.
(författare)
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Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide : a systematic review and meta-analysis of individual patient data
- 2022
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Forskningsöversikt (refereegranskat)abstract
- BackgroundIn 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.MethodsA systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.ResultsData comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.ConclusionsOur results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.
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