| 1. |
- Frostad, J. J., et al.
(författare)
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Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18: a geospatial modelling study
- 2022
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Ingår i: Lancet Global Health. - 2214-109X. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 2. |
- Singer, S., et al.
(författare)
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Methodological approach for determining the Minimal Important Difference and Minimal Important Change scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module (EORTC QLQ-HN43) exemplified by the Swallowing scale
- 2022
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 31, s. 841-853
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43. Methods In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods. Results From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14. Conclusions For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate.
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| 3. |
- Allum, F., et al.
(författare)
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A localized view on molecular dissociation via electron-ion partial covariance
- 2022
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Ingår i: Communications Chemistry. - : Springer Science and Business Media LLC. - 2399-3669. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Inner-shell photoelectron spectroscopy provides an element-specific probe of molecular structure, as core-electron binding energies are sensitive to the chemical environment. Short-wavelength femtosecond light sources, such as Free-Electron Lasers (FELs), even enable time-resolved site-specific investigations of molecular photochemistry. Here, we study the ultraviolet photodissociation of the prototypical chiral molecule 1-iodo-2-methylbutane, probed by extreme-ultraviolet (XUV) pulses from the Free-electron LASer in Hamburg (FLASH) through the ultrafast evolution of the iodine 4d binding energy. Methodologically, we employ electron-ion partial covariance imaging as a technique to isolate otherwise elusive features in a two-dimensional photoelectron spectrum arising from different photofragmentation pathways. The experimental and theoretical results for the time-resolved electron spectra of the 4d(3/2) and 4d(5/2) atomic and molecular levels that are disentangled by this method provide a key step towards studying structural and chemical changes from a specific spectator site. Coincidence experiments at free-electron lasers enable time resolved site-specific investigations of molecular photochemistry at high signal rates, but isolating individual dissociation processes still poses a considerable technical challenge. Here, the authors use electron-ion partial covariance imaging to isolate otherwise elusive chemical shifts in UV-induced photofragmentation pathways of the prototypical chiral molecule 1-iodo-2-methylbutane.
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| 4. |
- Jahnke, T., et al.
(författare)
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Inner-Shell-Ionization-Induced Femtosecond Structural Dynamics of Water Molecules Imaged at an X-Ray Free-Electron Laser
- 2021
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Ingår i: Physical Review X. - : American Physical Society. - 2160-3308. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- The ultrafast structural dynamics of water following inner-shell ionization is a crucial issue in high-energy radiation chemistry. We have exposed isolated water molecules to a short x-ray pulse from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we can image dissociation dynamics of individual molecules in unprecedented detail. We reveal significant molecular structural dynamics in H2O2+, such as asymmetric deformation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. We thus reconstruct several snapshots of structural dynamics at different time intervals, which highlight dynamical patterns that are relevant as initiating steps of subsequent radiation-damage processes.
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| 5. |
- Rasmussen, Jay, et al.
(författare)
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Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimers disease
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:49, s. 13018-13023
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Tidskriftsartikel (refereegranskat)abstract
- The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-beta peptide (A beta) has been shown to adopt distinct structural conformations with different biological activities, we asked whether A beta can assume structurally and functionally distinct conformations within the brain. To this end, we analyzed the LCO-stained cores of beta-amyloid plaques in postmortem tissue sections from frontal, temporal, and occipital neocortices in 40 cases of familial Alzheimers disease (AD) or sporadic (idiopathic) AD (sAD). The spectral attributes of LCO-bound plaques varied markedly in the brain, but the mean spectral properties of the amyloid cores were generally similar in all three cortical regions of individual patients. Remarkably, the LCO amyloid spectra differed significantly among some of the familial and sAD subtypes, and between typical patients with sAD and those with posterior cortical atrophy AD. Neither the amount of A beta nor its protease resistance correlated with LCO spectral properties. LCO spectral amyloid phenotypes could be partially conveyed to A beta plaques induced by experimental transmission in a mouse model. These findings indicate that polymorphic A beta-amyloid deposits within the brain cluster as clouds of conformational variants in different AD cases. Heterogeneity in the molecular architecture of pathogenic A beta among individuals and in etiologically distinct subtypes of AD justifies further studies to assess putative links between A beta conformation and clinical phenotype.
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| 6. |
- Lee, Ben H, et al.
(författare)
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Highly functionalized organic nitrates in the southeast United States: Contribution to secondary organic aerosol and reactive nitrogen budgets.
- 2016
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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. - 1091-6490. ; 113:6, s. 1516-21
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Tidskriftsartikel (refereegranskat)abstract
- Speciated particle-phase organic nitrates (pONs) were quantified using online chemical ionization MS during June and July of 2013 in rural Alabama as part of the Southern Oxidant and Aerosol Study. A large fraction of pONs is highly functionalized, possessing between six and eight oxygen atoms within each carbon number group, and is not the common first generation alkyl nitrates previously reported. Using calibrations for isoprene hydroxynitrates and the measured molecular compositions, we estimate that pONs account for 3% and 8% of total submicrometer organic aerosol mass, on average, during the day and night, respectively. Each of the isoprene- and monoterpenes-derived groups exhibited a strong diel trend consistent with the emission patterns of likely biogenic hydrocarbon precursors. An observationally constrained diel box model can replicate the observed pON assuming that pONs (i) are produced in the gas phase and rapidly establish gas-particle equilibrium and (ii) have a short particle-phase lifetime (∼2-4 h). Such dynamic behavior has significant implications for the production and phase partitioning of pONs, organic aerosol mass, and reactive nitrogen speciation in a forested environment.
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| 7. |
- Patridge, Erik V., et al.
(författare)
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7-Nitro-4-(phenylthio)benzofurazan is a potent generator of superoxide and hydrogen peroxide
- 2012
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 86:10, s. 1613-1625
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Tidskriftsartikel (refereegranskat)abstract
- Here, we report on 7-nitro-4-(phenylthio)benzofurazan (NBF-SPh), the most potent derivative among a set of patented anticancer 7-nitrobenzofurazans (NBFs), which have been suggested to function by perturbing protein-protein interactions. We demonstrate that NBF-SPh participates in toxic redox-cycling, rapidly generating reactive oxygen species (ROS) in the presence of molecular oxygen, and this is the first report to detail ROS production for any of the anticancer NBFs. Oxygraph studies showed that NBF-SPh consumes molecular oxygen at a substantial rate, rivaling even plumbagin, menadione, and juglone. Biochemical and enzymatic assays identified superoxide and hydrogen peroxide as products of its redox-cycling activity, and the rapid rate of ROS production appears to be sufficient to account for some of the toxicity of NBF-SPh (LC50 = 12.1 mu M), possibly explaining why tumor cells exhibit a sharp threshold for tolerating the compound. In cell cultures, lipid peroxidation was enhanced after treatment with NBF-SPh, as measured by 2-thiobarbituric acid-reactive substances, indicating a significant accumulation of ROS. Thioglycerol rescued cell death and increased survival by 15-fold to 20-fold, but pyruvate and uric acid were ineffective protectants. We also observed that the redox-cycling activity of NBF-SPh became exhausted after an average of approximately 19 cycles per NBF-SPh molecule. Electrochemical and computational analyses suggest that partial reduction of NBF-SPh enhances electrophilicity, which appears to encourage scavenging activity and contribute to electrophilic toxicity.
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| 8. |
- Singer, Susanne, et al.
(författare)
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International validation of the revised European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43: Phase IV.
- 2019
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Ingår i: Head & neck. - : Wiley. - 1097-0347 .- 1043-3074. ; 41:6, s. 1725-1737
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Tidskriftsartikel (refereegranskat)abstract
- We validated the new European Organisation for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN43).We enrolled 812 patients with head and neck cancer from 18 countries. Group 1 completed the questionnaire before therapy, and 3 and 6 months later. In group 2 (survivors), we determined test-retest reliability using intraclass correlation coefficients (ICC). Internal consistency was assessed using Cronbach's Alpha, the scale structure with confirmatory factor analysis, and discriminant validity with known-group comparisons.Cronbach's alpha was >0.70 in 10 of the 12 multi-item scales. All standardized factor loadings exceeded 0.40. The ICC was >0.70 in all but two scales. Differences in scale scores between known-groups were >10 points in 17 of the 19 scales. Sensitivity to change was found to be sufficient in 18 scales.Evidence supports the reliability and validity of the EORTC QLQ-HN43 as a measure of quality of life.
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