177 research outputs found
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The importance of the representation of air pollution emissions for the modeled distribution and radiative effects of black carbon in the Arctic
Aerosol particles can contribute to the Arctic amplification (AA) by direct and indirect radiative effects. Specifically, black carbon (BC) in the atmosphere, and when deposited on snow and sea ice, has a positive warming effect on the top-of-atmosphere (TOA) radiation balance during the polar day. Current climate models, however, are still struggling to reproduce Arctic aerosol conditions. We present an evaluation study with the global aerosol-climate model ECHAM6.3-HAM2.3 to examine emission-related uncertainties in the BC distribution and the direct radiative effect of BC. The model results are comprehensively compared against the latest ground and airborne aerosol observations for the period 2005–2017, with a focus on BC. Four different setups of air pollution emissions are tested. The simulations in general match well with the observed amount and temporal variability in near-surface BC in the Arctic. Using actual daily instead of fixed biomass burning emissions is crucial for reproducing individual pollution events but has only a small influence on the seasonal cycle of BC. Compared with commonly used fixed anthropogenic emissions for the year 2000, an up-to-date inventory with transient air pollution emissions results in up to a 30 % higher annual BC burden locally. This causes a higher annual mean all-sky net direct radiative effect of BC of over 0.1 W m−2 at the top of the atmosphere over the Arctic region (60–90∘ N), being locally more than 0.2 W m−2 over the eastern Arctic Ocean. We estimate BC in the Arctic as leading to an annual net gain of 0.5 W m−2 averaged over the Arctic region but to a local gain of up to 0.8 W m−2 by the direct radiative effect of atmospheric BC plus the effect by the BC-in-snow albedo reduction. Long-range transport is identified as one of the main sources of uncertainties for ECHAM6.3-HAM2.3, leading to an overestimation of BC in atmospheric layers above 500 hPa, especially in summer. This is related to a misrepresentation in wet removal in one identified case at least, which was observed during the ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) summer aircraft campaign. Overall, the current model version has significantly improved since previous intercomparison studies and now performs better than the multi-model average in the Aerosol Comparisons between Observation and Models (AEROCOM) initiative in terms of the spatial and temporal distribution of Arctic BC
A reactive transport model for geochemical mitigation of CO2 leaking into a confined aquifer
Long-term storage of anthropogenic CO2 in the subsurface generally assumes that caprock formations will serve as physical barriers to upward migration of CO2. However, as a precaution and to provide assurances to regulators and the public, monitoring is used detect any unexpected leakage from the storage reservoir. If a leak is found, the ability to rapidly deploy mitigation measures is needed. Here we use the TOUGHREACT code to develop a series of two-dimensional reactive transport simulations of the hydrogeochemical characteristics of a newly formed CO2 leak into an overlying aquifer. Using this model, we consider: (1) geochemical shifts in formation water indicative of a leak; (2) hydrodynamics of pumping wells in the vicinity of a leak; and (3) delivery of a sealant to a leak through an adjacent well bore.Our results demonstrate that characteristic shifts in pH and dissolved inorganic carbon can be detected in the aquifer prior to the breakthrough of supercritical CO2, and could offer a potential means of identifying small and newly formed leaks. Pumping water into the aquifer in the vicinity of the leak provides a hydrodynamic control that can temporarily mitigate the flux rate of CO2 and facilitate delivery of a sealant to the location of the caprock defect. Injection of a fluid-phase sealant through the pumping well is demonstrated by introduction of a silica-bearing alkaline flood, resulting in precipitation of amorphous silica in areas of neutral to acidic pH. Results show that a decrease in permeability of several orders of magnitude can be achieved with a high molar volume sealant, such that CO2 flux rate is decreased. However, individual simulation results are highly contingent upon both the properties of the sealant, the porosity-permeability relationship employed in the model, and the relative flux rates of CO2 and alkaline flood introduced into the aquifer. These conclusions highlight the need for both experimental data and controlled field tests to constrain modelling predictions
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors
Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15
IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets
Exploring DNA methylation changes in promoter, intragenic, and intergenic regions as early and late events in breast cancer formation
Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex
The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders
Genetic architecture of subcortical brain structures in 38,851 individuals
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth
Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020 : the right to sight : an analysis for the Global Burden of Disease Study
Background: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error.Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older.Findings: Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change −0·2% [95% UI −1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by −15·4% [–16·8 to −14·3], while avoidable MSVI showed no change (0·5% [–0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7–18·0]), followed by glaucoma (3·6 million cases [2·8–4·4]), undercorrected refractive error (2·3 million cases [1·8–2·8]), age-related macular degeneration (1·8 million cases [1·3–2·4]), and diabetic retinopathy (0·86 million cases [0·59–1·23]). Leading causes of MSVI were undercorrected refractive error (86·1 million cases [74·2–101·0]) and cataract (78·8 million cases [67·2–91·4]).Interpretation: Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached
Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016
Background A key component of achieving universal health coverage is ensuring that all populations have access to
quality health care. Examining where gains have occurred or progress has faltered across and within countries is
crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries,
and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access
and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from
1990 to 2016.
Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which
death should not occur in the presence of effective care to approximate personal health-care access and quality by
location and over time. To better isolate potential effects of personal health-care access and quality from underlying
risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local
joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion
of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised
death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We
transformed each cause to a scale of 0–100, with 0 as the first percentile (worst) observed between 1990 and 2016, and
100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational
locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values,
providing an overall score of 0–100 of personal health-care access and quality by location over time. We then compared
HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall
development. As derived from the broader GBD study and other data sources, we examined relationships between
national HAQ Index scores and potential correlates of performance, such as total health spending per capita.
Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by
96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in
the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of
progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and
2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and
elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000.
Striking subnational disparities emerged in personal health-care access and quality, with China and India having
particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged
from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point
disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam. Japan recorded the smallest range in
subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations
with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high
for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point
to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point
to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high
and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases.
Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from
2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was
positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these
relationships were quite heterogeneous, particularly among low-to-middle SDI countries.
Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving
personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-
SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or
minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities
of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium
Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health
coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive
view—and subsequent provision—of quality health care for all populations.info:eu-repo/semantics/publishedVersio
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