151 research outputs found
IMMUNOTHERAPY IN COMBINATION WITH BEHAVIORAL ENRICHMENT IN A CANINE MODEL OF AGING
Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment (VAC+ENR) for 18 months. Learning and memory was evaluated throughout the study. Serum IgG antibody titers, cerebral spinal fluid (CSF) and brain Aβ were measured. Serum anti-Aβ1-42 IgG increased significantly in VAC animals. ENR but not VAC significantly increased CSF Aβ1-40. No cognitive improvements were observed in any group. VAC significantly reduced brain Aβ1-40 and 1-42, as well as reduced plaque load. An overall slowing of plaque accumulation was seen in the ENR group. VAC and ENR were able to modify pathology when used as separate treatments; however, the combination treatment did not succeed in further reducing Aβ or improving cognition. Previous AD clinical trials using immunotherapy yielded similar outcomes to our study showing reduced Aβ pathology but little to no cognitive improvements. In combination these results suggest that future studies should focus on prevention approaches both in the canine model and in human clinical trials
Evaluation of a proposal for reliable low-cost grid power with 100% wind, water, and solar
A number of analyses, meta-Analyses, and assessments, including those performed by the Intergovernmental Panel on Climate Change, the National Oceanic and Atmospheric Administration, the National Renewable Energy Laboratory, and the International Energy Agency, have concluded that deployment of a diverse portfolio of clean energy technologies makes a transition to a low-carbon-emission energy system both more feasible and less costly than other pathways. In contrast, Jacobson et al. [Jacobson MZ, Delucchi MA, Cameron MA, Frew BA (2015) Proc Natl Acad Sci USA 112(49):15060-15065] argue that it is feasible to provide low-cost solutions to the grid reliability problem with 100% penetration of WWS [wind, water and solar power] across all energy sectors in the continental United States between 2050 and 2055 , with only electricity and hydrogen as energy carriers. In this paper, we evaluate that study and find significant shortcomings in the analysis. In particular, we point out that this work used invalid modeling tools, contained modeling errors, and made implausible and inadequately supported assumptions. Policy makers should treat with caution any visions of a rapid, reliable, and low-cost transition to entire energy systems that relies almost exclusively on wind, solar, and hydroelectric power
Aβ Vaccination in Combination with Behavioral Enrichment in Aged Beagles: Effects on Cognition, Aβ, and Microhemorrhages
Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer’s disease (AD). Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1–42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11–12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); (4) ENR and VAC (E/V) and treated for 20 months. VAC decreased brain Aβ, pyroglutamate Aβ, increased CSF Aβ42 and BDNF RNA levels but also increased microhemorrhages. ENR reduced brain Aβ and prevented microhemorrhages. The combination treatment resulted in a significant maintenance of learning over time, reduced Aβ and increased BDNF mRNA despite increased microhemorrhages, however there were no benefits to memory. These results suggest that the combination of immunotherapy with behavioral enrichment leads to cognitive maintenance associated with reduced neuropathology that may benefit people with AD
mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes
Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron
A global analysis of Y-chromosomal haplotype diversity for 23 STR loci
In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe
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
Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations
The psychological science accelerator’s COVID-19 rapid-response dataset
In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data
Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17
Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation
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