The Physics of Supernova Remnant Blast Waves. I. Kinematics of DEM L71 in the Large Magellanic Cloud

We present the results from Fabry-Perot imaging spectroscopy of the Balmer-dominated supernova remnant DEM L71 (0505-67.9) in the LMC. Spectra extracted from the entire circumference of the blast wave reveal the broad and narrow component H-alpha line emission characteristic of non-radiative shocks in partially neutral gas. The new spectra of DEM L71 include portions of the rim that have not been previously observed. We find that the broad component width varies azimuthally along the edge of DEM L71, ranging from 450+/-60 km/s along the eastern edge to values as high as 985 (+210)(-165) km/s along the faint western edge. In part of the faint northern rim the broad component is not detected, possibly indicating a lower density in these regions and/or a broad component width in excess of 1000 km/s. Between the limits of zero and full electron-ion temperature equilibration at the shock front, the allowed range of shock velocities is 430-560 km/s along the east rim and 700-1250 km/s along other parts of the blast wave. The H-alpha broad-to-narrow flux ratios vary considerably around the remnant, ranging from 0.4 to 0.8. These ratios lie below the values predicted by our shock models. We find that narrow component H-alpha emission from a cosmic ray precursor may be the cause of the discrepancy. The least decelerated portions of the blast wave (i.e., regions excluding the brightest filaments) are well characterized by Sedov models with a kinetic energy E_51= (0.37+/-0.06)*D_50**(5/2), where D_50 is the LMC distance in units of 50 kpc. The corresponding age for DEM L71 is (4360+/-290)*D_50 yr. This is the first time that velocity information from the entire blast wave has been utilized to study the global kinematics of a non-radiative SNR at a known distance.Comment: 21 pages, including 8 postscript figures and 4 tables, LaTeX, accepted to ApJ; see companion pape

Integrative Taxonomy for Continental-Scale Terrestrial Insect Observations

Although 21st century ecology uses unprecedented technology at the largest spatio-temporal scales in history, the data remain reliant on sound taxonomic practices that derive from 18th century science. The importance of accurate species identifications has been assessed repeatedly and in instances where inappropriate assignments have been made there have been costly consequences. The National Ecological Observatory Network (NEON) will use a standardized system based upon an integrative taxonomic foundation to conduct observations of the focal terrestrial insect taxa, ground beetles and mosquitoes, at the continental scale for a 30 year monitoring program. The use of molecular data for continental-scale, multi-decadal research conducted by a geographically widely distributed set of researchers has not been evaluated until this point. The current paper addresses the development of a reference library for verifying species identifications at NEON and the key ways in which this resource will enhance a variety of user communities

The state of hypertension care in 44 low-income and middle-income countries:a cross-sectional study of nationally representative individual-level data from 1·1 million adults

Evidence from nationally representative studies in low-income and middle-income countries (LMICs) on where in the hypertension care continuum patients are lost to care is sparse. This information, however, is essential for effective targeting of interventions by health services and monitoring progress in improving hypertension care. We aimed to determine the cascade of hypertension care in 44 LMICs-and its variation between countries and population groups-by dividing the progression in the care process, from need of care to successful treatment, into discrete stages and measuring the losses at each stage. In this cross-sectional study, we pooled individual-level population-based data from 44 LMICs. We first searched for nationally representative datasets from the WHO Stepwise Approach to Surveillance (STEPS) from 2005 or later. If a STEPS dataset was not available for a LMIC (or we could not gain access to it), we conducted a systematic search for survey datasets; the inclusion criteria in these searches were that the survey was done in 2005 or later, was nationally representative for at least three 10-year age groups older than 15 years, included measured blood pressure data, and contained data on at least two hypertension care cascade steps. Hypertension was defined as a systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or reported use of medication for hypertension. Among those with hypertension, we calculated the proportion of individuals who had ever had their blood pressure measured; had been diagnosed with hypertension; had been treated for hypertension; and had achieved control of their hypertension. We weighted countries proportionally to their population size when determining this hypertension care cascade at the global and regional level. We disaggregated the hypertension care cascade by age, sex, education, household wealth quintile, body-mass index, smoking status, country, and region. We used linear regression to predict, separately for each cascade step, a country's performance based on gross domestic product (GDP) per capita, allowing us to identify countries whose performance fell outside of the 95% prediction interval. Our pooled dataset included 1 100 507 participants, of whom 192 441 (17·5%) had hypertension. Among those with hypertension, 73·6% of participants (95% CI 72·9-74·3) had ever had their blood pressure measured, 39·2% of participants (38·2-40·3) had been diagnosed with hypertension, 29·9% of participants (28·6-31·3) received treatment, and 10·3% of participants (9·6-11·0) achieved control of their hypertension. Countries in Latin America and the Caribbean generally achieved the best performance relative to their predicted performance based on GDP per capita, whereas countries in sub-Saharan Africa performed worst. Bangladesh, Brazil, Costa Rica, Ecuador, Kyrgyzstan, and Peru performed significantly better on all care cascade steps than predicted based on GDP per capita. Being a woman, older, more educated, wealthier, and not being a current smoker were all positively associated with attaining each of the four steps of the care cascade. Our study provides important evidence for the design and targeting of health policies and service interventions for hypertension in LMICs. We show at what steps and for whom there are gaps in the hypertension care process in each of the 44 countries in our study. We also identified countries in each world region that perform better than expected from their economic development, which can direct policy makers to important policy lessons. Given the high disease burden caused by hypertension in LMICs, nationally representative hypertension care cascades, as constructed in this study, are an important measure of progress towards achieving universal health coverage. Harvard McLennan Family Fund, Alexander von Humboldt Foundation

Association between country preparedness indicators and quality clinical care for cardiovascular disease risk factors in 44 lower- and middle-income countries:A multicountry analysis of survey data

BackgroundCardiovascular diseases are leading causes of death, globally, and health systems that deliver quality clinical care are needed to manage an increasing number of people with risk factors for these diseases. Indicators of preparedness of countries to manage cardiovascular disease risk factors (CVDRFs) are regularly collected by ministries of health and global health agencies. We aimed to assess whether these indicators are associated with patient receipt of quality clinical care.Methods and findingsWe did a secondary analysis of cross-sectional, nationally representative, individual-patient data from 187,552 people with hypertension (mean age 48.1 years, 53.5% female) living in 43 low- and middle-income countries (LMICs) and 40,795 people with diabetes (mean age 52.2 years, 57.7% female) living in 28 LMICs on progress through cascades of care (condition diagnosed, treated, or controlled) for diabetes or hypertension, to indicate outcomes of provision of quality clinical care. Data were extracted from national-level World Health Organization (WHO) Stepwise Approach to Surveillance (STEPS), or other similar household surveys, conducted between July 2005 and November 2016. We used mixed-effects logistic regression to estimate associations between each quality clinical care outcome and indicators of country development (gross domestic product [GDP] per capita or Human Development Index [HDI]); national capacity for the prevention and control of noncommunicable diseases ('NCD readiness indicators' from surveys done by WHO); health system finance (domestic government expenditure on health [as percentage of GDP], private, and out-of-pocket expenditure on health [both as percentage of current]); and health service readiness (number of physicians, nurses, or hospital beds per 1,000 people) and performance (neonatal mortality rate). All models were adjusted for individual-level predictors including age, sex, and education. In an exploratory analysis, we tested whether national-level data on facility preparedness for diabetes were positively associated with outcomes. Associations were inconsistent between indicators and quality clinical care outcomes. For hypertension, GDP and HDI were both positively associated with each outcome. Of the 33 relationships tested between NCD readiness indicators and outcomes, only two showed a significant positive association: presence of guidelines with being diagnosed (odds ratio [OR], 1.86 [95% CI 1.08-3.21], p = 0.03) and availability of funding with being controlled (OR, 2.26 [95% CI 1.09-4.69], p = 0.03). Hospital beds (OR, 1.14 [95% CI 1.02-1.27], p = 0.02), nurses/midwives (OR, 1.24 [95% CI 1.06-1.44], p = 0.006), and physicians (OR, 1.21 [95% CI 1.11-1.32], p ConclusionIn this study, we observed that indicators of country preparedness to deal with CVDRFs are poor proxies for quality clinical care received by patients for hypertension and diabetes. The major implication is that assessments of countries' preparedness to manage CVDRFs should not rely on proxies; rather, it should involve direct assessment of quality clinical care

Wnt/β-catenin Signalling Is Active in a Highly Dynamic Pattern during Development of the Mouse Cerebellum

The adult cerebellum is composed of several distinct cell types with well defined developmental origins. However, the molecular mechanisms that govern the generation of these cell types are only partially resolved. Wnt/β-catenin signalling has a wide variety of roles in generation of the central nervous system, though the specific activity of this pathway during cerebellum development is not well understood. Here, we present data that delineate the spatio-temporal specific pattern of Wnt/β-catenin signaling during mouse cerebellum development between E12.5 and P21. Using the BAT-gal Wnt/β-catenin reporter mouse, we found that Wnt/β-catenin activity is present transiently at the embryonic rhombic lip but not at later stages during the expansion of cell populations that arise from there. At late embryonic and early postnatal stages, Wnt/β-catenin activity shifts to the cerebellar ventricular zone and to cells arising from this germinal centre. Subsequently, the expression pattern becomes progressively restricted to Bergmann glial cells, which show expression of the reporter at P21. These results indicate a variety of potential functions for Wnt/β-catenin activity during cerebellum development

Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study

For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS–identified variants in diverse population-based studies. We genotyped 49 GWAS–identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (∼20,000), African American (∼9,000), American Indian (∼6,000), Mexican American/Hispanic (∼2,500), Japanese/East Asian (∼690), and Pacific Islander/Native Hawaiian (∼175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Obesity in adults: a 2022 adapted clinical practice guideline for Ireland

This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay

COVID-19 first lockdown as a window into language acquisition : associations between caregiver-child activities and vocabulary gains

The COVID-19 pandemic, and the resulting closure of daycare centers worldwide, led to unprecedented changes in children’s learning environments. This period of increased time at home with caregivers, with limited access to external sources (e.g., daycares) provides a unique opportunity to examine the associations between the caregiver-child activities and children’s language development. The vocabularies of 1742 children aged8-36 months across 13 countries and 12 languages were evaluated at the beginning and end of the first lockdown period in their respective countries(from March to September 2020). Children who had less passive screen exposure and whose caregivers read more to them showed larger gains in vocabulary development during lockdown, after controlling for SES and other caregiver-child activities. Children also gained more words than expected (based on normative data) during lockdown; either caregivers were more aware of their child’s development or vocabulary development benefited from intense caregiver-child interaction during lockdown