Observations of chemical differentiation in clumpy molecular clouds

We have extensively mapped a sample of dense molecular clouds (L1512, TMC-1C, L1262, Per 7, L1389, L1251E) in lines of HC3N, CH3OH, SO and C^{18}O. We demonstrate that a high degree of chemical differentiation is present in all of the observed clouds. We analyse the molecular maps for each cloud, demonstrating a systematic chemical differentiation across the sample, which we relate to the evolutionary state of the cloud. We relate our observations to the cloud physical, kinematical and evolutionary properties, and also compare them to the predictions of simple chemical models. The implications of this work for understanding the origin of the clumpy structures and chemical differentiation observed in dense clouds are discussed.Comment: 20 pages, 7 figures. Higher quality figures appear in the published journal articl

Genome resequencing reveals multiscale geographic structure and extensive linkage disequilibrium in the forest tree Populus trichocarpa

This is the publisher’s final pdf. The article is copyrighted by the New Phytologist Trust and published by John Wiley & Sons, Inc. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291469-8137. To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.•Plant population genomics informs evolutionary biology, breeding, conservation and bioenergy feedstock development. For example, the detection of reliable phenotype–genotype associations and molecular signatures of selection requires a detailed knowledge about genome-wide patterns of allele frequency variation, linkage disequilibrium and recombination.\ud •We resequenced 16 genomes of the model tree Populus trichocarpa and genotyped 120 trees from 10 subpopulations using 29 213 single-nucleotide polymorphisms.\ud •Significant geographic differentiation was present at multiple spatial scales, and range-wide latitudinal allele frequency gradients were strikingly common across the genome. The decay of linkage disequilibrium with physical distance was slower than expected from previous studies in Populus, with r² dropping below 0.2 within 3–6 kb. Consistent with this, estimates of recent effective population size from linkage disequilibrium (N[subscript e] ≈ 4000–6000) were remarkably low relative to the large census sizes of P. trichocarpa stands. Fine-scale rates of recombination varied widely across the genome, but were largely predictable on the basis of DNA sequence and methylation features.\ud •Our results suggest that genetic drift has played a significant role in the recent evolutionary history of P. trichocarpa. Most importantly, the extensive linkage disequilibrium detected suggests that genome-wide association studies and genomic selection in undomesticated populations may be more feasible in Populus than previously assumed

Anthropogenic Disturbance and Population Viability of Woodland Caribou in Ontario

One of the most challenging tasks in wildlife conservation and management is to clarify how spatial variation in land cover due to anthropogenic disturbance influences wildlife demography and long‐term viability. To evaluate this, we compared rates of survival and population growth by woodland caribou (Rangifer tarandus caribou) from 2 study sites in northern Ontario, Canada that differed in the degree of anthropogenic disturbance because of commercial logging and road development, resulting in differences in predation risk due to gray wolves (Canis lupus). We used an individual‐based model for population viability analysis (PVA) that incorporated adaptive patterns of caribou movement in relation to predation risk and food availability to predict stochastic variation in rates of caribou survival. Field estimates of annual survival rates for adult female caribou in the unlogged ( x̄ = 0.90) and logged ( x̄ = 0.76) study sites recorded during 2010–2014 did not differ significantly (P \u3e 0.05) from values predicted by the individual‐based PVA model (unlogged:  x̄ = 0.87; logged:  x̄ = 0.79). Outcomes from the individual‐based PVA model and a simpler stage‐structured matrix model suggest that substantial differences in adult survival largely due to wolf predation are likely to lead to long‐term decline of woodland caribou in the commercially logged landscape, whereas the unlogged landscape should be considerably more capable of sustaining caribou. Estimates of population growth rates (λ) for the 2010–2014 period differed little between the matrix model and the individual‐based PVA model for the unlogged (matrix model  x̄ = 1.01; individual‐based model x̄ = 0.98) and logged landscape (matrix model x̄ = 0.88; individual‐based model x̄ = 0.89). We applied the spatially explicit PVA model to assess the viability of woodland caribou across 14 woodland caribou ranges in Ontario. Outcomes of these simulations suggest that woodland caribou ranges that have experienced significant levels of commercial forestry activities in the past had annual growth rates 0.96. These differences were strongly related to regional variation in wolf densities. Our results suggest that increased wolf predation risk due to anthropogenic disturbance is of sufficient magnitude to cause appreciable risk of population decline in woodland caribou in Ontario. © 2020 The Authors. The Journal of Wildlife Management published by Wiley Periodicals, Inc. on behalf of The Wildlife Society

Bacterial Pneumonias during an Influenza Pandemic: How Will We Allocate Antibiotics?

We are currently in the midst of the 2009 H1N1 pandemic, and a second wave of flu in the fall and winter could lead to more hospitalizations for pneumonia. Recent pathologic and historic data from the 1918 influenza pandemic confirms that many, if not most, of the deaths in that pandemic were a result of secondary bacterial pneumonias. This means that a second wave of 2009 H1N1 pandemic influenza could result in a widespread shortage of antibiotics, making these medications a scarce resource. Recently, our University of Michigan Health System (UMHS) Scarce Resource Allocation Committee (SRAC) added antibiotics to a list of resources (including ventilators, antivirals, vaccines) that might become scarce during an influenza pandemic. In this article, we summarize the data on bacterial pneumonias during the 1918 influenza pandemic, discuss the possible impact of a pandemic on the University of Michigan Health System, and summarize our committee's guiding principles for allocating antibiotics during a pandemic.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78141/1/bsp.2009.0019.pd

Rationale and design of the Kanyini guidelines adherence with the polypill (Kanyini-GAP) study: a randomised controlled trial of a polypill-based strategy amongst Indigenous and non Indigenous people at high cardiovascular risk

<p>Abstract</p> <p>Background</p> <p>The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP) Study aims to examine whether a polypill-based strategy (using a single capsule containing aspirin, a statin and two blood pressure-lowering agents) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline-indicated therapies, and lower blood pressure and cholesterol levels.</p> <p>Methods/Design</p> <p>The study is an open, randomised, controlled, multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practices and Aboriginal Medical Services, followed for an average of 18 months. The participants will be randomised to one of two versions of the polypill, the version chosen by the treating health professional according to clinical features of the patient, or to usual care. The primary study outcomes will be changes, from baseline measures, in serum cholesterol and systolic blood pressure and self-reported current use of aspirin, a statin and at least two blood pressure lowering agents. Secondary study outcomes include cardiovascular events, renal outcomes, self-reported barriers to indicated therapy, prescription of indicated therapy, occurrence of serious adverse events and changes in quality-of-life. The trial will be supplemented by formal economic and process evaluations.</p> <p>Discussion</p> <p>The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated.</p> <p>Trial Registration</p> <p>This trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN126080005833347.</p

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review.

BACKGROUND: Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. METHODS: A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. FINDINGS: This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. CONCLUSIONS: There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.This work was funded by the National Institute for Health and Care Excellence (NICE), invitation to tender reference DDER 42013, and supported by the National Institute for Health Research School for Public Health Research. The scope of the work was defined by NICE and the protocol was agreed with NICE prior to the start of work. The funders had no role in data analysis, preparation of the manuscript or decision to publish.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014440

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Genome resequencing reveals multiscale geographic structure and extensive linkage disequilibrium in the forest tree Populus trichocarpa

•Plant population genomics informs evolutionary biology, breeding, conservation and bioenergy feedstock development. For example, the detection of reliable phenotype–genotype associations and molecular signatures of selection requires a detailed knowledge about genome-wide patterns of allele frequency variation, linkage disequilibrium and recombination. •We resequenced 16 genomes of the model tree Populus trichocarpa and genotyped 120 trees from 10 subpopulations using 29 213 single-nucleotide polymorphisms. •Significant geographic differentiation was present at multiple spatial scales, and range-wide latitudinal allele frequency gradients were strikingly common across the genome. The decay of linkage disequilibrium with physical distance was slower than expected from previous studies in Populus, with r² dropping below 0.2 within 3–6 kb. Consistent with this, estimates of recent effective population size from linkage disequilibrium (N[subscript e] ≈ 4000–6000) were remarkably low relative to the large census sizes of P. trichocarpa stands. Fine-scale rates of recombination varied widely across the genome, but were largely predictable on the basis of DNA sequence and methylation features. •Our results suggest that genetic drift has played a significant role in the recent evolutionary history of P. trichocarpa. Most importantly, the extensive linkage disequilibrium detected suggests that genome-wide association studies and genomic selection in undomesticated populations may be more feasible in Populus than previously assumed.This is the publisher’s final pdf. The article is copyrighted by the New Phytologist Trust and published by John Wiley & Sons, Inc. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291469-8137Keywords: recombination., allele frequency gradients, linkage disequilibrium (LD), population structure, black cottonwood (Populus trichocarpa), genome resequencin

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

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\ub71 (95% UI 95\ub78-98\ub71) in Iceland, followed by 96\ub76 (94\ub79-97\ub79) in Norway and 96\ub71 (94\ub75-97\ub73) in the Netherlands, to values as low as 18\ub76 (13\ub71-24\ub74) in the Central African Republic, 19\ub70 (14\ub73-23\ub77) in Somalia, and 23\ub74 (20\ub72-26\ub78) 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\ub75 (89\ub71-93\ub76) in Beijing to 48\ub70 (43\ub74-53\ub72) in Tibet (a 43\ub75-point difference), while India saw a 30\ub78-point disparity, from 64\ub78 (59\ub76-68\ub78) in Goa to 34\ub70 (30\ub73-38\ub71) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4\ub78-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\ub79-point to 17\ub70-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17\ub72-point to 20\ub74-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