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The impact of COVID-19 on the burden of cardiovascular diseases (CVD) during the early pandemic remains unclear. COVID-19 has become one of the leading causes of global mortality, with a disproportionate impact on persons with CVD. Studies of health facility admissions for CVD found significant decreases during the pandemic. Studies of hospital mortality for CVD were more variable. Studies of population-level CVD mortality differed across countries, with most showing decreases, although some revealed increases in deaths. In some countries where large increases in CVD deaths were reported in vital registration systems, misclassification of COVID-19 as CVD may have occurred. Taken together, studies suggest heterogeneous effects of the COVID-19 pandemic on CVD without large increases in CVD mortality in 2020 for a number of countries. Clinical and population science research is needed to examine the ways in which the pandemic has affected CVD burden. [ABSTRACT FROM AUTHOR]

Adaptive radiations are known for rapid niche diversification in response to ecological opportunity. While most resources usually exist prior to adaptive radiation, novel niches associated with novel resources can be created as a clade diversifies. For example, in African lake cichlid radiations some species prey upon other species of the clade (intraclade consumers). Using a trait‐based eco‐evolutionary model, we investigate the evolution of intraclade consumers in adaptive radiations and the effect of this novel trophic interaction on the diversification process of the radiating clade. We find that the evolutionary emergence of intraclade consumers halts the diversification processes of other ecomorphs as a result of increased top‐down control of density. Because high productivity enables earlier evolution of intraclade consumers, highly productive environments come to harbour less species‐rich radiations than comparable radiations in less productive environments. Our results reveal how macroevolutionary and community patterns can emerge from ecological and microevolutionary processes. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases. [ABSTRACT FROM AUTHOR]

Oscillator systems achieve synchronization when oscillators are coupled. The presomitic mesoderm is a system of cellular oscillators, where coordinated genetic activity is necessary for proper periodic generation of somites. While Notch signaling is required for the synchronization of these cells, it is unclear what information the cells exchange and how they react to this information to align their oscillatory pace with that of their neighbors. Combining mathematical modeling and experimental data, we found that interaction between murine presomitic mesoderm cells is controlled by a phase-gated and unidirectional coupling mechanism and results in deceleration of their oscillation pace upon Notch signaling. This mechanism predicts that isolated populations of well-mixed cells synchronize, revealing a stereotypical synchronization in the mouse PSM and contradicting expectations from previously applied theoretical approaches. Collectively, our theoretical and experimental findings reveal the underlying coupling mechanisms of the presomitic mesoderm cells and provide a framework to quantitatively characterize their synchronization. [Display omitted] • "Walkie/talkie" coupling is based on unidirectional and periodic Notch signaling • Notch signaling decelerates the pace of PSM oscillations • Unidirectional and phase-gated communication synchronizes PSM oscillators • Walkie/talkie coupling brings in synchrony separate isolated cell populations Roth and Misailidis et al. propose a coupling mechanism based on unidirectional and periodic communication between oscillators, resembling a walkie/talkie system. It is based on Notch signaling properties and is applied to explain the synchronization of genetics oscillations happening in the presomitic mesoderm cells of mouse embryos. [ABSTRACT FROM AUTHOR]

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As an individual moves through its life cycle, it passes through a series of states (age classes, size classes, reproductive states, spatial locations, health statuses, etc.) before its eventual death. The occupancy time in a state is the time spent in that state over the individual’s life. Depending on the life cycle description, the occupancy times describe different demographic variables, for example, lifetime breeding success, lifetime habitat utilisation, or healthy longevity. Models based on absorbing Markov chains provide a powerful framework for the analysis of occupancy times. Current theory, however, can completely analyse only the occupancy of single states, although the occupancy time in a set of states is often desired. For example, a range of sizes in a size-classified model, an age class in an age × stage model, and a group of locations in a spatial stage model are all sets of states. We present a new mathematical approach to absorbing Markov chains that extends the analysis of life histories by providing a comprehensive theory for the occupancy of arbitrary sets of states, and for other demographic variables related to these sets (e.g., reaching time, return time). We apply this approach to a matrix population model of the Southern Fulmar ( Fulmarus glacialoides ). The analysis of this model provides interesting insight into the lifetime number of breeding attempts of this species. Our new approach to absorbing Markov chains, and its implementation in matrix oriented software, makes the analysis of occupancy times more accessible to population ecologists, and directly applicable to any matrix population models. [ABSTRACT FROM AUTHOR]

We consider ecological difference equations of the form xit+1 = xitAi(xt), where xlt is a vector of densities corresponding to the subpopulations of spec tes i (e.g., subpopulations of different ages or living in different patches), xt = (x¹t,x²t,... , xmt) is the state of the entire community, and Ai(xt) are matrices determining the update rule for species i. These equations are permanent if they are dissipative and the extinction set ... is repelling. If permanence persists under perturbations of the matrices Ai(x), the equations are robustly permanent. We provide sufficient and necessary conditions for robust permanence in terms of Lyapunov exponents for invariant measures supported by the extinction set. Applications to ecological and epidemiological models are given. [ABSTRACT FROM AUTHOR]

Background: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.Objectives: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.Methods: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.Results: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.Conclusions: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD. [ABSTRACT FROM AUTHOR]

The relationship between mRNA translation and decay is incompletely understood, with conflicting reports suggesting that translation can either promote decay or stabilize mRNAs. The effect of translation on mRNA decay has mainly been studied using ensemble measurements and global transcription and translation inhibitors, which can have pleiotropic effects. We developed a single-molecule imaging approach to control the translation of a specific transcript that enabled simultaneous measurement of translation and mRNA decay. Our results demonstrate that mRNA translation reduces mRNA stability, and mathematical modeling suggests that this process is dependent on ribosome flux. Furthermore, our results indicate that miRNAs mediate efficient degradation of both translating and non-translating target mRNAs and reveal a predominant role for mRNA degradation in miRNA-mediated regulation. Simultaneous observation of translation and decay of single mRNAs provides a framework to directly study how these processes are interconnected in cells. [Display omitted] • Active translation leads to mRNA destabilization • Ribosome flux promotes a basal level of mRNA degradation • Specialized mRNA decay pathways add to ribosome-flux-mediated degradation • miRNAs can promote mRNA degradation without prior inhibition of translation In the cytoplasm, mRNAs are translated before they are degraded, but how these processes are connected is poorly understood. Using single-molecule imaging of translation and mRNA decay in single cells, Dave et al. show that ribosome flux during translation reduces mRNA stability. [ABSTRACT FROM AUTHOR]

Importance: In the United States, regional variation in cardiovascular mortality is well-known but county-level estimates for all major cardiovascular conditions have not been produced.Objective: To estimate age-standardized mortality rates from cardiovascular diseases by county.Design and Setting: Deidentified death records from the National Center for Health Statistics and population counts from the US Census Bureau, the National Center for Health Statistics, and the Human Mortality Database from 1980 through 2014 were used. Validated small area estimation models were used to estimate county-level mortality rates from all cardiovascular diseases, including ischemic heart disease, cerebrovascular disease, ischemic stroke, hemorrhagic stroke, hypertensive heart disease, cardiomyopathy, atrial fibrillation and flutter, rheumatic heart disease, aortic aneurysm, peripheral arterial disease, endocarditis, and all other cardiovascular diseases combined.Exposures: The 3110 counties of residence.Main Outcomes and Measures: Age-standardized cardiovascular disease mortality rates by county, year, sex, and cause.Results: From 1980 to 2014, cardiovascular diseases were the leading cause of death in the United States, although the mortality rate declined from 507.4 deaths per 100 000 persons in 1980 to 252.7 deaths per 100 000 persons in 2014, a relative decline of 50.2% (95% uncertainty interval [UI], 49.5%-50.8%). In 2014, cardiovascular diseases accounted for more than 846 000 deaths (95% UI, 827-865 thousand deaths) and 11.7 million years of life lost (95% UI, 11.6-11.9 million years of life lost). The gap in age-standardized cardiovascular disease mortality rates between counties at the 10th and 90th percentile declined 14.6% from 172.1 deaths per 100 000 persons in 1980 to 147.0 deaths per 100 000 persons in 2014 (posterior probability of decline >99.9%). In 2014, the ratio between counties at the 90th and 10th percentile was 2.0 for ischemic heart disease (119.1 vs 235.7 deaths per 100 000 persons) and 1.7 for cerebrovascular disease (40.3 vs 68.1 deaths per 100 000 persons). For other cardiovascular disease causes, the ratio ranged from 1.4 (aortic aneurysm: 3.5 vs 5.1 deaths per 100 000 persons) to 4.2 (hypertensive heart disease: 4.3 vs 17.9 deaths per 100 000 persons). The largest concentration of counties with high cardiovascular disease mortality extended from southeastern Oklahoma along the Mississippi River Valley to eastern Kentucky. Several cardiovascular disease conditions were clustered substantially outside the South, including atrial fibrillation (Northwest), aortic aneurysm (Midwest), and endocarditis (Mountain West and Alaska). The lowest cardiovascular mortality rates were found in the counties surrounding San Francisco, California, central Colorado, northern Nebraska, central Minnesota, northeastern Virginia, and southern Florida.Conclusions and Relevance: Substantial differences exist between county ischemic heart disease and stroke mortality rates. Smaller differences exist for diseases of the myocardium, atrial fibrillation, aortic and peripheral arterial disease, rheumatic heart disease, and endocarditis. [ABSTRACT FROM AUTHOR]

Background: The contribution of modifiable risk factors to the increasing global and regional burden of stroke is unclear, but knowledge about this contribution is crucial for informing stroke prevention strategies. We used data from the Global Burden of Disease Study 2013 (GBD 2013) to estimate the population-attributable fraction (PAF) of stroke-related disability-adjusted life-years (DALYs) associated with potentially modifiable environmental, occupational, behavioural, physiological, and metabolic risk factors in different age and sex groups worldwide and in high-income countries and low-income and middle-income countries, from 1990 to 2013.Methods: We used data on stroke-related DALYs, risk factors, and PAF from the GBD 2013 Study to estimate the burden of stroke by age and sex (with corresponding 95% uncertainty intervals [UI]) in 188 countries, as measured with stroke-related DALYs in 1990 and 2013. We evaluated attributable DALYs for 17 risk factors (air pollution and environmental, dietary, physical activity, tobacco smoke, and physiological) and six clusters of risk factors by use of three inputs: risk factor exposure, relative risks, and the theoretical minimum risk exposure level. For most risk factors, we synthesised data for exposure with a Bayesian meta-regression method (DisMod-MR) or spatial-temporal Gaussian process regression. We based relative risks on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks, such as high body-mass index (BMI), through other risks, such as high systolic blood pressure (SBP) and high total cholesterol.Findings: Globally, 90·5% (95% UI 88·5-92·2) of the stroke burden (as measured in DALYs) was attributable to the modifiable risk factors analysed, including 74·2% (95% UI 70·7-76·7) due to behavioural factors (smoking, poor diet, and low physical activity). Clusters of metabolic factors (high SBP, high BMI, high fasting plasma glucose, high total cholesterol, and low glomerular filtration rate; 72·4%, 95% UI 70·2-73·5) and environmental factors (air pollution and lead exposure; 33·4%, 95% UI 32·4-34·3) were the second and third largest contributors to DALYs. Globally, 29·2% (95% UI 28·2-29·6) of the burden of stroke was attributed to air pollution. Although globally there were no significant differences between sexes in the proportion of stroke burden due to behavioural, environmental, and metabolic risk clusters, in the low-income and middle-income countries, the PAF of behavioural risk clusters in males was greater than in females. The PAF of all risk factors increased from 1990 to 2013 (except for second-hand smoking and household air pollution from solid fuels) and varied significantly between countries.Interpretation: Our results suggest that more than 90% of the stroke burden is attributable to modifiable risk factors, and achieving control of behavioural and metabolic risk factors could avert more than three-quarters of the global stroke burden. Air pollution has emerged as a significant contributor to global stroke burden, especially in low-income and middle-income countries, and therefore reducing exposure to air pollution should be one of the main priorities to reduce stroke burden in these countries.Funding: Bill & Melinda Gates Foundation, American Heart Association, US National Heart, Lung, and Blood Institute, Columbia University, Health Research Council of New Zealand, Brain Research New Zealand Centre of Research Excellence, and National Science Challenge, Ministry of Business, Innovation and Employment of New Zealand. [ABSTRACT FROM AUTHOR]

In 2011, the United Nations set key targets to reach by 2025 to reduce the risk of premature noncommunicable disease death by 25% by 2025. With cardiovascular disease being the largest contributor to global mortality, accounting for nearly half of the 36 million annual noncommunicable disease deaths, achieving the 2025 goal requires that cardiovascular disease and its risk factors be aggressively addressed. The Global Cardiovascular Disease Taskforce, comprising the World Heart Federation, American Heart Association, American College of Cardiology Foundation, European Heart Network, and European Society of Cardiology, with expanded representation from Asia, Africa, and Latin America, along with global cardiovascular disease experts, disseminates information and approaches to reach the United Nations 2025 targets. The writing committee, which reflects Global Cardiovascular Disease Taskforce membership, engaged the Institute for Health Metrics and Evaluation, University of Washington, to develop region-specific estimates of premature cardiovascular mortality in 2025 based on various scenarios. Results show that >5 million premature CVD deaths among men and 2.8 million among women are projected worldwide by 2025, which can be reduced to 3.5 million and 2.2 million, respectively, if risk factor targets for blood pressure, tobacco use, diabetes mellitus, and obesity are achieved. However, global risk factor targets have various effects, depending on region. For most regions, United Nations targets for reducing systolic blood pressure and tobacco use have more substantial effects on future scenarios compared with maintaining current levels of body mass index and fasting plasma glucose. However, preventing increases in body mass index has the largest effect in some high-income countries. An approach achieving reductions in multiple risk factors has the largest impact for almost all regions. Achieving these goals can be accomplished only if countries set priorities, implement cost-effective population wide strategies, and collaborate in public-private partnerships across multiple sectors. [ABSTRACT FROM AUTHOR]

Background: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is recommended before primary prevention implantable cardioverter-defibrillator (ICD) placement. Adherence to this recommendation and associated outcomes are unknown.Objectives: This study examined the use of GDMT (≥1 prescription filled for both a renin-angiotensin inhibitor [RAI] and a heart failure-approved beta-blocker [HFBB]) within 90 days before primary prevention ICD placement in patients with HFrEF.Methods: Data from the National Cardiovascular Data Registry ICD Registry were merged with a 40% random sample of Medicare administrative data. Prescription fills for recipients of primary prevention ICD between 2007 and 2011 were examined, analyzing GDMT overall and for each U.S. hospital referral region. We identified characteristics associated with GDMT and the association with 1-year mortality.Results: Among 19,733 patients with HFrEF and primary prevention ICD, 61.1% filled any GDMT before implantation. Across hospital referral regions, GDMT was applied in 51% to 71%. The strongest predictors of any GDMT included absence of chronic renal disease or nonsustained ventricular tachycardia, low-income prescription benefits subsidy, and less recent left ventricular ejection fraction evaluation. Patients receiving GDMT versus those without had a lower 1-year mortality rate after ICD implantation (11.1% vs. 16.2%), even after adjustment for comorbidities, left ventricular ejection fraction, and functional heart failure class.Conclusions: Rates of GDMT for HFrEF before primary prevention ICD implantation were low, and failure to achieve GDMT was associated with significantly decreased 1-year survival. [ABSTRACT FROM AUTHOR]

There is a global commitment to reduce premature cardiovascular diseases (CVDs) 25% by 2025. CVD mortality rates have declined dramatically over the past 2 decades, yet the number of life years lost to premature CVD deaths is increasing in low- and middle-income regions. Ischemic heart disease and stroke remain the leading causes of premature death in the world; however, there is wide regional variation in these patterns. Some regions, led by Central Asia, face particularly high rates of premature death from ischemic heart disease. Sub-Saharan Africa and Asia suffer disproportionately from death from stroke. The purpose of the present report is to (1) describe global trends and regional variation in premature mortality attributable to CVD, (2) review past and current approaches to the measurement of these trends, and (3) describe the limitations of existing models of epidemiological transitions for explaining the observed distribution and trends of CVD mortality. We describe extensive variation both between and within regions even while CVD remains a dominant cause of death. Policies and health interventions will need to be tailored and scaled for a broad range of local conditions to achieve global goals for the improvement of cardiovascular health. [ABSTRACT FROM AUTHOR]

Background: United Nations member states have agreed to reduce premature cardiovascular disease (CVD) mortality 25% by 2025. Global CVD risk factor targets have been recommended. We produced estimates to show how selected risk factor reduction would affect CVD mortality for different regions and countries.Methods and Results: We used mortality, risk factor, and relative risk data from the Global Burden of Disease, Risk Factors, and Injuries (GBD) 2013 study to project CVD mortality for 188 countries up to the year 2025. We disaggregated observed CVD mortality in 1990 and 2013 into deaths attributable and unattributable to hypertension, tobacco smoking, diabetes mellitus, and obesity using an age- and sex-specific population-attributable fraction. Risk factors were projected to 2025 assuming that current trends continue. Counterfactual scenarios were then constructed reflecting CVD premature mortality if United Nations risk factor targets are achieved in the year 2025, adjusting for joint effects of risk factors. We estimate 7.8 million premature CVD deaths in 2025 if current risk factor trends continue. Premature CVD deaths would be reduced to 5.7 million if these risk factors targets are achieved as a result of a 26% reduction for men and a 23% reduction for women in the global risk of premature CVD death. Globally, decreasing the prevalence of hypertension accounted for the largest risk reduction, followed by a reduction in tobacco smoking for men and obesity for women, but these results varied by region. The impact of meeting all risk factor targets on CVD mortality varied widely by region and sex.Conclusions: The United Nations target of a 25% reduction in premature CVD mortality by the year 2025 appears achievable for some countries, but more aggressive risk factor targets may be required if all regions are to reach this goal. Without these reductions in CVD risk factors, many countries will see no change or even an increase in premature CVD mortality. [ABSTRACT FROM AUTHOR]

The article focuses on a study of demographic and epidemiologic drivers of global cardiovascular mortality. Topics discussed include the study background and the study method, particularly, estimation of mortality and determination of drivers of cardiovascular mortality. Results, particularly, global deaths due to cardiovascular diseases, cardiovascular deaths by region, and cardiovascular deaths and national income per capita are also discussed.

To understand the interplay between environmental stochasticity and Allee effects, we analyse persistence, asymptotic extinction, and conditional persistence for stochastic difference equations. Our analysis reveals that persistence requires that the geometric mean of fitness at low densities is greater than one. When this geometric mean is less than one, asymptotic extinction occurs with high probability for low initial population densities. Additionally, if the population only experiences positive density-dependent feedbacks, conditional persistence occurs provided the geometric mean of fitness at high population densities is greater than one. However, if the population experiences both positive and negative density-dependent feedbacks, conditional persistence only occurs if environmental fluctuations are sufficiently small. We illustrate counter-intuitively that environmental fluctuations can increase the probability of persistence when populations are initially at low densities, and can cause asymptotic extinction of populations experiencing intermediate predation rates despite conditional persistence occurring at higher predation rates. [ABSTRACT FROM AUTHOR]

Individuals within any species exhibit differences in size, developmental state, or spatial location. These differences coupled with environmental fluctuations in demographic rates can have subtle effects on population persistence and species coexistence. To understand these effects, we provide a general theory for coexistence of structured, interacting species living in a stochastic environment. The theory is applicable to nonlinear, multi species matrix models with stochastically varying parameters. The theory relies on long-term growth rates of species corresponding to the dominant Lyapunov exponents of random matrix products. Our coexistence criterion requires that a convex combination of these long-term growth rates is positive with probability one whenever one or more species are at low density. When this condition holds, the community is stochastically persistent: the fraction of time that a species density goes below $$\delta >0$$ approaches zero as $$\delta $$ approaches zero. Applications to predator-prey interactions in an autocorrelated environment, a stochastic LPA model, and spatial lottery models are provided. These applications demonstrate that positive autocorrelations in temporal fluctuations can disrupt predator-prey coexistence, fluctuations in log-fecundity can facilitate persistence in structured populations, and long-lived, relatively sedentary competing populations are likely to coexist in spatially and temporally heterogenous environments. [ABSTRACT FROM AUTHOR]

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A successful method to describe the asymptotic behavior of various deterministic and stochastic processes such as asymptotically autonomous differential equations or stochastic approximation processes is to relate them to an appropriately chosen limit semiflow. Benaïm and Schreiber (2000) define a general class of such stochastic processes, which they call weak asymptotic pseudotrajectories and study their ergodic behavior. In particular, they prove that the weak* limit points of the empirical measures associated to such processes are almost surely invariant for the associated deterministic semiflow. Continuing a program started by Benaïm, Hofbauer and Sorin (2005), we generalize the ergodic results mentioned above to weak asymptotic pseudotrajectories relative to set-valued dynamical systems. [ABSTRACT FROM AUTHOR]

We consider stochastic approximation processes with constant step size whose associated deterministic system is an upper semicontinuous differential inclusion. We prove that over any finite time span, the sample paths of the stochastic process are closely approximated by a solution of the differential inclusion with high probability. We then analyze infinite horizon behavior, showing that if the process is Markov, its stationary measures must become concentrated on the Birkhoff center of the deterministic system. Our results extend those of Benaïm for settings in which the deterministic system is Lipschitz continuous and build on the work of Benaïm, Hofbauer, and Sorin for the case of decreasing step sizes. We apply our results to models of population dynamics in games, obtaining new conclusions about the medium and long run behavior of myopic optimizing agents. [ABSTRACT FROM AUTHOR]

Objective To determine the fraction of individuals with high total serum cholesterol who get diagnosed and effectively treated in eight high- and middle-income countries. Methods Using data from nationally representative health examination surveys conducted in 1998-2007, we studied a probability sample of 79039 adults aged 40-79 years from England, Germany, Japan, Jordan, Mexico, Scotland, Thailand and the United States of America. For each country we calculated the prevalence of high total serum cholesterol (total serum cholesterol ≥6.2 mmol/l or ≥ 240 mg/dl) and the mean total serum cholesterol level. We also determined the fractions of individuals being diagnosed, treated with cholesterol-lowering medication and effectively controlled (total serum cholesterol <6.2 mmol/l or < 240 mg/dl). Findings The proportion of undiagnosed individuals was highest in Thailand (78%; 95% confidence interval, CI: 74-82) and lowest in the United States (16%; 95% CI: 13-19). The fraction diagnosed but untreated ranged from 9% in Thailand (95% CI: 8-11) to 53% in Japan (95% CI: 50-57). The proportion being treated who had attained evidence of control ranged from 4% in Germany (95% CI: 3-5) to 58% in Mexico (95% CI: 54-63). Time series estimates showed improved control of high total serum cholesterol over the past two decades in England and the United States. Conclusion The percentage of people with high total serum cholesterol who are effectively treated remains small in selected high- and middle-income countries. Many of those affected are unaware of their condition. Untreated high blood cholesterol represents a missed opportunity in the face of a global epidemic of chronic diseases. [ABSTRACT FROM AUTHOR]

Abstract: An efficient synthesis of oxindole-based isoxazolines has been developed and the resulting spirocyclic intermediates have been elaborated to synthetically versatile 3-hydroxy-3-alkyl oxindole building blocks such as the 3-hydroxy-3-methylenecyano-2-oxindoles (6) and γ-amino alcohols (12). Utility of this methodology is demonstrated through the synthesis of pyrrolo[2,3-b]indolines including the marine natural product (±)-flustraminol-B. [Copyright &y& Elsevier]

Background: Spending on cardiovascular disease and cardiovascular risk factors (cardiovascular spending) accounts for a significant portion of overall US health care spending. Our objective was to describe US adult cardiovascular spending patterns in 2016, changes from 1996 to 2016, and factors associated with changes over time.Methods: We extracted information on adult cardiovascular spending from the Institute for Health Metrics and Evaluation's disease expenditure project, which combines data on insurance claims, emergency department and ambulatory care visits, inpatient and nursing care facility stays, and drug prescriptions to estimate >85% of all US health care spending. Cardiovascular spending (2016 US dollars) was stratified by age, sex, type of care, payer, and cardiovascular cause. Time trend and decomposition analyses quantified contributions of epidemiology, service price and intensity (spending per unit of utilization, eg, spending per inpatient bed-day), and population growth and aging to the increase in cardiovascular spending from 1996 to 2016.Results: Adult cardiovascular spending increased from $212 billion in 1996 to $320 billion in 2016, a period when the US population increased by >52 million people, and median age increased from 33.2 to 36.9 years. Over this period, public insurance was responsible for the majority of cardiovascular spending (54%), followed by private insurance (37%) and out-of-pocket spending (9%). Health services for ischemic heart disease ($80 billion) and hypertension ($71 billion) led to the most spending in 2016. Increased spending between 1996 and 2016 was primarily driven by treatment of hypertension, hyperlipidemia, and atrial fibrillation/flutter, for which spending rose by $42 billion, $18 billion, and $16 billion, respectively. Increasing service price and intensity alone were associated with a 51%, or $88 billion, cardiovascular spending increase from 1996 to 2016, whereas changes in disease prevalence were associated with a 37%, or $36 billion, spending reduction over the same period, after taking into account population growth and population aging.Conclusions: US adult cardiovascular spending increased by >$100 billion from 1996 to 2016. Policies tailored to control service price and intensity and preferentially reimburse higher quality care could help counteract future spending increases caused by population aging and growth. [ABSTRACT FROM AUTHOR]

The article presents contrary view in respect to views from Richard S. Cooper and his colleagues on limitations inherent in global estimates on the Global Burden of Disease (GBD) project which has made important contributions to the field of public health surveillance. The opinions on prevalence of number of deaths from coronary heart disease in Africa and Asia are also questioned.

Key Points: Question: How does maternal mortality vary by state and race and ethnicity over time in the US? Findings: Long-term trends in maternal mortality ratios from vital registration and census data were estimated. Increases in maternal mortality ratios in specific states were identified and showed previously unmeasured inequities for specific subpopulations. Meaning: Previous research has focused on trends at the national level or in selected states. Comprehensive reporting of disparities in maternal mortality provides evidence to guide intervention policies and benchmark progress for the prevention of maternal deaths. Importance: Evidence suggests that maternal mortality has been increasing in the US. Comprehensive estimates do not exist. Long-term trends in maternal mortality ratios (MMRs) for all states by racial and ethnic groups were estimated. Objective: To quantify trends in MMRs (maternal deaths per 100 000 live births) by state for 5 mutually exclusive racial and ethnic groups using a bayesian extension of the generalized linear model network. Design, Setting, and Participants: Observational study using vital registration and census data from 1999 to 2019 in the US. Pregnant or recently pregnant individuals aged 10 to 54 years were included. Main Outcomes and Measures: MMRs. Results: In 2019, MMRs in most states were higher among American Indian and Alaska Native and Black populations than among Asian, Native Hawaiian, or Other Pacific Islander; Hispanic; and White populations. Between 1999 and 2019, observed median state MMRs increased from 14.0 (IQR, 5.7-23.9) to 49.2 (IQR, 14.4-88.0) among the American Indian and Alaska Native population, 26.7 (IQR, 18.3-32.9) to 55.4 (IQR, 31.6-74.5) among the Black population, 9.6 (IQR, 5.7-12.6) to 20.9 (IQR, 12.1-32.8) among the Asian, Native Hawaiian, or Other Pacific Islander population, 9.6 (IQR, 6.9-11.6) to 19.1 (IQR, 11.6-24.9) among the Hispanic population, and 9.4 (IQR, 7.4-11.4) to 26.3 (IQR, 20.3-33.3) among the White population. In each year between 1999 and 2019, the Black population had the highest median state MMR. The American Indian and Alaska Native population had the largest increases in median state MMRs between 1999 and 2019. Since 1999, the median of state MMRs has increased for all racial and ethnic groups in the US and the American Indian and Alaska Native; Asian, Native Hawaiian, or Other Pacific Islander; and Black populations each observed their highest median state MMRs in 2019. Conclusion and Relevance: While maternal mortality remains unacceptably high among all racial and ethnic groups in the US, American Indian and Alaska Native and Black individuals are at increased risk, particularly in several states where these inequities had not been previously highlighted. Median state MMRs for the American Indian and Alaska Native and Asian, Native Hawaiian, or Other Pacific Islander populations continue to increase, even after the adoption of a pregnancy checkbox on death certificates. Median state MMR for the Black population remains the highest in the US. Comprehensive mortality surveillance for all states via vital registration identifies states and racial and ethnic groups with the greatest potential to improve maternal mortality. Maternal mortality persists as a source of worsening disparities in many US states and prevention efforts during this study period appear to have had a limited impact in addressing this health crisis. This study uses vital registration and census data from 1999 to 2019 to quantify trends in maternal mortality ratios (maternal deaths per 100 000 live births) by state for 5 mutually exclusive racial and ethnic groups in the US using a bayesian extension of the generalized linear model network. [ABSTRACT FROM AUTHOR]

Introduction: Reducing cardiovascular (CVD) health disparities is a major policy goal in the United States but comprehensive and comparable estimates of CVD disease burden do not exist. The GBD2015 study developed a method to estimate disability-adjusted life-years (DALYs) lost to CVD for each state. Hypothesis: We assessed the hypothesis that health loss due to CVD is no longer declining in the United States. Methods: We used death certificates, health surveys, commercial databases, and published literature to estimate CVD death rate and prevalence. Our analyses corrected for use of non-specific causes of death, readmission rates, and variation in the use of ICD codes. Models were run separately by age, sex, state, cause, and year. Disability weights were derived from large-scale surveys of the public. Uncertainty intervals (UI) were estimated using 1000 draws from the posterior distribution of each model. Results: In the U.S. in 2015, 13.63 million DALYs were lost due to CVD (95% UI 13.1-14.2), which accounted for 15.4% (95% UI 14.1-16.9%) of total DALYs for the United States. From 1990-2015, the annualized rate of change for CVD DALYs (per 100,000 persons) was -1.2%, but for 2010-2015, this rate was 0.5%. The smallest annualized rate of change for CVD DALYs (per 100,000, age-standardized) from 1990-2015 was observed in Oklahoma (-1.1%) while the largest change was in New York (-2.6%). For only 2010-2015, this rate declined in most states but increased in Idaho, Indiana, Mississippi, and Maine by 0.02-0.47%. Ischemic heart disease was the predominant cause of health loss for all states. Conclusions: The decline in CVD burden has slowed in all states, with rates rising in several states. Further efforts are needed to understand state-level factors influence changing rates of CVD burden. [ABSTRACT FROM AUTHOR]

The article reflects on a study performed by researcher C. Grey and others, on ingestion of statins in acute coronary syndrome (ACS) patients. Topics discussed include pharmacoepidemiology, analysis of medication possession ratio (MPR), and record linkage in pharmacotherapy population studies. Also mentions that the study included MI-FREEE (Mi-freee Post-Myocardial Infarction Free Rx Event and Economic Evaluation) trials.

This review describes trends in the burden of cardiovascular diseases (CVDs) and risk factors in India compared with the United States; provides potential explanations for these differences; and describes strategies to improve cardiovascular health behaviors, systems, and policies in India. The prevalence of CVD in India has risen over the past 2 decades due to population growth, aging, and a stable age-adjusted CVD mortality rate. Over the same time period, the United States has experienced an overall decline in age-adjusted CVD mortality, although the trend has begun to plateau. These improvements in CVD mortality in the United States are largely due to favorable population-level risk factor trends, specifically with regard to tobacco use, cholesterol, and blood pressure, although improvements in secondary prevention and acute care have also contributed. To realize similar gains in reducing premature death and disability from CVD, India needs to implement population-level policies while strengthening and integrating its local, regional, and national health systems. Achieving universal health coverage that includes financial risk protection should remain a goal to help all Indians realize their right to health. [ABSTRACT FROM AUTHOR]

Presents information on a study which described images showing the spatial distribution of nitric oxide after needle-plane pulsed negative corona discharge. Experimental details; Results and discussion.

Presents a polycyclic lactam that offers complementary selectivity upon alkylation reaction. Preparation of enolate-lactam system; Optical rotation and mechanistic activity of lactam; Verification of compound's exo selectivity.

1,3-Dipolar cycloaddition of nitrile oxides with oxoindole derivatives (I) and (IX) provides the title compounds. [ABSTRACT FROM AUTHOR]

This pilot study explores the relationship between perceived transformational leadership skills of college counselors and outcomes in counseling. College students receiving counseling (n = 46) were given a revised version of the Multifactor Leadership Questionnaire (MLQ), the Working Alliance Inventory, Short Form (WAI-S), and the Counseling Center Assessment of Psychological Symptoms (CCAPS-34). Results yielded significant relationships between improvement in areas of client functioning and subscales measuring aspects of transformational leadership in counselors as perceived by clients. In addition to significant correlations between alliance and subscales of the MLQ, there were strong negative relationships between social anxiety and management by exception (active); academic distress and idealized influence (behavior); and alcohol use and management by exception (passive). [ABSTRACT FROM PUBLISHER]

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions.Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015.Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis.Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year.Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg.Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Sorghum [Sorghum bicolor (L.) Moench] is a multipurpose crop that is highly susceptible to low temperature stress. Early season cold (ESC) greatly affects seed germination, seedling vigor, and root architecture, whereas late‐season frost (LSF) reduces fertility, yield, and nutrition quality and content in sorghum. Here, an association mapping study was conducted to delineate the genetics of ESC and LSF tolerance in sorghum. A total of 10 single nucleotide polymorphisms (SNPs) and 17 quantitative trait loci (QTL) were identified for ESC, and 40 SNPs were identified for LSF. The diversity panel exhibited extensive variation for plant traits measured for their association with ESC and LSF tolerance. Two QTL colocalized with the classical tannin genes Tan1 (S4_61580203) and Tan2 (S2_7777693) were identified for ESC tolerance. We also identified additional putative candidate genes such as Sobic.001G157100 (Nonphototropic hypocotyl 3, NPH3), Sobic.001G156600 (Lectin receptor‐like serine/threonine kinase), and Sobic.006G061100 (Sucrose nonfermenting 1 related protein kinase 1, SnRK1) for ESC tolerance and Sobic.006G139900 (UDP‐glucoronosyl and UDP‐glucosyl transferase), Sobic.002G187400 (Serine/threonine protein kinase), and Sobic.004G333700 (Ca2+/calmodulin‐dependent protein phosphatase) for LSF tolerance. Tan1 and Tan2 play a major role in seed dormancy and induce resistance against soil‐borne pathogens under cold and wet soil conditions. Seed tannin content may be used as an indirect selection marker for identifying cold tolerant germplasm for breeding. NPH3 and SnRK1 regulate seed germinability under cold stress in various crops. Candidates identified in this study could be further exploited to develop low temperature tolerant cultivars as proxies in marker‐assisted breeding, genomic selection, and genetic engineering. Core Ideas: Low temperature stress early and late in the season affects sorghum productivity tremendously.Association mapping study was conducted to uncover genes involved in low temperature tolerance.Our study identified a total of 50 SNPs and 17 QTLs for low temperature tolerance in sorghum.Two QTLs were colocalized with the classical tannin genese Tan1 and Tan2. [ABSTRACT FROM AUTHOR]

Pennsylvania farmers have a long history of harvesting corn ( Zea mays L.) stover after grain harvest for animal bedding and feed or as a component of mushroom compost, or as silage for dairy cattle feed. With the shallow soils and rolling topography, soil erosion and carbon losses have been minimized through extensive use of cover crops, no-till, and organic matter additions from animal manure. Our objective was to determine the effect of harvesting corn stover as a feedstock for bioenergy production in continuous corn or corn-soybean [ Glycine max (L.) Merr.] rotations on corn grain and stover yields, soil carbon, nitrogen, phosphorus, potassium, and the potential for cover crops to mitigate negative impacts of stover harvest. Although there was not a significant effect of stover harvest on corn grain yields in continuous corn, stover harvest tended to increase yields in years with wet springs but decreased them in dry years. Under the corn soybean rotation, 100 % stover removal always resulted in lower grain yields. The harvest index (HI) varied from 0.45 to >0.6 over the 5-year period with the lowest HI values being in response to a late summer drought and highest values being associated with an early summer drought. In most cases, 60 % soil cover was maintained in fall and spring with 50 % harvest of corn stover. Without a rye ( Secale cereale L.) cover crop, surface residue for 100 % stover harvest ranged from 20 to 30 %, whereas it was greater than 40 % when rye was established promptly in the fall. Soil carbon was similar across stover removal levels, crop rotations, and cover crops, as were soil nitrogen, phosphorus, and potassium concentrations, since nutrient removal by the grain and stover were replaced with fertilizer additions. Based on the crop yield, surface cover, and soil nutrient responses, partial stover removal could be sustainable under typical climate and management practices in Pennsylvania. [ABSTRACT FROM AUTHOR]

: In a systematic review and meta-analysis, Kazem Rahimi and colleagues examine the burden of heart failure in low- and middle-income countries. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is characterized by increased resistance in the pulmonary arterioles as a result of remodeled blood vessels. We sought all available epidemiologic data on population‐based prevalence, incidence, and 1‐year survival of PAH as part of the Global Burden of Disease Study. We performed a systematic review searching Global Index Medicus (GIM) for keywords related to PAH between 1980 and 2021 and identified population‐representative sources of prevalence, incidence, and mortality for clinically diagnosed PAH. Of 6772 articles identified we found 65 with population‐level data: 17 for prevalence, 17 for incidence, and 58 reporting case fatality. Reported prevalence ranged from 0.37 cases/100,000 persons in a referral center of French children to 15 cases/100,000 persons in an Australian study. Reported incidence ranged from 0.008 cases/100,000 person‐years in Finland, to 1.4 cases/100,000 person‐years in a retrospective chart review at a clinic in Utah, United States. Reported 1‐year survival ranged from 67% to 99%. All studies with sex‐specific estimates of prevalence or incidence reported higher levels in females than males. Studies varied in their size, study design, diagnostic criteria, and sampling procedures. Reported PAH prevalence, incidence, and mortality varied by location and study. Prevalence ranged from 0.4 to 1.4 per 100,000 persons. Harmonization of methods for PAH registries would improve efforts at disease surveillance. Results of this search contribute to ongoing efforts to quantify the global burden of PAH. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart disease (IHD) is the leading cause of death worldwide. The Global Burden of Diseases, Risk Factors and Injuries 2010 Study estimated global and regional IHD mortality from 1980 to 2010.Methods and Results: Sources for IHD mortality estimates were country-level surveillance, verbal autopsy, and vital registration data. Regional income, metabolic and nutritional risk factors, and other covariates were estimated from surveys and a systematic review. An estimation and validation process led to an ensemble model of IHD mortality for 21 world regions. Globally, age-standardized IHD mortality has declined since the 1980s, and high-income regions (especially Australasia, Western Europe, and North America) experienced the most remarkable declines. Age-standardized IHD mortality increased in former Soviet Union countries and South Asia in the 1990s and attenuated after 2000. In 2010, Eastern Europe and Central Asia had the highest age-standardized IHD mortality rates. More IHD deaths occurred in South Asia in 2010 than in any other region. On average, IHD deaths in South Asia, North Africa and the Middle East, and sub-Saharan Africa occurred at younger ages in comparison with most other regions.Conclusions: In most world regions, particularly in high-income regions, age-standardized IHD mortality rates have declined significantly since 1980. High age-standardized IHD mortality in Eastern Europe, Central Asia, and South Asia point to the need to prevent and control established risk factors in those regions and to research the unique behavioral and environmental determinants of higher IHD mortality. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart disease (IHD) burden consists of years of life lost from IHD deaths and years of disability lived with 3 nonfatal IHD sequelae: nonfatal acute myocardial infarction, angina pectoris, and ischemic heart failure. Our aim was to estimate the global and regional burden of IHD in 1990 and 2010.Methods and Results: Global and regional estimates of acute myocardial infarction incidence and angina and heart failure prevalence by age, sex, and world region in 1990 and 2010 were estimated based on data from a systematic review and nonlinear mixed-effects meta-regression methods. Age-standardized acute myocardial infarction incidence and angina prevalence decreased globally between 1990 and 2010; ischemic heart failure prevalence increased slightly. The global burden of IHD increased by 29 million disability-adjusted life-years (29% increase) between 1990 and 2010. About 32.4% of the growth in global IHD disability-adjusted life-years between 1990 and 2010 was attributable to aging of the world population, 22.1% was attributable to population growth, and total disability-adjusted life-years were attenuated by a 25.3% decrease in per capita IHD burden (decreased rate). The number of people living with nonfatal IHD increased more than the number of IHD deaths since 1990, but >90% of IHD disability-adjusted life-years in 2010 were attributable to IHD deaths.Conclusions: Globally, age-standardized acute myocardial infarction incidence and angina prevalence have decreased, and ischemic heart failure prevalence has increased since 1990. Despite decreased age-standardized fatal and nonfatal IHD in most regions since 1990, population growth and aging led to a higher global burden of IHD in 2010. [ABSTRACT FROM AUTHOR]