All Papers

Iqbal H. Sarker

Deep learning (DL), a branch of machine learning (ML) and artificial intelligence (AI) is nowadays considered as a core technology of today's Fourth Industrial Revolution (4IR or Industry 4.0). Due to its learning capabilities from data, DL technology originated from artificial neural network (ANN), has become a hot topic in the context of computing, and is widely applied in various application areas like healthcare, visual recognition, text analytics, cybersecurity, and many more. However, building an appropriate DL model is a challenging task, due to the dynamic nature and variations in real-world problems and data. Moreover, the lack of core understanding turns DL methods into black-box machines that hamper development at the standard level. This article presents a structured and comprehensive view on DL techniques including a taxonomy considering various types of real-world tasks like supervised or unsupervised. In our taxonomy, we take into account deep networks for supervised or discriminative learning , unsupervised or generative learning as well as hybrid learning and relevant others. We also summarize real-world application areas where deep learning techniques can be used. Finally, we point out ten potential aspects for future generation DL modeling with research directions . Overall, this article aims to draw a big picture on DL modeling that can be used as a reference guide for both academia and industry professionals.

Ehsanul Kabir, Pawan Kumar, Sandeep Kumar, Adedeji A. Adelodun et al.

Ting Shi, David McAllister, Katherine L. O’Brien, Eric A. F. Simões et al.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Ki‐Hyun Kim, Shamin Ara Jahan, Ehsanul Kabir, Richard J. C. Brown

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds comprised of two or more fused benzene rings arranged in various configurations. PAHs are widespread environmental contaminants formed as a result of incomplete combustion of organic materials such as fossil fuels. The occurrence of PAHs in ambient air is an increasing concern because of their carcinogenicity and mutagenicity. Although emissions and allowable concentrations of PAHs in air are now regulated, the health risk posed by PAH exposure suggests a continuing need for their control through air quality management. In light of the environmental significance of PAH exposure, this review offers an overview of PAH properties, fates, transformations, human exposure, and health effects (acute and chronic) associated with their emission to the atmosphere. Biomarkers of PAH exposure and their significance are also discussed.

Zulfiqar A Bhutta, Tahmeed Ahmed, Robert E. Black, Simon Cousens et al.

We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.

Elizabeth A. Ashley, Mehul Dhorda, Rick M. Fairhurst, Chanaki Amaratunga et al.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).

Nabil Ibtehaz, M. Sohel Rahman

In recent years Deep Learning has brought about a breakthrough in Medical Image Segmentation. In this regard, U-Net has been the most popular architecture in the medical imaging community. Despite outstanding overall performance in segmenting multimodal medical images, through extensive experimentations on some challenging datasets, we demonstrate that the classical U-Net architecture seems to be lacking in certain aspects. Therefore, we propose some modifications to improve upon the already state-of-the-art U-Net model. Following these modifications, we develop a novel architecture, MultiResUNet, as the potential successor to the U-Net architecture. We have tested and compared MultiResUNet with the classical U-Net on a vast repertoire of multimodal medical images. Although only slight improvements in the cases of ideal images are noticed, remarkable gains in performance have been attained for the challenging ones. We have evaluated our model on five different datasets, each with their own unique challenges, and have obtained a relative improvement in performance of 10.15%, 5.07%, 2.63%, 1.41%, and 0.62% respectively. We have also discussed and highlighted some qualitatively superior aspects of MultiResUNet over classical U-Net that are not really reflected in the quantitative measures.

Mirza Hasanuzzaman, Kamrun Nahar, Md. Shahidul Alam, Rajib Roychowdhury et al.

High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adaptive, avoidance, or acclimation mechanisms to cope with HT situations. In addition, major tolerance mechanisms that employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control are activated to offset stress-induced biochemical and physiological alterations. Plant survival under HT stress depends on the ability to perceive the HT stimulus, generate and transmit the signal, and initiate appropriate physiological and biochemical changes. HT-induced gene expression and metabolite synthesis also substantially improve tolerance. The physiological and biochemical responses to heat stress are active research areas, and the molecular approaches are being adopted for developing HT tolerance in plants. This article reviews the recent findings on responses, adaptation, and tolerance to HT at the cellular, organellar, and whole plant levels and describes various approaches being taken to enhance thermotolerance in plants.

Amy H.Y. Tong, Marie Evangelista, Ainslie B. Parsons, Hong Xu et al.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

Kashif Abbass, Muhammad Qasim, Huaming Song, Muntasir Murshed et al.

Climate change is a long-lasting change in the weather arrays across tropics to polls. It is a global threat that has embarked on to put stress on various sectors. This study is aimed to conceptually engineer how climate variability is deteriorating the sustainability of diverse sectors worldwide. Specifically, the agricultural sector’s vulnerability is a globally concerning scenario, as sufficient production and food supplies are threatened due to irreversible weather fluctuations. In turn, it is challenging the global feeding patterns, particularly in countries with agriculture as an integral part of their economy and total productivity. Climate change has also put the integrity and survival of many species at stake due to shifts in optimum temperature ranges, thereby accelerating biodiversity loss by progressively changing the ecosystem structures. Climate variations increase the likelihood of particular food and waterborne and vector-borne diseases, and a recent example is a coronavirus pandemic. Climate change also accelerates the enigma of antimicrobial resistance, another threat to human health due to the increasing incidence of resistant pathogenic infections. Besides, the global tourism industry is devastated as climate change impacts unfavorable tourism spots. The methodology investigates hypothetical scenarios of climate variability and attempts to describe the quality of evidence to facilitate readers’ careful, critical engagement. Secondary data is used to identify sustainability issues such as environmental, social, and economic viability. To better understand the problem, gathered the information in this report from various media outlets, research agencies, policy papers, newspapers, and other sources. This review is a sectorial assessment of climate change mitigation and adaptation approaches worldwide in the aforementioned sectors and the associated economic costs. According to the findings, government involvement is necessary for the country’s long-term development through strict accountability of resources and regulations implemented in the past to generate cutting-edge climate policy. Therefore, mitigating the impacts of climate change must be of the utmost importance, and hence, this global threat requires global commitment to address its dreadful implications to ensure global sustenance.

Ami D. Sperber, Shrikant I. Bangdiwala, Douglas A. Drossman, Uday C. Ghoshal et al.

BACKGROUND & AIMS Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on healthcare systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS Data were collected via the internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for internet and household groups, so data analyses were conducted and reported separately. RESULTS Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.7% persons who completed the internet surveys (95% CI, 40.2-41.1) and 20.9% of persons who completed the household surveys. FGIDs were more prevalent among women than men, based on responses to the internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.4; 95% CI, 1.3-1.5). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS In a large-scale multi-national study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and healthcare use. Although the absolute prevalence was higher among internet respondents, similar trends and relative distributions were found in people who completed internet vs personal interviews.

Cynthia Enloe

In this brand new radical analysis of globalization, Cynthia Enloe examines recent events—Bangladeshi garment factory deaths, domestic workers in the Persian Gulf, Chinese global tourists, and the UN gender politics of guns—to reveal the crucial role of women in international politics today. With all new and updated chapters, Enloe describes how many women's seemingly personal strategies—in their marriages, in their housework, in their coping with ideals of beauty—are, in reality, the stuff of global politics. Enloe offers a feminist gender analysis of the global politics of both masculinities and femininities, dismantles an apparently overwhelming world system, and reveals that system to be much more fragile and open to change than we think.

Kevin D. Haggerty, Richard V. Ericson

George Orwell's 'Big Brother' and Michel Foucault's 'panopticon' have dominated discussion of contemporary developments in surveillance. While such metaphors draw our attention to important attributes of surveillance, they also miss some recent dynamics in its operation. The work of Gilles Deleuze and Felix Guattari is used to analyse the convergence of once discrete surveillance systems. The resultant 'surveillant assemblage' operates by abstracting human bodies from their territorial settings, and separating them into a series of discrete flows. These flows are then reassembled in different locations as discrete and virtual 'data doubles'. The surveillant assemblage transforms the purposes of surveillance and the hierarchies of surveillance, as well as the institution of privacy.

Ki‐Hyun Kim, Ehsanul Kabir, Shamin Ara Jahan

Pesticides are used widely to control weeds and insect infestation in agricultural fields and various pests and disease carriers (e.g., mosquitoes, ticks, rats, and mice) in houses, offices, malls, and streets. As the modes of action for pesticides are not species-specific, concerns have been raised about environmental risks associated with their exposure through various routes (e.g., residues in food and drinking water). Although such hazards range from short-term (e.g., skin and eye irritation, headaches, dizziness, and nausea) to chronic impacts (e.g., cancer, asthma, and diabetes), their risks are difficult to elucidate due to the involvement of various factors (e.g., period and level of exposure, type of pesticide (regarding toxicity and persistence), and the environmental characteristics of the affected areas). There are no groups in the human population that are completely unexposed to pesticides while most diseases are multi-causal to add considerable complexity to public health assessments. Hence, development of eco-friendly pesticide alternatives (e.g., EcoSMART) and Integrated Pest Management (IPM) techniques is desirable to reduce the impacts of pesticides. This paper was hence organized to present a comprehensive review on pesticides with respect to their types, environmental distribution, routes of exposure, and health impacts.

Christopher J L Murray, Ryan M Barber, Kyle J Foreman, Ayşe Abbasoğlu Özgören et al.

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

A H Smith, Elena O. Lingas, Mizanur Rahman

The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. This paper describes the history of the discovery of arsenic in drinking-water in Bangladesh and recommends intervention strategies. Tube-wells were installed to provide "pure water" to prevent morbidity and mortality from gastrointestinal disease. The water from the millions of tube-wells that were installed was not tested for arsenic contamination. Studies in other countries where the population has had long-term exposure to arsenic in groundwater indicate that 1 in 10 people who drink water containing 500 micrograms of arsenic per litre may ultimately die from cancers caused by arsenic, including lung, bladder and skin cancers. The rapid allocation of funding and prompt expansion of current interventions to address this contamination should be facilitated. The fundamental intervention is the identification and provision of arsenic-free drinking water. Arsenic is rapidly excreted in urine, and for early or mild cases, no specific treatment is required. Community education and participation are essential to ensure that interventions are successful; these should be coupled with follow-up monitoring to confirm that exposure has ended. Taken together with the discovery of arsenic in groundwater in other countries, the experience in Bangladesh shows that groundwater sources throughout the world that are used for drinking-water should be tested for arsenic.

Salim Yusuf, Philip Joseph, Sumathy Rangarajan, Shofiqul Islam et al.

Background: Global estimates of the impact of common modifiable risk factors on cardiovascular disease (CVD) and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methodology to prospectively evaluate the impact of modifiable risk factors on CVD and mortality across 21 countries (spanning five continents) at different economic levels. Methods: In a multi-national, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and major CVD in 155,722 community-dwelling participants (ages 35–70 years at enrollment) from 21 high-, middle-, or low-income countries (HIC, MIC or LIC) followed for a median of 9·5 years. We describe the prevalence, hazard ratios, and population attributable fractions (PAFs) for CVD and mortality associated with a cluster of behavioural factors (i.e. tobacco, alcohol, diet, physical activity and sodium intake), metabolic factors (i.e. lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (i.e. education, symptoms of depression), strength, household (solid fuel for cooking) and ambient PM 2·5 air pollution. Findings: Mean age of the population was 50·2 years of age, 58·3% were female, 52·6% were from urban areas, 11·1% from HIC, 65·9% from MIC, and 23·0% from LIC. Over 70% of CVD cases and deaths in the overall cohort were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for CVD (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12.5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for CVD (although different statistical methods were used for this analysis). In MIC and LIC, the importance of household air pollution, poor diet, low education, and low grip strength were larger compared with HIC. Interpretation: The majority of CVD cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global impacts (e.g. hypertension, education), others (e.g. household air pollution, poor diet) vary by a country’s economic level. Health policies should focus on risk factors that have the greatest effects on averting CVD and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.

Darryl P. Leong, Koon Teo, Sumathy Rangarajan, Patricio López‐Jaramillo et al.

BACKGROUND Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries. METHODS The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally. FINDINGS Between January, 2003, and December, 2009, a total of 142,861 participants were enrolled in the PURE study, of whom 139,691 with known vital status were included in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%) of 139,691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1.16, 95% CI 1.13-1.20; p<0.0001), cardiovascular mortality (1.17, 1.11-1.24; p<0.0001), non-cardiovascular mortality (1.17, 1.12-1.21; p<0.0001), myocardial infarction (1.07, 1.02-1.11; p=0.002), and stroke (1.09, 1.05-1.15; p<0.0001). Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure. We found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated (0.916, 0.880-0.953; p<0.0001), but this association was not found in middle-income and low-income countries. INTERPRETATION This study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease. Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease. FUNDING Full funding sources listed at end of paper (see Acknowledgments).

Susan Walker, Theodore D. Wachs, Sally Grantham‐McGregor, Maureen M. Black et al.

Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.