The claudins

Claudins are crucial components of tight junctions and are important in regulating permeability and maintaining cell polarity in cell sheets

Identifying Hipk1 as a target of Mir-22-3p enhancing recombinant protein production from Hek 293 by using microarray and Htp sirna screen

Enhancing protein production in mammalian cells is of interest in the biomedical field for a variety of reasons, including structural studies and antibody production. Using small non-protein coding RNA such as microRNA has recently been a promising method of increasing protein expression. A high throughput human microRNA screen in HEK 293 cells previously identified miRNA 22-3p as a promising candidate for increasing recombinant protein expression. This microRNA enhanced the expression of luciferase, two hard-to-express membrane proteins and a secreted hFc-fusion protein. In order to explore the mechanisms of this increase in protein production and to understand the intracellular events, we conducted a gene expression analysis of cells transfected with a mir-22-3p mimic against a negative control. Following the microarray analysis, several genes that were differentially regulated were identified. These were cross-referenced with predicted mir-22-3p targets along with the results of a high throughput siRNA screen. We will present our selected gene, HIPK1, and its possible involvement in the process of enhanced cells productivity

Climate-smart agricultural practices influence the fungal communities and soil properties under major agri-food systems

Fungal communities in agricultural soils are assumed to be affected by climate, weather, and anthropogenic activities, and magnitude of their effect depends on the agricultural activities. Therefore, a study was conducted to investigate the impact of the portfolio of management practices on fungal communities and soil physical–chemical properties. The study comprised different climate-smart agriculture (CSA)-based management scenarios (Sc) established on the principles of conservation agriculture (CA), namely, ScI is conventional tillage-based rice–wheat rotation, ScII is partial CA-based rice–wheat–mungbean, ScIII is partial CSA-based rice–wheat–mungbean, ScIV is partial CSA-based maize–wheat–mungbean, and ScV and ScVI are CSA-based scenarios and similar to ScIII and ScIV, respectively, except for fertigation method. All the scenarios were flood irrigated except the ScV and ScVI where water and nitrogen were given through subsurface drip irrigation. Soils of these scenarios were collected from 0 to 15 cm depth and analyzed by Illumina paired-end sequencing of Internal Transcribed Spacer regions (ITS1 and ITS2) for the study of fungal community composition. Analysis of 5 million processed sequences showed a higher Shannon diversity index of 1.47 times and a Simpson index of 1.12 times in maize-based CSA scenarios (ScIV and ScVI) compared with rice-based CSA scenarios (ScIII and ScV). Seven phyla were present in all the scenarios, where Ascomycota was the most abundant phyla and it was followed by Basidiomycota and Zygomycota. Ascomycota was found more abundant in rice-based CSA scenarios as compared to maize-based CSA scenarios. Soil organic carbon and nitrogen were found to be 1.62 and 1.25 times higher in CSA scenarios compared with other scenarios. Bulk density was found highest in farmers' practice (Sc1); however, mean weight diameter and water-stable aggregates were found lowest in ScI. Soil physical, chemical, and biological properties were found better under CSA-based practices, which also increased the wheat grain yield by 12.5% and system yield by 18.8%. These results indicate that bundling/layering of smart agricultural practices over farmers' practices has tremendous effects on soil properties, and hence play an important role in sustaining soil quality/health

Can agroecological transition of intensive cereal system of Indo-Gangetic plains deliver sustainable and nutritious food?

As of Jan. 18, 2023 this article is listed as a pre-print and as such has not been peer reviewed.Indo-Gangetic plains (IGP) of South Asia have supported bulk of human and bovine population in the region since ages, and a spectacular progress has been made here on food production. However, this cereal-system-dominated region still suffers with challenges of malnourishment, declining total factor productivity and natural resource degradation with potential threats of climate change. Addressing these challenges would require a transition towards agroecological cropping systems. A study was, therefore, conducted on crop diversification and sustainable intensification options using agro-ecological approaches such as Conservation Agriculture (CA) to ensure food and nutritional security while sustaining the natural resources. On 2 years mean basis, CA-based cropping system management scenarios (mean of Sc2-Sc7) using diversified rotations; increased the system yield by 15.4%, net return by 28.7%, protein yield by 29.7%while using 53.0% less irrigation water compared to conventional tillage (CT)-based rice-wheat system (Sc1). Maize-mustard-mungbean on permanent beds (Sc4) recorded the highest productivity (+40.7%), profitability (+60.1%), and saved 81.8% of irrigation water compared to Sc1 (11.8 Mg ha-1; 2190 USD ha-1; 2514 mm ha-1). It was closely followed by Sc5 (32.3, 57.4, 413.8, 75.5%) i.e. maize-wheat-mungbean on permanent beds. In terms of nutritional value, Sc5 was more balanced than other scenarios, and produced 43.8, 27.5 and 259.8% higher protein, carbohydrate and fat yields, respectively, compared to Sc1 (0.93, 8.55 and 0.14 Mg ha-1). Scenario 5 was able to meet the nutrient demand of 19, 23 and 32 more persons ha-1 year-1 with respect to protein, carbohydrate and fat demand, respectively, compared to Sc1 (44, 86 and 13 persons ha-1 year-1).However, the highest protein and fat yield and their adult equivalents was associated with Sc6 (soybean based) and Sc4 (maize based), respectively. Soybean based system (Sc6) was economically more efficient with respect to nutrients than other systems. Mungbean integration improved the system productivity by 17.2 % and profitability by 32.1%, while improving the irrigation water productivity by three times compared to CT-based systems. In western IGP, CA-based maize-wheat-mungbean system was the most productive, profitable and nutritionally rich and efficient system compared to other systems. Therefore, CA- based crop diversification is an option to ensure quality and nutritious food for the dwelling communities in the region

Diverse and healthy cropping systems trial protocol

On-Farm Research Trials are part of TAFSSA’s Work Package 2 (WP2) activities. WP2 emphasizes farm-and landscape-level interdisciplinary research to identify strategies to increase farmers’ profits and nutritional yields, conserve resources, and maintain or enhance ecological services, while also mitigating greenhouse gas (GHG) emissions from farms and agricultural landscapes. Going beyond typical agriculture-nutrition programs in South Asia, we explore field-and landscape-scale crop and animal farm diversification options supporting multiple benefits, including potential nutritional yield, across environmental and socioeconomic gradients of rice and maize-based farming systems. ICAR-CSSRI (Central Soil Salinity Research Institute) Karnal of Haryana in the northwest Indo-Gangetic Plains of India has been selected as basic research and learning site based on key information on food and nutrition security gaps, environmental stresses, air pollution due to residue burning, groundwater exploitation and climate challenges as well as the prevalence of commodities and farming systems that offer the greatest potential to achieve TAFSSA’s outcomes

A decade of climate-smart agriculture in major agri-food systems: Earthworm abundance and soil physico-biochemical properties

Earthworms (EWs) could be a viable indicator of soil biology and agri-food system management. The influence of climate-smart agriculture (CSA)-based sustainable intensification practices (zero tillage, crop rotations, crop residue retention, and precision water and nutrients application) on earthworms’ (EWs) populations and soil physico-biochemical properties of rice-wheat cropping system in the Indo-Gangetic plains of South Asia was investigated. This study investigates the effect of 10-years adoption of various CSA practices on the abundance of earthworms and physical and biochemical properties of the soil and EWs’ casts (EWC). Five scenarios (Sc) were included: conventionally managed rice-wheat system (farmers’ practices, Sc1), CSA-based rice-wheat-mungbean system with flood irrigation (FI) (Sc2) and subsurface drip irrigation (SDI) (Sc3), CSA-based maize-wheat-mungbean system with FI (Sc4), and SDI (Sc5). Results revealed that EWs were absent under Sc1, while the 10-year adoption of CSA-based scenarios (mean of Sc2–5) increased EWs’ density and biomass to be 257.7 no. m−2 and 36.05 g m−2, respectively. CSA-based maize scenarios (Sc4 and Sc5) attained higher EWs’ density and biomass over rice-based CSA scenarios (Sc2 and Sc4). Also, SDI-based scenarios (Sc3 and Sc5) recorded higher EWs’ density and biomass over FI (Sc2 and Sc4). Maize-based CSA with SDI recorded the highest EWs’ density and EWs’ biomass. The higher total organic carbon in EWC (1.91%) than in the bulk soil of CSA-based scenarios (0.98%) and farmers’ practices (0.65%) suggests the shift of crop residue to a stable SOC (in EWC). EWC contained significant amounts of C and available NPK under CSA practices, which were nil under Sc1. All CSA-based scenarios attained higher enzymes activities over Sc1. CSA-based scenarios, in particular, maize-based scenarios using SDI, improved EWs’ proliferation, SOC, and nutrients storage (in soil and EWC) and showed a better choice for the IGP farmers with respect to C sequestration, soil quality, and nutrient availability

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODErn), to generate cause fractions and cause specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NC Ds) comprised the greatest fraction of deaths, contributing to 73.4% (95% uncertainty interval [UI] 72.5-74.1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 186% (17.9-19.6), and injuries 8.0% (7.7-8.2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22.7% (21.5-23.9), representing an additional 7.61 million (7. 20-8.01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7.9% (7.08.8). The number of deaths for CMNN causes decreased by 222% (20.0-24.0) and the death rate by 31.8% (30.1-33.3). Total deaths from injuries increased by 2.3% (0-5-4-0) between 2007 and 2017, and the death rate from injuries decreased by 13.7% (12.2-15.1) to 57.9 deaths (55.9-59.2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118.0% (88.8-148.6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36.4% (32.2-40.6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33.6% (31.2-36.1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respirator}, infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990 neonatal disorders, lower respiratory infections, and diarrhoeal diseases were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe