Репозиторий Университета

The first example of an unusual addition of chromone‐substituted acrylic acid to enamines is described. The process shows high versatility concerning both enamines and chromones. The reaction is catalyzed by tertiary amines and is highly likely of Morita–Baylis–Hillman‐type. The described compounds show combined moderate inhibitory action on BChE and antagonism towards NMDA receptors which makes them a perspective group for the development of anti‐Alzheimer drugs. An unusual addition of enamines to chromone‐substituted acrylic acid is an efficient and versatile method of synthesis of allylamine derivatives. The reaction is catalyzed by amines and is highly likely of Morita–Baylis–Hillman‐type. The described compounds show combined moderate inhibitory action on BChE and antagonism towards NMDA receptors

Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs. View Full-Text

Purpose

The interaction between malignant cells and surrounding healthy tissues is a critical factor in the metastatic progression of breast cancer (BC). Extracellular vesicles, especially exosomes, are known to be involved in inter-cellular communication during cancer progression. In the study presented herein, we aimed to evaluate the role of circulating plasma exosomes in the metastatic dissemination of BC and to investigate the underlying molecular mechanisms of this phenomenon.

Methods

Exosomes isolated from plasma of healthy female donors were applied in various concentrations into the medium of MDA-MB-231 and MCF-7 cell lines. Motility and invasive properties of BC cells were examined by random migration and Transwell invasion assays, and the effect of plasma exosomes on the metastatic dissemination of BC cells was demonstrated in an in vivo zebrafish model. To reveal the molecular mechanism of interaction between plasma exosomes and BC cells, a comparison between un-treated and enzymatically modified exosomes was performed, followed by mass spectrometry, gene ontology, and pathway analysis.

Certolizumab pegol (CZP) is a PEGylated antigen-binding fragment-fragment of a humanized mAb neutralizing TNF. It lacks Fc-fragment and has a very low potential to cross the placenta. We aimed to report the efficacy and safety of CZP in a case series of patients with refractory Takayasu arteritis (TA).

Background

Small intestinal bacterial overgrowth (SIBO) was detected in cirrhosis in many studies. The aim is to perform a systematic review and meta-analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO with features of cirrhosis.

Methods

PUBMED search (until 14 January 2018) was performed. Specific search terms were: ‘(cirrhosis) AND (SIBO OR bacterial overgrowth)’. Studies not relating to cirrhosis or SIBO, animal studies, and non-original articles were excluded. A meta-analysis of all studies was performed using a random-effects model.

Results

117 references were identified by the PUBMED search. 3 references were added after handsearching the reference lists of all the articles. 99 references were excluded. 21 studies (included in total 1264 cirrhotics and 306 controls) remained for qualitative analysis and quantitative synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8–47.1), while the prevalence of SIBO for controls was 10.7% (95% CI 5.7–19.0). OR 6.83 (95% CI 4.16–11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001). SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001), and was not associated with hypocoagulation. Further studies are required to clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt hepatic encephalopathy in past, esophageal varices and systemic inflammation.

Conclusion

Small intestinal bacterial overgrowth is more often detected in cirrhosis than in healthy persons and is associated with some features of cirrhosis.

Abstract

Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally.

Methods

The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8,259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analyzed separately and then incorporated into the estimation. We analyze the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardized and improved; and the analysis has been extended backward in time by two decades to start in 1950.

Findings

Globally, 18.7% (95% uncertainty interval 18.4–19.0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58.8% (58.2–59.3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48.1 years (46.5–49.6) to 70.5 years (70.1–70.8) for men and from 52.9 years (51.7–54.0) to 75.6 years (75.3–75.9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49.1 years (46.5–51.7) for men in the Central African Republic to 87.6 years (86.9–88.1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216.0 deaths (196.3–238.1) per 1,000 livebirths in 1950 to 38.9 deaths (35.6–42.8) per 1,000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5.4 million (5.2–5.6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development.

Interpretation

This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Abstract

Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind,” it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analyzed global attainment.

Methods 

We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2.5th percentile and 100 as the 97.5th percentile of 1,000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualized rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1,000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualized rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualized rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator.

Findings

The global median health-related SDG index in 2017 was 59.4 (IQR 35.4–67.3), ranging from a low of 11.6 (95% uncertainty interval 9.6–14.0) to a high of 84.9 (83.1–86.7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For 14 indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualized rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualized rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1,000 population by 2030.

Interpretation

The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—toward multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.

Abstract

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 standardized estimates of mortality. We present single calendar-year and single-year of age estimates of fertility and population by sex with standardized and replicable methods.

Methods

We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardized 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 7,817 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 1,000 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 1,257 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 1,000 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 (i.e., 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.

Abstract

How long one lives, how many years of life are spent in good and poor health, and how the population’s state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years.

Methods

We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analyzed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males.

Findings

Globally, from 1990 to 2017, life expectancy at birth increased by 7.4 years (95% uncertainty interval 7.1–7.8), from 65.6 years (65.3–65.8) in 1990 to 73.0 years (72.7–73.3) in 2017. The increase in years of life varied from 5.1 years (5.0–5.3) in high SDI countries to 12.0 years (11.3–12.8) in low SDI countries. Of the additional years of life expected at birth, 26.3% (20.1–33.1) were expected to be spent in poor health in high SDI countries compared with 11.7% (8.8–15.1) in low-middle SDI countries. HALE at birth increased by 6.3 years (5.9–6.7), from 57.0 years (54.6–59.1) in 1990 to 63.3 years (60.5–65.7) in 2017. The increase varied from 3.8 years (3.4–4.1) in high SDI countries to 10.5 years (9.8–11.2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1.0 year (0.4–1.7) in Saint Vincent and the Grenadines (62.4 years [59.9–64.7] in 1990 to 63.5 years [60.9–65.8] in 2017) to 23.7 years (21.9–25.6) in Eritrea (30.7 years [28.9–32.2] in 1990 to 54.4 years [51.5–57.1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1.4 years (0.6–2.3) in Algeria to 11.9 years (10.9–12.9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75.8 years [72.4–78.7]) and males (72.6 years [69.8–75.0]) and the lowest estimates were in Central African Republic (47.0 years [43.7–50.2] for females and 42.8 years [40.1–45.6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardized DALY rates decreased by 41.3% (38.8–43.5) for communicable diseases and by 49.8% (47.9–51.6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40.1% (36.8–43.0), although age-standardized DALY rates decreased by 18.1% (16.0–20.2).

Interpretation

With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low SDI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximize HALE, such as risk prevention and attention to upstream determinants of health.

Abstract

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesizing evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations.

Methods

We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life years (DALYs), by age group, sex, year, and location for 84 behavioral, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46,749 randomized controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modeling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioral risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.

Findings

In 2017, 34.1 million (95% uncertainty interval [UI] 33.3–35.0) deaths and 1.21 billion (1.14–1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6–62.4) of deaths and 48.3% (46.3–50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39–11.5) deaths and 218 million (198–237) DALYs, followed by smoking (7.10 million [6.83–7.37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6.53 million [5.23–8.23] deaths and 171 million [144–201] DALYs), high body mass index (BMI; 4.72 million [2.99–6.70] deaths and 148 million [98.6–202] DALYs), and short gestation for birthweight (1.43 million [1.36–1.51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3–6.5) between 2007 and 2017. In the absence of demographic changes (i.e., population growth and aging), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardized DALY rates was high SBP in four super-regions: Central Europe, Eastern Europe, and Central Asia; North Africa and Middle East; South Asia; and Southeast Asia, East Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in North Africa and the Middle East were notably low.

Interpretation

By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and program efforts might have been successful and highlights current priorities for public health action. Decreases in behavioral, environmental, and occupational risks have largely offset the effects of population growth and aging, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population aging will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision-making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesizing data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning.

Citation:

Abstract

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 modeling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), 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-standardized.

Findings

At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) 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 18.6% (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% (7.0–8.8). The number of deaths for CMNN causes decreased by 22.2% (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, respiratory 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 diarrheal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischemic 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.

Abstract

The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an aging global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world’s population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.

Methods 

We estimated incidence and prevalence for 354 diseases and injuries and 3,484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68,781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting.

Findings 

Globally, for females, the causes with the greatest age-standardized prevalence were oral disorders, headache disorders, and hemoglobinopathies and hemolytic anemias in both 1990 and 2017. For males, the causes with the greatest age-standardized prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardized YLD rates decreased by 3.9% (95% uncertainty interval [UI] 3.1–4.6) from 1990 to 2017; however, the all-age YLD rate increased by 7.2% (6.0–8.4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1,100). The increases for males and females were similar, with increases in all-age YLD rates of 7.9% (6.6–9.2) for males and 6.5% (5.4–7.7) for females. We found significant differences between males and females in terms of age-standardized prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3,018 cases [95% UI 2,782–3,252] per 100,000 in males versus 1,400 [1,279–1,524] per 100,000 in females), transport injuries (3,322 [3,082–3,583] versus 2,336 [2,154–2,535]), and self-harm and interpersonal violence (3,265 [2,943–3,630] versus 5,643 [5,057–6,302]).

Interpretation 

Global all-cause age-standardized YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasizes how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury.

Abstract

Over the past few decades, social and economic changes have had substantial effects on health and well-being in Russia. We aimed to use data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to evaluate trends in mortality, causes of death, years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and associated risk factors in Russia from 1980 to 2016.

Methods

We estimated all-cause mortality by use of a multistage modeling process that synthesized data from vital registration systems, surveys, and censuses. A composite measure of health loss due to both fatal and non-fatal disease burden (DALYs) was calculated as the sum of YLLs and YLDs for each age, sex, year, and location. Health progress was evaluated in comparison with patterns of change in similar countries by use of the Socio-demographic Index that was developed for GBD 2016.

Findings

Following rapid decreases in life expectancy after the collapse of the Soviet Union, life expectancy at birth in Russia improved between 2006 and 2016. The all-cause mortality rate decreased by 16.6% (95% uncertainty interval 9.4–33.8) between 1980 and 2016. This overall decrease encompasses the cycles of sharp increases and plateaus in mortality that occurred before 2005. Child mortality decreased by 57.5% (53.5–61.1) between 2000 and 2016. However, compared with countries at similar Socio-demographic Index levels, rates of mortality and disability in Russia remain high and life expectancy is low. Russian men have a disproportionate burden of disease relative to women. In 2016, 59.2% (55.3–62.6) of mortality in men aged 15–49 years and 46.8% (44.5–49.5) of mortality in women were attributable to behavioral risk factors, including alcohol use, drug use, and smoking.

Interpretation

Trends in mortality in Russia from 1980 to 2016 might be related to complicated patterns of behavioral risk factors associated with economic and social change, to shifts in disease burden, and to changes in the capacity of and access to health care. Ongoing mortality and disability from causes and risks amenable to health care interventions and behavior modifications present opportunities to continue to improve the well-being of Russian citizens.

Abstract

Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for five-year age groups between the ages of 15 years and 95 years and older.

Methods

Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.

Findings

Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5–3.0) of age-standardized female deaths and 6.8% (5.8–8.0) of age-standardized male deaths. Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2–4.3) of female deaths and 12.2% (10.8–13.6) of male deaths attributable to alcohol use. For the population aged 15–49 years, female attributable DALYs were 2.3% (95% UI 2.0–2.6) and male attributable DALYs were 8.9% (7.8–9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1.0–1.7] of total deaths), road injuries (1.2% [0.7–1.9]), and self-harm (1.1% [0.6–1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2–33.3) of total alcohol-attributable female deaths and 18.9% (15.3–22.6) of male deaths. The level of alcohol consumption that minimized harm across health outcomes was zero (95% UI 0.0–0.8) standard drinks per week.

Interpretation

Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimizes health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.

Laboratory of Nanomaterials, Skolkovo Institute of Science and Technology, Nobel str 3, Moscow, 143025, Russia.

The integration of energy harvesting and energy storage in a single device both enables the conversion of ambient energy into electricity and provides a sustainable power source for various electronic devices and systems. On the other hand, mechanical flexibility, coupled with optical transparency of the energy storage devices, is required for many applications, ranging from self-powered rolled-up displays to wearable optoelectronic devices. We integrate a piezoelectric poly(vinylidene-trifluoroethylene) (P(VDF-TrFE)) film into a flexible supercapacitor system to harvest and store the energy. The asymmetric output characteristics of the piezoelectric P(VDF-TrFE) film under mechanical impacts results in effective charging of the supercapacitors. The integrated piezo-supercapacitor exhibits a specific capacitance of 50 F g. The open-circuit voltage of the flexible and transparent supercapacitor reached 500 mV within 20 s during the mechanical action. Our hybridized energy harvesting and storage device can be further extended to provide a sustainable power source for various types of sensors integrated into wearable units.

Using Landau-Ginzburg-Devonshire (LGD) theory for BiFeO3 dense fine-grained ceramics with quasispherical grains and nanosized intergrain spaces enriched by elastic defects, we calculated a surprisingly strong size-induced increase in the antiferromagnetic transition temperature caused by the joint action of rotomagnetic and magnetostrictive coupling. Notably, all parameters included in the LGD functional have been extracted from experiments, not assumed. Complementarily, we performed experiments for dense BiFeO3 ceramics, which revealed that the shift of the antiferromagnetic transition is to TN∼690K instead of TN∼645K for a single crystal. To explain the result theoretically, we consider the possibility of controlling the antiferromagnetic state of multiferroic BiFeO3 via biquadratic antiferrodistortive rotomagnetic, rotoelectric, magnetoelectric, and magnetostrictive couplings. According to our calculations, the highest contribution is the rotostriction contribution, while the magnetostrictive and electrostriction contributions appear smaller.

Using Landau-Ginzburg-Devonshire (LGD) theory for BiFeO3 dense fine-grained ceramics with quasispherical grains and nanosized intergrain spaces enriched by elastic defects, we calculated a surprisingly strong size-induced increase in the antiferromagnetic transition temperature caused by the joint action of rotomagnetic and magnetostrictive coupling. Notably, all parameters included in the LGD functional have been extracted from experiments, not assumed. Complementarily, we performed experiments for dense BiFeO3 ceramics, which revealed that the shift of the antiferromagnetic transition is to TN∼690K instead of TN∼645K for a single crystal. To explain the result theoretically, we consider the possibility of controlling the antiferromagnetic state of multiferroic BiFeO3 via biquadratic antiferrodistortive rotomagnetic, rotoelectric, magnetoelectric, and magnetostrictive couplings. According to our calculations, the highest contribution is the rotostriction contribution, while the magnetostrictive and electrostriction contributions appear smaller.

The present communication aims at determining an optimum method of manufacture of orthopaedic arch titanium alloy dentures that would not cause galvano-sis in patients using such dentures. A clinical random-ized controlled retrospective study was conducted. Sixty patients who used arch titanium alloy dentures were examined. Three measurements of electrochemi-cal potentials in various areas of the oral cavity were done in all patients, using a biopotentiometer. Linear prediction of differences in potentials in measurement areas 1–3 for the control group (CG) of patients exhibited minor growth dynamics, which can be indicative of the risk of galvanosis in CG patients in the future.

This article presents a dataset for calculating the index of inclusive growth in the regions of the Russian Federation, estimated on key and institutional foundations of the performance of inclusive development. The authors of the research used the methodology of the World Economic Bank and the World Economic Forum, based on a comparative analysis of key and institutional indicators of the performance of territorial entities, which they adapted to the socio-economic features of the regional division of Russia. For the purpose of formation of a dataset was executed assessment of the inclusive growth index for 26 regions of the Russian Federation, it allowed to define the strengths and weaknesses of the inclusive development of each region of the Russian Federation. The dataset can be useful in the formation of strategic programs of inclusive development.