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

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

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 programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing 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 synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Growth Inhibitory Activity Of A Novel Lectin From Cliona Varians Against K562 Human Erythroleukemia Cells

Purpose: In this study, the antitumoral potential of a novel lectin (CvL) purified from the marine sponge Cliona varians was studied in different cancer cell lines. Methods: CvL cytotoxicity was evaluated in mammalian tumor cells and in normal human peripheral blood lymphocytes by the MTT assay using the same range of concentrations (1-150 μg ml-1). The mechanisms involved in K562 cell death were investigated by confocal fluorescence microscopy, flow cytometry and immunoblot. Results: CvL inhibited the growth of human leukemia cells, with IC50 values of 70 and 100 μg ml-1 for K562 and JURKAT cells, respectively, but it was ineffective on blood lymphocytes and solid tumor cell lines. K562 cell death occurred 72 h after exposure to the lectin and with signs of apoptosis, as analyzed by DAPI and annexin V/PI staining. Investigation of the possible mediators of this process showed that cell death occurred via a caspase-independent pathway. Confocal fluorescence microscopy indicated a pivotal role for the lysosomal protease cathepsin B in mediating cell death. Accordingly, pre-incubation of K562 cells with the cathepsin inhibitor l-trans-epoxysuccinyl-l-leucylamido-(4-guanidino)butane (E-64) abolished CvL cytotoxic effect. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B (NFκB) expression in CvL-treated cells. These effects were accompanied by increased levels of p21 and reduced expression of pRb, suggesting that CvL can induce cell cycle arrest. 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carbohydrates and their binding proteins (lectins) in tumor metastasis (2001) Cancer Metastasis Rev, 20, pp. 245-277Opric, M.M., Poznanovic, S., Kljajic, Z., Sladic, D., Pupic, G., Perunovic, B., Gasic, M.J., Labelling of breast carcinoma, thyroid carcinoma and melanoma with manno- and galacto-specific lectins from marine invertebrates (1996) Eur J Histochem, 40, pp. 211-218Bantel, H., Engels, I.H., Voelter, W., Schulze-Osthoff, K., Wesselborg, S., Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis (1999) Cancer Res, 59, pp. 2083-2090Miyoshi, N., Koyama, Y., Katsuno, Y., Hayakawa, S., Mita, T., Ohta, T., Kaji, K., Isemura, M., Apoptosis induction associated with cell cycle dysregulation by rice bran agglutinin (2001) J Biochem (Tokyo), 130, pp. 799-805Ohba, H., Moriwaki, S., Bakalova, R., Yasuda, S., Yamasaki, N., Plant-derived abrin-a induces apoptosis in cultured leukemic cell lines by different 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THE RATIONALE FOR GOVERNMENT INTERVENTION IN SELLER-CONSUMER RELATIONSHIPS

Government intervention in the form of consumer protection is appropriate where consumers have less than the required amount of information to protect themselves, where transaction costs act to reduce consumer self-protection below acceptable levels, where consumer welfare is not sufficiently considered in oligopolistic markets, where private costs and social costs diverge due to externalities, where a certain level of quality assurance is necessary if markets are to function and where riskier products removal from the market lowers firms' insurance premiums as well as serves the interest of public health and safety. Consumer protection is a public good which will not be available in optimal quantities without government intervention. Copyright 1983 by The Policy Studies Organization.