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In the past two decades, the under-5 mortality rate in China has fallen substantially, but progress with regards to the Millennium Development Goal (MDG) 4 at the subnational level has not been quantified. We aimed to estimate under-5 mortality rates in mainland China for the years 1970 to 2012. We estimated the under-5 mortality rate for 31 provinces in mainland China between 1970 and 2013 with data from censuses, surveys, surveillance sites, and disease surveillance points. We estimated under-5 mortality rates for 2851 counties in China from 1996 to 2012 with the reported child mortality numbers from the Annual Report System on Maternal and Child Health. We used a small area mortality estimation model, spatiotemporal smoothing, and Gaussian process regression to synthesise data and generate consistent provincial and county-level estimates. We compared progress at the county level with what was expected on the basis of income and educational attainment using an econometric model. We computed Gini coefficients to study the inequality of under-5 mortality rates across counties. In 2012, the lowest provincial level under-5 mortality rate in China was about five per 1000 livebirths, lower than in Canada, New Zealand, and the USA. The highest provincial level under-5 mortality rate in China was higher than that of Bangladesh. 29 provinces achieved a decrease in under-5 mortality rates twice as fast as the MDG 4 target rate; only two provinces will not achieve MDG 4 by 2015. Although some counties in China have under-5 mortality rates similar to those in the most developed nations in 2012, some have similar rates to those recorded in Burkina Faso and Cameroon. Despite wide differences, the inter-county Gini coefficient has been decreasing. Improvement in maternal education and the economic boom have contributed to the fall in child mortality; more than 60% of the counties in China had rates of decline in under-5 mortality rates significantly faster than expected. Fast reduction in under-5 mortality rates have been recorded not only in the Han population, the dominant ethnic majority in China, but also in the minority populations. All top ten minority groups in terms of population sizes have experienced annual reductions in under-5 mortality rates faster than the MDG 4 target at 4·4%. The reduction of under-5 mortality rates in China at the country, provincial, and county level is an extraordinary success story. Reductions of under-5 mortality rates faster than 8·8% (twice MDG 4 pace) are possible. Extremely rapid declines seem to be related to public policy in addition to socioeconomic progress. Lessons from successful counties should prove valuable for China to intensify efforts for those with unacceptably high under-5 mortality rates. National “Twelfth Five-Year” Plan for Science and Technology Support, National Health and Family Planning Commission of The People's Republic of China, Program for Changjiang Scholars and Innovative Research Team in University, the National Institute on Aging, and the Bill & Melinda Gates Foundation.

Young people's health has emerged as a neglected yet pressing issue in global development. Changing patterns of young people's health have the potential to undermine future population health as well as global economic development unless timely and effective strategies are put into place. We report the past, present, and anticipated burden of disease in young people aged 10–24 years from 1990 to 2013 using data on mortality, disability, injuries, and health risk factors. The Global Burden of Disease Study 2013 (GBD 2013) includes annual assessments for 188 countries from 1990 to 2013, covering 306 diseases and injuries, 1233 sequelae, and 79 risk factors. We used the comparative risk assessment approach to assess how much of the burden of disease reported in a given year can be attributed to past exposure to a risk. We estimated attributable burden by comparing observed health outcomes with those that would have been observed if an alternative or counterfactual level of exposure had occurred in the past. We applied the same method to previous years to allow comparisons from 1990 to 2013. We cross-tabulated the quantiles of disability-adjusted life-years (DALYs) by quintiles of DALYs annual increase from 1990 to 2013 to show rates of DALYs increase by burden. We used the GBD 2013 hierarchy of causes that organises 306 diseases and injuries into four levels of classification. Level one distinguishes three broad categories: first, communicable, maternal, neonatal, and nutritional disorders; second, non-communicable diseases; and third, injuries. Level two has 21 mutually exclusive and collectively exhaustive categories, level three has 163 categories, and level four has 254 categories. The leading causes of death in 2013 for young people aged 10–14 years were HIV/AIDS, road injuries, and drowning (25·2%), whereas transport injuries were the leading cause of death for ages 15–19 years (14·2%) and 20–24 years (15·6%). Maternal disorders were the highest cause of death for young women aged 20–24 years (17·1%) and the fourth highest for girls aged 15–19 years (11·5%) in 2013. Unsafe sex as a risk factor for DALYs increased from the 13th rank to the second for both sexes aged 15–19 years from 1990 to 2013. Alcohol misuse was the highest risk factor for DALYs (7·0% overall, 10·5% for males, and 2·7% for females) for young people aged 20–24 years, whereas drug use accounted for 2·7% (3·3% for males and 2·0% for females). The contribution of risk factors varied between and within countries. For example, for ages 20–24 years, drug use was highest in Qatar and accounted for 4·9% of DALYs, followed by 4·8% in the United Arab Emirates, whereas alcohol use was highest in Russia and accounted for 21·4%, followed by 21·0% in Belarus. Alcohol accounted for 9·0% (ranging from 4·2% in Hong Kong to 11·3% in Shandong) in China and 11·6% (ranging from 10·1% in Aguascalientes to 14·9% in Chihuahua) of DALYs in Mexico for young people aged 20–24 years. Alcohol and drug use in those aged 10–24 years had an annual rate of change of >1·0% from 1990 to 2013 and accounted for more than 3·1% of DALYs. Our findings call for increased efforts to improve health and reduce the burden of disease and risks for diseases in later life in young people. Moreover, because of the large variations between countries in risks and burden, a global approach to improve health during this important period of life will fail unless the particularities of each country are taken into account. Finally, our results call for a strategy to overcome the financial and technical barriers to adequately capture young people's health risk factors and their determinants in health information systems. Bill & Melinda Gates Foundation.

Peptidoglycans (PGNs) are structural polymers of the bacterial cell wall and a common microbial molecular pattern encountered by the immune system daily. Low levels of PGNs are constitutively present in the systemic circulation in humans and rise during inflammatory pathologies. Since all known PGN sensors are intracellular, PGN internalization is a prerequisite for the initiation of cellular immune responses. Here, we report the mechanisms controlling the recognition and uptake of polymeric PGNs by circulating human mononuclear phagocytes. We found that complement C3 and C4 opsonins govern PGN recognition and internalization, but no single opsonin is indispensable because of multiple uptake redundancies. We observed a bimodal internalization of polymeric PGNs with distinct requirements for complement C4. At low PGN concentrations, C3 mediated PGN recognition by surface receptors while the efficient internalization of PGN polymers critically required C4. Supraphysiologic PGN concentrations triggered a secondary uptake modality that was insensitive to C4 and mediated instead by C3 engagement of complement receptors 1 and 3. To our knowledge, this is the first description of nonoverlapping C3 and C4 opsonophagocytoses working in parallel. Controlling these uptake mechanisms has the potential to modulate PGN clearance or the dysregulated immune responses during bacterial infections.