摘要：
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
作者：
Naghavi, Mohsen;Wang, Haidong;Lozano, Rafael;Davis, Adrian;Liang, Xiaofeng;Zhou, Maigeng;Vollset, Stein Emil;Ozgoren, Ayse Abbasoglu;Abdalla, Safa;Abd-Allah, Foad;Aziz, Muna I. Abdel;Abera, Semaw Ferede;Aboyans, Victor;Abraham, Biju;Abraham, Jerry P.;Abuabara, Katrina E.;Abubakar, Ibrahim;Abu-Raddad, Laith J.;Abu-Rmeileh, Niveen M. E.;Achoki, Tom
期刊：
LANCET,2015年385(9963):117-171 ISSN：0140-6736
通讯作者：
Murray, CJL
作者机构：
[Nolte, Sandra; Papachristou, Christina; Alsharif, Ubai] Charite, D-13353 Berlin, Germany.;[Yonemoto, Naohiro] Natl Ctr Neurol & Psychiat, Tokyo, Japan.;[Kravchenko, Michael A.; Varakin, Yuri Y.] Res Ctr Neurol, Moscow, Russia.;[Mckee, Martin; Tillmann, Taavi; Hossain, Mazeda; Roberts, Bayard; Stoeckl, Heidi; Pearce, Neil; Larson, Heidi J.] London Sch Hyg & Trop Med, London WC1, England.;[Bose, Dipan] World Bank, Washington, DC 20433 USA.
通讯机构：
[Murray, CJL] 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
摘要：
Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
作者机构：
[Nolte, Sandra; Papachristou, Christina; Endres, Matthias; Alsharif, Ubai] Charite, D-13353 Berlin, Germany.;[Yonemoto, Naohiro] Natl Ctr Neurol & Psychiat, Kodaira, Tokyo, Japan.;[Bose, Dipan] World Bank, Washington, DC 20433 USA.;[Mills, Edward J.] Univ Ottawa, Ottawa, ON, Canada.;[Ozgoren, Ayse Abbasoglu] Hacettepe Univ, Inst Populat Studies, Ankara, Turkey.
通讯机构：
[Vos, T] Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
摘要：
Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
作者机构：
[Casey, Daniel C.; Kemmer, Laura; Friedman, Joseph; Wang, Haidong; Kassebaum, Nicholas J.; Sligar, Amber; Forouzanfar, Mohammad H.; Brown, Jonathan; Goldberg, Ellen M.; Flaxman, Abraham; Kutz, Michael; Wanga, Valentine; Zoeckler, Leo; Misganaw, Awoke; Wolock, Timothy; Pinho, Christine; Silpakit, Naris; Sandar, Logan; Johnson, Catherine; Mooney, Meghan D.; Stanaway, Jeffrey; Kulikoff, Xie Rachel; Frostad, Joseph; Futran, Neal D.; Morgan, Katherine; Reitsma, Marissa B.; Carter, Austin; Lindsay, M. Patrice; Steiner, Caitlyn; Murray, Christopher J. L.; Masiye, Felix; Ng, Marie; Fitzmaurice, Christina; Lim, Stephen S.; Graetz, Nicholas; Khalil, Ibrahim A.; Mirarefin, Mojde; Lopez, Alan D.; Rao, Puja; Nsoesie, Elaine; Alexander, Lily T.; Liu, Patrick Y.; Biryukov, Stan; VanderZanden, Amelia; Kasaeian, Amir; Charlson, Fiona J.; Estep, Kara; Sorensen, Reed J. D.; Cercy, Kelly; Mikesell, Joe; Hancock, Jamie; Nguyen, Grant; Fraser, Maya S.; Cohen, Aaron J.; Chen, Alan Zian; Wagner, Joseph A.; Roth, Gregory A.; Coates, Matthew M.; Quame-Amaglo, Justice; Erskine, Holly E.; Coggeshall, Megan; Dicker, Daniel J.; Achoki, Tom; Thomas, Bernadette A.; Foreman, Kyle; Brown, Alexandria; Leung, Janni; Pigott, David M.; Marquez, Neal; Blore, Jed D.; Dossou, Edem; Mokdad, Ali H.; Chew, Adrienne; Vollset, Stein Emil; Daoud, Farah; Vos, Theo; Ferrari, Alize J.; Whiteford, Harvey A.; Larson, Heidi J.; Dandona, Lalit; Shackelford, Katya A.; Teeple, Stephanie; Kyu, Hmwe H.; Afshin, Ashkan; Allen, Christine; Huynh, Chantal; Barber, Ryan M.; Sur, Patrick; Anderson, Gregory M.; Moradi-Lakeh, Maziar; Troeger, Christopher; Godwin, William W.; Lind, Margaret; Lozano, Rafael; Naghavi, Mohsen] Inst Hlth Metr & Evaluat, Seattle, WA USA.;[Yonemoto, Naohiro] Kyoto Univ, Sch Publ Hlth, Dept Biostatist, Kyoto, Japan.;[Mckee, Martin; Langan, Sinead M.; Satyanarayana Murthy, Gudlavalleti Venkata; Roberts, Bayard; Pearce, Neil; Faghmous, Imad D. A.] London Sch Hyg & Trop Med, London, England.;[Dhillon, Preet K.; Ganguly, Parthasarathi; Zodpey, Sanjay; Lal, Dharmesh Kumar] Publ Hlth Fdn India, Gurgaon, India.;[Mhimbira, Francis Apolinary] Ifakara Hlth Inst, Bagamoyo, Tanzania.
通讯机构：
[Murray, CJL] 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
摘要：
Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.
期刊：
Energy and Environmental Science,2014年7(8):2619-2623 ISSN：1754-5692
通讯作者：
Huang, JS
作者机构：
[Wang, Qi; Yuan, Yongbo; Dong, Qingfeng; Shao, Yuchuan; Bi, Cheng; Huang, Jinsong; Xiao, Zhengguo] Department of Mechanical and Materials Engineering, Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln NE 68588-0656, United States;[Gao, Yongli; Wang, Chenggong] Department of Physics and Astronomy, University of Rochester, Rochester NY 14627, United States;[Gao, Yongli] Institute of Super-microstructure and Ultrafast Process in Advanced Materials (ISUPAM), Central South University, Changsha Hunan 410083, China
通讯机构：
[Huang, JS] Univ Nebraska, Nebraska Ctr Mat & Nanosci, Dept Mech & Mat Engn, Lincoln, NE 68588 USA.
关键词：
Fill factor - Low temperatures - One-sun illumination - Perovskite films - Photovoltaic devices - Solution process - Solution-processed - Stacking layers
摘要：
The human brain has been described as a large, sparse, complex network characterized by efficient small-world properties, which assure that the brain generates and integrates information with high efficiency. Many previous neuroimaging studies have provided consistent evidence of 'dysfunctional connectivity' among the brain regions in schizophrenia; however, little is known about whether or not this dysfunctional connectivity causes disruption of the topological properties of brain functional networks. To this end, we investigated the topological properties of human brain functional networks derived from resting-state functional magnetic resonance imaging (fMRI). Data was obtained from 31 schizophrenia patients and 31 healthy subjects; then functional connectivity between 90 cortical and sub-cortical regions was estimated by partial correlation analysis and thresholded to construct a set of undirected graphs. Our findings demonstrated that the brain functional networks had efficient small-world properties in the healthy subjects; whereas these properties were disrupted in the patients with schizophrenia. Brain functional networks have efficient small-world properties which support efficient parallel information transfer at a relatively low cost. More importantly, in patients with schizophrenia the small-world topological properties are significantly altered in many brain regions in the prefrontal, parietal and temporal lobes. These findings are consistent with a hypothesis of dysfunctional integration of the brain in this illness. Specifically, we found that these altered topological measurements correlate with illness duration in schizophrenia. Detection and estimation of these alterations could prove helpful for understanding the pathophysiological mechanism as well as for evaluation of the severity of schizophrenia.
作者机构：
[Casey, Daniel C.; Wang, Haidong; Forouzanfar, Mohammad H.; Zhao, Yi; Zipkin, Ben; Mumford, John Everett; Misganaw, Awoke; Sandar, Logan; Reitsma, Marissa B.; Dicker, Daniel; Fleming, Tom; Murray, Christopher J. L.; Ng, Marie; Lim, Stephen S.; Mirarefin, Mojde; Lopez, Alan D.; Rao, Puja; Alexander, Lily T.; Liu, Patrick Y.; Biryukov, Stan; Charlson, Fiona J.; Estep, Kara; Sorensen, Reed J. D.; Reinig, Nikolas; Cercy, Kelly; Cornaby, Leslie; Roman, Yesenia; Santomauro, Damian F.; Griswold, Max; Cohen, Aaron J.; Wagner, Joseph A.; Roth, Gregory A.; Coates, Matthew M.; Cooperrider, Kimberly; Erskine, Holly E.; Fullman, Nancy; Olsen, Helen; Haagsma, Juanita A.; Ku, Tiffany; Johnson, Catherine O.; Thomas, Bernadette A.; Foreman, Kyle; Slepak, Erica Leigh; Leung, Janni; Mullany, Erin; Blore, Jed D.; Zhou, Maigeng; Mokdad, Ali H.; Sur, Patrick J.; Gakidou, Emmanuela; Frostad, Joseph J.; Brauer, Michael; Vollset, Stein Emil; Vos, Theo; Ferrari, Alize J.; Whiteford, Harvey A.; Larson, Heidi J.; Dandona, Lalit; Kyu, Hmwe H.; Afshin, Ashkan; Barber, Ryan M.; Moradi-Lakeh, Maziar; Godwin, William W.; Marczak, Laurie; Lozano, Rafael; Naghavi, Mohsen] Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.;[Yonemoto, Naohiro] Kyoto Univ, Sch Publ Hlth, Dept Biostat, Kyoto, Japan.;[Dhillon, Preet K.; Zodpey, Sanjay; Lal, Dharmesh Kumar] Publ Hlth Fdn India, Gurgaon, India.;[Mhimbira, Francis Apolinary] Ifakara Hlth Inst, Bagamoyo, Tanzania.;[Mills, Edward J.] Univ Ottawa, Ottawa, ON, Canada.
通讯机构：
[Murray, CJL] Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA.
摘要：
Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd.
摘要：
We have developed a microfluidic 3D hepatocyte chip (3D HepaTox Chip) for in vitro drug toxicity testing to predict in vivo drug hepatotoxicity. The 3D HepaTox Chip is based on multiplexed microfluidic channels where a 3D microenvironment is engineered in each channel to maintain the hepatocytes' synthetic and metabolic functions. The multiplexed channels allow for simultaneous administration of multiple drug doses to functional primary hepatocytes while an incorporated concentration gradient generator enables the in vitro dose-dependent drug responses to predict in vivo hepatotoxicity. The IC(50) values of 5 model drugs derived from the dose-dependent on-chip testing correlate well with the reported in vivo LD(50) values. The 3D HepaTox Chip can be integrated with on-chip sensors and actuators as the next generation cell-based on-chip drug testing platform.
作者机构：
[Yanqing Lai; Keyu Xie; Zhi'an Zhang; Jie Li; Yexiang Liu] Cent S Univ, Sch Met Sci & Engn, Changsha 410083, Hunan, Peoples R China.;[Limin Zhou] Hong Kong Polytech Univ, Dept Mech Engn, Hong Kong, Hong Kong, Peoples R China.;[Keyu Xie; Haitao Huang; Wei Lu] Hong Kong Polytech Univ, Dept Appl Phys, Hong Kong, Hong Kong, Peoples R China.;[Keyu Xie; Haitao Huang; Wei Lu] Hong Kong Polytech Univ, Mat Res Ctr, Hong Kong, Hong Kong, Peoples R China.
通讯机构：
[Huang, HT] Hong Kong Polytech Univ, Dept Appl Phys, Hong Kong, Hong Kong, Peoples R China.
关键词：
Iron oxide;Anodization;Nanotube array;Supercapacitors
摘要：
IMPORTANCE: Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. OBJECTIVE: To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. DESIGN, SETTING, AND PARTICIPANTS: The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. INTERVENTIONS: Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). MAIN OUTCOMES AND MEASURES: The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. RESULTS: During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00794885.
作者机构：
[Jin-hua She; Hashimoto, H.; Ohyama, Y.] School of Bionics, Tokyo University of Technology, Tokyo 192-0982, Japan;[Min Wu; Mingxing Fang] School of Information Science and Engineering, Central South University, Changsha 410083, China;[Mingxing Fang] College of Physics and Electronic Information, Anhui Normal University, Wuhu 241000, China
通讯机构：
[She, JH] Tokyo Univ Technol, Sch Bion, Tokyo 1920982, Japan.
作者机构：
[Shao, Yuchuan; Huang, Jinsong; Wang, Qi] Department of Mechanical and Materials Engineering, Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln;[Shao, Yuchuan; Huang, Jinsong; Wang, Qi] NE, United States;[Xie, Haipeng; Liu, Xiaoliang; Lyu, Lu] Hunan Key Laboratory for Super-microstructure and Ultrafast Process, College of Physics and Electronics, Central South University, Changsha, China;[Gao, Yongli] Department of Physics and Astronomy, University of Rochester, Rochester;[Gao, Yongli] NY, United States
通讯机构：
[Huang, JS] Univ Nebraska, Dept Mech & Mat Engn, Lincoln, NE 68588 USA.
作者机构：
[Yang, Bing-Chu; Xia, Hui; Li, Hong-Jian; Wang, Jun-Xi; Xiong, Zhi-Yong; Wang, Zhi-Jun; Li, Xue-Yong] College of Physics Science and Technology, Central South University, Changsha, 410083, China;[Li, Xue-Yong; Li, Hong-Jian] School of Materials Science and Engineering, Central South University, Changsha, 410083, China;[Li, Xue-Yong] School of Sciences, Hunan University of Technology, Zhuzhou, 412008, China
通讯机构：
[Li, HJ] Cent S Univ, Coll Phys Sci & Technol, Lusan Lu 8, Changsha 410083, Hunan, Peoples R China.
作者机构：
[ Loi, Maria Antonietta ; Fang, Hong-Hua ] Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, AG Groningen;[ Loi, Maria Antonietta ; Fang, Hong-Hua ] 9747, Netherlands;[ Wang, Congcong ; Gao, Yongli ; Ecker, Benjamin R. ] Department of Physics and Astronomy, University of Rochester, Rochester, NY;[ Wang, Congcong ; Gao, Yongli ; Ecker, Benjamin R. ] 14627-0171, United States;[ Fang, Yanjun ; Wei, Haotong ; Huang, Jinsong ] Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln
通讯机构：
[Cao, L] Ohio State Univ, Dept Mech & Aerosp Engn, Nucl Engn Program, Columbus, OH 43210 USA.;[Huang, JS] Univ Nebraska, Dept Mech & Mat Engn, Lincoln, NE 68588 USA.
摘要：
Graphene has attracted much interest in both academia and industry. The challenge of making it semiconducting is crucial for applications in electronic devices. A promising approach is to reduce its physical size down to the nanometer scale. Here, we present the surface-assisted bottom-up fabrication of atomically precise armchair graphene nanoribbons (AGNRs) with predefined widths, namely 7-, 14- and 21-AGNRs, on Ag(111) as well as their spatially resolved width-dependent electronic structures. STM/STS measurements reveal their associated electron scattering patterns and the energy gaps over 1 eV. The mechanism to form such AGNRs is addressed based on the observed intermediate products. Our results provide new insights into the local properties of AGNRs, and have implications for the understanding of their electrical properties and potential applications.
作者机构：
[Zou, Yingping; Liu, Bo; Yuan, Jun] Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.;[Zou, Yingping; Liu, Bo; He, Yuehui] Cent S Univ, State Key Lab Powder Met, Changsha 410083, Hunan, Peoples R China.;[Zou, Yingping] Cent S Univ, Sch Phys & Elect, Inst Super Microstruct & Ultrafast Proc Adv Mat, Changsha 410083, Hunan, Peoples R China.;[Zhang, Bo; Fukunaga, Chihiro; Zhang, Xiaodong; Dai, Hongjie; Wu, Justin Z.; Diao, Shuo; Wu, Di; Hong, Guosong; Tao, Zhimin; Antaris, Alexander L.; Chen, Changxin] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.;[Cheng, Kai] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA.
通讯机构：
[Zou, YP] Cent S Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
摘要：
In vivo fluorescence imaging in the second near-infrared window (1.0-1.7 mu m) can afford deep tissue penetration and high spatial resolution, owing to the reduced scattering of long-wavelength photons. Here we synthesize a series of low-bandgap donor/acceptor copolymers with tunable emission wavelengths of 1,050-1,350 nm in this window. Non-covalent functionalization with phospholipid-polyethylene glycol results in water-soluble and biocompatible polymeric nanoparticles, allowing for live cell molecular imaging at >1,000 nm with polymer fluorophores for the first time. Importantly, the high quantum yield of the polymer allows for in vivo, deep-tissue and ultrafast imaging of mouse arterial blood flow with an unprecedented frame rate of >25 frames per second. The high time-resolution results in spatially and time resolved imaging of the blood flow pattern in cardiogram waveform over a single cardiac cycle (similar to 200 ms) of a mouse, which has not been observed with fluorescence imaging in this window before.
作者机构：
[Can Liu; Mengshi Wu; Ya Pang; Lin Tang; Zhifeng Liu; Xiaoxia Lei; Gengxin Xie; Ming Chen; Yuanyuan Liu; Guangming Zeng; Zhen Li] College of Environmental Science and Engineering, Hunan University, Changsha 410082, Hunan, China;[Can Liu; Mengshi Wu; Ya Pang; Lin Tang; Zhifeng Liu; Xiaoxia Lei; Gengxin Xie; Ming Chen; Yuanyuan Liu; Guangming Zeng; Zhen Li] Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082, Hunan, China;[Pinyun Ren] Key Laboratory for Micro-Nano Physics and Technology of Hunan Province, Hunan University, Changsha 410082, China;[Pinyun Ren] College of Physics and Microelectronics Science, Hunan University, Changsha 410082, China;[Zhuotong Zeng] State Key Laboratory of Medical Genetics, Central South University, Changsha 410078, China
摘要：
A novel magnetically separable laccase immobilized system was constructed by adsorbing laccase into bimodal carbon-based mesoporous magnetic composites (CMMC). A large adsorption capacity (491.7 mg g(-1)), excellent activity recovery (91.0%) and broader pH and temperature profiles than free laccase have been exhibited by the immobilized laccase. Thermal stability was enhanced to a great extent and operational stability was increased to a certain extent. The shift of kinetic parameters indicated affinity change between enzyme and substrate. Application of the immobilized system in phenol and p-chlorophenol removal was investigated in a batch system. Adsorption effects of the support were responsible for the quick removal rate in the first hour, and up to 78% and 84% of phenol and p-chlorophenol were removed in the end of the reaction, respectively, indicating that the magnetic bimodal mesoporous carbon is a promising carrier for both immobilization of laccase and further application in phenol removal. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.
作者机构：
[ Tan, Ning ; Huang, Ke-Long ; Li, Xiao-gang ; Chen, Li-quan ; Liu, Su-qin ] School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China;[ Chen, Li-quan ] Institute of Physics, Chinese Academy of Sciences, Beijing, 100080, China;[ Li, Xiao-gang ] College of Bio-safety Science and Technology, Hunan Agricultural University, Changsha, 410128, China
通讯机构：
[Huang, KL] Cent S Univ, Sch Chem & Chem Engn, Changsha 410083, Peoples R China.
关键词：
Energy storage system - Vanadium redox flow battery
