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：
[Varakin, Yuri Y.; Kravchenko, Michael A.] Res Ctr Neurol, Moscow, Russia.;[Foigt, Nataliya] Ukraine Acad Med Sci, Inst Gerontol, UA-252655 Kiev, Ukraine.;[Riccio, Patricia M.] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON, Canada.;[Duber, Herbert C.; Naghavi, Mohsen; Lozano, Rafael; Naghavi, Paria; McLain, Abigail; Coffeng, Luc Edgar; Moradi-Lakeh, Maziar; Hamavid, Hannah; Roberts, D. Allen; Barber, Ryan M.; Huynh, Chantal; Levitz, Carly; Phillips, David E.; Dandona, Lalit; Apfel, Henry; Phillips, Bryan K.; Vos, Theo; Vollset, Stein Emil; Templin, Tara; Bertozzi-Villa, Amelia; Mokdad, Ali H.; Richardson, Lee; MacIntyre, Michael F.; Liddell, Chelsea; Fleming, Thomas D.; Schumacher, Austin E.; Atkinson, Charles; Kassebaum, Nicholas; Thomas, Bernadette A.; Robinson, Margaret; Margono, Christopher; Achoki, Tom; Wurtz, Brittany; Mullany, Erin C.; Coates, Matthew M.; Roth, Gregory A.; Ohno, Summer Lockett; Iannarone, Marissa; Nguyen, Grant; Hancock, Jamie; Shackelford, Katya; Kyu, Hmwe; Ortblad, Katrina F.; Joseph, Jonathan; Stanaway, Jeff Rey D.; Odell, Shaun; Estep, Kara; Lind, Maggie L.; Biryukov, Stan; Brown, Jonathan C.; Wolock, Timothy M.; Moyer, Madeline L.; Pain, Amanda W.; Singh, Lavanya; Graetz, Nicholas; Dansereau, Emily; Ng, Marie; Catala-Lopez, Ferrn; Murray, Christopher J. L.; Steiner, Caitlyn; Stevens, Antony; Hansen, Gillian M.; Dicker, Daniel; Heuton, Kyle R.; Lofgren, Katherine T.; Wulf, Sarah; Coggeshall, Megan S.; Mooney, Meghan D.; Higashi, Hideki; Sandar, Logan; Gonzalez-Medina, Diego; Haagsma, Juanita; Sioson, Edgar; Forouzanfar, Mohammad H.; Wang, Haidong] Inst Hlth Metr & Evaluat, Seattle, WA USA.;[Iburg, Kim M.] Aarhus Univ, Aarhus, Denmark.
通讯机构：
[Murray, Christopher J. L.] 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.
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.
期刊：
The Lancet. Oncology,2011年12(8):735-742 ISSN：1470-2045
通讯作者：
Zhou, Caicun
作者机构：
[Wu, Yi-Long] Guangdong Acad Med Sci, Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.;[Zhang, Shucai] Capital Med Univ, Beijing Chest Hosp, Beijing, Peoples R China.;[Zhang, Li] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China.;[Zhang, Li] Beijing Union Med Coll Hosp, Beijing, Peoples R China.;[Chen, Lei] Shantou Univ, Coll Med, Canc Hosp, Shantou, Peoples R China.
摘要：
BACKGROUND: Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. METHODS: We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT00874419, and has completed enrolment; patients are still in follow-up. FINDINGS: 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI 0.10-0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72 patients and thrombocytopenia in 29 [40%] patients on chemotherapy vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4%] of 83 patients) and skin rash (two [2%] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14%] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1] vs two [2%] of 83 patients [both hepatic dysfunction]). INTERPRETATION: Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. FUNDING: F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality.
期刊：
The New England journal of medicine,2010年362(12):1090-1101 ISSN：0028-4793
通讯作者：
Yang, WY
作者机构：
[Jia, Weiping] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200030, Peoples R China.;[Yang, Wenying] China Japan Friendship Hosp, Dept Endocrinol, Beijing 100029, Peoples R China.;[Lu, Juming] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China.;[Tian, Haoming] Sichuan Univ, W China Hosp, Chengdu 610064, Sichuan, Peoples R China.;[Zhu, Dalong] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China.
通讯机构：
[Yang, Wenying] China Japan Friendship Hosp, Dept Endocrinol, Beijing 100029, Peoples R China.
摘要：
BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed.
作者：
Scirica, Benjamin M.;Bhatt, Deepak L.;Braunwald, Eugene;Steg, P. Gabriel;Davidson, Jaime;Hirshberg, Boaz;Ohman, Peter;Frederich, Robert;Wiviott, Stephen D.;Hoffman, Elaine B.;Cavender, Matthew A.;Udell, Jacob A.;Desai, Nihar R.;Mosenzon, Ofri;McGuire, Darren K.;Ray, Kausik K.;Leiter, Lawrence A.;Raz, Itamar;Desai, Nihar;Abrahamsen, Timothy
期刊：
NEW ENGLAND JOURNAL OF MEDICINE,2013年369(14):1317-1326 ISSN：0028-4793
通讯作者：
Bhatt, DL
作者机构：
[Nischik, R.] Medamed GmbH, Leipzig, Germany.;[Gyimesi, A.] Rethy Pal Korhaz II Belgyogyaszati Osztaly, Bekescsaba, Hungary.;[Diaz, M.] MD Invest, Buenos Aires, DF, Argentina.;[Shi, Y.] Shanghai Changzheng Hosp, Shanghai, Peoples R China.;[Bhupati, S.] CARE Hosp, Hyderabad, Andhra Pradesh, India.
通讯机构：
[Bhatt, Deepak L.] VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA.
摘要：
BackgroundThe cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. MethodsWe randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. ResultsA primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the on-treatment analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). ConclusionsDPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes.
作者机构：
[Jassal, Simerjot K.] VA San Diego, San Diego, CA USA.;[Varakin, Yuri Y.; Kravchenko, Michael] Res Ctr Neurol, Moscow, Russia.;[Wallin, Mitchell T.] Georgetown Univ, Dept Neurol, Washington, DC USA.;[Wallin, Mitchell T.] VA Med Ctr, Washington, DC USA.;[Foigt, Nataliya] Ukraine Acad Med Sci, Inst Gerontol, UA-252655 Kiev, Ukraine.
通讯机构：
[Vos, Theo] 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：
Giugliano, Robert P.;Ruff, Christian T.;Braunwald, Eugene;Murphy, Sabina A.;Wiviott, Stephen D.;Halperin, Jonathan L.;Waldo, Albert L.;Ezekowitz, Michael D.;Weitz, Jeffrey I.;Spinar, Jindrich;Ruzyllo, Witold;Ruda, Mikhail;Koretsune, Yukihiro;Betcher, Joshua;Shi, Minggao;Grip, Laura T.;Patel, Shirali P.;Patel, Indravadan;Hanyok, James J.;Mercuri, Michele
期刊：
NEW ENGLAND JOURNAL OF MEDICINE,2013年369(22):2093-2104 ISSN：0028-4793
通讯机构：
[Giugliano, R. P.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, 350 Longwood Ave,1st Flr, Boston, MA 02115 USA.
摘要：
BackgroundEdoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. MethodsWe conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. ResultsThe annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). ConclusionsBoth once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)
作者机构：
[Jassal, Simerjot K.; Criqui, Michael H.; Stein, Murray B.] Univ Calif San Diego, La Jolla, CA 92093 USA.;[Terkawi, Abdullah S.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA.;[Terkawi, Abdullah S.] Outcomes Res Consortium, Cleveland, OH USA.;[Terkawi, Abdullah S.] King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia.;[Foigt, Nataliya] Acad Med Sci, Inst Gerontol, Kiev, Ukraine.
通讯机构：
[Murray, Christopher J. L.] Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
摘要：
Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6.2 years (95% UI 5.6-6.6), from 65.3 years (65.0-65.6) in 1990 to 71.5 years (71.0-71.9) in 2013, HALE at birth rose by 5.4 years (4.9-5.8), from 56.9 years (54.5-59.1) to 62.3 years (59.7-64.8), total DALYs fell by 3.6% (0.3-7.4), and age-standardised DALY rates per 100 000 people fell by 26.7% (24.6-29.1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.
作者：
Klionsky, Daniel J.;Abdelmohsen, Kotb;Abe, Akihisa;Abedin, Md Joynal;Abeliovich, Hagai;Arozena, Abraham Acevedo;Adachi, Hiroaki;Adams, Christopher M.;Adams, Peter D.;Adeli, Khosrow;Adhihetty, Peter J.;Adler, Sharon G.;Agam, Galila;Agarwal, Rajesh;Aghi, Manish K.;Agnello, Maria;Agostinis, Patrizia;Aguilar, Patricia V.;Aguirre-Ghiso, Julio;Airoldi, Edoardo M.
期刊：
AUTOPHAGY,2016年12(1):1-222 ISSN：1554-8627
通讯作者：
Klionsky, DJ
作者机构：
[Cho, William C.] akt Queen Elizabeth Hospital , Department of Clinical Oncology , Kowloon, Hong Kong;[Sukseree, Supawadee; Eckhart, Leopold] acn Medical University of Vienna , Department of Dermatology , Vienna , Austria;[Into, Takeshi; Inomata, Megumi] ar Asahi University, School of Dentistry , Department of Oral Microbiology , Division of Oral Infections and Health Sciences , Mizuho , Gifu , Japan;[Liu, Jing-Lan] ef Chang Gung Memorial Hospital , Department of Pathology , Chiayi , Taiwan;[Bassi, Maria Teresa] anf Scientific Institute IRCCS Eugenio Medea, Laboratory of Molecular Biology , Bosisio Parini, Lecco , Italy
通讯机构：
[Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
作者机构：
[Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Goldberg, Ellen M.; Graetz, Nicholas; Huynh, Chantal; Johnson, Catherine; Kassebaum, Nicholas J.; Kulikoff, Xie Rachel; Kutz, Michael; Kyu, Hmwe H.; Larson, Heidi J.; Leung, Janni; Lim, Stephen S.; Lind, Margaret; Lozano, Rafael; Marquez, Neal; Mikesell, Joe; Mokdad, Ali H.; Mooney, Meghan D.; Nguyen, Grant; Nsoesie, Elaine; Pigott, David M.; Pinho, Christine; Roth, Gregory A.; Sandar, Logan; Silpakit, Naris; Sligar, Amber; Sorensen, Reed J. D.; Stanaway, Jeffrey; Steiner, Caitlyn; Teeple, Stephanie; Thomas, Bernadette A.; Troeger, Christopher; VanderZanden, Amelia; Vollset, Stein Emil; Wanga, Valentine; Whiteford, Harvey A.; Wolock, Timothy; Zoeckler, Leo; Achoki, Tom; Afshin, Ashkan; Alexander, Lily T.; Anderson, Gregory M.; Biryukov, Stan; Blore, Jed D.; Brown, Alexandria; Brown, Jonathan; Cercy, Kelly; Chew, Adrienne; Cohen, Aaron J.; Daoud, Farah; Dossou, Edem; Estep, Kara; Flaxman, Abraham; Friedman, Joseph; Frostad, Joseph; Futran, Neal D.; Godwin, William W.; Hancock, Jamie; Kasaeian, Amir; Kemmer, Laura; Khalil, Ibrahim A.; Lindsay, M. Patrice; Liu, Patrick Y.; Masiye, Felix; Mirarefin, Mojde; Misganaw, Awoke; Moradi-Lakeh, Maziar; Morgan, Katherine; Ng, Marie; Quame-Amaglo, Justice; Rao, Puja; Reitsma, Marissa B.; Shackelford, Katya A.; Sur, Patrick; Wagner, Joseph A.; Vos, Theo; Lopez, Alan D.; Murray, Christopher J. L.] Inst Hlth Metr & Evaluat, Seattle, WA USA.;[Bhutta, Zulfiqar A.] Ctr Excellence Women & Child Hlth, Karachi, Pakistan.;[Bhutta, Zulfiqar A.; Akseer, Nadia] Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada.;[Charlson, Fiona J.; Erskine, Holly E.; Ferrari, Alize J.; Leung, Janni; Whiteford, Harvey A.; Alam, Khurshid; Knibbs, Luke D.] Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.;[Charlson, Fiona J.; Erskine, Holly E.; Leung, Janni; Whiteford, Harvey A.] Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
通讯机构：
[Murray, Christopher J. L.] 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.
作者：
Forouzanfar, Mohammad H.;Alexander, Lily;Anderson, H. Ross;Bachman, Victoria F.;Biryukov, Stan;Brauer, Michael;Burnett, Richard;Casey, Daniel;Coates, Matthew M.;Cohen, Aaron;Delwiche, Kristen;Estep, Kara;Frostad, Joseph J.;Astha, K. C.;Kyu, Hmwe H.;Moradi-Lakeh, Maziar;Ng, Marie;Slepak, Erica Leigh;Thomas, Bernadette A.;Wagner, Joseph
作者机构：
[Terkawi, Abdullah S.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA.;[Terkawi, Abdullah S.] Outcomes Res Consortium, Cleveland, OH USA.;[Terkawi, Abdullah S.] King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia.;[Jassal, Simerjot K.] Univ Calif San Diego, San Diego, CA USA.;[Foigt, Nataliya] Acad Med Sci, Inst Gerontol, Kiev, Ukraine.
通讯机构：
[Murray, CJ] Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
摘要：
Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57.2% (95% uncertainty interval [UI] 55.8-58.5) of deaths and 41.6% (40.1-43.0) of DALYs. Risks quantified account for 87.9% (86.5-89.3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11.3 million deaths and 241.4 million DALYs, high systolic blood pressure for 10.4 million deaths and 208.1 million DALYs, child and maternal malnutrition for 1.7 million deaths and 176.9 million DALYs, tobacco smoke for 6.1 million deaths and 143.5 million DALYs, air pollution for 5.5 million deaths and 141.5 million DALYs, and high BMI for 4.4 million deaths and 134.0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.
期刊：
Chemistry of Materials,2010年22(5):1915-1925 ISSN：0897-4756
通讯作者：
Wang, P.(peng.wang@dao.jl.cn)
作者机构：
[Wangdong Zeng; Min Zhang; Yinghui Wang; Yushuai Shi; Yiming Cao; Yu Bai; Fangfang Wang; Peng Wang] State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;[Wangdong Zeng; Chunyue Pan] College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China
通讯机构：
[Wang, Peng] Chinese Acad Sci, State Key Lab Polymer Phys & Chem, Changchun Inst Appl Chem, Changchun 130022, Peoples R China.
关键词：
Back electron transfer - Branching ratio - Dithienosilole - Dye regeneration - Dye-Sensitized solar cell - Ethylenedioxythiophenes - G-Condition - High yield - Indoor applications - Intramolecular charge transfers - Large-scale applications - Light-harvesting - Low light - Molar absorption coefficient - Nanocrystalline titania films - Net charges - Organic dye - Ruthenium sensitizers - Solvent free - Transient absorption measurements - Volatile electrolytes
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：
[Xiao, Zhengguo; Huang, Jinsong; Bi, Cheng; Shao, Yuchuan; Dong, Qingfeng; Yuan, Yongbo; Wang, Qi] Department of Mechanical and Materials Engineering, Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, Lincoln NE 68588-0656, United States;[Gao, Yongli] Institute of Super-microstructure and Ultrafast Process in Advanced Materials (ISUPAM), Central South University, Changsha Hunan 410083, China;[Wang, Chenggong; Gao, Yongli] Department of Physics and Astronomy, University of Rochester, Rochester NY 14627, United States
通讯机构：
[Huang, Jinsong] 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
作者机构：
[Lee, Jung Tae; Yushin, Gleb; Wu, Feixiang; Nitta, Naoki] School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, United States;[Wu, Feixiang] School of Metallurgy and Environment, Central South University, Changsha, China
通讯机构：
[Yushin, Gleb] Georgia Inst Technol, Sch Mat Sci & Engn, Atlanta, GA 30332 USA.
期刊：
The Lancet. Oncology,2014年15(2):213-222 ISSN：1470-2045
通讯作者：
Wu, YL
作者机构：
[Wu, Yi-Long] Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn;[Shi, Jian Hua] Lin Yi Tumor Hospital, Linyi, Shandong Province, China;[Hou, Mei] West China Hospital, Sichuan University, Chengdu, Sichuan, China;[Li, Wei] Cancer Center, First Hospital of Jilin University, Changchun, China;[Hu, Cheng-Ping] Department of Pulmonary Medicine, Xiangya Hospital, Central South University, Changsha, China
通讯机构：
[Wu, Yi-Long] Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:
摘要：
BACKGROUND: Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC. METHODS: This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m(2) on day 1 and day 8 plus cisplatin 75 mg/m(2) on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01121393. FINDINGS: 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11.0 months, 95% CI 9.7-13.7) than in the gemcitabine and cisplatin group (5.6 months, 5.1-6.7; hazard ratio 0.28, 95% CI 0.20-0.39; p<0.0001). The most common treatment-related grade 3 or 4 adverse events in the afatinib group were rash or acne (35 [14.6%] of 239 patients), diarrhoea (13 [5.4%]), and stomatitis or mucositis (13 [5.4%]), compared with neutropenia (30 [26.5%] of 113 patients), vomiting (22 [19.5%]), and leucopenia (17 [15.0%]) in the gemcitabine and cisplatin group. Treatment-related serious adverse events occurred in 15 (6.3%) patients in the afatinib group and nine (8.0%) patients in the gemcitabine and cisplatin group. INTERPRETATION: First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population. FUNDING: Boehringer Ingelheim.
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：
[Yu, Xueqing; Chen, Wei] Sun Yat Sen Univ, Affiliated Hosp 1, Div Nephrol, Guangzhou 510275, Guangdong, Peoples R China.;[Zhang, Luxia; Li, Xiaomei; Wang, Fang; Wang, Haiyan] Peking Univ, Hosp 1, Div Nephrol, Inst Nephrol, Beijing 100871, Peoples R China.;[Wang, Li; Hong, Daqing] Sichuan Acad Med Sci, Div Nephrol, Chengdu, Peoples R China.;[Wang, Li; Hong, Daqing] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China.;[Chen, Jianghua; He, Qiang] Zhejiang Univ, Affiliated Hosp 1, Div Nephrol, Hangzhou 310003, Zhejiang, Peoples R China.
通讯机构：
[Wang, Haiyan] Peking Univ, Hosp 1, Dept Med, Div Renal, Beijing 100871, Peoples R China.
摘要：
BACKGROUND: The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. METHODS: We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1.73 m(2) or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. FINDINGS: 50,550 people were invited to participate, of whom 47,204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1.73 m(2) was 1.7% (95% CI 1.5-1.9) and of albuminuria was 9.4% (8.9-10.0). The overall prevalence of chronic kidney disease was 10.8% (10.2-11.3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119.5 million (112.9-125.0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16.9% [15.1-18.7]) and southwest (18.3% [16.4-20.4]) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. INTERPRETATION: Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. FUNDING: The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.
通讯机构：
[Zhang, Xue-Jun] Anhui Med Univ, Hosp 1, Inst Dermatol, Hefei, Anhui, Peoples R China.
摘要：
We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) <= P(combined) <= 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) <= P(combined) <= 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.
期刊：
IEEE TRANSACTIONS ON EVOLUTIONARY COMPUTATION,2011年15(1):55-66 ISSN：1089-778X
通讯作者：
Wang, Y.(ywang@csu.edu.cn)
作者机构：
[Zhang, Qingfu] School of Computer Science and Electronic Engineering, University of Essex, Colchester, CO4 3SQ, United Kingdom;[Cai, Zixing; Wang, Yong] School of Information Science and Engineering, Central South University, Changsha 410083, China
通讯机构：
[Wang, Yong] Cent S Univ, Sch Informat Sci & Engn, Changsha 410083, Peoples R China.
关键词：
Control parameters - differential evolution - global numerical optimization - Novel methods - Test instances - trial vector generation strategy - Vector generation
摘要：
BACKGROUND: We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. METHODS: Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. FINDINGS: Median follow-up in LUX-Lung 3 was 41 months (IQR 35-44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31-37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28.2 months (95% CI 24.6-33.6) in the afatinib group and 28.2 months (20.7-33.2) in the pemetrexed-cisplatin group (HR 0.88, 95% CI 0.66-1.17, p=0.39). In LUX-Lung 6, median overall survival was 23.1 months (95% CI 20.4-27.3) in the afatinib group and 23.5 months (18.0-25.6) in the gemcitabine-cisplatin group (HR 0.93, 95% CI 0.72-1.22, p=0.61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33.3 months (95% CI 26.8-41.5) in the afatinib group versus 21.1 months (16.3-30.7) in the chemotherapy group (HR 0.54, 95% CI 0.36-0.79, p=0.0015); in LUX-Lung 6, it was 31.4 months (95% CI 24.2-35.3) versus 18.4 months (14.6-25.6), respectively (HR 0.64, 95% CI 0.44-0.94, p=0.023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27.6 months (19.8-41.7) in the afatinib group versus 40.3 months (24.3-not estimable) in the chemotherapy group (HR 1.30, 95% CI 0.80-2.11, p=0.29); in LUX-Lung 6, it was 19.6 months (95% CI 17.0-22.1) versus 24.3 months (19.0-27.0), respectively (HR 1.22, 95% CI 0.81-1.83, p=0.34). In both trials, the most common afatinib-related grade 3-4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3-4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3-4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). INTERPRETATION: Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials. FUNDING: Boehringer Ingelheim.
