作者：
Klionsky, Daniel J.;Abdalla, Fabio C.;Abeliovich, Hagai;Abraham, Robert T.;AcevedoArozena, Abraham;Adeli, Khosrow;Agholme, Lotta;Agnello, Maria;Agostinis, Patrizia;AguirreGhiso, Julio A.;Ahn, Hyung Jun;AitMohamed, Ouardia;AitSiAli, Slimane;Akematsu, Takahiko;Akira, Shizuo;AlYounes, Hesham M.;AlZeer, Munir A.;Albert, Matthew L.;Albin, Roger L.;AlegreAbarrategui, Javier
期刊：
AUTOPHAGY,2012年8(4):445-544 ISSN：1554-8627
作者机构：
[Klionsky, Daniel J.; Backues, Steven K.; Bartholomew, Clinton R.; Brech, Andreas; Bridges, Dave] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.;[Abdalla, Fabio C.] Fed Univ Sao Carlos UFSCar, Lab Struct & Funct Biol, Sao Carlos, SP, Brazil.;[Abeliovich, Hagai] Hebrew Univ Jerusalem, Dept Biochem & Food Sci, IL-76100 Rehovot, Israel.;[Abraham, Robert T.] Pfizer Worldwide Res & Dev, Oncol Res Unit, Pearl River, NY USA.;[AcevedoArozena, Abraham] MRC, Mammalian Genet Unit, Harwell, Berks, England.
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.
作者机构：
[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.;[Liu, XiaoQing] Acad Mil Med Sci, Hosp 307, Ctr Canc, Dept Pulm Oncol, Beijing, Peoples R China.
通讯机构：
[Zhou, CC (reprint author)] Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Oncol, Shanghai 200092, 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.
期刊：
NEW ENGLAND JOURNAL OF MEDICINE,2010年362(12):1090-1101 ISSN：0028-4793
通讯作者：
Yang, Wenying
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, WY (reprint author)] 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 >= 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 >= 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：
Naghavi, Mohsen;Wang, Haidong;Lozano, Rafael;Davis, Adrian;Liang, Xiaofeng;Zhou, Maigeng;Vollset, Stein Emil;Ozgoren, Ayse Abbasoglu;Abdalla, Safa;AbdAllah, Foad;Aziz, Muna I. Abdel;Abera, Semaw Ferede;Aboyans, Victor;Abraham, Biju;Abraham, Jerry P.;Abuabara, Katrina E.;Abubakar, Ibrahim;AbuRaddad, Laith J.;AbuRmeileh, Niveen M. E.;Achoki, Tom
期刊：
LANCET,2015年385(9963):117-171 ISSN：0140-6736
通讯作者：
Murray, Christopher J. L.
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; 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; Mokdad, Ali H.; Richardson, Lee; MacIntyre, Michael F.; Liddell, Chelsea; Fleming, Thomas D.; Schumacher, Austin E.; Atkinson, Charles; BertozziVilla, Amelia; 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.; MoradiLakeh, Maziar; GonzalezMedina, Diego; Biryukov, Stan; Brown, Jonathan C.; Wolock, Timothy M.; Moyer, Madeline L.; Pain, Amanda W.; Singh, Lavanya; Graetz, Nicholas; Dansereau, Emily; Ng, Marie; 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; Haagsma, Juanita; Sioson, Edgar; CatalaLopez, Ferrn; Forouzanfar, Mohammad H.; Wang, Haidong] Inst Hlth Metr & Evaluat, Seattle, WA USA.;[Iburg, Kim M.] Aarhus Univ, Aarhus, Denmark.
通讯机构：
[Murray, CJL (reprint author)] 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.
通讯机构：
[Comb, MJ (reprint author)] Cell Signaling Technol, 3 Trask Lane, Danvers, MA 01923 USA.
摘要：
Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFR alpha and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.
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
通讯作者：
Giugliano, Robert P.
作者机构：
[Giugliano, Robert P.; Ruff, Christian T.; Braunwald, Eugene; Murphy, Sabina A.; Wiviott, Stephen D.; Grip, Laura T.; Antman, Elliott M.] Brigham & Womens Hosp, Boston, MA 02115 USA.;[Giugliano, Robert P.; Ruff, Christian T.; Braunwald, Eugene; Murphy, Sabina A.; Wiviott, Stephen D.; Grip, Laura T.; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA.;[Halperin, Jonathan L.] Mt Sinai Med Ctr, New York, NY 10029 USA.;[Waldo, Albert L.] Univ Hosp Case Med Ctr, Cleveland, OH USA.;[Ezekowitz, Michael D.] Thomas Jefferson Med Coll, Philadelphia, PA USA.
通讯机构：
[Giugliano, RP (reprint author)] 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：
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, Deepak L.
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, DL (reprint author)] 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, T (reprint author)] 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：
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.;AguirreGhiso, Julio;Airoldi, Edoardo M.
期刊：
AUTOPHAGY,2016年12(1):1-222 ISSN：1554-8627
通讯作者：
Klionsky, Daniel J.
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;[Bassi, Maria Teresa] anf Scientific Institute IRCCS Eugenio Medea, Laboratory of Molecular Biology , Bosisio Parini, Lecco , Italy;[UmemiyaShirafuji, Rika] aig Obihiro University of Agriculture and Veterinary Medicine, National Research Center for Protozoan Diseases , Obihiro, Hokkaido , Japan
通讯机构：
[Klionsky, DJ (reprint author)] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
通讯机构：
[Wang, P (reprint author)] Chinese Acad Sci, State Key Lab Polymer Phys & Chem, Changchun Inst Appl Chem, Changchun 130022, Peoples R China.
摘要：
In view of the limited ruthenium resource, metal-free organic dyes may play a prominent role in the coming large-scale application of cost-effective dye-sensitized solar cells, if their efficiency and stability can be considerably improved. In this paper we utilized a binay pi-conjugated spacer of ethylenedioxythiophene and dithienosilole to construct a high molar absorption coefficient push-pull dye, characteristic of an intramolecular charge-transfer band peaking at 584 nm measured in chloroform. In comparison with the standard ruthenium sensitizer Z907, this metal-free chromophore C219 endowed a nanocrystalline titania Film with all evident light-harvesting enhancement. leading to an unprecedented 10 0- 10 3% efficiency at the AM 1 5G conditions for dye-sensitized solar cells with nonruthenium dyestuffs, although a highly volatile electrolyte was used. Transient absorption measurements have revealed that even if the kinetics of back-electron transfer and dye regeneration am considerably different for Z907 and C219, the branching ratios of these two charge-transfer channels are over 35 for both dyes, ensuring a high yield of net charge separation at the titania/dye/electrolyte interface. A solvent-free ionic liquid cell with C219 as the sensitizer exhibited an impressive efficiency or 8 9% under a low light intensity of 14.39 mW cm(-2), making it very favorable for the indoor application of flexible dye-sensitized solar cells.
摘要：
This paper is concerned with the stability analysis for systems with time-varying delay in a range. An appropriate type of Lyapunov functionals is proposed to investigate the delay-range-dependent stability problem. The present results may improve the existing ones due to a method to estimate the upper bound of the derivative of Lyapunov functional without ignoring some useful terms and the introduction of additional terms into the proposed Lyapunov functional, which take into account the range of delay. Numerical examples are given to demonstrate the effectiveness and the benefits of the proposed method. (C) 2006 Elsevier Ltd. All rights reserved.
期刊：
ENERGY & ENVIRONMENTAL SCIENCE,2014年7(8):2619-2623 ISSN：1754-5692
通讯作者：
Huang, Jinsong
作者机构：
[Bi, Cheng; Yuan, Yongbo; Wang, Qi; Huang, Jinsong; Dong, Qingfeng; Shao, Yuchuan; Xiao, Zhengguo] Univ Nebraska, Nebraska Ctr Mat & Nanosci, Dept Mech & Mat Engn, Lincoln, NE 68588 USA.;[Gao, Yongli; Wang, Chenggong] Univ Rochester, Dept Phys & Astron, Rochester, NY 14627 USA.;[Gao, Yongli] Cent S Univ, ISUPM, Changsha 410083, Peoples R China.
通讯机构：
[Huang, JS (reprint author)] Univ Nebraska, Nebraska Ctr Mat & Nanosci, Dept Mech & Mat Engn, Lincoln, NE 68588 USA.
摘要：
We report on an interdiffusion method to fabricate pin-hole free perovskite films using a low temperature (<105 degrees C) solution process. A high efficiency of 15.4%, with a fill factor of similar to 80%, was achieved for the devices under one sun illumination. The interdiffusion method results in high device yield, with an efficiency of above 14.5% for more than 85% of the devices.
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.
通讯机构：
[Zhang, XJ (reprint author)] 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.
摘要：
A novel method is proposed in this note for stability analysis of systems with a time-varying delay. Appropriate Lyapunov functional and augmented Lvapunov functional are introduced to establish some improved delay-dependent stability criteria. Less conservative results are obtained by considering the additional useful terms (which are ignored in previous methods) when estimating the upper bound of the derivative of Lyapunov functionals and introducing the new free-weighting matrices. The resulting criteria are extended to the stability analysis for uncertain systems with time-varying structured uncertainties and polytopic-type uncertainties. Numerical examples are given to demonstrate the effectiveness and the benefits of the proposed method.
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, HY (reprint author)] 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.
期刊：
The Lancet. Oncology,2014年15(2):213-222 ISSN：1470-2045
通讯作者：
[Wu, Yi-Long;syylwu@live.cn]Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:
作者机构：
[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;[Kim, Miyoung] Boehringer Ingelheim Korea, Seoul, South Korea;[Zhou, Caicun] Shanghai Pulmonary Hospital, Yangpu District, Shanghai, China
通讯机构：
[Wu, YL (reprint author)] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.
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.
通讯机构：
[Wang, Y (reprint author)] Cent S Univ, Sch Informat Sci & Engn, Changsha 410083, Peoples R China.
关键词：
Control parameters;differential evolution;global numerical optimization;trial vector generation strategy
摘要：
Trial vector generation strategies and control parameters have a significant influence on the performance of differential evolution (DE). This paper studies whether the performance of DE can be improved by combining several effective trial vector generation strategies with some suitable control parameter settings. A novel method, called composite DE (CoDE), has been proposed in this paper. This method uses three trial vector generation strategies and three control parameter settings. It randomly combines them to generate trial vectors. CoDE has been tested on all the CEC2005 contest test instances. Experimental results show that CoDE is very competitive.
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.;MoradiLakeh, 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 (reprint author)] 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.
作者机构：
[Chen, XiaoMin; Lin, Y. C.] Cent S Univ, Sch Mech & Elect Engn, Changsha 410083, Peoples R China.
通讯机构：
[Lin, YC (reprint author)] Cent S Univ, Sch Mech & Elect Engn, Changsha 410083, Peoples R China.
关键词：
Forming;Plastic behavior;Metal matrix
摘要：
In industrial forming processes, the metals and alloys are subject to complex strain, strain-rate, and temperature histories. Understanding the flow behaviors of metals and alloys in hot working has a great importance for designers of metal forming processes. In order to study the workability and establish the optimum hot formation processing parameters for some metals and alloys, a number of research groups have made efforts to carry out the thermo-mechanical experiments (compressive, tensile and torsion tests) over wide forming temperatures and strain-rates, and some constitutive equations were developed to describe the hot deformation behaviors. This paper presents a critical review on some experimental results and constitutive descriptions for metals and alloys in hot working, which were reported in international publications in recent years. In this review paper, the constitutive models are divided into three categories, including the phenomenological, physical-based and artificial neural network models, to introduce their developments, prediction capabilities, and application scopes, respectively. Additionally, some limitations and objective suggestions for the further development of constitutive descriptions for metals and alloys in hot working are proposed. (C) 2010 Elsevier Ltd. All rights reserved.
