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Showing papers by "University of São Paulo published in 2017"


Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

10,401 citations


Journal ArticleDOI
TL;DR: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence‐based interventions to address this problem.
Abstract: BACKGROUND Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHOD ...

4,519 citations


Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.

2,995 citations


Journal ArticleDOI
TL;DR: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden, finding that CVDs remain a major cause of health loss for all regions of the world.

2,525 citations


Journal ArticleDOI
Seth Flaxman1, Rupert R A Bourne2, Serge Resnikoff3, Serge Resnikoff4, Peter Ackland5, Tasanee Braithwaite6, Maria V Cicinelli, Aditi Das7, Jost B. Jonas8, Jill E Keeffe9, John H. Kempen10, Janet L Leasher11, Hans Limburg, Kovin Naidoo4, Kovin Naidoo12, Konrad Pesudovs13, Alexander J Silvester, Gretchen A Stevens14, Nina Tahhan4, Nina Tahhan3, Tien Yin Wong15, Hugh R. Taylor16, Rupert R A Bourne2, Aries Arditi, Yaniv Barkana, Banu Bozkurt17, Alain M. Bron, Donald L. Budenz18, Feng Cai, Robert J Casson19, Usha Chakravarthy20, Jaewan Choi, Maria Vittoria Cicinelli, Nathan Congdon20, Reza Dana21, Rakhi Dandona22, Lalit Dandona23, Iva Dekaris, Monte A. Del Monte24, Jenny deva25, Laura E. Dreer26, Leon B. Ellwein27, Marcela Frazier26, Kevin D. Frick28, David S. Friedman28, João M. Furtado29, H. Gao30, Gus Gazzard31, Ronnie George32, Stephen Gichuhi33, Victor H. Gonzalez, Billy R. Hammond34, Mary Elizabeth Hartnett35, Minguang He16, James F. Hejtmancik, Flavio E. Hirai36, John J Huang37, April D. Ingram38, Jonathan C. Javitt28, Jost B. Jonas8, Charlotte E. Joslin39, John H Kempen10, Moncef Khairallah, Rohit C Khanna9, Judy E. Kim40, George N. Lambrou41, Van C. Lansingh, Paolo Lanzetta42, Jennifer I. Lim43, Kaweh Mansouri, Anu A. Mathew44, Alan R. Morse, Beatriz Munoz, David C. Musch24, Vinay Nangia, Maria Palaiou10, Maurizio Battaglia Parodi, Fernando Yaacov Pena, Tunde Peto20, Harry A. Quigley, Murugesan Raju45, Pradeep Y. Ramulu46, Zane Rankin15, Dana Reza21, Alan L. Robin23, Luca Rossetti47, Jinan B. Saaddine46, Mya Sandar15, Janet B. Serle48, Tueng T. Shen23, Rajesh K. Shetty49, Pamela C. Sieving27, Juan Carlos Silva50, Rita S. Sitorus51, Dwight Stambolian52, Gretchen Stevens14, Hugh Taylor16, Jaime Tejedor, James M. Tielsch28, Miltiadis K. Tsilimbaris53, Jan C. van Meurs, Rohit Varma54, Gianni Virgili55, Ya Xing Wang56, Ningli Wang56, Sheila K. West, Peter Wiedemann57, Tien Wong15, Richard Wormald6, Yingfeng Zheng15 
Imperial College London1, Anglia Ruskin University2, University of New South Wales3, Brien Holden Vision Institute4, International Agency for the Prevention of Blindness5, Moorfields Eye Hospital6, York Hospital7, Heidelberg University8, L V Prasad Eye Institute9, Massachusetts Eye and Ear Infirmary10, Nova Southeastern University11, University of KwaZulu-Natal12, National Health and Medical Research Council13, World Health Organization14, National University of Singapore15, University of Melbourne16, Selçuk University17, University of Miami18, University of Adelaide19, Queen's University Belfast20, Harvard University21, The George Institute for Global Health22, University of Washington23, University of Michigan24, Universiti Tunku Abdul Rahman25, University of Alabama at Birmingham26, National Institutes of Health27, Johns Hopkins University28, University of São Paulo29, Henry Ford Health System30, University College London31, Sankara Nethralaya32, University of Nairobi33, University of Georgia34, University of Utah35, Federal University of São Paulo36, Yale University37, Alberta Children's Hospital38, University of Illinois at Chicago39, Medical College of Wisconsin40, Novartis41, University of Udine42, University of Illinois at Urbana–Champaign43, Royal Children's Hospital44, University of Missouri45, Centers for Disease Control and Prevention46, University of Milan47, Icahn School of Medicine at Mount Sinai48, Mayo Clinic49, Pan American Health Organization50, University of Indonesia51, University of Pennsylvania52, University of Crete53, University of Southern California54, University of Florence55, Capital Medical University56, Leipzig University57
TL;DR: A series of regression models were fitted to estimate the proportion of moderate or severe vision impairment and blindness by cause, age, region, and year, and found that world regions varied markedly in the causes of blindness and vision impairment in this age group.

1,909 citations


Journal ArticleDOI
Joan B. Soriano1, Joan B. Soriano2, Amanuel Alemu Abajobir3, Kalkidan Hassen Abate4, Semaw Ferede Abera, Anurag Agrawal, Muktar Beshir Ahmed4, Amani Nidhal Aichour, Ibtihel Aichour, Miloud Taki Eddine Aichour, Khurshid Alam, Noore Alam, Juma Alkaabi5, Fatma Al-Maskari5, Nelson Alvis-Guzman6, Alemayehu Amberbir, Yaw Ampem Amoako, Mustafa Geleto Ansha, Josep M. Antó, Hamid Asayesh7, Tesfay Mehari Atey8, Euripide Frinel G Arthur Avokpaho, Aleksandra Barac9, Sanjay Basu10, Neeraj Bedi, Isabela M. Benseñor11, Adugnaw Berhane12, Addisu Shunu Beyene13, Addisu Shunu Beyene14, Zulfiqar A Bhutta, Stan Biryukov, Dube Jara Boneya15, Michael Brauer, David O. Carpenter16, David O. Carpenter17, Daniel C Casey, Devasahayam J. Christopher18, Lalit Dandona, Rakhi Dandona, Samath D Dharmaratne19, Huyen Phuc Do, Florian Fischer20, TT Gebrehiwot21, TT Gebrehiwot22, TT Gebrehiwot13, Ayele Geleto22, Ayele Geleto21, Ayele Geleto13, Aloke Gopal Ghoshal, Richard F. Gillum23, Ibrahim Abdelmageem Mohamed Ginawi, Vipin Gupta24, Simon I. Hay, Mohammad Taghi Hedayati25, Nobuyuki Horita26, Nobuyuki Horita27, H. Dean Hosgood28, Mihajlo Jakovljevic, Spencer L. James, Jost B. Jonas, Amir Kasaeian, Yousef Khader, Ibrahim A Khalil, Ejaz Ahmad Khan, Young-Ho Khang, Jagdish Khubchandani, Luke D. Knibbs, Soewarta Kosen, Parvaiz A Koul, G Anil Kumar, Cheru Tesema Leshargie, Xiaofeng Liang, Hassan Magdy Abd El Razek, Azeem Majeed, Deborah Carvalho Malta, Treh Manhertz, Neal Marquez, Alem Mehari, George A. Mensah, Ted R. Miller, Karzan Abdulmuhsin Mohammad, Kedir Endris Mohammed, Shafiu Mohammed, Ali H. Mokdad, Mohsen Naghavi, Cuong Tat Nguyen, Grant Nguyen, Quyen Nguyen, Trang Huyen Nguyen, Dina Nur Anggraini Ningrum, Vuong Minh Nong, Jennifer Ifeoma Obi, Yewande E Odeyemi, Felix Akpojene Ogbo, Eyal Oren, Padukudru Anand Mahesh, Eun-Kee Park, George C Patton, Katherine R. Paulson, Mostafa Qorbani, Reginald Quansah, Anwar Rafay, Mohammad Hifz Ur Rahman, Rajesh Kumar Rai, Salman Rawaf, Nik Reinig, Saeid Safiri, Rodrigo Sarmiento-Suarez, Benn Sartorius, Miloje Savic, Monika Sawhney, Mika Shigematsu, Mari Smith, Fentaw Tadese, George D. Thurston, Roman Topor-Madry, Bach Xuan Tran, Kingsley N. Ukwaja, Job F M van Boven, Vasiliy Victorovich Vlassov, Stein Emil Vollset, Xia Wan, Andrea Werdecker, Sarah Wulf Hanson, Yuichiro Yano, Hassen Hamid Yimam, Naohiro Yonemoto, Chuanhua Yu, Zoubida Zaidi, Maysaa El Sayed Zaki, Alan D. Lopez, Christopher J L Murray, Theo Vos 
TL;DR: The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.

1,601 citations


Journal ArticleDOI
Bin Zhou1, James Bentham1, Mariachiara Di Cesare2, Honor Bixby1  +787 moreInstitutions (231)
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.

1,573 citations


Journal ArticleDOI
Mohammad H. Forouzanfar1, Patrick Liu1, Gregory A. Roth1, Marie Ng1, Stan Biryukov1, Laurie B. Marczak1, Lily Alexander1, Kara Estep1, Kalkidan Hassen Abate2, Tomi Akinyemiju3, Raghib Ali4, Nelson Alvis-Guzman5, Peter Azzopardi, Amitava Banerjee6, Till Bärnighausen7, Till Bärnighausen8, Arindam Basu9, Tolesa Bekele10, Derrick A Bennett4, Sibhatu Biadgilign, Ferrán Catalá-López11, Ferrán Catalá-López12, Valery L. Feigin13, João C. Fernandes14, Florian Fischer15, Alemseged Aregay Gebru16, Philimon Gona17, Rajeev Gupta, Graeme J. Hankey18, Graeme J. Hankey19, Jost B. Jonas20, Suzanne E. Judd3, Young-Ho Khang21, Ardeshir Khosravi, Yun Jin Kim22, Ruth W Kimokoti23, Yoshihiro Kokubo, Dhaval Kolte24, Alan D. Lopez25, Paulo A. Lotufo26, Reza Malekzadeh, Yohannes Adama Melaku16, Yohannes Adama Melaku27, George A. Mensah28, Awoke Misganaw1, Ali H. Mokdad1, Andrew E. Moran29, Haseeb Nawaz30, Bruce Neal, Frida Namnyak Ngalesoni31, Takayoshi Ohkubo32, Farshad Pourmalek33, Anwar Rafay, Rajesh Kumar Rai, David Rojas-Rueda, Uchechukwu K.A. Sampson28, Itamar S. Santos26, Monika Sawhney34, Aletta E. Schutte35, Sadaf G. Sepanlou, Girma Temam Shifa36, Girma Temam Shifa37, Ivy Shiue38, Ivy Shiue39, Bemnet Amare Tedla40, Amanda G. Thrift41, Marcello Tonelli42, Thomas Truelsen43, Nikolaos Tsilimparis, Kingsley N. Ukwaja, Olalekan A. Uthman44, Tommi Vasankari, Narayanaswamy Venketasubramanian, Vasiliy Victorovich Vlassov45, Theo Vos1, Ronny Westerman, Lijing L. Yan46, Yuichiro Yano47, Naohiro Yonemoto, Maysaa El Sayed Zaki, Christopher J L Murray1 
10 Jan 2017-JAMA
TL;DR: In international surveys, although there is uncertainty in some estimates, the rate of elevatedSBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased.
Abstract: Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 95.9 million (95% UI, 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

1,494 citations


Journal ArticleDOI
Rupert R A Bourne1, Seth Flaxman2, Tasanee Braithwaite1, Maria V Cicinelli, Aditi Das, Jost B. Jonas3, Jill E Keeffe4, John H Kempen5, Janet L Leasher6, Hans Limburg, Kovin Naidoo7, Kovin Naidoo8, Konrad Pesudovs9, Serge Resnikoff7, Serge Resnikoff10, Alexander J Silvester11, Gretchen A Stevens12, Nina Tahhan10, Nina Tahhan7, Tien Yin Wong13, Hugh R. Taylor14, Rupert R A Bourne1, Peter Ackland, Aries Arditi, Yaniv Barkana, Banu Bozkurt15, Alain M. Bron16, Donald L. Budenz17, Feng Cai, Robert J Casson18, Usha Chakravarthy19, Jaewan Choi, Maria Vittoria Cicinelli, Nathan Congdon19, Reza Dana20, Rakhi Dandona21, Lalit Dandona22, Iva Dekaris, Monte A. Del Monte23, Jenny deva24, Laura Dreer25, Leon B. Ellwein26, Marcela Frazier25, Kevin D. Frick27, David S. Friedman27, João M. Furtado28, H. Gao29, Gus Gazzard30, Ronnie George, Stephen Gichuhi31, Victor H. Gonzalez, Billy R. Hammond32, Mary Elizabeth Hartnett33, Minguang He14, James F. Hejtmancik26, Flavio E. Hirai34, John J Huang35, April D. Ingram36, Jonathan C. Javitt27, Jost B. Jonas3, Charlotte E. Joslin, John H. Kempen37, John H. Kempen20, Moncef Khairallah, Rohit C Khanna4, Judy E. Kim38, George N. Lambrou39, Van C. Lansingh, Paolo Lanzetta40, Jennifer I. Lim41, Kaweh Mansouri, Anu A. Mathew42, Alan R. Morse, Beatriz Munoz27, David C. Musch23, Vinay Nangia, Maria Palaiou20, Maurizio Battaglia Parodi, Fernando Yaacov Pena42, Tunde Peto19, Harry A. Quigley27, Murugesan Raju43, Pradeep Y. Ramulu27, Alan L. Robin27, Luca Rossetti44, Jinan B. Saaddine45, Mya Sandar46, Janet B. Serle47, Tueng T. Shen22, Rajesh K. Shetty48, Pamela C. Sieving26, Juan Carlos Silva49, Rita S. Sitorus50, Dwight Stambolian37, Gretchen Stevens12, Hugh Taylor14, Jaime Tejedor, James M. Tielsch27, Miltiadis K. Tsilimbaris51, Jan C. van Meurs52, Rohit Varma53, Gianni Virgili54, Jimmy Volmink55, Ya Xing Wang, Ningli Wang56, Sheila K. West27, Peter Wiedemann57, Tien Wong13, Richard Wormald58, Yingfeng Zheng46 
Anglia Ruskin University1, University of Oxford2, Heidelberg University3, L V Prasad Eye Institute4, Massachusetts Eye and Ear Infirmary5, Nova Southeastern University6, Brien Holden Vision Institute7, University of KwaZulu-Natal8, Flinders University9, University of New South Wales10, Royal Liverpool University Hospital11, World Health Organization12, National University of Singapore13, University of Melbourne14, Selçuk University15, University of Burgundy16, University of Miami17, University of Adelaide18, Queen's University Belfast19, Harvard University20, The George Institute for Global Health21, University of Washington22, University of Michigan23, Universiti Tunku Abdul Rahman24, University of Alabama25, National Institutes of Health26, Johns Hopkins University27, University of São Paulo28, Henry Ford Health System29, University College London30, University of Nairobi31, University of Georgia32, University of Utah33, Federal University of São Paulo34, Yale University35, Alberta Children's Hospital36, University of Pennsylvania37, Medical College of Wisconsin38, Novartis39, University of Udine40, University of Illinois at Urbana–Champaign41, Royal Children's Hospital42, University of Missouri43, University of Milan44, Centers for Disease Control and Prevention45, Singapore National Eye Center46, Icahn School of Medicine at Mount Sinai47, Mayo Clinic48, Pan American Health Organization49, University of Indonesia50, University of Crete51, Erasmus University Rotterdam52, University of Southern California53, University of Florence54, Stellenbosch University55, Capital Medical University56, Leipzig University57, Moorfields Eye Hospital58
TL;DR: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected, highlighting the need to scale up vision impairment alleviation efforts at all levels.

1,473 citations


Journal ArticleDOI
Eric Pujade-Lauraine1, Jonathan A. Ledermann2, Frédéric Selle, Val Gebski3, Richard T Penson4, Amit M. Oza5, Jacob Korach6, Tomasz Huzarski7, Andres Poveda, Sandro Pignata, Michael Friedlander8, Nicoletta Colombo9, Philipp Harter, Keiichi Fujiwara10, Isabelle Ray-Coquard11, Susana Banerjee12, Joyce F. Liu4, Elizabeth S. Lowe13, Ralph Bloomfield13, Patricia Pautier14, Tomasz Byrski15, Giovanni Scambia, Maria Ornella Nicoletto, Fiona Nussey, Andrew R Clamp, Richard T. Penson4, Amit M. Oza5, Andrés Poveda Velasco, Manuel Rodrigues, Jean-Pierre Lotz, Diane Provencher, Aleix Prat Aparicio, Laura Vidal Boixader, Clare L. Scott, Kenji Tamura, Mayu Yunokawa, Alla Lisyanskaya16, Jacques Medioni, Nicolas Pécuchet, Coraline Dubot, Thibault De La Motte Rouge, Marie-Christine Kaminsky, Béatrice Weber, Alain Lortholary, Christine Parkinson, Jonathan A. Ledermann2, Sarah Williams, Jonathan Cosin, James Hoffman, Marie Plante, Allan Covens, Gabe S. Sonke17, Florence Joly, Anne Floquet, H. Hirte, Amnon Amit, Tjoung-Won Park-Simon18, Koji Matsumoto, Sergei Tjulandin, Jae Hoon Kim19, Jae Hoon Kim20, Laurence Gladieff, Roberto Sabbatini, David M. O'Malley, Patrick Timmins, Daniel Kredentser, Nuria Laínez Milagro, Maria Pilar Barretina Ginesta, Ariadna Tibau Martorell, Alfonso Gómez de Liaño Lista, Belén Ojeda González, Linda Mileshkin, Masaki Mandai, Ingrid A. Boere, Petronella B. Ottevanger, Joo-Hyun Nam, Elias Abdo Filho21, Salima Hamizi, Francesco Cognetti, David Warshal, Elizabeth Dickson-Michelson, Scott Kamelle, Nathalie McKenzie, Gustavo C. Rodriguez, Deborah K. Armstrong, Eva Chalas, Paul Celano, Kian Behbakht, Susan E Davidson, Stephen Welch, Limor Helpman, Ami Fishman, Ilan Bruchim, Magdalena Sikorska, Anna Słowińska, Wojciech Rogowski, Mariusz Bidziński, Beata Śpiewankiewicz, Antonio Casado Herraez, César Mendiola Fernández, Martina Gropp-Meier, Toshiaki Saito, Kazuhiro Takehara, Takayuki Enomoto, Hidemichi Watari, Chel Hun Choi, Byoung-Gie Kim, Jae Weon Kim20, Jae Weon Kim19, Roberto Hegg, Ignace Vergote15 
TL;DR: Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation.
Abstract: Summary Background Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2 ) mutation using a tablet formulation of olaparib. Methods This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population; safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Findings Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]; hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. Interpretation Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. Funding AstraZeneca.

1,280 citations


Journal ArticleDOI
Tomi Akinyemiju1, Semaw Ferede Abera2, Semaw Ferede Abera3, Muktar Beshir Ahmed4, Noore Alam5, Noore Alam6, Mulubirhan Assefa Alemayohu7, Christine Allen8, Rajaa Al-Raddadi, Nelson Alvis-Guzman9, Yaw Ampem Amoako10, Al Artaman11, Tadesse Awoke Ayele12, Aleksandra Barac, Isabela M. Benseñor13, Adugnaw Berhane2, Zulfiqar A Bhutta14, Jacqueline Castillo-Rivas, Abdulaal A Chitheer, Jee-Young Choi15, Benjamin C Cowie, Lalit Dandona8, Lalit Dandona16, Rakhi Dandona16, Rakhi Dandona8, Subhojit Dey, Daniel Dicker8, Huyen Do Phuc17, Donatus U. Ekwueme18, Maysaa El Sayed Zaki, Florian Fischer19, Thomas Fürst20, Thomas Fürst21, Thomas Fürst22, Jamie Hancock8, Simon I. Hay8, Peter J. Hotez23, Peter J. Hotez24, Sun Ha Jee25, Amir Kasaeian26, Yousef Khader27, Young-Ho Khang15, G Anil Kumar16, Michael Kutz8, Heidi J. Larson28, Alan D. Lopez8, Alan D. Lopez29, Raimundas Lunevicius30, Raimundas Lunevicius31, Reza Malekzadeh26, Colm McAlinden, Toni Meier32, Walter Mendoza33, Ali H. Mokdad8, Maziar Moradi-Lakeh34, Gabriele Nagel35, Quyen Nguyen17, Grant Nguyen8, Felix Akpojene Ogbo36, George C Patton29, David M. Pereira37, Farshad Pourmalek38, Mostafa Qorbani, Amir Radfar39, Gholamreza Roshandel40, Joshua A. Salomon41, Juan Sanabria42, Juan Sanabria43, Benn Sartorius44, Maheswar Satpathy45, Maheswar Satpathy46, Monika Sawhney42, Sadaf G. Sepanlou26, Katya Anne Shackelford8, Hirbo Shore47, Jiandong Sun48, Desalegn Tadese Mengistu7, Roman Topór-Mądry49, Roman Topór-Mądry50, Bach Xuan Tran51, Bach Xuan Tran52, Kingsley N. Ukwaja, Vasiliy Victorovich Vlassov53, Stein Emil Vollset54, Stein Emil Vollset55, Theo Vos8, Tolassa Wakayo4, Elisabete Weiderpass56, Elisabete Weiderpass57, Andrea Werdecker, Naohiro Yonemoto58, Mustafa Z. Younis59, Mustafa Z. Younis41, Chuanhua Yu60, Zoubida Zaidi, Liguo Zhu18, Christopher J L Murray8, Mohsen Naghavi8, Christina Fitzmaurice61, Christina Fitzmaurice8 
University of Alabama at Birmingham1, College of Health Sciences, Bahrain2, University of Hohenheim3, Jimma University4, University of Queensland5, Queensland Government6, Mekelle University7, Institute for Health Metrics and Evaluation8, University of Cartagena9, Komfo Anokye Teaching Hospital10, University of Manitoba11, University of Gondar12, University of São Paulo13, Aga Khan University14, New Generation University College15, Public Health Foundation of India16, Duy Tan University17, Centers for Disease Control and Prevention18, Bielefeld University19, Swiss Tropical and Public Health Institute20, Imperial College London21, University of Basel22, Boston Children's Hospital23, Baylor College of Medicine24, Yonsei University25, Tehran University of Medical Sciences26, Jordan University of Science and Technology27, University of London28, University of Melbourne29, University of Liverpool30, Aintree University Hospitals NHS Foundation Trust31, Martin Luther University of Halle-Wittenberg32, United Nations Population Fund33, Iran University of Medical Sciences34, University of Ulm35, University of Sydney36, University of Porto37, University of British Columbia38, A.T. Still University39, Golestan University40, Harvard University41, Marshall University42, Case Western Reserve University43, University of KwaZulu-Natal44, AIIMS, New Delhi45, Utkal University46, Haramaya University47, Queensland University of Technology48, Wrocław Medical University49, Jagiellonian University Medical College50, Hanoi Medical University51, Johns Hopkins University52, National Research University – Higher School of Economics53, Norwegian Institute of Public Health54, University of Bergen55, University of Tromsø56, Karolinska Institutet57, Kyoto University58, Jackson State University59, Wuhan University60, University of Washington61
TL;DR: In this article, the authors report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol, and an “other” group that encompasses residual causes.
Abstract: Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.

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TL;DR: SDSS-IV as mentioned in this paper is a project encompassing three major spectroscopic programs: the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA), the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and the Time Domain Spectroscopy Survey (TDSS).
Abstract: We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.

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TL;DR: The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA and three overarching principles and 13 recommendations deal with surgery and spinal fractures.
Abstract: To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

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TL;DR: This work describes an electrochemical neuromorphic organic device (ENODe) operating with a fundamentally different mechanism from existing memristors, opening a path towards extreme interconnectivity comparable to the human brain.
Abstract: A neuromorphic device based on the stable electrochemical fine-tuning of the conductivity of an organic ionic/electronic conductor is realized. These devices show high linearity, low noise and extremely low switching voltage. The brain is capable of massively parallel information processing while consuming only ∼1–100 fJ per synaptic event1,2. Inspired by the efficiency of the brain, CMOS-based neural architectures3 and memristors4,5 are being developed for pattern recognition and machine learning. However, the volatility, design complexity and high supply voltages for CMOS architectures, and the stochastic and energy-costly switching of memristors complicate the path to achieve the interconnectivity, information density, and energy efficiency of the brain using either approach. Here we describe an electrochemical neuromorphic organic device (ENODe) operating with a fundamentally different mechanism from existing memristors. ENODe switches at low voltage and energy ( 500 distinct, non-volatile conductance states within a ∼1 V range, and achieves high classification accuracy when implemented in neural network simulations. Plastic ENODes are also fabricated on flexible substrates enabling the integration of neuromorphic functionality in stretchable electronic systems6,7. Mechanical flexibility makes ENODes compatible with three-dimensional architectures, opening a path towards extreme interconnectivity comparable to the human brain.

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TL;DR: The focus of this guideline is to cover nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care.

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TL;DR: While ultrasound elastography has shown promising results for non-invasive assessment of liver fibrosis, new applications in breast, thyroid, prostate, kidney and lymph node imaging are emerging.
Abstract: Elastography-based imaging techniques have received substantial attention in recent years for non-invasive assessment of tissue mechanical properties. These techniques take advantage of changed soft tissue elasticity in various pathologies to yield qualitative and quantitative information that can be used for diagnostic purposes. Measurements are acquired in specialized imaging modes that can detect tissue stiffness in response to an applied mechanical force (compression or shear wave). Ultrasound-based methods are of particular interest due to its many inherent advantages, such as wide availability including at the bedside and relatively low cost. Several ultrasound elastography techniques using different excitation methods have been developed. In general, these can be classified into strain imaging methods that use internal or external compression stimuli, and shear wave imaging that use ultrasound-generated traveling shear wave stimuli. While ultrasound elastography has shown promising results for non-invasive assessment of liver fibrosis, new applications in breast, thyroid, prostate, kidney and lymph node imaging are emerging. Here, we review the basic principles, foundation physics, and limitations of ultrasound elastography and summarize its current clinical use and ongoing developments in various clinical applications.


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TL;DR: A protocol for generating coding-sequence-complete genomes, comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimized library preparation methods for the portable MinION sequencer and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences.
Abstract: Genome sequencing has become a powerful tool for studying emerging infectious diseases; however, genome sequencing directly from clinical samples (ie, without isolation and culture) remains challenging for viruses such as Zika, for which metagenomic sequencing methods may generate insufficient numbers of viral reads Here we present a protocol for generating coding-sequence-complete genomes, comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimized library preparation methods for the portable MinION sequencer (Oxford Nanopore Technologies) and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences The MinION protocol does not require an Internet connection for analysis, making it suitable for field applications with limited connectivity Our method relies on multiplex PCR for targeted enrichment of viral genomes from samples containing as few as 50 genome copies per reaction Viral consensus sequences can be achieved in 1-2 d by starting with clinical samples and following a simple laboratory workflow This method has been successfully used by several groups studying Zika virus evolution and is facilitating an understanding of the spread of the virus in the Americas The protocol can be used to sequence other viral genomes using the online Primal Scheme primer designer software It is suitable for sequencing either RNA or DNA viruses in the field during outbreaks or as an inexpensive, convenient method for use in the lab

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Philip S. Cowperthwaite1, Edo Berger1, V. A. Villar1, Brian D. Metzger2  +158 moreInstitutions (47)
TL;DR: In this article, the Gordon and Betty Moore Foundation (GBMF5076) and the Heising-Simons Foundation (HSPF) have contributed to the creation of the DES-Brazil Consortium.
Abstract: NSF [AST-1411763, AST-1714498, DGE 1144152, PHY-1707954, AST-1518052]; NASA [NNX15AE50G, NNX16AC22G]; National Science Foundation; Kavli Foundation; Danish National Research Foundation; Niels Bohr International Academy; DARK Cosmology Centre; Gordon & Betty Moore Foundation; Heising-Simons Foundation; UCSC; Alfred P. Sloan Foundation; David and Lucile Packard Foundation; European Research Council [ERC-StG-335936]; Gordon and Betty Moore Foundation [GBMF5076]; DOE (USA); NSF (USA); MISE (Spain); STFC (UK); HEFCE (UK); NCSA (UIUC); KICP (U. Chicago); CCAPP (Ohio State); MIFPA (Texas AM); MINECO (Spain); DFG (Germany); CNPQ (Brazil); FAPERJ (Brazil); FINEP (Brazil); Argonne Lab; UC Santa Cruz; University of Cambridge; CIEMAT-Madrid; University of Chicago; University College London; DES-Brazil Consortium; University of Edinburgh; ETH Zurich; Fermilab; University of Illinois; ICE (IEEC-CSIC); IFAE Barcelona; Lawrence Berkeley Lab; LMU Munchen; Excellence Cluster Universe; University of Michigan; NOAO; University of Nottingham; Ohio State University; University of Pennsylvania; University of Portsmouth; SLAC National Lab; Stanford University; University of Sussex; Texas AM University; Gemini Observatory [GS-2017B-Q-8, GS-2017B-DD-4]

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TL;DR: It became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size.
Abstract: The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

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28 Dec 2017-Cell
TL;DR: It is demonstrated that selenolate-based catalysis of the essential mammalian selenoprotein GPX4 is unexpectedly dispensable for normal embryogenesis and the survival of a specific type of interneurons emerges to exclusively depend on selenocysteine-containing GPX 4, thereby preventing fatal epileptic seizures.

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Florence M.G. Cavalli1, Marc Remke2, Marc Remke1, Marc Remke3, Ladislav Rampášek1, John Peacock1, David Shih1, Betty Luu1, Livia Garzia1, Jonathon Torchia1, Carolina Nor1, A. Sorana Morrissy1, Sameer Agnihotri4, Yuan Yao Thompson1, Claudia M. Kuzan-Fischer1, Hamza Farooq1, Keren Isaev1, Keren Isaev5, Craig Daniels1, Byung Kyu Cho6, Seung-Ki Kim6, Kyu-Chang Wang6, Ji Yeoun Lee6, Wiesława Grajkowska7, Marta Perek-Polnik7, Alexandre Vasiljevic, Cécile Faure-Conter, Anne Jouvet8, Caterina Giannini9, Amulya A. Nageswara Rao9, Kay Ka Wai Li10, Ho Keung Ng10, Charles G. Eberhart11, Ian F. Pollack4, Ronald L. Hamilton4, G. Yancey Gillespie12, James M. Olson13, James M. Olson14, Sarah Leary14, William A. Weiss15, Boleslaw Lach16, Boleslaw Lach17, Lola B. Chambless18, Reid C. Thompson18, Michael K. Cooper18, Rajeev Vibhakar19, Peter Hauser20, Marie Lise C. van Veelen21, Johan M. Kros21, Pim J. French21, Young Shin Ra22, Toshihiro Kumabe23, Enrique López-Aguilar24, Karel Zitterbart25, Jaroslav Sterba25, Gaetano Finocchiaro, Maura Massimino, Erwin G. Van Meir26, Satoru Osuka26, Tomoko Shofuda, Almos Klekner27, Massimo Zollo28, Jeffrey R. Leonard29, Joshua B. Rubin29, Nada Jabado30, Steffen Albrecht31, Steffen Albrecht30, Jaume Mora, Timothy E. Van Meter32, Shin Jung33, Andrew S. Moore34, Andrew R. Hallahan34, Jennifer A. Chan35, Daniela Pretti da Cunha Tirapelli36, Carlos Gilberto Carlotti36, Maryam Fouladi37, José Pimentel, Claudia C. Faria, Ali G. Saad38, Luca Massimi39, Linda M. Liau40, Helen Wheeler41, Hideo Nakamura42, Samer K. Elbabaa43, Mario Perezpeña-Diazconti, Fernando Chico Ponce de León, Shenandoah Robinson44, Michal Zapotocky1, Alvaro Lassaletta1, Annie Huang1, Cynthia Hawkins1, Uri Tabori1, Eric Bouffet1, Ute Bartels1, Peter B. Dirks1, James T. Rutka1, Gary D. Bader1, Jüri Reimand5, Jüri Reimand1, Anna Goldenberg1, Vijay Ramaswamy1, Michael D. Taylor1 
TL;DR: Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes.


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TL;DR: Structured interviews are provided and recommend their use in future controlled studies, in particular when trying to extend the parameters applied, to discuss recent regulatory issues, reporting practices and ethical issues.

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10 Oct 2017-JAMA
TL;DR: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality, and these findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.
Abstract: Importance The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory–system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration clinicaltrials.gov Identifier:NCT01374022

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TL;DR: It is shown that, across multiple tree species, loss of xylem conductivity above 60% is associated with mortality, while carbon starvation is not universal, indicating that evidence supporting carbon starvation was not universal.
Abstract: Widespread tree mortality associated with drought has been observed on all forested continents and global change is expected to exacerbate vegetation vulnerability. Forest mortality has implications for future biosphere-atmosphere interactions of carbon, water and energy balance, and is poorly represented in dynamic vegetation models. Reducing uncertainty requires improved mortality projections founded on robust physiological processes. However, the proposed mechanisms of drought-induced mortality, including hydraulic failure and carbon starvation, are unresolved. A growing number of empirical studies have investigated these mechanisms, but data have not been consistently analysed across species and biomes using a standardized physiological framework. Here, we show that xylem hydraulic failure was ubiquitous across multiple tree taxa at drought-induced mortality. All species assessed had 60% or higher loss of xylem hydraulic conductivity, consistent with proposed theoretical and modelled survival thresholds. We found diverse responses in non-structural carbohydrate reserves at mortality, indicating that evidence supporting carbon starvation was not universal. Reduced non-structural carbohydrates were more common for gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and may have a role in reducing hydraulic function. Our finding that hydraulic failure at drought-induced mortality was persistent across species indicates that substantial improvement in vegetation modelling can be achieved using thresholds in hydraulic function.

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TL;DR: This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of Breast cancer, stages of breastcancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.
Abstract: Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

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TL;DR: Only a minority of participants with MDD received minimally adequate treatment: 1 in 5 people in high-income and 1 in 27 in low-/lower-middle-income countries.
Abstract: Background Major depressive disorder (MDD) is a leading cause of disability worldwide. Aims To examine the: (a) 12-month prevalence of DSM-IV MDD; (b) proportion aware that they have a problem needing treatment and who want care; (c) proportion of the latter receiving treatment; and (d) proportion of such treatment meeting minimal standards. Method Representative community household surveys from 21 countries as part of the World Health Organization World Mental Health Surveys. Results Of 51 547 respondents, 4.6% met 12-month criteria for DSM-IV MDD and of these 56.7% reported needing treatment. Among those who recognised their need for treatment, most (71.1%) made at least one visit to a service provider. Among those who received treatment, only 41.0% received treatment that met minimal standards. This resulted in only 16.5% of all individuals with 12-month MDD receiving minimally adequate treatment. Conclusions Only a minority of participants with MDD received minimally adequate treatment: 1 in 5 people in high-income and 1 in 27 in low-/lower-middle-income countries. Scaling up care for MDD requires fundamental transformations in community education and outreach, supply of treatment and quality of services.

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01 Jan 2017-Thorax
TL;DR: A new classification of core processes involved in chest EIT examinations and data analysis is provided, and a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles is provided.
Abstract: Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.

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TL;DR: In patients with Sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell–related pain crises than placebo and was associated with a low incidence of adverse events.
Abstract: BackgroundThe up-regulation of P-selectin in endothelial cells and platelets contributes to the cell–cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell–related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. MethodsIn this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell–related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined a...