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54. READER RESPONSES SATURDAY TALK

Author

Richardson, Robert, Andrews, Robert, Fulton, Barbara, Phillips, Bryan, and Torres, Linda

Subjects
General interest, News, opinion and commentary
Abstract

Baptist leaders embarrassing When the calendar moves around to June, which is the month of the annual meeting of the Southern Baptist Convention, it is time for the convention leadership [...]

Published
2000

55. Viewpoints

Author

Israni, Haku, Vyas, Himanshu, Ahmed, Mustafa, Mintz, Steven, Philips, Lloyd C., Phillips, Bryan, Meagher, John, Pierce, Theodore, and Mcneill, Kindel P.

Subjects
General interest, News, opinion and commentary
Published
2000

60. The tumor suppressor APC differentially regulates multiple β-catenins through the function of axin and CKIα during C. elegans asymmetric stem cell divisions.

Author

Baldwin, Austin T. and Phillips*, Bryan T.

Subjects
*TUMOR suppressor genes, *CATENINS, *AXIN, *STEM cell culture, *CELL division, *CAENORHABDITIS elegans
Abstract

The APC tumor suppressor regulates diverse stem cell processes including gene regulation through Wnt-β-catenin signaling and chromosome stability through microtubule interactions, but how the disparate functions of APC are controlled is not well understood. Acting as part of a Wnt-β-catenin pathway that controls asymmetric cell division, Caenorhabditis elegans APC, APR-1, promotes asymmetric nuclear export of the β-catenin WRM-1 by asymmetrically stabilizing microtubules. Wnt function also depends on a second β-catenin, SYS-1, which binds to the C. elegans TCF POP-1 to activate gene expression. Here, we show that APR-1 regulates SYS-1 levels in asymmetric stem cell division, in addition to its known role in lowering nuclear levels of WRM-1. We demonstrate that SYS-1 is also negatively regulated by the C. elegans homolog of casein kinase 1a (CKIa), KIN-19. We show that KIN-19 restricts APR-1 localization, thereby regulating nuclear WRM-1. Finally, the polarity of APR-1 cortical localization is controlled by PRY-1 (C. elegans Axin), such that PRY-1 controls the polarity of both SYS-1 and WRM-1 asymmetries. We propose a model whereby Wnt signaling, through CKIa, regulates the function of two distinct pools of APC -- one APC pool negatively regulates SYS-1, whereas the second pool stabilizes microtubules and promotes WRM-1 nuclear export. [ABSTRACT FROM AUTHOR]

Published
2014
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62. Reciprocal asymmetry of SYS-1/β-catenin and POP-1 ITCF controls asymmetric divisions in Caenorhabditis elegans.

Author

Phillips, Bryan T., Kidd III, Ambrose R., King, Ryan, Hardin, Jeff, and Kimble, Judith

Subjects
CAENORHABDITIS elegans, CARRIER proteins, DNA, TISSUES, GENE expression, CELL division
Abstract

β-Catenins are conserved regulators of metazoan development that function with TCF DNA-binding proteins to activate transcription. In Caenorhabditis elegans, SYS-1β-catenin and POP-1/TCF regulate several asymmetric divisions, including that of the somatic gonadal precursor cell (SGP). In the distal but not the proximal SGP daughter, SYS-1/β-catenin and POP-1/TCF transcriptionally activate ceh-22 to specify the distal fate. Here, we investigate the distribution of SYS-1/β-catenin and its regulation. Using a rescuing transgene, VNS::SYS-1, which fuses VENUS fluorescent protein to SYS-1, we find more VNS::SYS-1 in distal than proximal SGP daughters, a phenomenon we call "SYS-1 asymmetry." In addition, SYS-1 asymmetry is seen in many other tissues, consistent with the idea that SYS-1 regulates asymmetric divisions broadly during C. elegans development. In particular, SYS-1 is more abundant in E than MS. and SYS-1 is critical for the endodermal fate. In all cases, SYS-1 is reciprocal to POP-1 asymmetry: cells with higher SYS-1 have lower POP-1, and vice versa. SYS-1 asymmetry is controlled posttranslationally and relies on frizzled and dishevelled homologs, which also control POP-1 asymmetry. Therefore, upstream regulators modulate the SYS-1 to POP-1 ratio by increasing SYS-1 and decreasing POP-1 within the same cell. By contrast. SYS-1 asymmetry does not rely on WRM-1, which appears specialized for POP-1 asymmetry. We suggest a two-pronged pathway for control of SYS-1:POP-1, which can robustly accomplish differential gene expression in daughters of an asymmetric cell division. [ABSTRACT FROM AUTHOR]

Published
2007
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63. An expanded domain of fgf3 expression in the hindbrain of zebrafish valentino mutants results in mis-patterning of the otic vesicle.

Author

Su-Jin, Kwak, T, Phillips Bryan, Rebecca, Heck, and B, Riley Bruce

Abstract

The valentino (val) mutation in zebrafish perturbs hindbrain patterning and, as a secondary consequence, also alters development of the inner ear. We have examined the relationship between these defects and expression of fgf3 and fgf8 in the hindbrain. The otic vesicle in val/val mutants is smaller than normal, yet produces nearly twice the normal number of hair cells, and some hair cells are produced ectopically between the anterior and posterior maculae. Anterior markers pax5 and nkx5.1 are expressed in expanded domains that include the entire otic epithelium juxtaposed to the hindbrain, and the posterior marker zp23 is not expressed. In the mutant hindbrain, expression of fgf8 is normal, whereas the domain of fgf3 expression expands to include rhombomere 4 through rhombomere X (an aberrant segment that forms in lieu of rhombomeres 5 and 6). Depletion of fgf3 by injection of antisense morpholino (fgf3-MO) suppresses the ear patterning defects in val/val embryos: Excess and ectopic hair cells are eliminated, expression of anterior otic markers is reduced or ablated, and zp23 is expressed throughout the medial wall of the otic vesicle. By contrast, disruption of fgf8 does not suppress the val/val phenotype but instead interacts additively, indicating that these genes affect distinct developmental pathways. Thus, the inner ear defects observed in val/val mutants appear to result from ectopic expression of fgf3 in the hindbrain. These data also indicate that val normally represses fgf3 expression in r5 and r6, an interpretation further supported by the effects of misexpressing val in wild-type embryos. This is in sharp contrast to the mouse, in which fgf3 is normally expressed in r5 and r6 because of positive regulation by kreisler, the mouse ortholog of val. Implications for co-evolution of the hindbrain and inner ear are discussed.

Published
2002

64. An expanded domain of fgf3 expression in the hindbrain of zebrafish valentino mutants results in mis-patterning of the otic vesicle

Author

Kwak, Su-Jin, Phillips, Bryan T., Heck, Rebecca, and Riley, Bruce B.

Abstract

The valentino (val) mutation in zebrafish perturbs hindbrain patterning and, as a secondary consequence, also alters development of the inner ear. We have examined the relationship between these defects and expression of fgf3 and fgf8 in the hindbrain. The otic vesicle in val/val mutants is smaller than normal, yet produces nearly twice the normal number of hair cells, and some hair cells are produced ectopically between the anterior and posterior maculae. Anterior markerspax5 and nkx5.1 are expressed in expanded domains that include the entire otic epithelium juxtaposed to the hindbrain, and the posterior marker zp23 is not expressed. In the mutant hindbrain,expression of fgf8 is normal, whereas the domain of fgf3expression expands to include rhombomere 4 through rhombomere X (an aberrant segment that forms in lieu of rhombomeres 5 and 6). Depletion of fgf3by injection of antisense morpholino (fgf3-MO) suppresses the ear patterning defects in val/val embryos: Excess and ectopic hair cells are eliminated, expression of anterior otic markers is reduced or ablated, andzp23 is expressed throughout the medial wall of the otic vesicle. By contrast, disruption of fgf8 does not suppress the val/valphenotype but instead interacts additively, indicating that these genes affect distinct developmental pathways. Thus, the inner ear defects observed inval/val mutants appear to result from ectopic expression offgf3 in the hindbrain. These data also indicate that valnormally represses fgf3 expression in r5 and r6, an interpretation further supported by the effects of misexpressing val in wild-type embryos. This is in sharp contrast to the mouse, in which fgf3 is normally expressed in r5 and r6 because of positive regulation by kreisler, the mouse ortholog of val. Implications for co-evolution of the hindbrain and inner ear are discussed.

Published
2002
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65. Zebrafish fgf3and fgf8Encode Redundant Functions Required for Otic Placode Induction

Author

Phillips, Bryan T., Bolding, Kevin, and Riley, Bruce B.

Abstract

Members of the fibroblast growth factor (FGF) family of peptide ligands have been implicated in otic placode induction in several vertebrate species. Here, we have functionally analyzed the roles of fgf3and fgf8in zebrafish otic development. The role of fgf8was assessed by analyzing acerebellar(ace) mutants. fgf3function was disrupted by injecting embryos with antisense morpholino oligomers (MO) specifically designed to block translation of fgf3transcripts. Disruption of either fgf3or fgf8causes moderate reduction in the size of the otic vesicle. Injection of fgf3-MO into ace/acemutants causes much more severe reduction or complete loss of otic tissue. Moreover, preplacode cells fail to express pax8and pax2.1,indicating disruption of early stages of otic induction in fgf3-depleted ace/acemutants. Both fgf3and fgf8are normally expressed in the germring by 50% epiboly and are induced in the primordium of rhombomere 4 by 80% epibloy. In addition, fgf3is expressed during the latter half of gastrulation in the prechordal plate and paraxial cephalic mesendoderm, tissues that either pass beneath or persist near the prospective otic ectoderm. Conditions that alter the pattern of expression of fgf3 and/or fgf8 cause corresponding changes in otic induction. Loss of maternal and zygotic one-eyed pinhead(oep) does not alter expression of fgf3or fgf8in the hindbrain, but ablates mesendodermal sources of fgf signaling and delays otic induction by several hours. Conversely, treatment of wild-type embryos with retinoic acid greatly expands the periotic domains of expression of fgf3, fgf8,and pax8and leads to formation of supernumerary and ectopic otic vesicles. These data support the hypothesis that fgf3 and fgf8 cooperate during the latter half of gastrulation to induce differentiation of otic placodes.

Published
2001
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66. Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013

Author

Meghan D. Mooney, Ken Takahashi, Andrea Stewart, Jonathan C Brown, Shireen Sindi, Amany H Refaat, Ruben Castro, Sara Sheikhbahaei, Kyle R. Heuton, Gillian M. Hansen, Chante Karimkhani, Bryan K. Phillips, Ibrahim Abubakar, Yohannes Kinfu, Victoria F Bachman, Konstantinos Stroumpoulis, Megan Coggeshall, Lucía Cuevas-Nasu, Yichong Li, Vineet K. Chadha, Andrew G. M. Bulloch, Takayoshi Ohkubo, Don C. Des Jarlais, Giancarlo Logroscino, Francis Apolinary Mhimbira, Jefferson G Fernandes, Cheng Huang, Ejaz Ahmad Khan, Fortuné Gbètoho Gankpé, Roderick J Hay, Itamar S. Santos, Zanfina Ademi, Fiona J Charlson, Norlinah Mohamed Ibrahim, Anwar Rafay, Andrew L. Thorne-Lyman, Juanita A. Haagsma, Emmanuel A. Ameh, John J. McGrath, Massimo Cirillo, Wubegzier Mekonnen, Holly Hagan, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Dietrich Plass, Matias Trillini, David Phillips, Braden Te Ao, Wanqing Chen, Yun Jin Kim, David Rojas-Rueda, Christina Papachristou, Andrew E. Moran, Richard A. Gosselin, Maziar Moradi-Lakeh, Soraya Seedat, Janet L Leasher, Belinda K Lloyd, Lorenzo Monasta, Bruno F. Sunguya, Eun-Kee Park, Eduardo A. Undurraga, Mohammad A. AlMazroa, Mohammad H. Forouzanfar, Young-Ho Khang, Vasiliki Stathopoulou, Dima M. Qato, James Scott, Ileana Heredia-Pi, Luca Ronfani, Haidong Kan, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Taavi Tillmann, Wang Wenzhi, Neil Pearce, Eric Y. Tenkorang, Aliya Naheed, Ferrán Catalá-López, Sudan Prasad Neupane, Emily Dansereau, Michael McKee, Derrick A Bennett, Mazeda Hossain, Paul S. F. Yip, Grant Nguyen, Norberto Perico, Miguel Angel Alegretti, Babak Eshrati, Boris Bikbov, Palwasha Anwari, Guoqing Hu, Amelia Bertozzi-Villa, Peter A. Meaney, Farshad Farzadfar, Svetlana Popova, Tara Templin, Hmwe H Kyu, Uche S. Uchendu, Kebede Deribe, Sergey Soshnikov, Nobhojit Roy, Daniel Kim, Ilana N. Ackerman, Homie Razavi, Leslie T. Cooper, Sandra Nolte, David T. Felson, John J Huang, Yang Liu, Fiorella Cavalleri, Adrian Davis, Héctor Gómez Dantés, Klara Dokova, Yuantao Hao, Catalina Medina, Austin E Schumacher, Stan Biryukov, Jane Rowley, Arindam Basu, Jose C. Adsuar, Rosana E. Norman, Yousef Khader, Rafael Alfonso-Cristancho, Sukanta Saha, Simón Barquera, Diego Gonzalez-Medina, Philip B. Mitchell, Lars Barregard, Haidong Wang, Yongmei Li, Ami R. Moore, Marie Ng, Raghib Ali, Peter T. Serina, Lijing L Yan, Ayse Abbasoglu Ozgoren, Ricky Leung, Michelle L. Bell, Tim Driscoll, Azmeraw T. Amare, Farshad Pourmalek, Tea Lallukka, Benjamin O Anderson, Raimundas Lunevicius, Corine Karema, Robert G. Weintraub, Erin C Mullany, Anders Larsson, Glen Mola, Paulo A. Lotufo, Luke Nyakarahuka, Sayed Saidul Alam, Louisa Degenhardt, Hugh R. Taylor, E. Ray Dorsey, Suzanne Polinder, Hilton Lam, Urbano Fra Paleo, David Zonies, Rahman Shiri, Marco A Avila, Alicia Elena Beatriz Lawrynowicz, Katya Anne Shackelford, Lynne Gaffikin, Konstantin Kazanjan, Mark T Mackay, Jasvinder A. Singh, Bryan L. Sykes, Sadaf G. Sepanlou, Chantal Huynh, Rakhi Dandona, Logan Sandar, Lavanya Singh, Dietrich Rothenbacher, Theo Vos, Steven E. Lipshultz, Coen H. Van Gool, Peggy P. Chiang, Mark G. Shrime, Christopher J L Murray, Scott Weichenthal, Jae-Hyun Park, Samia Alhabib, Philimon Gona, Christian Kieling, Yuichiro Yano, Ronny Westerman, Thomas Truelsen, Rajeev Gupta, Megan Bohensky, Abdullatif Husseini, Qing Lan, Luke D. Knibbs, Yousef M. Elshrek, H. Ross Anderson, Guohong Jiang, Madeline L. Moyer, Vinod K. Paul, Wim H. van Brakel, Emin Murat Tuzcu, Kara Estep, Lalit Dandona, Uchechukwu K.A. Sampson, Mohammad Tavakkoli, Ying Jiang, Joseph A Wagner, Mitsuru Mukaigawara, In-Hwan Oh, Siyi Shangguan, Noela M. Prasad, Charles D.A. Wolfe, Borja del Pozo-Cruz, Gokalp Kadri Yentur, Hilda L Harb, Elena Alvarez, Carlos A Castañeda-Orjuela, Mustafa Z. Younis, Herbert C. Duber, Erica Leigh Slepak, George A. Mensah, Knud Juel, Graeme J. Hankey, Natan M. Bornstein, Martha Híjar, Johan Ärnlöv, Mohamed Hsairi, Katherine T. Lofgren, Murray B. Stein, Renata Micha, Luigi Naldi, Margreet ten Have, Bolajoko O. Olusanya, Kyle J Foreman, Kenji Shibuya, F. Gerry R. Fowkes, Abdullah Sulieman Terkawi, Rana J. Asghar, Karen M. Tabb, Kovin Naidoo, Rogelio Pérez-Padilla, Honglei Chen, Antônio Luiz Pinho Ribeiro, Rasmus Havmoeller, Yukito Shinohara, Bongani M. Mayosi, Ernst J Kuipers, Konrad Pesudovs, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Thomas D. Fleming, Pouria Heydarpour, Stephen G. Waller, Nicholas Graetz, Chanda Kulkarni, Peter Brooks, Gulfaraz Khan, Marcel Tanner, Van C. Lansingh, François Alla, Jamie Hancock, Yohannes Adama Melaku, Neeraj Bedi, Anthony D. Woolf, Tariku Jibat Beyene, Amanda W Pain, Eric L. Ding, Narayanaswamy Venketasubramanian, Semaw Ferede Abera, Devina Nand, Odgerel Chimed-Ochir, George D Thurston, Victor Aboyans, Alanur Çavlin, Jefferson Traebert, Michael R. Phillips, Yingfeng Zheng, Baffour Awuah, Carlo Irwin A. Panelo, Selen Begüm Uzun, Muhammad Imran Nisar, Samir Soneji, Veena S. Kulkarni, Mukesh Dherani, Stephen S Lim, Andre Keren, Kingsley N. Ukwaja, Sajjad Ur Rahman, Giuseppe Remuzzi, Kjetil Søreide, Blake Thomson, Samath D Dharmaratne, Christopher D. Blosser, David H. Rothstein, Amanda G. Thrift, Fabrizio Tediosi, Andrew H. Kemp, H. Dean Hosgood, Yoshihiro Kokubo, Miia Kivipelto, Amitava Banerjee, Edgar P. Simard, Reza Malekzadeh, Maggie Lind, Robert P. Dellavalle, Emerito Jose A. Faraon, Lydia S. Atkins, Tom Achoki, Aslam Pervaiz, Peter Scarborough, Hans W. Hoek, Ettore Beghi, Emilie Agardh, Abraham D. Flaxman, Dariush Mozaffarian, Juan R. Sanabria, Muluken Dessalegn, David C. Schwebel, Caitlyn Steiner, Ubai Alsharif, Richard C. Franklin, Gail Davey, Gelin Xu, Reyna A Gutiérrez, Joannie Lortet-Tieulent, Ashish Bhalla, Jost B. Jonas, Paul N. Jensen, Simon I. Hay, Xiaonong Zou, Andre Pascal Kengne, Tolesa Bekele, Brittany Wurtz, Jung-Chen Chang, Joseph Murray, Luciano A. Sposato, Stefan Ma, Summer Lockett Ohno, Charles R. Newton, Bradford D. Gessner, JianLi Wang, Scott B. Patten, Thomas Fürst, Carol Brayne, Christina Fitzmaurice, Peilin Shi, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Peter W. Gething, Cesar Diaz-Torne, Burcu Kucuk Bicer, Bo Norrving, Carly E Levitz, Adam D M Briggs, Sungroul Kim, Isabela M. Benseñor, John A. Crump, Sergey Petrovich Ermakov, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Marcella Montico, Sanjay Krishnaswami, Kim Moesgaard Iburg, Ann Kristin Knudsen, Sun Ha Jee, Valery L. Feigin, Christine M. Budke, Anne Bulchis, Anand Dayama, Jonathan R. Carapetis, Cyrus Cooper, Teresa Shamah Levy, Ismael R. Campos-Nonato, Nataliya A. Foigt, Beth E. Ebel, Max Petzold, Heresh Amini, Ole Frithjof Norheim, Zulfiqar A Bhutta, Dan Poenaru, Jim van Os, Michele E. Murdoch, Samantha M. Colquhoun, Michael H. Criqui, Giorgia Giussani, Man Mohan Mehndiratta, Thomas N. Williams, Chandrashekhar T Sreeramareddy, Chuanhua Yu, Luis M. Coppola, Thomas J. Montine, Alaa Badawi, Eduardo Bernabé, Melvin Barrientos Marzan, James Leigh, Frédéric B. Piel, Ratilal Lalloo, Panniyammakal Jeemon, Maheswar Satpathy, Hélène Carabin, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Ryan M Barber, Fotis Topouzis, Bin Li, Serge Resnikoff, Taavi Lai, Rachelle Buchbinder, Randah R. Hamadeh, Valeria Caso, Holly E. Erskine, Dragos Virgil Davitoiu, Miltiadis K. Tsilimbaris, Rachel L. Pullan, Ben Schöttker, Rafael Lozano, Damian G Hoy, Fiona M. Blyth, Belinda J. Gabbe, Hebe N. Gouda, Farhad Islami, Atte Meretoja, Christopher Margono, Marissa Iannarone, Ronan A Lyons, Wilkister N. Moturi, Donald H. Silberberg, Alexandra Brazinova, Monica Cortinovis, Deena Alasfoor, Richard Matzopoulos, Jerry Abraham, Francesco Saverio Violante, Monika Sawhney, Dorairaj Prabhakaran, Valentina Colistro, Derek F J Fay, Mamta Swaroop, Nima Hafezi-Nejad, John Nelson Opio, Hanne Christensen, Jun She, Soewarta Kosen, Atsushi Goto, Costas A. Christophi, Jeyaraj D. Pandian, Peter J. Hotez, K. Srinath Reddy, Al Artaman, Peter Allebeck, Jonas Minet Kinge, Graham S Cooke, Dan J. Stein, Kawkab Shishani, Laith J. Abu-Raddad, Katrina F Ortblad, Deborah Jarvis, Arsène Kouablan Adou, Barthelemy Kuate Defo, Alan D. Lopez, G Anil Kumar, K.M. Venkat Narayan, Yong Zhao, Rajiv Chowdhury, Hadi Danawi, George C Patton, Vasiliy Victorovich Vlassov, André Karch, Tommi J. Vasankari, Matthias Endres, Ione Jayce Ceola Schneider, Nelson Alvis-Guzman, Charles N Mock, Katharine J Looker, Bach Xuan Tran, Fernando Perez-Ruiz, Harish Chander Gugnani, Reza Assadi, Hannah Hamavid, Rosario Cárdenas, Mohammed I. Albittar, Sarah Derrett, Mohammad Yahya Saeedi, Traolach S. Brugha, Jan Hendrik Richardus, Alireza Esteghamati, Seok Jun Yoon, Josep Maria Haro, Michael Brainin, Ziad A. Memish, Rupert R A Bourne, Katherine B Gibney, David M. Pereira, Kathryn H. Jacobsen, Luc E. Coffeng, Joshua A. Salomon, Xia Wan, Ian Bolliger, Boris I. Pavlin, Karen Sliwa, Tati S. Warouw, Geoffrey Buckle, Chakib Nejjari, Diego De Leo, Ashkan Afshin, Vinay Nangia, Daniel Pope, Johanna M. Geleijnse, Nikhil Tandon, Kelly Bienhoff, Jed D. Blore, Walid Ammar, D. Allen Roberts, Elisabete Weiderpass, Gregory A. Roth, Manami Inoue, James D. Wilkinson, Hideaki Toyoshima, Soufiane Boufous, Ivy Shiue, Edward J Mills, Leilei Duan, Matthew M Coates, Ganesan Karthikeyan, Alberto Ortiz, Steven van de Vijver, David Carpenter, Suzanne Lyn Barker-Collo, Antony Stevens, Sanjay Basu, Maria Cecilia Bahit, Kaire Innos, Lindsay N. Boyers, Nicholas J K Breitborde, Alize J. Ferrari, Timothy M. Wolock, Simerjot K. Jassal, Mohammad Ali Sahraian, Joanna Moschandreas, Howard J. Hoffman, Hideki Higashi, George M. Ruhago, Karzan Abdulmuhsin Mohammad, Mohammed Basulaiman, D. Alex Quistberg, Justin Beardsley, Marcello Tonelli, Maurice Giroud, Karen Edmond, Norito Kawakami, Mohammad T Mashal, Neeraj Bhala, Carl Abelardo T. Antonio, David Tanne, Abhishek Singh, Kazem Rahimi, Vivekanand Jha, Wagner Marcenes, David J. Margolis, Yara A. Halasa, Zewdie Aderaw Alemu, Carrie Beth Peterson, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Robyn M. Lucas, Sarah Wulf, Lars Jacob Stovner, Mohsen Naghavi, Vegard Skirbekk, Ulrich Otto Mueller, Pengpeng Ye, Ali H. Mokdad, Dipan Bose, Saleem M Rana, Jeffrey D Stanaway, Abigail Mclain, Timothy J. Steiner, Amira Shaheen, Stein Emil Vollset, Andrea Werdecker, Michele Meltzer, Richie G Poulton, Joseph R. Masci, Inga Dora Sigfusdottir, Daniel Dicker, Maysaa El Sayed Zaki, Shiwei Liu, Julio C. Montañez Hernandez, Valentina Arsić Arsenijević, William Msemburi, Lope H Barrero, Linhong Wang, Soumya Swaminathan, Harvey Whiteford, Michael F. Macintyre, Berrak Bora Basara, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Carolyn C. Gotay, Niveen M E Abu-Rmeileh, Nicholas J Kassebaum, Shams Eldin Ali Hassan Khalifa, Neil McGill, Murray, Christopher J. L, Barber, Ryan M., Foreman, Kyle J., Ozgoren, Ayse Abbasoglu, Abd-Allah, Foad, Abera, Semaw F., Aboyans, Victor, Abraham, Jerry P., Abubakar, Ibrahim, Abu-Raddad, Laith J., Abu-Rmeileh, Niveen M., Achoki, Tom, Ackerman, Ilana N., Ademi, Zanfina, Adou, Arsène K., Adsuar, José C., Afshin, Ashkan, Agardh, Emilie E., Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I., Alegretti, Miguel A., Alemu, Zewdie A., Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Alla, Françoi, Allebeck, Peter, Almazroa, Mohammad A., Alsharif, Ubai, Alvarez, Elena, Alvis-Guzman, Nelson, Amare, Azmeraw T., Ameh, Emmanuel A., Amini, Heresh, Ammar, Walid, Anderson, H. Ro, Anderson, Benjamin O., Antonio, Carl Abelardo T., Anwari, Palwasha, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J., Assadi, Reza, Atkins, Lydia S., Avila, Marco A., Awuah, Baffour, Bachman, Victoria F., Badawi, Alaa, Bahit, Maria C., Balakrishnan, Kalpana, Banerjee, Amitava, Barker-Collo, Suzanne L., Barquera, Simon, Barregard, Lar, Barrero, Lope H., Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O., Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Bekele, Tolesa, Bell, Michelle L., Benjet, Corina, Bennett, Derrick A., Bensenor, Isabela M., Benzian, Habib, Bernabé, Eduardo, Bertozzi-Villa, Amelia, Beyene, Tariku J., Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A., Bienhoff, Kelly, Bikbov, Bori, Biryukov, Stan, Blore, Jed D., Blosser, Christopher D., Blyth, Fiona M., Bohensky, Megan A., Bolliger, Ian W., Başara, Berrak Bora, Bornstein, Natan M., Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R. A., Boyers, Lindsay N., Brainin, Michael, Brayne, Carol E., Brazinova, Alexandra, Breitborde, Nicholas J. K., Brenner, Hermann, Briggs, Adam D., Brooks, Peter M., Brown, Jonathan C., Brugha, Traolach S., Buchbinder, Rachelle, Buckle, Geoffrey C., Budke, Christine M., Bulchis, Anne, Bulloch, Andrew G., Campos-Nonato, Ismael R., Carabin, Hélène, Carapetis, Jonathan R., Cárdenas, Rosario, Carpenter, David O., Caso, Valeria, Castañeda-Orjuela, Carlos A., Castro, Ruben E., Catalá-López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K., Chang, Jung-Chen, Charlson, Fiona J., Chen, Honglei, Chen, Wanqing, Chiang, Peggy P., Chimed-Ochir, Odgerel, Chowdhury, Rajiv, Christensen, Hanne, Christophi, Costas A., Cirillo, Massimo, Coates, Matthew M., Coffeng, Luc E., Coggeshall, Megan S., Colistro, Valentina, Colquhoun, Samantha M., Cooke, Graham S., Cooper, Cyru, Cooper, Leslie T., Coppola, Luis M., Cortinovis, Monica, Criqui, Michael H., Crump, John A., Cuevas-Nasu, Lucia, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dansereau, Emily, Dargan, Paul I., Davey, Gail, Davis, Adrian, Davitoiu, Dragos V., Dayama, Anand, De Leo, Diego, Degenhardt, Louisa, Del Pozo-Cruz, Borja, Dellavalle, Robert P., Deribe, Kebede, Derrett, Sarah, Des Jarlais, Don C., Dessalegn, Muluken, Dharmaratne, Samath D., Dherani, Mukesh K., Diaz-Torné, Cesar, Dicker, Daniel, Ding, Eric L., Dokova, Klara, Dorsey, E Ray, Driscoll, Tim R., Duan, Leilei, Duber, Herbert C., Ebel, Beth E., Edmond, Karen M., Elshrek, Yousef M., Endres, Matthia, Ermakov, Sergey P., Erskine, Holly E., Eshrati, Babak, Esteghamati, Alireza, Estep, Kara, Faraon, Emerito Jose A., Farzadfar, Farshad, Fay, Derek F., Feigin, Valery L., Felson, David T., Fereshtehnejad, Seyed-Mohammad, Fernandes, Jefferson G., Ferrari, Alize J., Fitzmaurice, Christina, Flaxman, Abraham D., Fleming, Thomas D., Foigt, Nataliya, Forouzanfar, Mohammad H., Fowkes, F Gerry R., Paleo, Urbano Fra., Franklin, Richard C., Fürst, Thoma, Gabbe, Belinda, Gaffikin, Lynne, Gankpé, Fortuné G., Geleijnse, Johanna M., Gessner, Bradford D., Gething, Peter, Gibney, Katherine B., Giroud, Maurice, Giussani, Giorgia, Dantes, Hector Gomez, Gona, Philimon, González-Medina, Diego, Gosselin, Richard A., Gotay, Carolyn C., Goto, Atsushi, Gouda, Hebe N., Graetz, Nichola, Gugnani, Harish C., Gupta, Rahul, Gupta, Rajeev, Gutiérrez, Reyna A., Haagsma, Juanita, Hafezi-Nejad, Nima, Hagan, Holly, Halasa, Yara A., Hamadeh, Randah R., Hamavid, Hannah, Hammami, Mouhanad, Hancock, Jamie, Hankey, Graeme J., Hansen, Gillian M., Hao, Yuantao, Harb, Hilda L., Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I., Hay, Roderick J., Heredia-Pi, Ileana B., Heuton, Kyle R., Heydarpour, Pouria, Higashi, Hideki, Hijar, Martha, Hoek, Hans W., Hoffman, Howard J., Hosgood, H Dean, Hossain, Mazeda, Hotez, Peter J., Hoy, Damian G., Hsairi, Mohamed, Hu, Guoqing, Huang, Cheng, Huang, John J., Husseini, Abdullatif, Huynh, Chantal, Iannarone, Marissa L., Iburg, Kim M., Innos, Kaire, Inoue, Manami, Islami, Farhad, Jacobsen, Kathryn H., Jarvis, Deborah L., Jassal, Simerjot K., Jee, Sun Ha, Jeemon, Panniyammakal, Jensen, Paul N., Jha, Vivekanand, Jiang, Guohong, Jiang, Ying, Jonas, Jost B., Juel, Knud, Kan, Haidong, Karch, André, Karema, Corine K., Karimkhani, Chante, Karthikeyan, Ganesan, Kassebaum, Nicholas J., Kaul, Anil, Kawakami, Norito, Kazanjan, Konstantin, Kemp, Andrew H., Kengne, Andre P., Keren, Andre, Khader, Yousef S., Khalifa, Shams Eldin A., Khan, Ejaz A., Khan, Gulfaraz, Khang, Young-Ho, Kieling, Christian, Kim, Daniel, Kim, Sungroul, Kim, Yunjin, Kinfu, Yohanne, Kinge, Jonas M., Kivipelto, Miia, Knibbs, Luke D., Knudsen, Ann Kristin, Kokubo, Yoshihiro, Kosen, Soewarta, Krishnaswami, Sanjay, Defo, Barthelemy Kuate, Bicer, Burcu Kucuk, Kuipers, Ernst J., Kulkarni, Chanda, Kulkarni, Veena S., Kumar, G Anil, Kyu, Hmwe H., Lai, Taavi, Lalloo, Ratilal, Lallukka, Tea, Lam, Hilton, Lan, Qing, Lansingh, Van C., Larsson, Ander, Lawrynowicz, Alicia E. B., Leasher, Janet L., Leigh, Jame, Leung, Ricky, Levitz, Carly E., Li, Bin, Li, Yichong, Li, Yongmei, Lim, Stephen S., Lind, Maggie, Lipshultz, Steven E., Liu, Shiwei, Liu, Yang, Lloyd, Belinda K., Lofgren, Katherine T., Logroscino, Giancarlo, Looker, Katharine J., Lortet-Tieulent, Joannie, Lotufo, Paulo A., Lozano, Rafael, Lucas, Robyn M., Lunevicius, Raimunda, Lyons, Ronan A., Ma, Stefan, Macintyre, Michael F., Mackay, Mark T., Majdan, Marek, Malekzadeh, Reza, Marcenes, Wagner, Margolis, David J., Margono, Christopher, Marzan, Melvin B., Masci, Joseph R., Mashal, Mohammad T., Matzopoulos, Richard, Mayosi, Bongani M., Mazorodze, Tasara T., Mcgill, Neil W., Mcgrath, John J., Mckee, Martin, Mclain, Abigail, Meaney, Peter A., Medina, Catalina, Mehndiratta, Man Mohan, Mekonnen, Wubegzier, Melaku, Yohannes A., Meltzer, Michele, Memish, Ziad A., Mensah, George A., Meretoja, Atte, Mhimbira, Francis A., Micha, Renata, Miller, Ted R., Mills, Edward J., Mitchell, Philip B., Mock, Charles N., Ibrahim, Norlinah Mohamed, Mohammad, Karzan A., Mokdad, Ali H., Mola, Glen L. D., Monasta, Lorenzo, Hernandez, Julio C. Montañez, Montico, Marcella, Montine, Thomas J., Mooney, Meghan D., Moore, Ami R., Moradi-Lakeh, Maziar, Moran, Andrew E., Mori, Rintaro, Moschandreas, Joanna, Moturi, Wilkister N., Moyer, Madeline L., Mozaffarian, Dariush, Msemburi, William T., Mueller, Ulrich O., Mukaigawara, Mitsuru, Mullany, Erin C., Murdoch, Michele E., Murray, Joseph, Murthy, Kinnari S., Naghavi, Mohsen, Naheed, Aliya, Naidoo, Kovin S., Naldi, Luigi, Nand, Devina, Nangia, Vinay, Narayan, K M. Venkat, Nejjari, Chakib, Neupane, Sudan P., Newton, Charles R., Ng, Marie, Ngalesoni, Frida N., Nguyen, Grant, Nisar, Muhammad I., Nolte, Sandra, Norheim, Ole F., Norman, Rosana E., Norrving, Bo, Nyakarahuka, Luke, Oh, In-Hwan, Ohkubo, Takayoshi, Ohno, Summer L., Olusanya, Bolajoko O., Opio, John Nelson, Ortblad, Katrina, Ortiz, Alberto, Pain, Amanda W., Pandian, Jeyaraj D., Panelo, Carlo Irwin A., Papachristou, Christina, Park, Eun-Kee, Park, Jae-Hyun, Patten, Scott B., Patton, George C., Paul, Vinod K., Pavlin, Boris I., Pearce, Neil, Pereira, David M., Perez-Padilla, Rogelio, Perez-Ruiz, Fernando, Perico, Norberto, Pervaiz, Aslam, Pesudovs, Konrad, Peterson, Carrie B., Petzold, Max, Phillips, Michael R., Phillips, Bryan K., Phillips, David E., Piel, Frédéric B., Plass, Dietrich, Poenaru, Dan, Polinder, Suzanne, Pope, Daniel, Popova, Svetlana, Poulton, Richie G., Pourmalek, Farshad, Prabhakaran, Dorairaj, Prasad, Noela M., Pullan, Rachel L., Qato, Dima M., Quistberg, D Alex, Rafay, Anwar, Rahimi, Kazem, Rahman, Sajjad U., Raju, Murugesan, Rana, Saleem M., Razavi, Homie, Reddy, K Srinath, Refaat, Amany, Remuzzi, Giuseppe, Resnikoff, Serge, Ribeiro, Antonio L., Richardson, Lee, Richardus, Jan Hendrik, Roberts, D Allen, Rojas-Rueda, David, Ronfani, Luca, Roth, Gregory A., Rothenbacher, Dietrich, Rothstein, David H., Rowley, Jane T., Roy, Nobhojit, Ruhago, George M., Saeedi, Mohammad Y., Saha, Sukanta, Sahraian, Mohammad Ali, Sampson, Uchechukwu K. A., Sanabria, Juan R., Sandar, Logan, Santos, Itamar S., Satpathy, Maheswar, Sawhney, Monika, Scarborough, Peter, Schneider, Ione J., Schöttker, Ben, Schumacher, Austin E., Schwebel, David C., Scott, James G., Seedat, Soraya, Sepanlou, Sadaf G., Serina, Peter T., Servan-Mori, Edson E., Shackelford, Katya A., Shaheen, Amira, Shahraz, Saeid, Levy, Teresa Shamah, Shangguan, Siyi, She, Jun, Sheikhbahaei, Sara, Shi, Peilin, Shibuya, Kenji, Shinohara, Yukito, Shiri, Rahman, Shishani, Kawkab, Shiue, Ivy, Shrime, Mark G., Sigfusdottir, Inga D., Silberberg, Donald H., Simard, Edgar P., Sindi, Shireen, Singh, Abhishek, Singh, Jasvinder A., Singh, Lavanya, Skirbekk, Vegard, Slepak, Erica Leigh, Sliwa, Karen, Soneji, Samir, Søreide, Kjetil, Soshnikov, Sergey, Sposato, Luciano A., Sreeramareddy, Chandrashekhar T., Stanaway, Jeffrey D., Stathopoulou, Vasiliki, Stein, Dan J., Stein, Murray B., Steiner, Caitlyn, Steiner, Timothy J., Stevens, Antony, Stewart, Andrea, Stovner, Lars J., Stroumpoulis, Konstantino, Sunguya, Bruno F., Swaminathan, Soumya, Swaroop, Mamta, Sykes, Bryan L., Tabb, Karen M., Takahashi, Ken, Tandon, Nikhil, Tanne, David, Tanner, Marcel, Tavakkoli, Mohammad, Taylor, Hugh R., Te Ao, Braden J., Tediosi, Fabrizio, Temesgen, Awoke M., Templin, Tara, Ten Have, Margreet, Tenkorang, Eric Y., Terkawi, Abdullah S., Thomson, Blake, Thorne-Lyman, Andrew L., Thrift, Amanda G., Thurston, George D., Tillmann, Taavi, Tonelli, Marcello, Topouzis, Foti, Toyoshima, Hideaki, Traebert, Jefferson, Tran, Bach X., Trillini, Matia, Truelsen, Thoma, Tsilimbaris, Miltiadi, Tuzcu, Emin M., Uchendu, Uche S., Ukwaja, Kingsley N., Undurraga, Eduardo A., Uzun, Selen B., Van Brakel, Wim H., Van De Vijver, Steven, Van Gool, Coen H., Van Os, Jim, Vasankari, Tommi J., Venketasubramanian, N, Violante, Francesco S., Vlassov, Vasiliy V., Vollset, Stein Emil, Wagner, Gregory R., Wagner, Joseph, Waller, Stephen G., Wan, Xia, Wang, Haidong, Wang, Jianli, Wang, Linhong, Warouw, Tati S., Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Wenzhi, Wang, Werdecker, Andrea, Westerman, Ronny, Whiteford, Harvey A., Wilkinson, James D., Williams, Thomas N., Wolfe, Charles D., Wolock, Timothy M., Woolf, Anthony D., Wulf, Sarah, Wurtz, Brittany, Xu, Gelin, Yan, Lijing L., Yano, Yuichiro, Ye, Pengpeng, Yentür, Gökalp K., Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa Z., Yu, Chuanhua, Zaki, Maysaa E., Zhao, Yong, Zheng, Yingfeng, Zonies, David, Zou, Xiaonong, Salomon, Joshua A., Lopez, Alan D., Vos, Theo, Medische Sociologie, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, Barber, Ryan M, Foreman, Kyle J, Abd Allah, Foad, Abera, Semaw F, Abraham, Jerry P, Abu Raddad, Laith J, Abu Rmeileh, Niveen M, Ackerman, Ilana N, Adou, Arsène K, Adsuar, José C, Agardh, Emilie E, Albittar, Mohammed I, Alegretti, Miguel A, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Almazroa, Mohammad A, Alvis Guzman, Nelson, Amare, Azmeraw T, Ameh, Emmanuel A, Anderson, Benjamin O, Antonio, Carl Abelardo T, Asghar, Rana J, Atkins, Lydia S, Avila, Marco A, Bachman, Victoria F, Bahit, Maria C, Barker Collo, Suzanne L, Barrero, Lope H, Basulaiman, Mohammed O, Bell, Michelle L, Bennett, Derrick A, Bensenor, Isabela M, Bertozzi Villa, Amelia, Beyene, Tariku J, Bhutta, Zulfiqar A, Blore, Jed D, Blosser, Christopher D, Blyth, Fiona M, Bohensky, Megan A, Bolliger, Ian W, Bornstein, Natan M, Bourne, Rupert R. A, Boyers, Lindsay N, Brayne, Carol E, Breitborde, Nicholas J. K, Briggs, Adam D, Brooks, Peter M, Brown, Jonathan C, Brugha, Traolach S, Buckle, Geoffrey C, Budke, Christine M, Bulloch, Andrew G, Campos Nonato, Ismael R, Carapetis, Jonathan R, Carpenter, David O, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chiang, Peggy P, Chimed Ochir, Odgerel, Christophi, Costas A, Coates, Matthew M, Coffeng, Luc E, Coggeshall, Megan S, Colquhoun, Samantha M, Cooke, Graham S, Cooper, Leslie T, Coppola, Luis M, Criqui, Michael H, Crump, John A, Cuevas Nasu, Lucia, Dargan, Paul I, Davitoiu, Dragos V, Del Pozo Cruz, Borja, Dellavalle, Robert P, Jarlais, Don C. De, Dharmaratne, Samath D, Dherani, Mukesh K, Diaz Torné, Cesar, Ding, Eric L, Dorsey, E. 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Dean, Hotez, Peter J, Hoy, Damian G, Huang, John J, Iannarone, Marissa L, Iburg, Kim M, Jacobsen, Kathryn H, Jarvis, Deborah L, Jassal, Simerjot K, Jensen, Paul N, Jonas, Jost B, Karema, Corine K, Kassebaum, Nicholas J, Kemp, Andrew H, Kengne, Andre P, Khader, Yousef S, Khalifa, Shams Eldin A, Khan, Ejaz A, Khang, Young Ho, Kinge, Jonas M, Knibbs, Luke D, Kuipers, Ernst J, Kulkarni, Veena S, Kumar, G. Anil, Kyu, Hmwe H, Lansingh, Van C, Lawrynowicz, Alicia E. B, Leasher, Janet L, Levitz, Carly E, Lim, Stephen S, Lipshultz, Steven E, Lloyd, Belinda K, Lofgren, Katherine T, Looker, Katharine J, Lortet Tieulent, Joannie, Lotufo, Paulo A, Lucas, Robyn M, Lyons, Ronan A, Macintyre, Michael F, Mackay, Mark T, Margolis, David J, Marzan, Melvin B, Masci, Joseph R, Mashal, Mohammad T, Mayosi, Bongani M, Mazorodze, Tasara T, Mcgill, Neil W, Mcgrath, John J, Meaney, Peter A, Melaku, Yohannes A, Memish, Ziad A, Mensah, George A, Mhimbira, Francis A, Miller, Ted R, Mills, Edward J, Mitchell, Philip B, Mock, Charles N, Mohammad, Karzan A, Mokdad, Ali H, Mola, Glen L. D, Montine, Thomas J, Mooney, Meghan D, Moore, Ami R, Moradi Lakeh, Maziar, Moran, Andrew E, Moturi, Wilkister N, Moyer, Madeline L, Msemburi, William T, Mueller, Ulrich O, Mullany, Erin C, Murdoch, Michele E, Murthy, Kinnari S, Naidoo, Kovin S, Narayan, K. M. Venkat, Neupane, Sudan P, Newton, Charles R, Ngalesoni, Frida N, Nisar, Muhammad I, Norheim, Ole F, Norman, Rosana E, Oh, In Hwan, Ohno, Summer L, Olusanya, Bolajoko O, Pain, Amanda W, Pandian, Jeyaraj D, Panelo, Carlo Irwin A, Park, Eun Kee, Park, Jae Hyun, Patten, Scott B, Patton, George C, Paul, Vinod K, Pavlin, Boris I, Pereira, David M, Perez Padilla, Rogelio, Perez Ruiz, Fernando, Peterson, Carrie B, Phillips, Michael R, Phillips, Bryan K, Phillips, David E, Piel, Frédéric B, Poulton, Richie G, Prasad, Noela M, Pullan, Rachel L, Qato, Dima M, Quistberg, D. Alex, Rahman, Sajjad U, Rana, Saleem M, Reddy, K. Srinath, Ribeiro, Antonio L, Roberts, D. Allen, Rojas Rueda, David, Roth, Gregory A, Rothstein, David H, Rowley, Jane T, Ruhago, George M, Saeedi, Mohammad Y, Sampson, Uchechukwu K. A, Sanabria, Juan R, Santos, Itamar S, Schneider, Ione J, Schumacher, Austin E, Schwebel, David C, Scott, James G, Sepanlou, Sadaf G, Serina, Peter T, Servan Mori, Edson E, Shackelford, Katya A, Shrime, Mark G, Sigfusdottir, Inga D, Silberberg, Donald H, Simard, Edgar P, Singh, Jasvinder A, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Stanaway, Jeffrey D, Stein, Dan J, Stein, Murray B, Steiner, Timothy J, Stovner, Lars J, Sunguya, Bruno F, Sykes, Bryan L, Tabb, Karen M, Taylor, Hugh R, Ao, Braden J. Te, Temesgen, Awoke M, Tenkorang, Eric Y, Terkawi, Abdullah S, Thorne Lyman, Andrew L, Thrift, Amanda G, Thurston, George D, Tran, Bach X, Tuzcu, Emin M, Uchendu, Uche S, Ukwaja, Kingsley N, Undurraga, Eduardo A, Uzun, Selen B, Van Brakel, Wim H, van Gool, Coen H, Vasankari, Tommi J, Violante, Francesco S, Vlassov, Vasiliy V, Wagner, Gregory R, Waller, Stephen G, Warouw, Tati S, Weintraub, Robert G, Whiteford, Harvey A, Wilkinson, James D, Williams, Thomas N, Wolfe, Charles D, Wolock, Timothy M, Woolf, Anthony D, Yan, Lijing L, Yentür, Gökalp K, Yoon, Seok Jun, Younis, Mustafa Z, Zaki, Maysaa E, Salomon, Joshua A, Lopez, Alan D, Computational Science and Engineering Department [Daresbury] ( STFC ), Science & Technologie Facilities Council, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Weill Cornell Medical College - Qatar, Qatar Foundation - Education City, Doha, Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Karolinska Institute, karolinska institute, Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Wisconsin Division of Public Health, Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department [Bristol], University of Bristol [Bristol], Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, University of Southampton [Southampton], Imperial College London, Neurology Department, Ichilov Medical Center, Department of Public Health and Primary Care, Cambridge University, Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Université de Tours, Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Parasitology, STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Tennent Institute of Ophthalmology, National University of Singapore ( NUS ), Multidisciplinary Nanotechnology Centre, Swansea University, Department of Computer Sciences [Scheffield], University of Sheffield [Sheffield], Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Glasgow Centre for Physical Organic Chemistry, University of Glasgow, King‘s College London, Université Panthéon-Sorbonne - UFR Science Politique ( UP1 UFR11 ), Université Panthéon-Sorbonne ( UP1 ), National Diagnostics Centre ( NDC ), National University of Ireland [Galway] ( NUI Galway ), Arthritis Research UK Epidemiology Unit ( MANCHESTER - Arthritis Research ), University of Manchester [Manchester], CEGOT - Porto, Universidade do Porto [Porto], Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Department of Biology [Miami], University of Miami [Coral Gables], Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] ( WUR ), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), University of Connecticut ( UCONN ), Norwegian Institute for Air Research ( NILU ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), School of Physics and Astronomy, Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Université Catholique de Louvain ( UCL ), Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Univ New Delhi, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Karolinska Institutet [Stockholm], Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center ( TRDDC ), TCS Innovation Labs, Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency ( FOI ), Centre de Recherche en Information Biomédicale sino-français ( CRIBS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Southeast University [Jiangsu]-School of Computer Science and Engineering, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), School of Business and Informatics, University of Boras, Department of Mechanical and Automation Engineering ( CAD Laboratory ), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), Department of plant pathology and microbiology - centre for sustainable pest and disease management, Rothamsted Research, RGU, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), Istituto Dalle Molle di Studi sull'Intelligenza Artificiale ( IDSIA ), Università della Svizzera italiana ( USI ) -Scuola universitaria professionale della Svizzera italiana [Manno] ( SUPSI ), Anaesthetics, Southampton University Hospital, Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, PennState University [Pennsylvania] ( PSU ), University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Department of epidemiology and Public Health, Faculty of Medicine, Hong Kong Baptist University ( HKBU ), Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Department of Neurology Lunds University Hospital Lund, Services répartis, Architectures, MOdélisation, Validation, Administration des Réseaux ( SAMOVAR ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ) -Centre National de la Recherche Scientifique ( CNRS ), Département Réseaux et Services Multimédia Mobiles ( RS2M ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ), Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], Institut Lumière Matière [Villeurbanne] ( ILM ), Université Claude Bernard Lyon 1 ( UCBL ), World Health Organization, Nordic School of Public Health, The James Hutton Institute, Sero, Sero consulting, Evolutionary Ecology of Infectious Disease Group, Department of Zoology, Horia Hulubei National Institute for Physics and Nuclear Engineering, Dunedin School of Medicine, University of Otago, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Dept.of Computer Science, Indian Institute of Technology Madras ( IIT Madras ), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Clinical Epidemiology and Aging Research, German Cancer Research Center, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Symantec, European Microsoft Innovation Center ( EMIC ), Microsoft Corporation [Redmond, Wash.], Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), Novartis institute for tropical diseases, Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Departments of Anatomy and Cell Biology, Wayne State University School of Medicine, Departments of Ophthalmology, Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), Laboratory for Atmospheric and Space Physics [Boulder] ( LASP ), University of Colorado Boulder [Boulder], University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Yale School of Medicine-Yale School of Medicine-Yale Stem Cell Center, Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute ( NEST ), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology ( LICB ), National Institutes of Health ( NIH ), Institute of Human Genetics, Bonn Universität [Bonn], Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] ( KTH ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, NICTA [Eveleigh], National ICT Australia [Sydney] ( NICTA ), Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), German Research Centre for Geosciences - Helmholtz-Centre Potsdam ( GFZ ), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Neurorestoration Group, King‘s College London-Wolfson Centre for Age-related Diseases, Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Computational Science and Engineering Department [Daresbury] (STFC), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Weill Cornell Medicine [Qatar], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, University of Southampton, University of Cambridge [UK] (CAM), Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours (UT), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Stanford University, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), National University of Singapore (NUS), Université Paris 1 Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), Université Paris 1 Panthéon-Sorbonne (UP1), National Diagnostics Centre (NDC), National University of Ireland [Galway] (NUI Galway), Arthritis Research UK Epidemiology Unit (MANCHESTER - Arthritis Research), Universidade do Porto = University of Porto, Advanced Laboratories on Embedded Systems [Roma] (ALES), Wageningen University and Research [Wageningen] (WUR), University of Oxford, Universitat Politècnica de Catalunya [Barcelona] (UPC), Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), University of Connecticut (UCONN), Norwegian Institute for Air Research (NILU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Tehran, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), The George Washington University (GW), Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Catholique de Louvain = Catholic University of Louvain (UCL), Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), School of Physics and Astronomy [St Andrews], Tata Research Development and Design Center (TRDDC), MOLTECH-Anjou, Université d'Angers (UA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Swedish Defense Research Agency (FOI), Centre de Recherche en Information Biomédicale sino-français (CRIBS), Université de Rennes (UR)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Image Science and Technology [Nanjing] (LIST), Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Biotechnology and Biological Sciences Research Council (BBSRC)-Biotechnology and Biological Sciences Research Council (BBSRC), Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituto Dalle Molle di Studi sull'Intelligenza Artificiale (IDSIA), Università della Svizzera italiana = University of Italian Switzerland (USI)-Scuola universitaria professionale della Svizzera italiana = University of Applied Sciences and Arts of Southern Switzerland [Manno] (SUPSI), Pennsylvania State University (Penn State), Penn State System-Penn State System, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Hong Kong Baptist University (HKBU), Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Services répartis, Architectures, MOdélisation, Validation, Administration des Réseaux (SAMOVAR), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), Département Réseaux et Services Multimédia Mobiles (TSP - RS2M), University of Melbourne, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Otago [Dunedin, Nouvelle-Zélande], Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Indian Institute of Technology Madras (IIT Madras), Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Microsoft Innovation Center (EMIC), Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Novartis Institute for Tropical Diseases (NITD), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Mathematical Modeling (CMM), Universidad de Chile = University of Chile [Santiago] (UCHILE), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), University of Colorado [Boulder], University of Occupational and Environmental Health [Kitakyushu] (UEOH), Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Yale University [New Haven]-Yale School of Medicine [New Haven, Connecticut] (YSM), Nanoscience Institute (NEST), University of Pisa - Università di Pisa, Laboratory Of Immune Cell Biology (LICB), National Institutes of Health [Bethesda] (NIH), Rheinische Friedrich-Wilhelms-Universität Bonn, Royal Institute of Technology [Stockholm] (KTH ), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), National ICT Australia [Sydney] (NICTA), Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Paris 1 Panthéon-Sorbonne (UP1)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), German Research Centre for Geosciences - Helmholtz-Centre Potsdam (GFZ), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Kardiyoloji, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota [Twin Cities], Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Université Panthéon-Sorbonne - UFR Science Politique (UP1 UFR11), Université Panthéon-Sorbonne (UP1), Wageningen University and Research Centre [Wageningen] (WUR), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), George Washington University (GW), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Catholique de Louvain (UCL), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Southeast University [Jiangsu]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Università della Svizzera italiana (USI)-Scuola universitaria professionale della Svizzera italiana [Manno] (SUPSI), California Institute of Technology (CALTECH)-NASA, Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP)-Centre National de la Recherche Scientifique (CNRS), Département Réseaux et Services Multimédia Mobiles (RS2M), Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Université Grenoble Alpes (UGA), Universidad de Santiago de Chile [Santiago] (USACH), Yale University [New Haven]-Yale University School of Medicine, Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Université de Nantes - Faculté des Sciences et des Techniques, Grelier, Elisabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Universidade do Porto, Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Toulouse 1 Capitole (UT1), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Università degli studi di Bari Aldo Moro (UNIBA), École des Ponts ParisTech (ENPC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università della Svizzera italiana = University of Italian Switzerland (USI)-Scuola universitaria professionale della Svizzera italiana [Manno] (SUPSI), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Universiteit Gent = Ghent University [Belgium] (UGENT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-CHU Limoges-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut de Chimie du CNRS (INC)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Nantes (ECN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Wolfson Centre for Age-related Diseases-King‘s College London, Cell biology, Public Health, Epidemiology, Health Technology Assessment (HTA), Erasmus MC other, Pathology, and Cardiothoracic Surgery

Subjects
Gerontology, Male, CHANGING RELATION, Nutrition and Disease, MESH : Life Expectancy, MESH : Aged, ECONOMIC-DEVELOPMENT, Poison control, MESH: Global Health, Global Health, Socioeconomic Factor, Communicable Disease, MESH : Chronic Disease, Health Transition, Voeding en Ziekte, Quality-Adjusted Life Year, SELF-RATED HEALTH, MESH : Socioeconomic Factors, Medicine, MESH : Female, MESH: Mortality, Premature, 2. Zero hunger, MESH: Aged, education.field_of_study, MESH: Middle Aged, Mortality rate, Medicine (all), GBD2013 diseases, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Middle Aged, 3. Good health, MESH : Wounds and Injuries, Epidemiological transition, MESH: Quality-Adjusted Life Years, MESH: Communicable Diseases, NONCOMMUNICABLE DISEASES, Female, Quality-Adjusted Life Years, MESH: Life Expectancy, MESH: Health Transition, Human, MESH: Socioeconomic Factors, ACUTE MYOCARDIAL-INFARCTION, MESH : Male, MORTALITY TRENDS, Population, MESH : Health Transition, Communicable Diseases, Article, Life Expectancy, EUROPEAN-UNION, SDG 3 - Good Health and Well-being, General & Internal Medicine, SYSTEMATIC ANALYSIS, Disability-adjusted life year, Humans, Life Science, MESH : Middle Aged, Mortality, education, Premature, MESH : Mortality, Premature, VLAG, Aged, MESH: Humans, business.industry, Mortality, Premature, MESH: Chronic Disease, MESH : Communicable Diseases, Wounds and Injurie, MESH : Humans, MESH : Quality-Adjusted Life Years, Non-communicable disease, Chronic Disease, Socioeconomic Factors, Wounds and Injuries, medicine.disease, MESH: Male, LOW SOCIOECONOMIC-STATUS, Years of potential life lost, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Wounds and Injuries, Life expectancy, RISK-FACTORS, MESH : Global Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Demography
Abstract

Summary Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. Funding Bill & Melinda Gates Foundation. BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

Published
2015

67. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Author

Haidong Wang, Liddell, Chelsea A., Coates, Matthew M., Mooney, Meghan D., Levitz, Carly E., Schumacher, Austin E., Apfel, Henry, lannarone, Marissa, Phillips, Bryan, Lofgren, Katherine T., Sandar, Logan, Dorrington, Rob E., Rakovac, Ivo, Jacobs, Troy A., Xiaofeng Liang, Maigeng Zhou, Jun Zhu, Gonghuan Yang, Yanping Wang, and Shiwei Liu

Subjects
*CHILD mortality, *INFANT mortality, *NEONATAL mortality, *CHILDBIRTH
Abstract

The article discusses a study which examined global trends in neonatal, infant and under-5 mortality from 1990 to 2013. Topics discussed include a reduction in child mortality rate, an increase in the number of child births in 2013 as compared to 1990, and developing countries expected to achieve the Millennium Development Goal 4 (MDG 4).

Published
2014
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68. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013

Author

Soumya Swaminathan, Berrak Bora Basara, Niveen M E Abu-Rmeileh, Shams Eldin Ali Hassan Khalifa, Nadim E. Karam, Jongmin Lee, Roberto Tchio Talongwa, Inga Dora Sigfusdottir, Yang Yang, Stein Emil Vollset, Joseph R. Masci, Daniel Dicker, Maysaa El Sayed Zaki, Shiwei Liu, Valentina Arsić Arsenijević, Ting Wu Chuang, Linhong Wang, Xiao Rong Wang, Bryan K. Phillips, Don C. Des Jarlais, Vasco Manuel Pedro Machado, Vasiliki Stathopoulou, David Phillips, Luke Nyakarahuka, Leslie T. Cooper, Sandra Nolte, Charles R. Newton, Christina Papachristou, Stephen G. Waller, Carlos Magis-Rodriguez, D. Allen Roberts, Elisabete Weiderpass, Aliya Naheed, Andre Keren, Amanda J. Mason-Jones, Karen J. Courville, Ted R. Miller, Kinnari S. Murthy, Bolajoko O. Olusanya, Tommi Vasankari, Kyle J Foreman, Gabriel Alcalá-Cerra, Yousef Khader, Lorenzo Monasta, Austine Olufemi Adeyemo, Rakhi Dandona, Sanjay Basu, Samir Soneji, Rana J. Asghar, Yohannes Adama Melaku, Rafael Alfonso-Cristancho, John Q. Wong, Yoshihiro Kokubo, Young-Ho Khang, Dhruv S. Kazi, Tom Achoki, Homie Razavi, Uche S. Uchendu, Ashish Bhalla, Ferrán Catalá-López, Peggy Pei-Chia Chiang, Kim Moesgaard Iburg, Kaire Innos, Nicholas J K Breitborde, Zacharie Tsala Dimbuene, Elena Alvarez, Vafa Rahimi-Movaghar, Qing Lan, Simon I. Hay, Kaushalendra Kumar, Ubai Alsharif, Scott B. Patten, Gelin Xu, Theo Vos, Kalpana Balakrishnan, Raghib Ali, Marcella Montico, Andrea P. Silva, Robert G. Weintraub, Timothy M. Wolock, Mohammad Ali Sahraian, Heidi J. Larson, Kingsley N. Ukwaja, Saad B. Omer, Scott Weichenthal, D. Alex Quistberg, Justin Beardsley, Chandrashekhar T Sreeramareddy, Jennifer H MacLachlan, Hsien-Ho Lin, H. Dean Hosgood, Karzan Abdulmuhsin Mohammad, Ryan M Barber, Ibrahim Abubakar, Irma Khonelidze, Ileana B. Heredia Pi, Cyrus Cooper, Hilton Lam, Urbano Fra Paleo, Joshua A. Salomon, Ricky Leung, Farshad Pourmalek, Robert G. Nelson, Konstantinos Stroumpoulis, Megan Coggeshall, Mazin J. Al Kahbouri, Richard G. Ellenbogen, Hwashin Hyun Shin, Ida Kankindi, Guohong Jiang, Yanping Wang, Daniel Obadare Fijabi, Carlos A Castañeda-Orjuela, Chakib Nejjari, Diego De Leo, Rashmi Gupta, Gene F. Kwan, Johanna M. Geleijnse, Kenji Shibuya, Hassan Amini, Nsanzimana Sabin, Benjamin C Cowie, Karen M. Tabb, Chanda Kulkarni, Jed D. Blore, Amado D Quezada, Norito Kawakami, Walid Ammar, Van C. Lansingh, François Alla, Seyed-Mohammad Fereshtehnejad, Yichong Li, Vineet K. Chadha, Jasvinder A. Singh, Agnes Binagwaho, Andrew L. Thorne-Lyman, Denis Nash, Palwasha Anwari, Mohammad T Mashal, Kim Yun Jin, Steven E. Lipshultz, Veena S. Kulkarni, Amitava Banerjee, Naohiro Yonemoto, James D. Wilkinson, Aslam Pervaiz, Emilie Agardh, Barthelemy Kuate Defo, Alan D. Lopez, Carl Abelardo T. Antonio, Abraham D. Flaxman, Boris I. Pavlin, Karen Sliwa, Dima M. Qato, G Anil Kumar, Lynne Gaffikin, K.M. Venkat Narayan, Luca Ronfani, Kazem Rahimi, Vivekanand Jha, Gokalp Kadri Yentur, Wagner Marcenes, Giuseppe Remuzzi, Anwar Rafay, Anand Dayama, Robert Quentin Reilly, Alaa Badawi, Selen Begüm Uzun, James Leigh, Vinay Nangia, Ivy Shiue, J Brown, Nobhojit Roy, Genesis May J. Samonte, Edward J Mills, Soewarta Kosen, Atsushi Goto, Sajjad Ur Rahman, Jose C. Adsuar, Semaw Ferede Abera, Jefferson Traebert, Amiran Gamkrelidze, Andrew H. Kemp, Vasiliy Victorovich Vlassov, André Karch, Edgar P. Simard, Aref A. Bin Abdulhak, Samath D Dharmaratne, Ione Jayce Ceola Schneider, Andre Pascal Kengne, Corine Karema, Harish Chander Gugnani, Reza Assadi, Glen Mola, Paulo A. Lotufo, Christopher J L Murray, Rajeev Gupta, Philimon Gona, Mustafa Z. Younis, Herbert C. Duber, Mitchell T. Wallin, Arjun Lakshmana Balaji, Max Petzold, Francesco Saverio Violante, Monika Sawhney, Kovin Naidoo, Mercedes Colomar, Chuanhua Yu, Mitsuru Mukaigawara, Emerito Jose A. Faraon, Jung-Chen Chang, A Artaman, Muhammad Imran Nisar, Dickens Akena, Xiao Nong Zou, Knud Juel, Mohammed I. Albittar, Mohammad Yahya Saeedi, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Graeme J. Hankey, Jerry Puthenpurakal Abraham, Mouhanad Hammami, Zulfiqar A Bhutta, Rintaro Mori, Maia Kereselidze, Josep Maria Haro, Emily Dansereau, Michael Brainin, Elizabeth Glaser, Ziad A. Memish, Anders Larsson, Solomon Meseret Woldeyohannes, Azmeraw T. Amare, Louisa Degenhardt, Yuichiro Yano, Luke D. Knibbs, Sadaf G. Sepanlou, Hilda L Harb, In-Hwan Oh, Katherine B Gibney, Abdullah Sulieman Terkawi, Adansi A. Amankwaa, Nicholas Graetz, Fortuné Gbètoho Gankpé, Vincent Nowaseb, David M. Pereira, Alan J Thomson, Miguel Angel Alegretti, Rupak Shivakoti, Adnan M. Durrani, Dipan Bose, Saleem M Rana, Mohammad Taghi Hedayati, Mohsen Naghavi, Vegard Skirbekk, Walter Mendoza, Ali H. Mokdad, Soraya Seedat, Zewdie Aderaw Alemu, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Paul S. F. Yip, Marek Majdan, Peter A. Meaney, Kebede Deribe, Paul N. Jensen, Fabiola Mejía-Rodríguez, Bradford D. Gessner, Ami R. Moore, Marie Ng, Maigeng Zhou, Mohammad H. Forouzanfar, John J Huang, Tim Driscoll, Samia Alhabib, Jun Zhu, Michael H. Criqui, Eduardo Bernabé, Lalit Dandona, Miltiadis K. Tsilimbaris, Borja del Pozo-Cruz, Johan Ärnlöv, Luigi Naldi, Tariku Jibat Beyene, Rasmus Havmoeller, Bongani M. Mayosi, Konrad Pesudovs, Richard A. White, Ejaz Ahmad Khan, Orish Ebere Orisakwe, Graça Maria Ferreira De Lima, Yang Liu, Haidong Wang, Yongmei Li, Bryan L. Sykes, Ronny Westerman, Vinod K. Paul, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Narayanaswamy Venketasubramanian, Uur Dilmen, Stephen S Lim, Andrew Vallely, Alireza Esteghamati, Seok Jun Yoon, John Hornberger, Kathryn H. Jacobsen, Yong Zhao, Thomas D. Fleming, Nelson Alvis-Guzman, Damian G Hoy, Hebe N. Gouda, Mall Leinsalu, Elizabeth Johnson, Wilkister N. Moturi, Bach Xuan Tran, Donald H. Silberberg, Yingfeng Zheng, Lydia S. Atkins, Hans W. Hoek, Muluken Dessalegn, David C. Schwebel, Christopher C. Mapoma, Jost B. Jonas, Tolesa Bekele, Ibrahim Abdelmageem Mohamed Ginawi, Bulat Idrisov, Man Mohan Mehndiratta, Thomas N. Williams, Jeffrey A. Towbin, Caterina Guinovart, Jeyaraj D Pandian, Panniyammakal Jeemon, Taavi Lai, Haidong Kan, Tasara T. Mazorodze, Murugesan Raju, Randah R. Hamadeh, Neil Pearce, Melvin Barrientos Marzan, Nima Hafezi-Nejad, John Nelson Opio, Deena Alasfoor, Peter J. Hotez, Jonas Minet Kinge, Peter J. Allen, Eric Y. Tenkorang, Sudan Prasad Neupane, Laith J. Abu-Raddad, Katrina F Ortblad, Arsène Kouablan Adou, Farshad Farzadfar, Sergey Soshnikov, Neeraj Bhala, Sara Sheikhbahaei, Kyle R. Heuton, Michelle L. Bell, Yohannes Kinfu, Takayoshi Ohkubo, Belinda K Lloyd, R. Kumar, Jan Hendrik Richardus, Benjamin O. Anderson, Cell biology, Epidemiology, Public Health, Erasmus MC other, Pathology, Cardiothoracic Surgery, Murray, Christopher J.L, Ortblad, Katrina F., Guinovart, Caterina, Lim, Stephen S., Wolock, Timothy M., Roberts, D. Allen, Dansereau, Emily A., Graetz, Nichola, Barber, Ryan M., Brown, Jonathan C., Wang, Haidong, Duber, Herbert C., Naghavi, Mohsen, Dicker, Daniel, Dandona, Lalit, Salomon, Joshua A., Heuton, Kyle R., Foreman, Kyle, Phillips, David E., Fleming, Thomas D., Flaxman, Abraham D., Phillips, Bryan K., Johnson, Elizabeth K., Coggeshall, Megan S., Abd-Allah, Foad, Abera, Semaw Ferede, Abraham, Jerry P., Abubakar, Ibrahim, Abu-Raddad, Laith J., Abu-Rmeileh, Niveen Me, Achoki, Tom, Adeyemo, Austine Olufemi, Adou, Arsène Kouablan, Adsuar, José C., Agardh, Emilie Elisabet, Akena, Dicken, Al Kahbouri, Mazin J., Alasfoor, Deena, Albittar, Mohammed I., Alcalá-Cerra, Gabriel, Alegretti, Miguel Angel, Alemu, Zewdie Aderaw, Alfonso-Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Alla, Francoi, Allen, Peter J., Alsharif, Ubai, Alvarez, Elena, Alvis-Guzman, Nelson, Amankwaa, Adansi A., Amare, Azmeraw T., Amini, Hassan, Ammar, Walid, Anderson, Benjamin O., Antonio, Carl Abelardo T., Anwari, Palwasha, Ärnlöv, Johan, Arsic Arsenijevic, Valentina S., Artaman, Ali, Asghar, Rana J., Assadi, Reza, Atkins, Lydia S., Badawi, Alaa, Balakrishnan, Kalpana, Banerjee, Amitava, Basu, Sanjay, Beardsley, Justin, Bekele, Tolesa, Bell, Michelle L., Bernabe, Eduardo, Beyene, Tariku Jibat, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A., Bin Abdulhak, Aref, Binagwaho, Agne, Blore, Jed D., Bora Basara, Berrak, Bose, Dipan, Brainin, Michael, Breitborde, Nichola, Castañeda-Orjuela, Carlos A., Catalá-López, Ferrán, Chadha, Vineet K., Chang, Jung-Chen, Chiang, Peggy Pei-Chia, Chuang, Ting-Wu, Colomar, Mercede, Cooper, Leslie Trumbull, Cooper, Cyru, Courville, Karen J., Cowie, Benjamin C., Criqui, Michael H., Dandona, Rakhi, Dayama, Anand, De Leo, Diego, Degenhardt, Louisa, Del Pozo-Cruz, Borja, Deribe, Kebede, Des Jarlais, Don C., Dessalegn, Muluken, Dharmaratne, Samath D., Dilmen, Uur, Ding, Eric L., Driscoll, Tim R., Durrani, Adnan M., Ellenbogen, Richard G., Ermakov, Sergey Petrovich, Esteghamati, Alireza, Faraon, Emerito Jose A., Farzadfar, Farshad, Fereshtehnejad, Seyed-Mohammad, Fijabi, Daniel Obadare, Forouzanfar, Mohammad H., Paleo, Urbano Fra., Gaffikin, Lynne, Gamkrelidze, Amiran, Gankpé, Fortuné Gbètoho, Geleijnse, Johanna M., Gessner, Bradford D., Gibney, Katherine B., Ginawi, Ibrahim Abdelmageem Mohamed, Glaser, Elizabeth L., Gona, Philimon, Goto, Atsushi, Gouda, Hebe N., Gugnani, Harish Chander, Gupta, Rajeev, Gupta, Rahul, Hafezi-Nejad, Nima, Hamadeh, Randah Ribhi, Hammami, Mouhanad, Hankey, Graeme J., Harb, Hilda L., Haro, Josep Maria, Havmoeller, Rasmu, Hay, Simon I., Hedayati, Mohammad T., Heredia Pi, Ileana B., Hoek, Hans W., Hornberger, John C., Hosgood, H. Dean, Hotez, Peter J., Hoy, Damian G., Huang, John J., Iburg, Kim M., Idrisov, Bulat T., Innos, Kaire, Jacobsen, Kathryn H., Jeemon, Panniyammakal, Jensen, Paul N., Jha, Vivekanand, Jiang, Guohong, Jonas, Jost B., Juel, Knud, Kan, Haidong, Kankindi, Ida, Karam, Nadim E., Karch, André, Karema, Corine Kakizi, Kaul, Anil, Kawakami, Norito, Kazi, Dhruv S., Kemp, Andrew H., Kengne, Andre Pascal, Keren, Andre, Kereselidze, Maia, Khader, Yousef Saleh, Khalifa, Shams Eldin Ali Hassan, Khan, Ejaz Ahmed, Khang, Young-Ho, Khonelidze, Irma, Kinfu, Yohanne, Kinge, Jonas M., Knibbs, Luke, Kokubo, Yoshihiro, Kosen, S., Kuate Defo, Barthelemy, Kulkarni, Veena S., Kulkarni, Chanda, Kumar, Kaushalendra, Kumar, Ravi B., Kumar, G. Anil, Kwan, Gene F., Lai, Taavi, Lakshmana Balaji, Arjun, Lam, Hilton, Lan, Qing, Lansingh, Van C., Larson, Heidi J., Larsson, Ander, Lee, Jong-Tae, Leigh, Jame, Leinsalu, Mall, Leung, Ricky, Li, Yichong, Li, Yongmei, De Lima, Graça Maria Ferreira, Lin, Hsien-Ho, Lipshultz, Steven E., Liu, Shiwei, Liu, Yang, Lloyd, Belinda K., Lotufo, Paulo A., Machado, Vasco Manuel Pedro, Maclachlan, Jennifer H., Magis-Rodriguez, Carlo, Majdan, Marek, Mapoma, Christopher Chabila, Marcenes, Wagner, Marzan, Melvin Barriento, Masci, Joseph R., Mashal, Mohammad Taufiq, Mason-Jones, Amanda J., Mayosi, Bongani M., Mazorodze, Tasara T., Mckay, Abigail Cecilia, Meaney, Peter A., Mehndiratta, Man Mohan, Mejia-Rodriguez, Fabiola, Melaku, Yohannes Adama, Memish, Ziad A., Mendoza, Walter, Miller, Ted R., Mills, Edward J., Mohammad, Karzan Abdulmuhsin, Mokdad, Ali H., Mola, Glen Liddell, Monasta, Lorenzo, Montico, Marcella, Moore, Ami R., Mori, Rintaro, Moturi, Wilkister Nyaora, Mukaigawara, Mitsuru, Murthy, Kinnari S., Naheed, Aliya, Naidoo, Kovin S., Naldi, Luigi, Nangia, Vinay, Narayan, K.M. Venkat, Nash, Deni, Nejjari, Chakib, Nelson, Robert G., Neupane, Sudan Prasad, Newton, Charles R., Ng, Marie, Nisar, Muhammad Imran, Nolte, Sandra, Norheim, Ole F., Nowaseb, Vincent, Nyakarahuka, Luke, Oh, In-Hwan, Ohkubo, Takayoshi, Olusanya, Bolajoko O., Omer, Saad B., Opio, John Nelson, Orisakwe, Orish Ebere, Pandian, Jeyaraj D., Papachristou, Christina, Paternina Caicedo, Angel J., Patten, Scott B., Paul, Vinod K., Pavlin, Boris Igor, Pearce, Neil, Pereira, David M., Pervaiz, Aslam, Pesudovs, Konrad, Petzold, Max, Pourmalek, Farshad, Qato, Dima, Quezada, Amado D., Quistberg, D. Alex, Rafay, Anwar, Rahimi, Kazem, Rahimi-Movaghar, Vafa, Rahman, Sajjad Ur, Raju, Murugesan, Rana, Saleem M., Razavi, Homie, Reilly, Robert Quentin, Remuzzi, Giuseppe, Richardus, Jan Hendrik, Ronfani, Luca, Roy, Nobhojit, Sabin, Nsanzimana, Saeedi, Mohammad Yahya, Sahraian, Mohammad Ali, Samonte, Genesis May J., Sawhney, Monika, Schneider, Ione J.C., Schwebel, David C., Seedat, Soraya, Sepanlou, Sadaf G., Servan-Mori, Edson E., Sheikhbahaei, Sara, Shibuya, Kenji, Shin, Hwashin Hyun, Shiue, Ivy, Shivakoti, Rupak, Sigfusdottir, Inga Dora, Silberberg, Donald H., Silva, Andrea P., Simard, Edgar P., Singh, Jasvinder A., Skirbekk, Vegard, Sliwa, Karen, Soneji, Samir, Soshnikov, Sergey S., Sreeramareddy, Chandrashekhar T., Stathopoulou, Vasiliki Kalliopi, Stroumpoulis, Konstantino, Swaminathan, Soumya, Sykes, Bryan L., Tabb, Karen M., Talongwa, Roberto Tchio, Tenkorang, Eric Yeboah, Terkawi, Abdullah Sulieman, Thomson, Alan J., Thorne-Lyman, Andrew L., Towbin, Jeffrey A., Traebert, Jefferson, Tran, Bach X., Tsala Dimbuene, Zacharie, Tsilimbaris, Miltiadi, Uchendu, Uche S., Ukwaja, Kingsley N., Uzun, Selen Begüm, Vallely, Andrew J., Vasankari, Tommi J., Venketasubramanian, N., Violante, Francesco S., Vlassov, Vasiliy Victorovich, Vollset, Stein Emil, Waller, Stephen, Wallin, Mitchell T., Wang, Linhong, Wang, Xiao Rong, Wang, Yanping, Weichenthal, Scott, Weiderpass, Elisabete, Weintraub, Robert G., Westerman, Ronny, White, Richard A., Wilkinson, James D., Williams, Thomas Neil, Woldeyohannes, Solomon Meseret, Wong, John Q., Xu, Gelin, Yang, Yang C., Yano, Yuichiro, Yentur, Gokalp Kadri, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Younis, Mustafa, Yu, Chuanhua, Jin, Kim Yun, El Sayed Zaki, Maysaa, Zhao, Yong, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Jun, Zou, Xiao Nong, Lopez, Alan D., and Vos, Theo

Subjects
Gerontology, SEVERE FEBRILE ILLNESS, Male, verbal autopsy, Nutrition and Disease, Cost effectiveness, MILLENNIUM DEVELOPMENT GOALS, HIV Infections, active antiretroviral therapy, Global Health, COST-EFFECTIVENESS, 0302 clinical medicine, Voeding en Ziekte, Global health, HIV Infection, 030212 general & internal medicine, 0303 health sciences, ACTIVE ANTIRETROVIRAL THERAPY, Incidence (epidemiology), Medicine (all), Incidence, General Medicine, Millennium Development Goals, 3. Good health, middle-income countries, projection package, World Health, VERBAL AUTOPSY, Female, Human, Tuberculosis, Tuberculosi, PROJECTION PACKAGE, prospective cohort, Epidemic, millennium development goals, 03 medical and health sciences, Age Distribution, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, MIDDLE-INCOME COUNTRIES, medicine, Organizational Objective, Humans, Organizational Objectives, FEMALE SEX WORKERS, Mortality, Sex Distribution, Epidemics, cost-effectiveness, female sex workers, 030304 developmental biology, VLAG, business.industry, plasmodium-falciparum malaria, PLASMODIUM-FALCIPARUM MALARIA, medicine.disease, Verbal autopsy, Malaria, PROSPECTIVE COHORT, severe febrile illness, business, Demography
Abstract

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.FUNDING: Bill & Melinda Gates Foundation.

Published
2014

69. SYS-1/beta-catenin inheritance and regulation by Wnt-signaling during asymmetric cell division.

Author

Valdes Michel MF and Phillips BT

Abstract

Asymmetric cell division (ACD) allows daughter cells of a polarized mother to acquire different developmental fates. In C. elegans , the Wnt/β-catenin Asymmetry (WβA) pathway oversees many embryonic and larval ACDs; here, a Wnt gradient induces an asymmetric distribution of Wnt signaling components within the dividing mother cell. One terminal nuclear effector of the WβA pathway is the transcriptional activator SYS-1/β-catenin. SYS-1 is sequentially negatively regulated during ACD; first by centrosomal regulation and subsequent proteasomal degradation and second by asymmetric activity of the β-catenin "destruction complex" in one of the two daughter cells, which decreases SYS-1 levels in the absence of WβA signaling. However, the extent to which mother cell SYS-1 influences cell fate decisions of the daughters is unknown. Here, we quantify inherited SYS-1 in the differentiating daughter cells and the role of SYS-1 inheritance in Wnt-directed ACD. Photobleaching experiments demonstrate the GFP::SYS-1 present in daughter cell nuclei is comprised of inherited and de novo translated SYS-1 pools. We used a photoconvertible DENDRA2::SYS-1, to directly observe the dynamics of inherited SYS-1. Photoconversion during mitosis reveals that SYS-1 clearance at the centrosome preferentially degrades older SYS-1, and this accumulation is regulated via dynein trafficking. Photoconversion of the EMS cell during Wnt-driven ACD shows daughter cell inheritance of mother cell SYS-1. Additionally, loss of centrosomal SYS-1 increased inherited SYS-1 and, surprisingly, loss of centrosomal SYS-1 also resulted in increased levels of de novo SYS-1 in both EMS daughter cells. Lastly, we show that daughter cell negative regulation of SYS-1 via the destruction complex member APR-1/APC is key to limit both the de novo and the inherited SYS-1 pools in both the E and the MS cells. We conclude that regulation of both inherited and newly translated SYS-1 via centrosomal processing in the mother cell and daughter cell regulation via Wnt signaling are critical to maintain sister SYS-1 asymmetry during ACD.

Published
2023
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71. A new look at TCF and beta-catenin through the lens of a divergent C. elegans Wnt pathway.

Author

Phillips BT and Kimble J

Subjects
Animals, Caenorhabditis elegans Proteins genetics, Cell Polarity, Gene Expression Regulation, Humans, Mitogen-Activated Protein Kinases genetics, Mitogen-Activated Protein Kinases metabolism, Models, Molecular, Phylogeny, Protein Structure, Tertiary, TCF Transcription Factors genetics, Wnt Proteins genetics, beta Catenin genetics, Caenorhabditis elegans physiology, Caenorhabditis elegans Proteins metabolism, Signal Transduction physiology, TCF Transcription Factors metabolism, Wnt Proteins metabolism, beta Catenin metabolism
Abstract

The canonical Wnt/beta-catenin pathway is extensively characterized, broadly conserved, and clinically important. In this review, we describe the C. elegans Wnt/beta-catenin asymmetry pathway and suggest that some of its unusual features may have important implications for the canonical Wnt/beta-catenin pathway.

Published
2009
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72. The C. elegans SYS-1 protein is a bona fide beta-catenin.

Author

Liu J, Phillips BT, Amaya MF, Kimble J, and Xu W

Subjects
Amino Acid Sequence, Animals, Crystallography, X-Ray, Cytoskeletal Proteins chemistry, Cytoskeletal Proteins metabolism, DNA-Binding Proteins chemistry, DNA-Binding Proteins metabolism, High Mobility Group Proteins chemistry, High Mobility Group Proteins metabolism, Humans, Models, Molecular, Molecular Sequence Data, Phylogeny, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, beta Catenin chemistry, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins chemistry, Caenorhabditis elegans Proteins metabolism, Transcription Factors chemistry, Transcription Factors metabolism, beta Catenin metabolism
Abstract

C. elegans SYS-1 has key functional characteristics of a canonical beta-catenin, but no significant sequence similarity. Here, we report the SYS-1 crystal structure, both on its own and in a complex with POP-1, the C. elegans TCF homolog. The two structures possess signature features of canonical beta-catenin and the beta-catenin/TCF complex that could not be predicted by sequence. Most importantly, SYS-1 bears 12 armadillo repeats and the SYS-1/POP-1 interface is anchored by a conserved salt-bridge, the "charged button." We also modeled structures for three other C. elegans beta-catenins to predict the molecular basis of their distinct binding properties. Finally, we generated a phylogenetic tree, using the region of highest structural similarity between SYS-1 and beta-catenin, and found that SYS-1 clusters robustly within the beta-catenin clade. We conclude that the SYS-1 protein belongs to the beta-catenin family and suggest that additional divergent beta-catenins await discovery.

Published
2008
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