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bioRxiv.org : the preprint server for biology. 2021.DOI: 10.1101/2020.09.15.296749

Gpr125 identifies myoepithelial progenitors at tips of lacrimal ducts and is essential for tear film [PrePrint]

Spina, Elena; Handlin, Rebecca; Simundza, Julia; Incassati, Angela; Faiq, Muneeb; Sainulabdeen, Anoop; Chan, Kevin C; Cowin, Pamela
Gpr125, encoded by Adgra3, is an orphan adhesion G-protein coupled receptor (aGPCR) implicated in modulating Wnt signaling and planar polarity. Here we establish both physiological and pathological roles for Gpr125. We show that mice lacking Gpr125 or its signaling domains display an ocular phenotype with many hallmarks of human dry eye syndrome. These include squinting, abnormal lacrimation, mucus accumulation, swollen eyelids and inflammatory infiltration of lacrimal and meibomian glands. Utilizing a Gpr125-β-gal reporter and scRNAseq, we identify Gpr125 expression in a discrete population of cells located at the tips of migrating embryonic lacrimal ducts. By lineage tracing we show these cells function as progenitors of the adult lacrimal myoepithelium. Beyond defining an essential role for Gpr125 in tear film and identifying its utility as a marker of lacrimal progenitors, this study implicates Gpr125 in the etiology of blepharitis and dry eye syndrome, and defines novel animal models of these common maladies
ORIGINAL:0015379
ISSN: 2692-8205
CID: 5069122
Scientific reports. 2021:11(1).DOI: 10.1038/s41598-021-98518-3

Sensory integration abilities for balance in glaucoma, a preliminary study

O'Connell, Caitlin; Redfern, Mark; Chan, Kevin C; Wollstein, Gadi; Conner, Ian P; Cham, Rakié
The goal of this study was to quantify the association between sensory integration abilities relevant for standing balance and disease stage in glaucoma. The disease stage was assessed using both functional (visual field deficit) and structural (retinal nerve fiber layer thickness) deficits in the better and worse eye. Balance was assessed using an adapted version of the well-established Sensory Organization Test (SOT). Eleven subjects diagnosed with mild to moderate glaucoma stood for 3 min in 6 sensory challenging postural conditions. Balance was assessed using sway magnitude and sway speed computed based on center-of-pressure data. Mixed linear regression analyses were used to investigate the associations between glaucoma severity and balance measures. Findings revealed that the visual field deficit severity in the better eye was associated with increased standing sway speed. This finding was confirmed in eyes open and closed conditions. Balance was not affected by the extent of the visual field deficit in the worse eye. Similarly, structural damage in either eye was not associated with the balance measures. In summary, this study found that postural control performance was associated with visual field deficit severity. The fact that this was found during eyes closed as well suggests that reduced postural control in glaucoma is not entirely attributed to impaired peripheral visual inputs. A larger study is needed to further investigate potential interactions between visual changes and central processing changes contributing to reduced balance function and increased incidence of falls in adults with glaucoma.
PMCID:8490466
PMID: 34608185
ISSN: 2045-2322
CID: 5061842
Neuroscientist. 2021.DOI: 10.1177/10738584211037619

Visual Plasticity in Adulthood: Perspectives from Hebbian and Homeostatic Plasticity

Bang, Ji Won; Hamilton-Fletcher, Giles; Chan, Kevin C
The visual system retains profound plastic potential in adulthood. In the current review, we summarize the evidence of preserved plasticity in the adult visual system during visual perceptual learning as well as both monocular and binocular visual deprivation. In each condition, we discuss how such evidence reflects two major cellular mechanisms of plasticity: Hebbian and homeostatic processes. We focus on how these two mechanisms work together to shape plasticity in the visual system. In addition, we discuss how these two mechanisms could be further revealed in future studies investigating cross-modal plasticity in the visual system.
PMID: 34382456
ISSN: 1089-4098
CID: 5018042
Investigative ophthalmology & visual science. IOVS. 2021:62(10).DOI: 10.1167/iovs.62.10.21

Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models

Colbert, Max K; Ho, Leon C; van der Merwe, Yolandi; Yang, Xiaoling; McLellan, Gillian J; Hurley, Samuel A; Field, Aaron S; Yun, Hongmin; Du, Yiqin; Conner, Ian P; Parra, Carlos; Faiq, Muneeb A; Fingert, John H; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C
Purpose:To characterize the visual pathway integrity of five glaucoma animal models using diffusion tensor imaging (DTI). Methods:Two experimentally induced and three genetically determined models of glaucoma were evaluated. For inducible models, chronic IOP elevation was achieved via intracameral injection of microbeads or laser photocoagulation of the trabecular meshwork in adult rodent eyes. For genetic models, the DBA/2J mouse model of pigmentary glaucoma, the LTBP2 mutant feline model of congenital glaucoma, and the transgenic TBK1 mouse model of normotensive glaucoma were compared with their respective genetically matched healthy controls. DTI parameters, including fractional anisotropy, axial diffusivity, and radial diffusivity, were evaluated along the optic nerve and optic tract. Results:Significantly elevated IOP relative to controls was observed in each animal model except for the transgenic TBK1 mice. Significantly lower fractional anisotropy and higher radial diffusivity were observed along the visual pathways of the microbead- and laser-induced rodent models, the DBA/2J mice, and the LTBP2-mutant cats compared with their respective healthy controls. The DBA/2J mice also exhibited lower axial diffusivity, which was not observed in the other models examined. No apparent DTI change was observed in the transgenic TBK1 mice compared with controls. Conclusions:Chronic IOP elevation was accompanied by decreased fractional anisotropy and increased radial diffusivity along the optic nerve or optic tract, suggestive of disrupted microstructural integrity in both inducible and genetic glaucoma animal models. The effects on axial diffusivity differed between models, indicating that this DTI metric may represent different aspects of pathological changes over time and with severity.
PMCID:8383913
PMID: 34410298
ISSN: 1552-5783
CID: 5010982
Scientific reports. 2021:11(1).DOI: 10.1038/s41598-021-93991-2

In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes

Au, Jeannie M; Kancherla, Swarupa; Hamade, Malack; Mendoza, Monica; Chan, Kevin C
This study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague-Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188-289%. Upon unilateral hypoxic-ischemic encephalopathy at P7, monocular deprivation at P15, and monocular enucleation at P1, T2-weighted imaging of the adult rats showed decreased ocular volumes to different extents. In summary, in vivo high-field MRI allows for non-invasive evaluation of early postnatal development in the normal and impaired rat eyes. Chromium-enhanced MRI appeared effective in examining the developing retina before natural eyelid opening at P14 with relevance to lipid metabolism. The reduced ocular volumes upon neonatal visual impairments provided evidence to the emerging problems of why some impaired visual outcomes cannot be solely predicted by neurological assessments and suggested the need to look into both the eye and the brain under such conditions.
PMCID:8324881
PMID: 34330952
ISSN: 2045-2322
CID: 4988402
Neurotherapeutics. 2021:18(2):1339-1359.DOI: 10.1007/s13311-021-01033-6

Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control

van der Merwe, Yolandi; Murphy, Matthew C; Sims, Jeffrey R; Faiq, Muneeb A; Yang, Xiao-Ling; Ho, Leon C; Conner, Ian P; Yu, Yu; Leung, Christopher K; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C
Glaucoma is a neurodegenerative disease that causes progressive, irreversible vision loss. Currently, intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. However, glaucomatous degeneration may continue despite adequate IOP control. Therefore, there exists a need for treatment that protects the visual system, independent of IOP. This study sought, first, to longitudinally examine the neurobehavioral effects of different magnitudes and durations of IOP elevation using multi-parametric magnetic resonance imaging (MRI), optokinetics and histology; and, second, to evaluate the effects of oral citicoline treatment as a neurotherapeutic in experimental glaucoma. Eighty-two adult Long Evans rats were divided into six groups: acute (mild or severe) IOP elevation, chronic (citicoline-treated or untreated) IOP elevation, and sham (acute or chronic) controls. We found that increasing magnitudes and durations of IOP elevation differentially altered structural and functional brain connectivity and visuomotor behavior, as indicated by decreases in fractional anisotropy in diffusion tensor MRI, magnetization transfer ratios in magnetization transfer MRI, T1-weighted MRI enhancement of anterograde manganese transport, resting-state functional connectivity, visual acuity, and neurofilament and myelin staining along the visual pathway. Furthermore, 3 weeks of oral citicoline treatment in the setting of chronic IOP elevation significantly reduced visual brain integrity loss and visual acuity decline without altering IOP. Such effects sustained after treatment was discontinued for another 3 weeks. These results not only illuminate the close interplay between eye, brain, and behavior in glaucomatous neurodegeneration, but also support a role for citicoline in protecting neural tissues and visual function in glaucoma beyond IOP control.
PMID: 33846961
ISSN: 1878-7479
CID: 4847842
Frontiers in medicine. 2021:8.DOI: 10.3389/fmed.2021.681169

Oral Scutellarin Treatment Ameliorates Retinal Thinning and Visual Deficits in Experimental Glaucoma

Zhu, Jingyuan; Sainulabdeen, Anoop; Akers, Krystal; Adi, Vishnu; Sims, Jeffrey R; Yarsky, Eva; Yan, Yi; Yu, Yu; Ishikawa, Hiroshi; Leung, Christopher K; Wollstein, Gadi; Schuman, Joel S; Wei, Wenbin; Chan, Kevin C
PMCID:8369066
PMID: 34414202
ISSN: 2296-858x
CID: 4988952
Conference Proceedings (IEEE Engineering in Medicine & Biology Society). 2021:5868-5871.DOI:

Auditory Scene Analysis Principles Improve Image Reconstruction Abilities of Novice Vision-to-Audio Sensory Substitution Users [Meeting Abstract]

Hamilton-Fletcher, Giles; Chan, Kevin C.
ISI:000760910505110
ISSN: 1557-170x
CID: 5243002
Annual International Conference of the IEEE Engineering in Medicine & Biology Society. 2020:2020:1746-1749.DOI: 10.1109/EMBC44109.2020.9176192

Diffusion Kurtosis Imaging Reveals Optic Tract Damage That Correlates with Clinical Severity in Glaucoma

Sun, Zhe; Parra, Carlos; Bang, Ji Won; Fieremans, Els; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C
Glaucoma is a neurodegenerative disease of the visual system and is the leading cause of irreversible blindness worldwide. To date, its pathophysiological mechanisms remain unclear. This study evaluated the feasibility of advanced diffusion magnetic resonance imaging techniques for examining the microstructural environment of the visual pathway in glaucoma. While conventional diffusion tensor imaging (DTI) showed lower fractional anisotropy and higher directional diffusivities in the optic tracts of glaucoma patients than healthy controls, diffusion kurtosis imaging (DKI) and the extended white matter tract integrity (WMTI) model indicated lower radial kurtosis, higher axial and radial diffusivities in the extra-axonal space, lower axonal water fraction, and lower tortuosity in the same regions in glaucoma patients. These findings suggest glial involvements apart from compromised axonal integrity in glaucoma. In addition, DKI and WMTI but not DTI parameters significantly correlated with clinical ophthalmic measures via optical coherence tomography and visual field perimetry testing. Taken together, DKI and WMTI provided sensitive and comprehensive imaging biomarkers for quantifying glaucomatous damage in the white matter tract across clinical severity complementary to DTI.
PMCID:8163524
PMID: 33018335
ISSN: 2694-0604
CID: 4898522
New England journal of medicine. 2020:382(15):1395-1407.DOI: 10.1056/NEJMoa1915922

Initial Invasive or Conservative Strategy for Stable Coronary Disease

Maron, David J; Hochman, Judith S; Reynolds, Harmony R; Bangalore, Sripal; O'Brien, Sean M; Boden, William E; Chaitman, Bernard R; Senior, Roxy; López-Sendón, Jose; Alexander, Karen P; Lopes, Renato D; Shaw, Leslee J; Berger, Jeffrey S; Newman, Jonathan D; Sidhu, Mandeep S; Goodman, Shaun G; Ruzyllo, Witold; Gosselin, Gilbert; Maggioni, Aldo P; White, Harvey D; Bhargava, Balram; Min, James K; Mancini, G B John; Berman, Daniel S; Picard, Michael H; Kwong, Raymond Y; Ali, Ziad A; Mark, Daniel B; Spertus, John A; Krishnan, Mangalath N; Elghamaz, Ahmed; Moorthy, Nagaraja; Hueb, Whady A; Demkow, Marcin; Mavromatis, Kreton; Bockeria, Olga; Peteiro, Jesus; Miller, Todd D; Szwed, Hanna; Doerr, Rolf; Keltai, Matyas; Selvanayagam, Joseph B; Steg, P Gabriel; Held, Claes; Kohsaka, Shun; Mavromichalis, Stavroula; Kirby, Ruth; Jeffries, Neal O; Harrell, Frank E; Rockhold, Frank W; Broderick, Samuel; Ferguson, T Bruce; Williams, David O; Harrington, Robert A; Stone, Gregg W; Rosenberg, Yves; Ricci, Joseph; Tello Montoliu, A; Robero Aniorte, A I; Mulder, Abbey; Laddu, Abhay A; Goyal, Abhinav; Dubey, Abhishek; Goyal, Abhishek; Knighton, Abigail; Oomman, Abraham; Jaskowiak, Adam J; Kolodziej, Adam; Witkowski, Adam; Hameed, Adnan; Anesini, Adriana; Hussain, Afshan; Juceviciene, Agne; Urboniene, Agne; Jakal, Agnes; Szramowska, Agnieszka; Khairuddin, Ahmad; Abdel-Latif, Ahmed; Adel, Ahmed; Aljzeeri, Ahmed; Kamal, Ahmed; Talaat, Ahmed; Mann, Aimee; Contreras, Aira; Kumar, Ajit; Kumar, V K; Furukawa, Akemi; Bagai, Akshay; Smigelskaite, Akvile; Furber, Alain; Rheault, Alain; Loehr, Alaine Melanie; Rosen, Alan; Varga, Albert; Qelaj, Albertina; Barioli, Alberto; Russo, Aldo; Moorman, Alec; Gisbert, Alejandro; Fratczak, Aleksandra; Laucevicius, Aleksandras; Kuleshova, Alena; Sionis, Alessandro; Sirker, Alexander A; Chernyavskiy, Alexander M; Craft, Alexandra; Vazquez, Alexandra; Ciappina Hueb, Alexandre; Colafranseschi, Alexandre S; Schaan de Quadros, Alexandre; Tognon, Alexandre; Alghamdi, Ali; Manica Muller, Alice; Nogueira Rabaça, Aline; Peixoto Deiro, Aline; Hallam, Alison; Stone, Allegra; Schley, Allison; Castro, Almudena; Rabelo Ales, Alvaro; Germann, Amanda; O'Malley, Amanda; Uxa, Amar; Ojajuni, Amarachi; Oliveira, Amarino C Jr; Hull, Amber B; Roy, Ambuj; Zarka, Amer; Janmohamed, Amir; Brown, Ammani; Malinay, Ammy; Martinez Monzonis, Amparo; Richards, Amy J; Iskandrian, Amy; Ollinger, Amy; Djordjevic-Dikic, Ana D; Fernández Martínez, Ana; Gomes Almeida, Ana; Batista, Ana Paula; Francisco, Ana Rita; Mladenovic, Ana S; Santana, Ana; Siddiqui, Anam; Kuzmina-Krutetskaya, Anastasia M; Vertes, Andras; Sousa, Andre S; Gabriel, Andre; Schmidt, André; Lundeen, Andrea M; Bartykowszki, Andrea; Lorimer, Andrea; Mortara, Andrea; Pascual, Andrea; Coelho, Andreia; Rocha, Andreia; García-Rincón, Andrés; Howarth, Andrew G; Moriarty, Andrew J; Docherty, Andrew; Starovoytov, Andrew; Zurick, Andrew; Łabyk, Andrzej; Swiatkowski, Andrzej; Lam, Andy; Kawakami, Anelise; Hoye, Angela; Kim, Angela; Smit, Angelique; Nobre, Angelo; Shah, Anil V; Ljubez, Anja; Anand, Anjali; Sachdeva, Ankush; Greenberg, Ann; Luyten, Ann; Ostrander, Ann; Di Donato, Anna; Cichocka-Radwan, Anna; Fojt, Anna; Plachcinska, Anna; Proietti, Anna; Teresinska, Anna; Webb, Anne Marie; Cartwright, Anne; Heath, Anne; Mackin, Anne; Amaritakomol, Anong; Chaiyasri, Anong; Chauhan, Anoop; Mathew, Anoop; Gemignani, Anthony; Andres, Anto Luigi; Vega, Antonia; Hansen, Antonietta; Iglesias, Antonino Ginel; Carvalho, Antonio Carlos; Di Chiara, Antonio; Serra Peñaranda, Antonio; Carvalho, Antonio; Colombo, Antonio; Fiarresga, Antonio; Rao, Anupama; Valdespino-Estrada, Aquiles; Boan, Araceli; Ishani, Areef; Diaz, Ariel; Ghosh, Arijit; Prommintikul, Arintaya; Roberts, Arline; Seto, Arnold H; Good, Arnold P; Quyyumi, Arshed; Labovitz, Arthur J; Kerner, Arthur; Campos-Santaolalla, Arturo S; Misra, Arunima; Mukherjee, Ashok; Seth, Ashok; Seedhom, Ashraf; Cheema, Asim N; Ahmed, Asker; Mathur, Atul; Verma, Atul; Leong, Audrey W; Åkerblom, Axel; Fuentes, Axelle; Naher, Aynun; Valaiyapathi, Badhma; Kaur, Baljeet; Guruge, Bandula; Brzezińska, Barbara; Nardi, Barbara; Czarniak, Bartosz; Singh, Bebek; Igual, Begoña; Merkely, Bela; Alvarez, Belen Cid; Spooner, Benjamin J; Chow, Benjamin J W; Cheong, Benjamin; Shah, Benoy N; de Bruyne, Bernard; Valecka, Bernardas; Jäger, Bernhard; Archer, Beth A; Abramson, Beth; Jorgenson, Beth; Harvey, Bethany; O'Neal, Betsy; Atkinson, Bev; Bozek, Bev; Lang, Bevin; Sasidharan, Bijulal; Yang, Bin; Zhang, Bin; Kurian, Binoy Mannekkattukudy; Goebel, Bjoern; Hu, Bob; Popescu, Bogdan A; Crnokrak, Bogdan; Zhu, Bolin; Kirby, Bonnie J; Zimbelman, Brandi D; Starks, Brandy; Beleslin, Branko D; Hart, Brenda; Shapiro, Brian P; McCandless, Brian; Wisniewski, Brianna; Smith, Brigham R; Mirrer, Brooks; McManus, Bruce; Rutkin, Bruce; Paulino, Bruna Edilena; Ascoli, Bruna Maria; Smith, Bryn; Allen, Byron J; Gibson, C Michael; Bairey Merz, C Noel; Pop, Calin; Hague, Cameron; Thais de Ormundo, Camila; Gopaul, Candace; Edillo, Candice P; Polanczyk, Carísi A; Krannila, Carita; Vicente, Carla; Gagné, Carl-Éric; Briguori, Carlo; Peña Gil, Carlos; Alvarez, Carlos; Ohmart, Carly; Beladan, Carmen C; Ginghina, Carmen; Kartje, Carol M; Alsweiler, Caroline; Brown, Caroline; Callison, Caroline; Pinheiro, Caroline; Rodgers, Caroline; Spindler, Caroline; Corbett, Carolyn; Drum, Carrie; Riedberger, Casey; Bone, Catherine; Fleming, Catherine; Gordon, Catherine; Jahrsdorfer, Catherine; Lemay, Catherine; Weick, Catherine; Patten, Cathrine; Goletto, Cecilia; Kepka, Cezary; Suvarna, Chandini; Xu, Chang; Mercure, Chantale; Viljoen, Charle A; Wiyarand, Charlene; Jia-Yin Hou, Charles; Lui, Charles Y; Cannan, Charles; Cornet, Charles; Pirro, Charlotte; Rimsukcharoenchai, Chataroon; Wang, Chen; Tsai, Cheng-Ting; Chien, Chen-Yen; Allardyce, Cheryl A; Hedgepeth, Chester M; Patel, Chetan; Attanasio, Chiara; Yen, Chih-Hsuan; Chow, Chi-Ming; Er, Ching Min; Ong, Ching-Ching; Manjunath, Cholenahally Nanjappa; Beck, Chris; Buller, Chris; Vassaliere, Christel; Hamm, Christian; Caldeira, Christiano; Ballantyne, Christie; Björklund, Christina; Hinton, Christine R; Bergeron, Christine; Masson, Christine; Roraff, Christine; Shelley, Christine; Laure, Christophe; Thuaire, Christophe; Kinsey, Christopher; McFarren, Christopher; Spizzieri, Christopher; Travill, Christopher; Liu, Chun-Chieh; Hung, Chung-Lieh; Li, Chunguang; Yun, Chun-Ho; Xia, Chunli; Heard, Ciarra; Schultz, Cidney; Venn-Edmonds, Clare; Hochberg, Claudia P; Wegmayr, Claudia; Cortés, Claudia; Escobar, Claudia; Freixo, Cláudia; Mesquita, Claudio T; Kadalie, Clemens T; Berry, Colin; Philander, Constance; Thobois, Corine; Costantini, Costantino; Page, Courtney; Atkinson, Craig; Barr, Craig; Paterson, Craig; Bare, Cristina; Baumann, Cynthia; Burman, Cynthia; Espinosa, Dalisa; Collison, Damien; Deleanu, Dan; Elian, Dan; Gao, Dan; Oliver, Dana; Vezina, Daniel P; O'Rourke, Daniel; Komar, Daniele; Schade, Danielle; Francis, Darrel P; Malaev, Dastan; Bull, David A; Winchester, David E; Faxon, David P; Booth, David; Cohen, David; DeMets, David; Foo, David; Schlichting, David; Taggart, David; Waters, David; Wohns, David; Vo, Davis; Teodorczyk, Dawid; Shelstad, Dawn; Turnbull, Dawn; Li, Dayuan; Kereiakes, Dean; O'Neill, Deborah; Yip, Deborah; Johnson, Debra K; Dees, Debra; Bhatt, Deepak L; Gopal, Deepika; Kumar, Deepti; Mattina, Deirdre; Murphy, Deirdre; Small, Delano R; Rose, Delsa K; Jiang, Dengke; Phaneuf, Denis Carl; Braganza, Denise; Fine, Denise; Cyr, Derek; Tobin, Desiree; Cukali, Diana; Parra, Diana; Camara, Diane; Minshall Liu, Diane; Vences, Diego Adrián; Franca de Cunha, Diego; Stournaras, Dimitrios; Patel, Dipti; Li, Dongze; Exley, Donna; Grahl, Dorit; Stanojevic, Dragana; Cacela, Duarte; Conway, Dwayne S G; Bermudez, E Pinar; Punnoose, Eapen; Tay, Edgar L; Karanjah, Edgar; Verna, Edoardo; Hernandez-Rangel, Eduardo; Nicol, Edward D; McFalls, Edward O; Martin, Edward T; Kaczmarska, Edyta; Lubinskaya, Ekaterina I; Demchenko, Elena A; Refoyo Salicio, Elena; Feen, Eli; Durán-Cortés, Elihú; Janzen, Elisabeth M; Hannemann, Elise L; Dongen, Elise van; Piloto, Elissa Restelli; Kaplan, Eliza; Srbinovska Kostovska, Elizabeta; Capasso-Gulve, Elizabeth; Congdon, Elizabeth; Ferguson, Elizabeth; Zbyshevskaya, Elizaveta V; Magedanz, Ellen; Fridell, Ellie; Lader, Ellis W; Kedhi, Elvin; Racca, Emanuela; Tachot, Emilie; DeRosa, Emily; Alonso-Álvarez, Encarnación; Nicollet, Eric; Peterson, Eric; Rosas, Erick Alexánderson; Morales, Erick Donato; Orvis, Erin; Moga, Ermina; Montpetit, Estelle; Figueiredo, Estevao; Passamani, Eugene; Nikolsky, Eugenia; Yeoh, Eunice; Kretov, Evgeniy I; Szczerba, Ewa; Wojtala, Ewelina; Ribeiro Silva, Expedito Eustáquio; Ortuño, F Marin; Farias, Fabio R; Fimiani, Fabio; Rolfo, Fabrizio; Yu, Fa-Chang; Hage, Fadi; Matar, Fadi; Haider Jafary, Fahim; Feng, Fang; Liu, Fang; Ranjbaran, Fatima; Rodriguez, Fatima; Pinto, Fausto J; Rashid, Fauzia; Ramani, Federica; Wang, Fei; Igansi, Fernanda; Silva, Filipa; Ottani, Filippo; Haines, Fiona; Al Solaiman, Firas; Egydio, Flávia; Lyra, Flavio; Egger, Florian; Farquharson, Fran; Laube, Frances; Carreras Costa, Francesc; de Micco, Francesca; Bianchini, Francesca; Pezzetta, Francesca; Pietrucci, Francesca; Orso, Francesco; Pisano, Francesco; Burt, Francis; Patuleia Figueiras, Francisca; Fernandez-Aviles, Francisco; Mongeon, Francois Pierre; Van de Werf, Frans; Guenther, Franziska; Witherow, Fraser N; Mohr, Fred; Dall'Orto, Frederico; Otsuka, Fumiyuki; De La Morena, G; Karthikeyan, G; Dekany, Gabor; Kerecsen, Gabor; Galeote, Gabriel; Grossmann, Gabriel; Vorobiof, Gabriel; Sanchez de Souza, Gabriela; Guzman, Gabriela; Zeballos, Gabriela; Gabrielli, Gabriele; Jakl-Kotauschek, Gabriele; Shammas, Gail A; Brandt, Gail; Chen, Gang; Lane, Gary E; Luckasen, Gary J; Sharma, Gautam; Mikolaitiene, Gelmina; Yee, Gennie; Nickenig, Georg; Revtyak, George E; Juang, George J; Fletcher, Gerald; Leonard, Gerald; Devlin, Gerard Patrick; Esposito, Gerard; Ágoston, Gergely; Lamas, Gervasio; Fontos, Geza; Mikhail, Ghada; Cobb, Gia; Perna, Gian Piero; Leone, Gianpiero; Roditi, Giles; Barone-Rochette, Gilles; Mishra, Girish; Tarantini, Giuseppe; Wong, Glenda; Hamroff, Glenn S; Rayos, Glenn; Cheng, Gong; Barge-Caballero, Gonzalo; Davidović, Goran; Stankovic, Goran; Stevanovic, Gordana; Jingyan Wang, Grace; Young, Grace M; Wayser, Graceanne; Scaro, Graciela; Hillis, Graham S; Wong, Graham; Szulczyk, Grazyna Anna; Simonis, Gregor; Kumkumian, Gregory; Peichel, Gretchen Ann; Gajos, Grzegorz; Steinmaurer, Gudrun; Rucatti, Guilherme G; Portugal, Guilherme; Cantinho Lopes, Guilhermina; Pons Lladó, Guillem; Frostfelt, Gunnar; Wander, Gurpreet S; Gulati, Gurpreet; Pucci, Gustavo; Abd Hadi, Hafidz; Zhang, Haibo; Wang, Haitao; Marciniak, Halina; Chen, Han; Kerr, Hanan; Najm, Hani; Douglas, Hanna; Phillips, Hannah; Dai, Hao; Dong, Haojian; Jamil, Haqeel; Sivadasanpillai, Harikrishnan; Suryapranata, Harry; Reda, Hassan; Pomeroy, Hayley; Barrentine, Heather; Golden, Heather; Hurlburt, Heather; Wilson, Heidi; Tucker, Helen C; Abergel, Helene; Siddaram, Hemalata; Osseni, Hermine; Schuchlenz, Herwig; Zeng, Hesong; Skali, Hicham; Solomon, Hilda; Horton, Hollie; Hetrick, Holly; Little, Holly; Park, Holly; Chi, Hongjie; Mahrous, Hossam; Levite, Howard A; Pejkov, Hristo; Li, Huajun; Bloise-Adames, Hugo; Marques, Hugo; Zhong, Hui; Zhang, Hui-Min; Hashim, Humayrah; Yeh, Hung-I; El Fishawy, Hussien; Webb, Ian; Kullo, Iftikhar; Grazhdankin, Igor O; Hamzeh, Ihab; Hassan, Ikraam; Ueda, Ikuko; Pina, Ileana L; Tamasauskiene, Ilona; Bouwhuis, Ilse; Arif, Imran; Wenzelburger, Ina; Zimbarra Cabrita, Inês; Rodrigues, Ines; Robbins, Inga H; Soveri, Inga; Schnittger, Ingela; Karimullah, Iqbal; Dauber, Ira M; Rehman, Iram; Peovska Mitevska, Irena; Marthe Lang, Irene; Subbotina, Irina; Kalibataite-Rutkauskiene, Irma; Yusnida, Irni; Carvajal, Isabel Estela; Palazzo, Isabella C; Hogan, Isabelle; Roy, Isabelle; Syed, Ishba; Tejani, Ishita; Naryshkin, Ivan A; Jankovic, Ivana; Niedzwiecka, Iwona; Knight, J David; Kusmierek, Jacek; White, Jackie M; Chow, Jackie; Udell, Jacob; Tamis-Holland, Jacqueline E; Fannon, Jacqueline; Quin, Jacquelyn A; Do, Jacquelyn; Heo, Jaekyeong; Maksym, Jakub; Davies, James E; O'Keefe, James H Jr; Jang, James J; Cha, James; Harrison, James; Hirsch, James; Stafford, James; Tatoulis, James; Rankin, Jamie; Henzel, Jan; Orga, Jan; Tancredi, Jana; Oliveira, Janaina; Burton, Jane; Eckstein, Jane; Marucci, Jane; Knight, Janet P; Blount, Janet; Halliday, Janet; Kourzenkova, Janetta; Raj, Janitha; Sinning, Jan-Malte; Pozzibon, Jaqueline; Drozdz, Jaroslaw; Karwowski, Jaroslaw; Glover, Jason D; Kwok, Jason Loh; Call, Jason T; Linefsky, Jason; Gomes, Jassira; Anumpa, Jati; Garcia, Javier J; Courtis, Javier; Meisner, Jay; Jayakumar, K; Scales, Jayne; Denaro, Jean E; Juliard, Jean Michel; Ho, Jean; Stansborough, Jeanette K; Juliard, Jean-Michel; Russo, Jeanne; Schoep, Jeannette J M; Thambyrajah, Jeet; Leimberger, Jeff; Breall, Jeffery A; Kohn, Jeffrey A; Milliken, Jeffrey C; Anderson, Jeffrey; Blume, Jeffrey; Kanters, Jeffrey; Lorin, Jeffrey; Moses, Jeffrey; Stepanovic, Jelena J; Celutkiene, Jelena; Djokic, Jelena; Stojkovic, Jelena; Jose, Jenne M; Manchery, Jenne; Mull, Jennifer A; Czerniak, Jennifer H; Stanford, Jennifer L; Gillis, Jennifer; Horst, Jennifer; Isaacs, Jennifer; Langdon, Jennifer; Thomson, Jennifer; Tomfohr, Jennifer; White, Jennifer; Kuo, Jen-Yuan; Rautureau, Jeremy; Fleg, Jerome; Berg, Jessica; Rodriguez, Jessica; Waldron, Jessica; Patro, Jhina; Li, Jia; Mao, Jiajia; Liu, Jiamin; Wang, Jian'an; Li, Jianhua; Zhang, Jianxin; Qi, Jie; Lyo, Jihyun; Marcus, Jill; Blankenship, Jim; Zhang, Jing; Liu, Jingjing; Fan, Jing-Yao; Li, Jiun-Yi; Pradhan, Jiwan; Chen, Jiyan; Rivera Caravaca, J M; Evans, Jo; Garcia Picart, Joan; Hecht, Joan; Jaroch, Joanna; Zalewska, Joanna; Kelly, Joanne; Taaffe, Joanne; Abbud, João Reynaldo; Vitola, João V; Peñafiel, Joaquín V; Benatar, Jocelyne; Bindeman, Jody; Sabik, Joe; Klitch, Joel; Christopher, Johann; Aspberg, Johannes; Friedman, John D; Beltrame, John F; Heitner, John F; Graham, John Joseph; Davies, John R; Doan, John; Kotter, John; Kurian, John; Mukai, John; Pownall, John; Sobolewska, Jolanta; Kobashigawa, Jon; Goldberg, Jonathan L; Bazeley, Jonathan W; Byrne, Jonathan; Himmelfarb, Jonathan; Leipsic, Jonathan; Thorsen, Jonean; Trejo Gutierrez, Jorge F; Escobedo, Jorge; Timmer, Jorik; Ortega-Ramírez, José A; Marin-Neto, José Antonio; Salas, Jose D; Castillo, Jose Enrique; Saraiva, Jose Francisco; Cuenca-Castillo, José J; Diez, Jose L; Narro Villanueva, José Luis; da Vieira, José Luiz; Flores-Palacios, José M; Gonzalez, Jose Ramon; Seijas Amigo, Jose; Fragata, Jose; Padró, Josep Maria; McGarvey, Josheph F X Jr; Hannan, Joseph; Sacco, Joseph; Sweeny, Joseph; Wiesel, Joseph; Abraham, Josephine D; Loh, Joshua P; Burkhardt, Joy; White, Joyce R; Riestenberg-Smith, Joyce; Sebo, Judit; Meadows, Judith L; Wright, Judith; Foltz, Judy Mae; Hung, Judy; Otis, Judy; Stumpf, Juergen; Tsai, Jui-Peng; Dionne, Julia S; de Aveiro Morata, Julia; Bunke, Julie; Morrow, Julie; Figal, Julio César; Fujita, Jun; Jiang, Jun; Li, Junhua; Yang, Junqing; Euathrongchit, Juntima; Garg, Jyotsna; Manjula Rani, K; Preethi, K; Goetschalckx, Kaatje; Eggers, Kai; Surineni, Kamalakar; Hirase, Kanae; Kapilamoorthy, T R; Calfas, Karen; Gratrix, Karen; Hallett, Karen; Hultberg, Karen; Nugent, Karen; Petrosyan, Karen; Swan, Karen; Kryczka, Karolina; Wojtczak-Soska, Karolina; Wojtera, Karolina; Lenk, Karsten; Ramasamy, Karthik; Łuczak, Katarzyna; Malinowska, Katarzyna; Pointon, Kate; Robb, Kate; Martin, Katherine; Claes, Kathleen; Carruthers, Kathryn; Siegel, Kathy E; Drouin, Katia; Fowler-Lehman, Katie; Rawat, Kavita; Rowe, Kay; Fukuda, Keiichi; Fox, Keith A A; Mahaffey, Ken; Unterbrink, Kendra; Giedd, Kenneth; Van Loo, Kerrie; Lee, Kerry; Bonin, Kerstin; Bainey, Kevin R; Harley, Kevin T; Anstrom, Kevin; Chan, Kevin; Croce, Kevin; Landolfo, Kevin; Marzo, Kevin; Patel, Keyur; Abdul-Nour, Khaled; Alfakih, Khaled; Dajani, Khaled; Ziada, Khaled; Baloch, Khaula; Kushniriuk, Khrystyna; Poh, Kian-Keong; Ireland, Kim F; Holland, Kim; Byrne, Kimberly Ann; Halverson, Kimberly E; Elmore, Kimberly; Miller-Cox, Kimberly; Reddy, Kiran; Quiles, Kirsten J; Abercrombie, Kirsty; Matschke, Klaus; Szymczyk, Konrad; Chan, Koo Hui; Preethi, Kotiboinna; Sokhon, Kozhaya; Meemuk, Krissada; Thygesen, Kristian; Salmi, Kristin M; Newby, Kristin; Wippler, Kristina; Arges, Kristine; Teoh, Kristine; Etherington, Krystal; Łoboz-Grudzień, Krystyna; Reczuch, Krzysztof W; Bury, Krzysztof; Drzymalski, Krzysztof; Kukuła, Krzysztof; Sung, Kuo-Tzu; Huber, Kurt; Douangvila, Ladda; Sullenberger, Lance; Trama, Larissa Miranda; Matics, Laszlone; Drew, Laura; Flint, Laura; Keinaite, Laura; Sarti, Laura; Kolakaluri, Laurel; Phillips, Lawrence M; Friedman, Lawrence; Phillips, Lawrence; Velicki, Lazar; Howell, Leah; Maranan, Leandro C; Cox, Leanne; Daba, Ledjalem; Zhang, Lei; Dharmarajan, Lekshmi; Bockeria, Leo; Pizzol Caetano, Leonardo; Bridi, Leonardo; Bershtein, Leonid L; Sokalski, Leszek; Yan, Li Hai; Li, Li; Nijmeijer, Lia; Sousa, Lidia; Xu, Lihong; Zhang, Lihua; Zhang, Lili; Schiavi, Lilia; Barbosa, Lilian Mazza; Khor, Lillian L; Felix-Stern, Lina; Hall, Linda L; Hollenweger, Linda M; Arcand, Linda; Davidson-Ray, Linda; Schwarz, Linda; Sikora, Lindsey N; Chi, Lingping; Patricio, Lino; Zhang, Liping; Chaytor, Lisa; Hatch, Lisa; McCloy, Lisa; Wong, Lisa; Persson, Liselotte; Jiang, Lixin; Low, Liz; Pupic, Ljiljana; Bière, Loïc; Monti, Lorenzo; Christensen, Lori; Pritchard, Lori; Black, Loriane; Desimone, Lori-Ann; Larmand, Lori-Ann; McGregor, Lorraine; Morby, Louise; Thomson, Louise; Harvey, Luc; de Pádua Baptista, Luciana; Garcia, Lucilla; Eliahou, Ludivine; Helmer, Ludmila; Smidt, Luis F; Bernanrdes, Luis; Guzman, Luis; Carvalho, Luiz A; Xiong, Luyang; Teo, Lynette L; Neeson, Lynn M; Winstanley, Lynne; Srichai-Parsia, M Barbara; Quintana Giner, M; Sowjanya Reddy, M; Valdés Chávarri, M; Grazia Rossi, M; Simoons, Maarten; Konigstein, Maayan; Lesiak, Maciej; Olsowka, Maciej; Selas, Mafalda; Corfias, Magalie; Madero Rovalo, Magdalena; Łanocha, Magdalena; Miller, Magdalena; Misztal-Teodorczyk, Magdalena; Rantinella, Magdalena; Abdelhamid, Magdy; Jimenez, Magnolia; Alam, Mahboob; Mylarappa, Mahevamma; El Shahawy, Mahfouz; Mohamed, Mahmoud; Al-Bustami, Mahmud; Joseph, Majo X; Frach, Malgorzata; Celińska-Spodar, Małgorzta; Helm, Malte; Chacko, Manas; Murphy, Mandy; Vinod, Manitha; Rani, Manjula; Dhawan, Manu; Mombelli, Manuela; Weber, Marcel; Galvani, Marcello; Rodrigues, Marcelo Jamus; Dubin, Marcia F; Werner Bayer, Marcia F; Szkopiak, Marcin; Monsalve, Marco Antonio; Santos, Marco Bizzaro; Magnoni, Marco; Marini, Marco; Sicuro, Marco; Zenati, Marco; Coimbra Resende, Marcos Valério; Roik, Marek; Bentzvi, Margalit; Gilsenan, Margaret; Iraola, Margaret; Quinn, Margot C; Alfonso, Maria A; Pereira Moraes, Maria Antonieta; Martínez-Ruíz, María Dolores; Canales, María Fernanda; Caetano, Maria Inês; Corral, Maria P; Pérez García, Maria; Actis, Maria Victoria; Aguirre, Maria; Andreasson, Maria; Aprile, Maria; Colton, Maria; Martin, Maria Eugenia; Lasala, Maria; Lorenzo, Maria; Posada, Maria; Shier, Maria; Thottam, Maria; Furtado, Mariana V; Okada, Mariana Yumi; Dracoulakis, Marianna D A; De Andrade, Marianne; Rubio, Mariano; Essermark, Marie; Scherrer-Crosbie, Marielle; Petrovic, Marija T; Zdravkovic, Marija; Black, Marilyn; Garcia, Marina; Garcia, Mario J; Szulik, Mariola; Orgera, Marisa; de Belder, Mark A; Harbinson, Mark; Hyun, Mark; Peterson, Mark; Xavier, Mark; Mosley, Marlowe; Capinha, Marta; Marcinkiewicz-Siemion, Marta; Swiderek, Marta; Meyer, Martha; Ceseri, Martina; Tricoli, Martina; Kronenberg, Marvin; Williams, Mary; Champagne, Mary Ann; Rogge, Mary Colleen; Soltau, Mary R; Streif, Mary; Villella, Massimo; Leesar, Massoud; Claudia, Matei; Solecki, Mateusz; Mungo, Matías Nicolás; Wall, Matthew Jr; Budoff, Matthew; Jezior, Matthew; Luckie, Matthew; Friedrich, Matthias; Haeffner, Mauren P; Tscharre, Maximilian; Winter, Max-Paul; Almeida, Mayana; Krishnam, Mayil S; Patel, Mayuri; Mishra, Meenakshi; Manocchia, Megan; Kakade, Meghana; Munro, Melanie J; Chaplin, Melissa D; LeFevre, Melissa; Andiapen, Mervyn; Gibson, Michael A; Rubens, Michael B; Turner, Michael C; Shapiro, Michael D; Lee, Michael W; Berlowitz, Michael; Davidson, Michael; Mack, Michael; McDaniel, Michael; Mumma, Michael; Wlodarczyk, Michal; Khouri, Michel G; Slama, Michel S; Rawlins, Michele; Bonner, Michelle M; Seib, Michelle M; Chang, Michelle; Crowder, Michelle; Dixon, Michelle; Mayon, Michelle; McEvoy, Michelle; Yee, Michelle; Fernandes, Miguel M; Nobre Menezes, Miguel; Souto Bayarri, Miguel; Barrero, Miguel; Torosoff, Mikhail T; Dobric, Milan R; Dobric, Milan; Dekleva, Milica Nikola; Gadkari, Milind Avdhoot; Gomez, Millie; Kyaw, Min Tun; Brooks, Miriam; Stevo Martinovic, Miroslav; Lustre, Mitchel B; Vakani, Mohammad Tariq; El-Hajjar, Mohammad; Al-Amoodi, Mohammed; Hussain, Mohammed; Saleem, Mohammed; Blanco-Calvo, Moisés; Jiménez-Santos, Moisés; Bhatia, Mona; Rosca, Monica; Laukyte, Monika; Gracida Blanca, Montserrat; Vila Perales, Montserrat; Al-Mallah, Mouaz H; de Oliveira Filho, Moysés; Ntsekhe, Mpiko; Saric, Muhamed; Chen, Mulei; Brousseau, Myriam; Takiuti, Myrthes Emy; Cemerlic-Adjic, Nada; Asif, Nadia; Gakou, Nadia; Hussain, Nafisa; Katamadze, Nana O; Clapp, Nancy L; Aedy, Nancy; Nataraj, Nandita; Wenger, Nanette K; Uchida, Naomi; Ismail, Nasrul; Oliveira, Natalia S; de Carvalho Maffei, Natalia; Spitzer, Natalie; Putnam, Natasha C; Aslam, Naved; Mowafy, Neamat; Pandit, Neeraj; Parakh, Neeraj; Garcevic, Nevena; Meadows, Ngaire; Tran, Nhi N; Danchin, Nicholas; Lakeman, Nicki; Johnston, Nicola; Shammas, Nicolas W; Saint Vrestil, Nicole; Deming, Nicole; Zhong, Nier; Patel, Niket; Boskovic, Nikola N; Karogiannis, Nikolaos; Werner, Nikos; Johnston, Nina; Zhang, Ning; Zhou, Ning; Hindoyan, Niree; Kumar, Nirmal; Chadha, Nitika; Naik, Nitish; Aripova, Nodira; Mtana, Noloyiso; Eskelson, Nona A; Mokhtar, Noor Syamira; Taksaudom, Noppon; Basri, Nor Asiah; Marchelletta, Nora; Hogg, Norma; Jungla, Nungshi; Ferreira, Nuno; Lubyanaya, Oksana A; Nikolaeva, Olga B; Cañavate, Olga; Sobrino, Olga; Walesiak, Olga; Walter, Olga; Zdończyk, Olga; Lim, Olivia J; Anaya, Olivia; Mancilla, Olivia; Dubourg, Olivier; Bello, Olugbenga; Almousalli, Omar; Thompson, Omar; Olurinde, Oni; Harel, Or; Raheem, Osama; Méndiz, Oscar; Prada-Delgado, Óscar; Shapira, Oz; Schulze, P Christian; Panpunuan, Pachara; Maurovich-Horvat, Pal; Garg, Pallav; Moraga, Paloma; Singh, Pam; Julian, Pamela; Ouyang, Pamela; Sigel, Pamela; Woodard, Pamela; Zhou, Panpan; Poggio, Paola Emanuela; Smanio, Paola; Calabro, Paolo; Jeetley, Paramjit; Goube, Pascal; Nguyen, Patricia K; Alarie, Patricia; Arakelian, Patricia; Arsenault, Patricia; Blaise, Patricia; Brito, Patricia; Cowper, Patricia; Endsley, Patricia; Mieses, Patricia; Alexander, Patrick B; Donnelly, Patrick; Wilmot, Patrick; Lebioda, Patrycja; Gordon, Paul C; Mesropian, Paul Der; Galiwango, Paul; Hauptman, Paul; Kennedy, Paul; Beardsley, Paula; García-González, Paula; Rezende, Paulo Cury; Caramori, Paulo Ricardo; Kozlov, Pavel S; Canas Silva, Pedro; Melo Barros E Silva, Pedro Gabriel; Píccaro de Oliveira, Pedro; Carvalho, Pedro; Modas, Pedro; Rio, Pedro; Jain, Peeyush; He, Peiyu; McCullough, Peter A; Stone, Peter H; Pollak, Peter M; Douglass, Peter; Henriksen, Peter; OKane, Peter; Ong, Peter; Jones, Philip; Rogal, Philip; Généreux, Philippe; Menasche, Philippe; Rheault, Philippe; Goold, Phoebe; Gervais, Pierre; Michaud, Pierre; Calvillo, Pilar; Chai, Ping; Jakubowski, Piotr; Pruszczyk, Piotr; Slomka, Piotr; Sritara, Piyamitr; Loh, Poay-Huan; Sonawane, Poonam; Samadi, Pouneh; Parikh, Pragnesh P; Deedwania, Prakash; Patel, Pranav M; Polamuri, Praneeth; Sharma, Pratiksha; Vasquez, Precilia; Kamath, Preeti; Thomas, Prince; Arambam, Priyadarshani; Mehta, Puja K; Grant, Purvez; Naik, Pushpa; Zhong, Qi; Zhao, Qian; Zhou, Qiang; Yuan, Qianqian; Yu, Qin; Li, Qingxian; Xie, Qiulan; Zeng, Qiutang; Vindhya, R J; Gerlach, R James; King, Rachel; Vučić, Rada; Lyubarova, Radmila; Pracon, Radoslaw; Fisher, Raewyn; Beyar, Rafael; Diaz, Rafael; Selgas, Rafael; Bugiardini, Raffaele; Fanelli, Raffaele; Kavalakkat, Raisa; Rajalekshmi, V S; Barua, Rajat S; Menon, Rajeev; Nair, Rajesh Gopalan; Francis, Rajesh; Narang, Rajiv; Yadav, Rakesh; Huston, Ralph Alan; Ramakrishnan, T; de Silva, Ramesh; Mahmoud, Rami El; Carvalho, Ramiro; de Jesús-Pérez, Ramon; Stevens, Ramona; Leng, Ran; Kachru, Ranjan; Nath, Ranjit Kumar; Sanchez, Raquel; Dwyer, Raven R; Lee, Raven; Wyman, Ray; Wong, Raymond C; Little, Raymond W; Ocaranza Sanchez, Raymundo; Wimmer, Rebecca J; Bariciano, Rebecca; Otis, Rebecca; Herrmann, Rebekah R; Yunis, Reem; Hampson, Reinette; Karam, Renato Abdala; Hessian, Renee C; Kaneshiro, Renee; Ravindran, Reshma; Gamma, Reto Andreas; Bhandari, Reyna; Arsanjani, Reza; Lopes, Ricardo L; Mendes Oliveira, Ricardo; Costa, Ricardo; Bhatt, Richa; Davies, Richard F; Trimlett, Richard H J; Goldweit, Richard; Hermanides, Rik; Nakanishi, Rine; Sidh, Rinu R; Patel, Risha; Coram, Rita; Siddiqui, Rizwan A; Beanlands, Rob S; Hamburger, Robert J; Riezebos, Robert K; Donnino, Robert M; Bojar, Robert; Chilton, Robert; Guyton, Robert; Henderson, Robert; Kornberg, Robert; Leber, Robert; Mao, Robert; Stenberg, Robert; Santos, Roberta P; Favaloro, Roberto René; Amati, Roberto; Lima, Rodolfo G S D; Cerci, Rodrigo J; Tumelero, Rogerio; Tandon, Rohit; Tewari, Roma; Miranda-Peats, Romalisa; Wald, Ron; Mastouri, Ronald A; Morford, Ronald G; Schwartz, Ronald G; Pedalino, Ronald P; Hu, Rongrong; Hansen, Ronnell A; Cohen, Ronny A; Hachamovitch, Rory; Homem, Rosa; Sandonato, Rosa; Laimer, Rosane; Gans, Rosann; Yost, Roxanne; Mathew, Roy; Baleón-Espinosa, Rubén; Ramos, Ruben; Gevorgyan, Rubine; Ferreira, Rui; Jing, Rui; Pérez-Fernández, Ruth; Dwivedi, S K; Ramakrishnan, S; Khan, Saadat; Bokhari, Sabahat; Thomas, Sabu; Lubna, Sadath; Khan, Sajeeda Parveen; Govindan, Sajeev Chakanalil; Girotra, Saket; Kassam, Saleem; Canada, Sallie; Cruz-Flores, Salvador; Mohamed, Samaa; Ly, Samantha; El Kaffas, Sameh; Massalha, Samia; Setty, Sampoornima; Nwosu, Samuel; Seth, Sandeep; Singh, Sandeep; Niehe, Sander R; Rivest, Sandra M; Zier, Sandra S; Ahoud, Sandra; Carr, Sandy; Ganapathi, Sanjay; Shetty, Sanjay; Sharma, Sanjeev; Jimenez, Santa; Satheesh, Santhosh; Garcia, Santiago A; Fernandez, Sara; Karlsson, Sara; Salkind, Sara; Temiyasathit, Sara; Medina Rodriguez, Sarah; Beaudry, Sarah; Hadjih, Sarah; Williams, Sarah; Zahrani, Sarah; Ralhan, Sarju; Hinic, Sasa; Kedev, Sasko; Singh, Satinder; Yasuda, Satoshi; Manjunath, Satvic Cholenahally; Lee, Sau; Kaczkowski, Scott M; Kinlay, Scott; Hayes, Sean W; Sobczak, Sebastian; Asier, Senait; Sayganov, Sergey A; Sokol, Seth I; Pandie, Shaheen; Yahaya, Shaiful Azmi; Mehta, Shamir; Nie, Shao-Ping; Chandra, Sharad; Islam, Sharder; Tai, Sharon; Karwa, Sheetal Rupesh; Ussery, Sheri; Bajaj, Sheromani; Crook, Sherron C; Nishimura, Shigeyuki; Nakano, Shintaro; Heydari, Shirin; Choudhary, Shiv Kumar; Patel, Shivali; Ganesan, Shobana; Pandey, Shruti; Zhang, Shuyang; Hande, Shweta; Gadage, Siddharth; Tan, Sik-Yin V; Zottis Poletti, Silvia; Riera, Silvia; Valbuena, Silvia; Walsh, Simon; Maspoli, Simona; Savaris, Simone; Feng, Si-Ting; Cho, So Yang; Yakubov, Solomon; Zhu, Songlin; Wang, Songtao; Guerrero, Sonia; Gupta, Sonika; Salinger Martinovic, Sonja; Brons, Sonya; Brener, Sorin; Gurunathan, Sothinathan; Saba, Souheil; Nayak, Soundarya; Reddy, Sowjanya; Potluri, Srinivasa; Sudarshan, Sriram; Kuanprasert, Srun; Van Oosterhout, Stacie; Lerakis, Stamatios; Cobos, Stanley E; Bertog, Stefan C; Simović, Stefan M; Weikl, Stefan; Di Marco, Stefano; Provasoli, Stefano; Tirado, Stephanie A; Boer, Stephanie C; Lane, Stephanie M; Ferket, Stephanie; Kelly, Stephanie; Wasmiller, Stephanie; McKellar, Stephen H; Hoole, Stephen P; Fremes, Stephen; Preston, Stephen; Leung, Steve; Fein, Steven A; Lindsay, Steven J; Sedlis, Steven P; Giovannone, Steven; Michael, Steven; Weitz, Steven; van Vugt, Stijn; Banerjee, Subhash; Naik, Sudhir; Hosino, Suellen; Desire, Sukie; Yamwong, Sukit; Thambar, Suku T; Mookherjee, Sulagna; Singh, Suman; Mishra, Sundeep; Verma, Sunil Kumar; Kulthawong, Supap; Khwakhong, Supatchara; Naik, Surendra; Babu, Suresh; Woragidpoonpol, Surin; Narayanappa, Suryaprakash; Derbyshire, Susan; Gent, Susan; Mathus, Susan; Milbrandt, Susan; Moore, Susan; Regan, Susan; Stinson, Susan; Webber, Susan; Silva, Susana; Stevens, Susanna; Gruensfelder, Susanne; Aramcharoen, Suthara; Kolhe, Suvarna; Tavares, Suzana; Arnold, Suzanne; Welsh, Suzanne; Apostolovic, Svetlana; Kunhunny, Swapna; Hung, Ta-Chuan; Zappernick, Taissa; Sharir, Tali; Silva, Talita; Soares, Tamara Colaiácovo; Pillay, Tapan Umesh; Mittal, Tarun K; Trifonova, Tatiana; Duarte, Tauane Bello; Huk, Tauqir; Dutoiu, Téodora; Chua, Terrance; Weyand, Terry; Charles, Thabitha; Kofidis, Theodoros; McCreary, Theresa; Lefevre, Thierry; Arumairajah, Thippeekaa; Tepsuwan, Thitipong; Mulhearn, Thomas J; Meyer, Thomas M; Rocco, Thomas P; Downes, Thomas R; Crain, Thomas; Haldis, Thomas; Mathew, Thomas; Redick, Thomas; Devi, Thounaojam Indira; Nageh, Thuraia; Cauthren, Tia; Silva, Tiago; Little, Tiffany; Andric, Tijana; Harding, Tina; Lau, Titus; Formisano, Tiziana; Moccetti, Tiziano; Ciurus, Tomasz; Mazurek, Tomasz; Tarchalski, Tomasz; Nagai, Toshiyuki; Tran, Tri; Youn, Tricia; Tucker, Trish; Milner, Trudie; Bose, Tuhina; Kotecha, Tushar; Sechtem, Udo; Valeti, Uma S; Cucchini, Umberto; Badami, Umesh; Kaul, Upendra; Bahl, V K; Narain, V S; Casali, Valentina; Godoy, Valeria; Robesyn, Valerie; Priya, Vamshi P; Yadav, Vandana; McKinney, Vera; De Lenges, Veronica; Tinnirello, Veronica; Miro, Vicente; Navarro, Victor; Gumerova, Victoria; Hernandez, Victoria; Seeratan, Vidya; Kumar, Vijay; Kozulin, Vikentiy Y; Bulkley, Viktoria; Veiga, Vilmar Jr; Setang, Vincent; Vineeth, C P; Pubull Nuñez, Virginai; Fernández-Figares, Virginia; Gomes, Vitor; Gabriel, Viviana; Dos Santos, Viviane; Almeida, Viviane; Iliescu, Vlad A; Mudrenovic, Vladan; Dzavik, Vladimir; Giga, Vojislav L; Mogrovejo, Walter Enrique; Chan, Wan Xian; Marfori, Wanda C; Parker, Wanda; Mekara, Warangkana; Nona, Wassim; Old, Wayne; Pennachi, Wayne; Nawarawong, Weerachai; Chen, Wei; Su, Wei; Xing, Weibing; Lan, Wei-Ren; Crawford, Wenda; Stewart, Wendy L; Drewes, Wendy; Lin, Wenhua; Abernethy, William B; Salerno, William D; Fearon, William F; Vergoni, William; Weintraub, William; Sia, Winnie C; Musial, Wlodzimierz J; Flores-Ríos, Xacobe; Garcia-Moll Marimon, Xavier; Su, Xi; Ma, Xiang; Gu, Xiangqiong; Wang, Xiao; Li, Xiaomei; Yao, Xiaowei; Fu, Xin; Su, Xin; Zeng, Xin; Yang, Xinchun; Li, Xiuhong; Fang, Xuehua; Wang, Xutong; Geng, Yaming; Yan, Yan; Pépin-Dubois, Yanek; Wang, Yanfu; Wang, Yang; Tian, Yanmeng; Huang, Yaping; Han, Yechen; Zambrano, Yesenia; Yang, Yi-Hsuan; Sia, Ying Tung; Yang, Yining; Ma, Yitong; Peralta, Yolayfi; Wu, Yongjian; Kunwu, Yu; Zhao, Yu; Peng, Yudong; Lin, Yueh-Hung; Zhao, Yulan; Dong, Yumei; Zhao, Yunhai; Wannasopha, Yutthaphan; Taul, Yvonne; Sahul, Zakir; Kudzoeva, Zalina; Kalarus, Zbigniew; Markovic, Zeljko Z; Huang, Zhen; Ji, Zheng; Liu, Zhenyu; Yue, Zhou; Zhang, Zhulin; Li, Zhuxi; Singh Meharwal, Zile; Bai, Ziliang; Yu, Zixiang; Huda, Zohra; Davidovits, Zoltan
BACKGROUND:Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS:We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS:Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS:Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
PMID: 32227755
ISSN: 1533-4406
CID: 5451242