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https://www.readbyqxmd.com/read/29791286/metastatic-pancreatic-cancer-asco-clinical-practice-guideline-update
#1
Davendra P S Sohal, Erin B Kennedy, Alok Khorana, Mehmet S Copur, Christopher H Crane, Ignacio Garrido-Laguna, Smitha Krishnamurthi, Cassadie Moravek, Eileen M O'Reilly, Philip A Philip, Ramesh K Ramanathan, Joseph T Ruggiero, Manish A Shah, Susan Urba, Hope E Uronis, Michelle W Lau, Daniel Laheru
Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018...
May 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29771793/the-association-of-chronic-pain-and-long-term-opioid-therapy-with-hiv-treatment-outcomes
#2
Jessica S Merlin, Dustin Long, William C Becker, Edward R Cachay, Katerina A Christopolous, Kasey Claborn, Heidi M Crane, E Jennifer Edelman, Richard Harding, Stefan G Kertesz, Jane M Liebschutz, W Christopher Mathews, Michael J Mugavero, Sonia Napravnik, Connall O'Cleirigh, Michael S Saag, Joanna L Starrels, Robert Gross
BACKGROUND: Chronic pain occurs in up to 85% of persons living with HIV (PLWH) and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes. METHODS: This was prospective cohort study conducted between 7/2015-7/2016 in five HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire and ≥4/10 on the Pain Enjoyment of life and General activity (PEG) questionnaire...
May 4, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29668116/a-bis-triazacyclononane-tris-pyridyl-n9-azacryptand-beer-can-receptor-for-complexation-of-alkali-metal-and-lead-ii-cations
#3
Asha Brown, Thanthapatra Bunchuay, Christopher Crane, Nicholas White, Amber Thompson, Paul D Beer
A new bis-triazacyclononane tris-pyridyl N9-azacryptand ligand is synthesised via a convenient one-pot [2 + 3] condensation reaction between triazacyclononane and 2,6-bis(bromomethyl) pyridine in the presence of M2CO3 (M = Na, K). The proton, lithium, sodium, potassium and lead(II) complexes of the ligand are characterised in the solid state. A preliminary solution-phase competition experiment indicates that the cryptand ligand preferentially binds lead(II) in the presence of sodium, calcium, potassium and zinc cations in methanol solution...
April 18, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29623578/trajectories-of-depressive-symptoms-among-a-population-of-hiv-infected-men-and-women-in-routine-hiv-care-in-the-united-states
#4
Angela M Bengtson, Brian W Pence, Kimberly A Powers, Mark A Weaver, Matthew J Mimiaga, Bradley N Gaynes, Conall O'Cleirigh, Katerina Christopoulos, W Christopher Mathews, Heidi Crane, Michael Mugavero
Depressive symptoms vary in severity and chronicity. We used group-based trajectory models to describe trajectories of depressive symptoms (measured using the Patient Health Questionnaire-9) and predictors of trajectory group membership among 1493 HIV-infected men (84%) and 292 HIV-infected women (16%). At baseline, 29% of women and 26% of men had depressive symptoms. Over a median of 30 months of follow-up, we identified four depressive symptom trajectories for women (labeled "low" [experienced by 56% of women], "mild/moderate" [24%], "improving" [14%], and "severe" [6%]) and five for men ("low" [61%], "mild/moderate" [14%], "rebounding" [5%], "improving" [13%], and "severe" [7%])...
April 6, 2018: AIDS and Behavior
https://www.readbyqxmd.com/read/29594206/definitive-radiation-therapy-for-hepatocellular-carcinoma-with-portal-vein-tumor-thrombus
#5
Emma B Holliday, Randa Tao, Zachary Brownlee, Prajnan Das, Sunil Krishnan, Cullen Taniguchi, Bruce D Minsky, Joseph M Herman, Ahmed Kaseb, Kanwal Raghav, Claudius Conrad, Jean-Nicholas Vauthey, Thomas A Aloia, Yun Shin Chun, Christopher H Crane, Eugene J Koay
Background: The purpose of this study is to review the results of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal venous tumor thrombus (PVTT) in a Western patient population. Methods: Thirty-four patients with HCC PVTT treated from 2007 to 2014 with RT were identified. Biologically effective dose (BED) was calculated for each patient, and greater than the median dose delivered (75 Gray (Gy)) was evaluated as a potential prognostic factor. Survival was compared and independent prognostic variables were evaluated by a Cox proportional hazards regression model...
June 2017: Clinical and translational radiation oncology
https://www.readbyqxmd.com/read/29566109/adoption-of-total-neoadjuvant-therapy-for-locally-advanced-rectal-cancer
#6
Andrea Cercek, Campbell S D Roxburgh, Paul Strombom, J Joshua Smith, Larissa K F Temple, Garrett M Nash, Jose G Guillem, Philip B Paty, Rona Yaeger, Zsofia K Stadler, Kenneth Seier, Mithat Gonen, Neil H Segal, Diane L Reidy, Anna Varghese, Jinru Shia, Efsevia Vakiani, Abraham J Wu, Christopher H Crane, Marc J Gollub, Julio Garcia-Aguilar, Leonard B Saltz, Martin R Weiser
Importance: Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. Objective: To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC...
March 22, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29556578/trends-in-intensity-modulated-radiation-therapy-use-for-locally-advanced-rectal-cancer-at-national-comprehensive-cancer-network-centers
#7
Marsha Reyngold, Joyce Niland, Anna Ter Veer, Tanios Bekaii-Saab, Lily Lai, Joshua E Meyer, Steven J Nurkin, Deborah Schrag, John M Skibber, Al B Benson, Martin R Weiser, Christopher H Crane, Karyn A Goodman
Purpose: Intensity modulated radiation therapy (IMRT) has been rapidly incorporated into clinical practice because of its technological advantages over 3-dimensional conformal radiation therapy (CRT). We characterized trends in IMRT utilization in trimodality treatment of locally advanced rectal cancer at National Comprehensive Cancer Network cancer centers between 2005 and 2011. Methods and materials: Using the prospective National Comprehensive Cancer Network Colorectal Cancer Database, we determined treatment patterns for 976 patients with stage II-III rectal cancer who received pelvic radiation therapy at contributing centers between 2005 and 2011...
January 2018: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29421973/multimodal-characterization-of-the-late-effects-of-tbi-letbi-a-methodological-overview-of-the-letbi-project
#8
Brian L Edlow, C Dirk Keene, Daniel Perl, Diego Iacono, Rebecca Folkerth, William Stewart, Christine L MacDonald, Jean Augustinack, Ramon Diaz-Arrastia, Camilo Estrada, Elissa Flannery, Wayne Gordon, Tom Grabowski, Kelly Hansen, Jeanne Hoffman, Christopher Kroenke, Eric Larson, Patricia Lee, Azma Mareyam, Jennifer A McNab, Jeanne McPhee, Allison L Moreau, Anne Renz, KatieRose Richmire, Allison Stevens, Cheuk Y Tang, Lee S Tirrell, Emily Trittschuh, Andre van der Kouwe, Ani Varjabedian, Lawrence L Wald, Ona Wu, Anastasia Yendiki, Liza Young, Lilla Zollei, Bruce Fischl, Paul K Crane, Kristen Dams-O'Connor
Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's and Parkinson's disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood...
February 8, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29382433/a-survey-of-the-regulatory-requirements-for-bcs-based-biowaivers-for-solid-oral-dosage-forms-by-participating-regulators-and-organisations-of-the-international-generic-drug-regulators-programme
#9
Joy Elizabeth Van Oudtshoorn, Alfredo García-Arieta, Gustavo Mendes Lima Santos, Christopher Crane, Clare Rodrigues, Craig Simon, Ji Myoung Kim, Sang Aeh Park, Yusuke Okada, Ryosuke Kuribayashi, Chantal Pfäffli, Arno Nolting, Iván Omar Calderón Lojero, Zulema Rodríguez Martínez, Wen-Yi Hung, April C Braddy, Nancy Arciniegas Leal, Diego Gutierrez Triana, Mitch Clarke, Peter Bachmann
PURPOSE:  The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions. Despite being based on the same principles, BCS-based biowaivers are interpreted and regulated differently among international regulatory agencies. In this survey, the Bioequivalence Working Group (BEWG) of the International Generic Drug Regulators Programme (IGDRP) compared the criteria for BCS-based biowaivers applied by the participating regulators and organisations...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29370450/imaging-based-biomarkers-changes-in-the-tumor-interface-of-pancreatic-ductal-adenocarcinoma-on-computed-tomography-scans-indicate-response-to-cytotoxic-therapy
#10
Ahmed M Amer, Mohamed Zaid, Baishali Chaudhury, Dalia Elganainy, Yeonju Lee, Christopher T Wilke, Jordan Cloyd, Huamin Wang, Anirban Maitra, Robert A Wolff, Gauri Varadhachary, Michael J Overman, Jeffery E Lee, Jason B Fleming, Ching Wei Tzeng, Matthew H Katz, Emma B Holliday, Sunil Krishnan, Bruce D Minsky, Joseph M Herman, Cullen M Taniguchi, Prajnan Das, Christopher H Crane, Ott Le, Priya Bhosale, Eric P Tamm, Eugene J Koay
BACKGROUND: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response. METHODS: Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry)...
April 15, 2018: Cancer
https://www.readbyqxmd.com/read/29189331/ablative-radiotherapy-doses-for-locally-advanced-pancreatic-cancer-lapc
#11
Christopher H Crane, Eileen M O'Reilly
Standard palliative doses of radiation for locally advanced unresectable pancreatic cancer have had minimal to no impact on survival. Randomized trials evaluating these palliative doses have not shown a significant survival benefit with the use of radiation as consolidation after chemotherapy. Results from nonrandomized studies of 3- to 5-fraction low-dose stereotactic radiation (SBRT) have likewise had a minimal impact, but with less toxicity and a shorter treatment time. Doses of SBRT have been reduced to half the level that is necessary (biological equivalent dose, BED of 53 Gy) to achieve tumor ablation in the treatment of other solid tumors (100 Gy BED) to protect the gastrointestinal (GI) tract...
November 2017: Cancer Journal
https://www.readbyqxmd.com/read/29148090/assessment-of-cumulative-health-risk-in-the-world-trade-center-general-responder-cohort
#12
Ghalib A Bello, Susan L Teitelbaum, Roberto G Lucchini, Christopher R Dasaro, Moshe Shapiro, Julia R Kaplan, Michael A Crane, Denise J Harrison, Benjamin J Luft, Jacqueline M Moline, Iris G Udasin, Andrew C Todd
BACKGROUND: Multiple comorbidities have been reported among rescue/recovery workers responding to the 9/11/2001 WTC disaster. In this study, we developed an index that quantifies the cumulative physiological burden of comorbidities and predicts life expectancy in this cohort. METHODS: A machine learning approach (gradient boosting) was used to model the relationship between mortality and several clinical parameters (laboratory test results, blood pressure, pulmonary function measures)...
January 2018: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/29114609/dose-escalation-with-an-imrt-technique-in-15-to-28-fractions-is-better-tolerated-than-standard-doses-of-3dcrt-for-lapc
#13
Lauren E Colbert, Shalini Moningi, Awalpreet Chadha, Ahmed Amer, Yeonju Lee, Robert A Wolff, Gauri Varadhachary, Jason Fleming, Matthew Katz, Prajnan Das, Sunil Krishnan, Eugene J Koay, Peter Park, Christopher H Crane, Cullen M Taniguchi
Purpose: To review acute and late toxicities after chemoradiation for locally advanced pancreatic ductal adenocarcinoma in patients who were treated with escalated dose radiation (EDR). Methods and materials: Maximum Common Terminology Criteria for Adverse Events Version 4.0 acute toxicities (AT) during radiation and within 60 days after radiation were recorded for both acute gastrointestinal toxicity and overall toxicity (OT). Late toxicities were also recorded...
July 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29053185/expression-of-the-dna-repair-gene-mlh1-correlates-with-survival-in-patients-who-have-resected-pancreatic-cancer-and-have-received-adjuvant-chemoradiation-nrg-oncology-rtog-study-9704
#14
Yaacov R Lawrence, Jennifer Moughan, Anthony M Magliocco, Alexander C Klimowicz, William F Regine, Rex B Mowat, Thomas A DiPetrillo, William Small, Jeffry P Simko, Talia Golan, Kathryn A Winter, Chandan Guha, Christopher H Crane, Adam P Dicker
BACKGROUND: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials...
February 1, 2018: Cancer
https://www.readbyqxmd.com/read/28992096/evaluating-the-population-impact-on-racial-ethnic-disparities-in-hiv-in-adulthood-of-intervening-on-specific-targets-a-conceptual-and-methodological-framework
#15
Chanelle J Howe, Akilah Dulin-Keita, Stephen R Cole, Joseph W Hogan, Bryan Lau, Richard D Moore, W Christopher Mathews, Heidi M Crane, Daniel R Drozd, Elvin Geng, Stephen L Boswell, Sonia Napravnik, Joseph J Eron, Michael J Mugavero
Reducing racial/ethnic disparities in human immunodeficiency virus (HIV) disease is a high priority. Reductions in HIV racial/ethnic disparities can potentially be achieved by intervening on important intermediate factors. The potential population impact of intervening on intermediates can be evaluated using observational data when certain conditions are met. However, using standard stratification-based approaches commonly employed in the observational HIV literature to estimate the potential population impact in this setting may yield results that do not accurately estimate quantities of interest...
February 1, 2018: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28938910/creating-a-data-resource-what-will-it-take-to-build-a-medical-information-commons
#16
Patricia A Deverka, Mary A Majumder, Angela G Villanueva, Margaret Anderson, Annette C Bakker, Jessica Bardill, Eric Boerwinkle, Tania Bubela, Barbara J Evans, Nanibaa' A Garrison, Richard A Gibbs, Robert Gentleman, David Glazer, Melissa M Goldstein, Hank Greely, Crane Harris, Bartha M Knoppers, Barbara A Koenig, Isaac S Kohane, Salvatore La Rosa, John Mattison, Christopher J O'Donnell, Arti K Rai, Heidi L Rehm, Laura L Rodriguez, Robert Shelton, Tania Simoncelli, Sharon F Terry, Michael S Watson, John Wilbanks, Robert Cook-Deegan, Amy L McGuire
National and international public-private partnerships, consortia, and government initiatives are underway to collect and share genomic, personal, and healthcare data on a massive scale. Ideally, these efforts will contribute to the creation of a medical information commons (MIC), a comprehensive data resource that is widely available for both research and clinical uses. Stakeholder participation is essential in clarifying goals, deepening understanding of areas of complexity, and addressing long-standing policy concerns such as privacy and security and data ownership...
September 22, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28816138/lymphocyte-nadir-and-esophageal-cancer-survival-outcomes-after-chemoradiation-therapy
#17
Rajayogesh Davuluri, Wen Jiang, Penny Fang, Cai Xu, Ritsuko Komaki, Daniel R Gomez, James Welsh, James D Cox, Christopher H Crane, Charles C Hsu, Steven H Lin
PURPOSE: Host immunity may affect the outcome in patients with esophageal cancer. We sought to identify factors that influenced absolute lymphocyte count (ALC) nadir during chemoradiation therapy (CRT) for esophageal cancer (EC) and looked for clinically relevant associations with survival. METHODS AND MATERIALS: 504 patients with stage I-III EC (2007-2013) treated with neoadjuvant or definitive CRT with weekly ALC determinations made during treatment were analyzed...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28761945/prescription-opioid-use-misuse-and-use-disorders-in-u-s-adults-2015-national-survey-on-drug-use-and-health
#18
Beth Han, Wilson M Compton, Carlos Blanco, Elizabeth Crane, Jinhee Lee, Christopher M Jones
Background: Despite the continuing epidemic of opioid misuse, data on the prevalence of prescription opioid use, misuse, and use disorders are limited. Objective: To estimate the prevalence of prescription opioid use, misuse, and use disorders and motivations for misuse among U.S. adults. Design: Survey. Setting: The 2015 National Survey on Drug Use and Health (NSDUH). Participants: 72 600 eligible civilian, noninstitutionalized adults were selected for NSDUH, and 51 200 completed the survey interview...
September 5, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28749824/the-relationship-between-efavirenz-as-initial-antiretroviral-therapy-and-suicidal-thoughts-among-hiv-infected-adults-in-routine-care
#19
MULTICENTER STUDY
Angela M Bengtson, Brian W Pence, Katie R Mollan, Jessie K Edwards, Richard D Moore, Conall OʼCleirigh, Ellen F Eaton, Joseph J Eron, Mari M Kitahata, William C Mathews, Heidi Crane, Michael J Mugavero
BACKGROUND: Evidence about the effect of initiating efavirenz-containing combination antiretroviral therapy (ART) as the first-line therapy on suicidal thoughts remains conflicting. METHODS: Using data from a cohort of HIV-infected adults enrolled in routine care across 5 sites in the United States, we included participants with a baseline patient-reported outcome measure and detectable viral load who initiated ART between 2011 and 2014. Participants were followed until the earliest of the following: first suicidal thoughts, discontinuation of initial ART regimen, death, loss to care (>12 months with no HIV appointments), or administrative censoring (2014-2015)...
December 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28714976/rare-coding-variants-in-plcg2-abi3-and-trem2-implicate-microglial-mediated-innate-immunity-in-alzheimer-s-disease
#20
Rebecca Sims, Sven J van der Lee, Adam C Naj, Céline Bellenguez, Nandini Badarinarayan, Johanna Jakobsdottir, Brian W Kunkle, Anne Boland, Rachel Raybould, Joshua C Bis, Eden R Martin, Benjamin Grenier-Boley, Stefanie Heilmann-Heimbach, Vincent Chouraki, Amanda B Kuzma, Kristel Sleegers, Maria Vronskaya, Agustin Ruiz, Robert R Graham, Robert Olaso, Per Hoffmann, Megan L Grove, Badri N Vardarajan, Mikko Hiltunen, Markus M Nöthen, Charles C White, Kara L Hamilton-Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W Beecham, Cécile Dulary, Stefan Herms, Albert V Smith, Cory C Funk, Céline Derbois, Andreas J Forstner, Shahzad Ahmad, Hongdong Li, Delphine Bacq, Denise Harold, Claudia L Satizabal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A Brody, Liming Qu, Pascual Sánchez-Juan, Taniesha Morgan, Frank J Wolters, Yi Zhao, Florentino Sanchez Garcia, Nicola Denning, Myriam Fornage, John Malamon, Maria Candida Deniz Naranjo, Elisa Majounie, Thomas H Mosley, Beth Dombroski, David Wallon, Michelle K Lupton, Josée Dupuis, Patrice Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno-Grau, Jeremy D Burgess, Vincenzo Solfrizzi, Petra Proitsi, Hieab H Adams, Mariet Allen, Davide Seripa, Pau Pastor, L Adrienne Cupples, Nathan D Price, Didier Hannequin, Ana Frank-García, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa S Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K Crane, Florence Pasquier, Virginia Boccardi, Isabel Henández, Robert C Barber, Martin Scherer, Lluis Tarraga, Perrie M Adams, Markus Leber, Yuning Chen, Marilyn S Albert, Steffi Riedel-Heller, Valur Emilsson, Duane Beekly, Anne Braae, Reinhold Schmidt, Deborah Blacker, Carlo Masullo, Helena Schmidt, Rachelle S Doody, Gianfranco Spalletta, W T Longstreth, Thomas J Fairchild, Paola Bossù, Oscar L Lopez, Matthew P Frosch, Eleonora Sacchinelli, Bernardino Ghetti, Qiong Yang, Ryan M Huebinger, Frank Jessen, Shuo Li, M Ilyas Kamboh, John Morris, Oscar Sotolongo-Grau, Mindy J Katz, Chris Corcoran, Melanie Dunstan, Amy Braddel, Charlene Thomas, Alun Meggy, Rachel Marshall, Amy Gerrish, Jade Chapman, Miquel Aguilar, Sarah Taylor, Matt Hill, Mònica Díez Fairén, Angela Hodges, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Makrina Daniilidou, James Uphill, Yogen Patel, Joseph T Hughes, Jenny Lord, James Turton, Annette M Hartmann, Roberta Cecchetti, Chiara Fenoglio, Maria Serpente, Marina Arcaro, Carlo Caltagirone, Maria Donata Orfei, Antonio Ciaramella, Sabrina Pichler, Manuel Mayhaus, Wei Gu, Alberto Lleó, Juan Fortea, Rafael Blesa, Imelda S Barber, Keeley Brookes, Chiara Cupidi, Raffaele Giovanni Maletta, David Carrell, Sandro Sorbi, Susanne Moebus, Maria Urbano, Alberto Pilotto, Johannes Kornhuber, Paolo Bosco, Stephen Todd, David Craig, Janet Johnston, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Nick C Fox, John Hardy, Roger L Albin, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Clinton T Baldwin, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Eileen H Bigio, Thomas D Bird, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Chuanhai Cao, Chris S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Steven L Carroll, Carolina Ceballos Diaz, Helena C Chui, David G Clark, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Malcolm Dick, Ranjan Duara, Denis A Evans, Kelley M Faber, Kenneth B Fallon, David W Fardo, Martin R Farlow, Steven Ferris, Tatiana M Foroud, Douglas R Galasko, Marla Gearing, Daniel H Geschwind, John R Gilbert, Neill R Graff-Radford, Robert C Green, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Lawrence S Honig, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Erin Abner, Lee-Way Jin, Gyungah Jun, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James J Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Kathryn L Lunetta, Constantine G Lyketsos, Daniel C Marson, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, John C Morris, Jill R Murrell, Amanda J Myers, Sid O'Bryant, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, William Perry, Elaine Peskind, Aimee Pierce, Wayne W Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Mark A Sager, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Russell H Swerdlow, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Linda J Van Eldik, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Kirk C Wilhelmsen, Jennifer Williamson, Thomas S Wingo, Randall L Woltjer, Clinton B Wright, Chang-En Yu, Lei Yu, Fabienne Garzia, Feroze Golamaully, Gislain Septier, Sebastien Engelborghs, Rik Vandenberghe, Peter P De Deyn, Carmen Muñoz Fernadez, Yoland Aladro Benito, Hakan Thonberg, Charlotte Forsell, Lena Lilius, Anne Kinhult-Stählbom, Lena Kilander, RoseMarie Brundin, Letizia Concari, Seppo Helisalmi, Anne Maria Koivisto, Annakaisa Haapasalo, Vincent Dermecourt, Nathalie Fievet, Olivier Hanon, Carole Dufouil, Alexis Brice, Karen Ritchie, Bruno Dubois, Jayanadra J Himali, C Dirk Keene, JoAnn Tschanz, Annette L Fitzpatrick, Walter A Kukull, Maria Norton, Thor Aspelund, Eric B Larson, Ron Munger, Jerome I Rotter, Richard B Lipton, María J Bullido, Albert Hofman, Thomas J Montine, Eliecer Coto, Eric Boerwinkle, Ronald C Petersen, Victoria Alvarez, Fernando Rivadeneira, Eric M Reiman, Maura Gallo, Christopher J O'Donnell, Joan S Reisch, Amalia Cecilia Bruni, Donald R Royall, Martin Dichgans, Mary Sano, Daniela Galimberti, Peter St George-Hyslop, Elio Scarpini, Debby W Tsuang, Michelangelo Mancuso, Ubaldo Bonuccelli, Ashley R Winslow, Antonio Daniele, Chuang-Kuo Wu, Oliver Peters, Benedetta Nacmias, Matthias Riemenschneider, Reinhard Heun, Carol Brayne, David C Rubinsztein, Jose Bras, Rita Guerreiro, Ammar Al-Chalabi, Christopher E Shaw, John Collinge, David Mann, Magda Tsolaki, Jordi Clarimón, Rebecca Sussams, Simon Lovestone, Michael C O'Donovan, Michael J Owen, Timothy W Behrens, Simon Mead, Alison M Goate, Andre G Uitterlinden, Clive Holmes, Carlos Cruchaga, Martin Ingelsson, David A Bennett, John Powell, Todd E Golde, Caroline Graff, Philip L De Jager, Kevin Morgan, Nilufer Ertekin-Taner, Onofre Combarros, Bruce M Psaty, Peter Passmore, Steven G Younkin, Claudine Berr, Vilmundur Gudnason, Dan Rujescu, Dennis W Dickson, Jean-François Dartigues, Anita L DeStefano, Sara Ortega-Cubero, Hakon Hakonarson, Dominique Campion, Merce Boada, John Keoni Kauwe, Lindsay A Farrer, Christine Van Broeckhoven, M Arfan Ikram, Lesley Jones, Jonathan L Haines, Christophe Tzourio, Lenore J Launer, Valentina Escott-Price, Richard Mayeux, Jean-François Deleuze, Najaf Amin, Peter A Holmans, Margaret A Pericak-Vance, Philippe Amouyel, Cornelia M van Duijn, Alfredo Ramirez, Li-San Wang, Jean-Charles Lambert, Sudha Seshadri, Julie Williams, Gerard D Schellenberg
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p...
September 2017: Nature Genetics
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