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Robert C. Whitaker

David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
Thomas J Whitaker, Charles S Mayo, Daniel J Ma, Michael G Haddock, Robert C Miller, Kimberly S Corbin, Michelle Neben-Wittich, James L Leenstra, Nadia N Laack, Mirek Fatyga, Steven E Schild, Carlos E Vargas, Katherine S Tzou, Austin R Hadley, Steven J Buskirk, Robert L Foote
Patient- and provider-reported outcomes are recognized as important in evaluating quality of care, guiding health care policy, comparative effectiveness research, and decision-making in radiation oncology. Combining patient and provider outcome data with a detailed description of disease and therapy is the basis for these analyses. We report on the combination of technical solutions and clinical process changes at our institution that were used in the collection and dissemination of this data. This initiative has resulted in the collection of treatment data for 23 541 patients, 20 465 patients with provider-based adverse event records, and patient-reported outcome surveys submitted by 5622 patients...
March 1, 2018: Journal of Radiation Research
Judith A Owens, Tracy Dearth-Wesley, Allison N Herman, J Michael Oakes, Robert C Whitaker
OBJECTIVE: To determine whether simultaneous school start time changes (delay for some schools; advance for others) impact adolescents' sleep. DESIGN: Quasi-experimental study using cross-sectional surveys before and after changes to school start times in September 2015. SETTING: Eight middle (grades 7-8), 3 secondary (grades 7-12), and 8 high (grades 9-12) schools in Fairfax County (Virginia) public schools. PARTICIPANTS: A total of 2017 (6% of ~34,900) students were surveyed before start time changes, and 1180 (3% of ~35,300) were surveyed after...
December 2017: Sleep Health
Brandon D Becker, Kathleen C Gallagher, Robert C Whitaker
The quality of teachers' relationships with children is a key predictor of children's later social emotional competence and academic achievement. Interventions to increase mindfulness among teachers have focused primarily on the impacts on teachers' subjective well-being, but not on the quality of their relationships with children. Furthermore, none of these interventions have involved preschool teachers. To consider the potential of mindfulness-based interventions to improve the quality of teachers' relationships with preschool-aged children, we examined data from an online survey of 1001 classroom teachers in 37 Pennsylvania Head Start Programs...
December 2017: Journal of School Psychology
Bogdan-Alexandru Luca, Daniel S Brewer, Dylan R Edwards, Sandra Edwards, Hayley C Whitaker, Sue Merson, Nening Dennis, Rosalin A Cooper, Steven Hazell, Anne Y Warren, Rosalind Eeles, Andy G Lynch, Helen Ross-Adams, Alastair D Lamb, David E Neal, Krishna Sethia, Robert D Mills, Richard Y Ball, Helen Curley, Jeremy Clark, Vincent Moulton, Colin S Cooper
BACKGROUND: A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. OBJECTIVE: To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches...
March 6, 2017: European Urology Focus
Shaoman Zhou, Sawsan Mahmoud, Peng Liu, Longhu Zhou, Maryam Ehteshami, Leda Bassit, Sijia Tao, Robert A Domaoal, Ozkan Sari, Coralie De Schutter, Sheida Amiralaei, Ahmed Khalil, Olivia Ollinger Russell, Tamara McBrayer, Tony Whitaker, Nageh Abou-Taleb, Franck Amblard, Steven J Coats, Raymond F Schinazi
Pan-genotypic nucleoside HCV inhibitors display a high genetic barrier to drug resistance and are the preferred direct-acting agents to achieve complete sustained virologic response in humans. Herein, we report, the discovery of a β-d-2'-Cl,2'-F-uridine phosphoramidate nucleotide 16, as a nontoxic pan-genotypic anti-HCV agent. Phosphoramidate 16 in its 5'-triphosphate form specifically inhibited HCV NS5B polymerase with no marked inhibition of human polymerases and cellular mitochondrial RNA polymerase. Studies on the intracellular half-life of phosphoramidate 16-TP in live cells demonstrated favorable half-life of 11...
July 13, 2017: Journal of Medicinal Chemistry
Krishan R Jethwa, Mohamed M Kahila, Thomas J Whitaker, William S Harmsen, Kimberly S Corbin, Sean S Park, Elizabeth S Yan, Valerie Lemaine, Judy C Boughey, Robert W Mutter
PURPOSE: Increasingly, women are choosing immediate breast reconstruction (IBR) following mastectomy. Reports have indicated IBR may compromise post-mastectomy radiotherapy (PMRT). We investigated the impact of IBR on timing of PMRT, target coverage, and doses to organs at risk in a modern radiotherapy practice using advanced planning techniques. METHODS: Between 2013 and 2015, PMRT was delivered to 116 patients (66 mastectomy alone, 50 IBR). PMRT was delivered with a median dose of 50 Gy in 25 fractions...
July 2017: Breast Cancer Research and Treatment
Fred Gould, Richard M Amasino, Dominique Brossard, C Robin Buell, Richard A Dixon, Jose B Falck-Zepeda, Michael A Gallo, Ken E Giller, Leland L Glenna, Timothy Griffin, Bruce R Hamaker, Peter M Kareiva, Daniel Magraw, Carol Mallory-Smith, Kevin V Pixley, Elizabeth P Ransom, Michael Rodemeyer, David M Stelly, C Neal Stewart, Robert J Whitaker
No abstract text is available yet for this article.
April 11, 2017: Nature Biotechnology
Y Cheng, M C D Whitaker, R Makkia, S Cocklin, V R Whiteside, L A Bumm, E Adcock-Smith, K P Roberts, P Hari, I R Sellers
The roles of bulk surface states and interfacial defects are probed experimentally using a combination of current-voltage, capacitance-voltage, and impedance measurements. The critical importance of the quality of both the film and interfaces is evident in current-voltage measurements where shunting and interface states result in large dark currents and the subsequent loss of Jsc. These properties are shown to be critically related to the nature and role of the PbS QD interface with the (nominally) ohmic gold contact...
April 7, 2017: ACS Applied Materials & Interfaces
Matthew J O'Brien, Alberly Perez, Adam B Scanlan, Victor A Alos, Robert C Whitaker, Gary D Foster, Ronald T Ackermann, Jody D Ciolino, Carol Homko
INTRODUCTION: Although the Diabetes Prevention Program and other clinical trials demonstrated the efficacy of intensive lifestyle interventions (ILI) and metformin to prevent type 2 diabetes, no studies have tested their comparative effects in pragmatic settings. This study was designed to compare the real-world effectiveness of ILI, metformin, and standard care among Hispanic women (Latinas) with prediabetes. STUDY DESIGN: RCT. SETTING/PARTICIPANTS: Ninety-two Latinas, who had a mean hemoglobin A1c of 5...
June 2017: American Journal of Preventive Medicine
Judith A Owens, Tracy Dearth-Wesley, Daniel Lewin, Gerard Gioia, Robert C Whitaker
OBJECTIVE: To determine whether shorter school-night sleep duration, greater daytime sleepiness, and greater eveningness chronotype were associated with lower self-regulation among adolescents. METHODS: An online survey of 7th- to 12th-grade students in 19 schools in Fairfax County, Virginia Public Schools was conducted in 2015. Self-regulation was measured with the Behavior Rating Inventory of Executive Function, 2nd edition, Screening Self-Report Form. Sleep measures included school night-sleep duration (hours between usual bedtime and wake time), daytime sleepiness (Sleepiness Scale in the Sleep Habits Survey, tertiles), and chronotype (Morningness-Eveningness Scale for Children, continuous score and tertiles)...
December 2016: Pediatrics
Bradley J Stish, Deanna H Pafundi, Tina J Hieken, Thomas J Whitaker, Keith M Furutani, James W Jakub, Judy C Boughey, Amy C Degnim, Luke B McLemore, Benjamin Mou, Robert W Mutter, Sean S Park
PURPOSE: Determine feasibility and resultant dosimetry of an intraoperatively placed multichannel intracavitary brachytherapy catheter for accelerated partial breast irradiation (APBI). METHODS: Patients with breast cancer underwent intraoperative brachytherapy catheter placement based on frozen section analysis with immediate postoperative APBI. The planning target volume evaluation (PTVEval) and organs at risk were contoured on daily pretreatment CT scans for each patient, and the original treatment plan was applied to assess full-course dosimetry...
November 2016: Brachytherapy
Justin G Boyles, Liam P McGuire, Esmarie Boyles, Jesika P Reimer, Christopher A C Brooks, Robert W Rutherford, Teresa A Rutherford, John O Whitaker, Gary F McCracken
Widespread animals at the extremes of the species' distribution experience ecological constraints different than individuals in the core of the distribution. For example, small endotherms at very high latitudes face short summers with cool temperatures and a lack of true darkness. In particular, insectivorous bats at high latitudes may experience constraints because of their unique life history traits, and may have different energy requirements than bats at lower latitudes. To evaluate the extent of these differences, we estimated an energy budget and refueling rates for reproductively active female little brown bats (Myotis lucifugus) roosting in buildings in eastern Alaska (~63°N)...
October 15, 2016: Physiology & Behavior
Tina J Hieken, Robert W Mutter, James W Jakub, Judy C Boughey, Amy C Degnim, William R Sukov, Stephanie Childs, Kimberly S Corbin, Keith M Furutani, Thomas J Whitaker, Sean S Park
No abstract text is available yet for this article.
December 2016: Annals of Surgical Oncology
Sarah E Anderson, Rebecca Andridge, Robert C Whitaker
OBJECTIVE: To determine whether preschool-aged children with earlier bedtimes have a lower risk for adolescent obesity and whether this risk reduction is modified by maternal sensitivity. STUDY DESIGN: Data from 977 of 1364 participants in the Study of Early Child Care and Youth Development were analyzed. Healthy singleton-births at 10 US sites in 1991 were eligible for enrollment. In 1995-1996, mothers reported their preschool-aged (mean = 4.7 years) child's typical weekday bedtime, and mother-child interaction was observed to assess maternal sensitivity...
September 2016: Journal of Pediatrics
Tina J Hieken, Robert W Mutter, James W Jakub, Judy C Boughey, Amy C Degnim, William R Sukov, Stephanie Childs, Kimberly S Corbin, Keith M Furutani, Thomas J Whitaker, Sean S Park
BACKGROUND: Data support the use of accelerated partial-breast irradiation (APBI) for early-stage breast cancer. We initiated a prospective protocol for intraoperative APBI catheter placement using a multi-lumen strut-based device. We hypothesized that with intraoperative pathology assessment of margins and sentinel nodes, all locoregional treatment (surgery and APBI) could be completed within 10 days with acceptable complication rates and cosmesis. METHODS: Eligible patients included women age 50 years or older with clinical T1 estrogen receptor positive (ER+) sentinel lymph node (SLN)-negative invasive ductal cancer or pure ductal carcinoma in situ...
October 2016: Annals of Surgical Oncology
Maryam Ehteshami, Sijia Tao, Tugba Ozturk, Longhu Zhou, Jong Hyun Cho, Hongwang Zhang, Sheida Amiralaei, Jadd R Shelton, Xiao Lu, Ahmed Khalil, Robert A Domaoal, Richard A Stanton, Justin E Suesserman, Biing Lin, Sam S Lee, Franck Amblard, Tony Whitaker, Steven J Coats, Raymond F Schinazi
Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on β-d-2'-C-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhibitor of HCV. DAPN-PD1 is metabolized intracellularly into two distinct bioactive nucleoside triphosphate (TP) analogs. The first metabolite, 2'-C-methyl-GTP, is a well-characterized inhibitor of NS5B polymerase, whereas the second metabolite, 2'-C-methyl-DAPN-TP, behaves as an adenosine base analog...
August 2016: Antimicrobial Agents and Chemotherapy
Raymond K M Fong, Aaron R H LeBlanc, David S Berman, Robert R Reisz
Studies of dinosaur teeth have focused primarily on external crown morphology and thus, use shed or in situ tooth crowns, and are limited to the enamel and dentine dental tissues. As a result, the full suites of periodontal tissues that attach teeth to the jaws remain poorly documented, particularly in early dinosaurs. These tissues are an integral part of the tooth and thus essential to a more complete understanding of dental anatomy, development, and evolution in dinosaurs. To identify the tooth attachment tissues in early dinosaurs, histological thin sections were prepared from the maxilla and dentary of a partial skull of the early theropod Coelophysis bauri from the Upper Triassic (Rhaetian- 209-201 Ma) Whitaker Quarry, New Mexico, USA...
July 2016: Journal of Morphology
K Wagstyl, L Ronan, K J Whitaker, I M Goodyer, N Roberts, T J Crow, P C Fletcher
In vivo structural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organization, including relative contributions of different layers to sulcal and gyral thickness, regional patterns of variation in thickness of different layers across the cortical sheet and profiles of layer variation across functional hierarchies, it is possible to develop indirect morphological measures as markers of more specific cytoarchitectural changes...
April 12, 2016: Translational Psychiatry
Nathan J Marchant, Erin J Campbell, Leslie R Whitaker, Brandon K Harvey, Konstantin Kaganovsky, Sweta Adhikary, Bruce T Hope, Robert C Heins, Thomas E Prisinzano, Eyal Vardy, Antonello Bonci, Jennifer M Bossert, Yavin Shaham
UNLABELLED: In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock...
March 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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