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Canhua Xiao, Qiang Zhang, Phuc Felix Nguyen-Tân, Marcie List, Randal S Weber, K Kian Ang, David Rosenthal, Edith J Filion, Harold Kim, Craig Silverman, Adam Raben, Thomas Galloway, Andre Fortin, Elizabeth Gore, Eric Winquist, Christopher U Jones, William Robinson, David Raben, Quynh-Thu Le, Deborah Bruner
PURPOSE/OBJECTIVE(S): To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival. METHODS AND MATERIALS: Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment...
July 25, 2016: International Journal of Radiation Oncology, Biology, Physics
Nedyalka Radeva, Johannes Schiebel, Xiaojie Wang, Stefan G Krimmer, Kan Fu, Martin Stieler, Frederik R Ehrmann, Alexander Metz, Thomas Rickmeyer, Michael Betz, Johan Winquist, Ah Young Park, Franziska U Huschmann, Manfred S Weiss, Uwe Mueller, Andreas Heine, Gerhard Klebe
Crystallography is frequently used as follow-up method to validate hits identified by biophysical screening cascades. The capacity of crystallography to directly screen fragment libraries is often underestimated, due to its supposed low-throughput and need for high-quality crystals. We applied crystallographic fragment screening to map the protein-binding site of the aspartic protease endothiapepsin by individual soaking experiments. Here, we report on 41 fragments binding to the catalytic dyad and adjacent specificity pockets...
October 11, 2016: Journal of Medicinal Chemistry
Leila Heidari, Andrea Winquist, Mitchel Klein, Cassandra O'Lenick, Andrew Grundstein, Stefanie Ebelt Sarnat
Identification of populations susceptible to heat effects is critical for targeted prevention and more accurate risk assessment. Fluid and electrolyte imbalance (FEI) may provide an objective indicator of heat morbidity. Data on daily ambient temperature and FEI emergency department (ED) visits were collected in Atlanta, Georgia, USA during 1993-2012. Associations of warm-season same-day temperatures and FEI ED visits were estimated using Poisson generalized linear models. Analyses explored associations between FEI ED visits and various temperature metrics (maximum, minimum, average, and diurnal change in ambient temperature, apparent temperature, and heat index) modeled using linear, quadratic, and cubic terms to allow for non-linear associations...
October 2, 2016: International Journal of Environmental Research and Public Health
Ilyas Singec, Andrew M Crain, Junjie Hou, Brian T D Tobe, Maria Talantova, Alicia A Winquist, Kutbuddin S Doctor, Jennifer Choy, Xiayu Huang, Esther La Monaca, David M Horn, Dieter A Wolf, Stuart A Lipton, Gustavo J Gutierrez, Laurence M Brill, Evan Y Snyder
Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry...
September 13, 2016: Stem Cell Reports
Sunil Parimi, Misha Eliasziw, Scott North, Marc Trudeau, Eric Winquist, Kim N Chi, Dean Ruether, Tina Cheng, Bernhard J Eigl
Background Docetaxel is a standard first-line treatment option for men with metastatic castration resistant prostate cancer (mCRPC). Sunitinib is attractive as a maintenance therapy due to its mechanism of action, oral route of administration, and acceptable toxicity profile. We designed a phase II study of sunitinib in patients with mCRPC who responded to docetaxel. Methods Patients with responding or stable disease at the completion of docetaxel treatment received 50 mg of sunitinib on 4 week on 2 week off cycles...
August 26, 2016: Investigational New Drugs
Radhika Dhingra, Andrea Winquist, Lyndsey A Darrow, Mitchel Klein, Kyle Steenland
BACKGROUND: Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in prior cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations. OBJECTIVE: We compared measured (subject to reverse causation) vs. modeled (unaffected by reverse causation) serum PFOA in association with these outcomes, to examine the possible role of reverse causation in these associations...
August 16, 2016: Environmental Health Perspectives
Michael Yan, Cheryl Ho, Eric Winquist, Derek Jonker, Daniel Rayson, Larry Stitt, Sonya Tokmakejian, Anna Tomiak, Mark D Vincent
BACKGROUND: 5-Fluorouracil (5-FU) chemotherapy is associated with severe and unpredictable toxicity in a significant proportion of patients. 5,10-Methylenetetrahydrofolate and 5-fluorodeoxyuridine monophosphate bind to thymidylate synthase and together inhibit its function, resulting in cytotoxicity. We hypothesized that susceptibility to 5-FU toxicity might be related to individual differences in the serum components of folate metabolism affecting intracellular 5,10-methylenetetrahydrofolate levels...
June 23, 2016: Clinical Colorectal Cancer
Cassandra R O'Lenick, Andrea Winquist, James A Mulholland, Mariel D Friberg, Howard H Chang, Michael R Kramer, Lyndsey A Darrow, Stefanie Ebelt Sarnat
BACKGROUND: A broad literature base provides evidence of association between air pollution and paediatric asthma. Socioeconomic status (SES) may modify these associations; however, previous studies have found inconsistent evidence regarding the role of SES. METHODS: Effect modification of air pollution-paediatric asthma morbidity by multiple indicators of neighbourhood SES was examined in Atlanta, Georgia. Emergency department (ED) visit data were obtained for 5-18 years old with a diagnosis of asthma in 20-county Atlanta during 2002-2008...
July 15, 2016: Journal of Epidemiology and Community Health
Brandace Winquist, Nazeem Muhajarine, Keith Ogle, Debbie Mpofu, Denis Lehotay, Gary Teare
OBJECTIVES: The objectives of the study were to assess differences in utilization of maternal serum screening (MSS) and prenatal diagnostic testing between population subgroups and to determine the impact on chromosomal anomaly birth rates. METHODS: This population-based cohort study included all female residents from Saskatchewan, Canada, who delivered a baby, experienced a fetal loss, or had a pregnancy termination between 2000 and 2005. In total, 93 171 women were included in the study dataset, with a subset (n = 35 527) evaluated to identify predictors of screening and diagnostic testing...
September 2016: Prenatal Diagnosis
Jenna R Krall, James A Mulholland, Armistead G Russell, Sivaraman Balachandran, Andrea Winquist, Paige E Tolbert, Lance A Waller, Stefanie Ebelt Sarnat
BACKGROUND: Short-term exposure to ambient PM2.5 concentrations has been associated with increased mortality and morbidity. Determining which sources of PM2.5 are most toxic can help guide targeted reduction of PM2.5. However, conducting multicity epidemiologic studies of sources is difficult because source-specific PM2.5 is not directly measured and source chemical compositions can vary between cities. OBJECTIVES: We determine how the chemical composition of primary ambient PM2...
June 17, 2016: Environmental Health Perspectives
Fred Saad, Eric Winquist, Stacey Hubay, Scott Berry, Hazem Assi, Eric Levesque, Nathalie Aucoin, Piotr Czaykowski, Jean-Baptiste Lattouf, Karine Alloul, John Stewart, Srikala S Sridhar
INTRODUCTION: In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiraterone use was obtained and its impact on clinical parameters was examined...
March 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
J A Khan, G P Singh, A Pandey
Background Femoral-shaft fractures are among the most common fractures of the lower extremity in children. There are several different options for treating femoral-shaft fractures in children. Elastic stable intramedullary nailing (ESIN) has become the standard treatment for fractures of shaft of femur in children for reasons including mini-invasive surgery, no need for casting, early mobilization and discharge as well as growing concerns toward cost-effectiveness. Objective To demonstrate the effectiveness of intramedullary fixation of fracture shaft of femur in skeletally immature children using the titanium elastic intramedullary nails...
July 2015: Kathmandu University Medical Journal (KUMJ)
David Henry, Colin Dormuth, Brandace Winquist, Greg Carney, Shawn Bugden, Gary Teare, Linda E Lévesque, Anick Bérard, J Michael Paterson, Robert W Platt
BACKGROUND: Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario. METHODS: Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011...
July 12, 2016: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
M B Hannouf, E Winquist, S M Mahmud, M Brackstone, S Sarma, G Rodrigues, P Rogan, J S Hoch, G S Zaric
We aimed to investigate the cost-effectiveness of a 2000-gene-expression profiling (GEP) test to help identify the primary tumor site when clinicopathological diagnostic evaluation was inconclusive in patients with cancer of unknown primary (CUP). We built a decision-analytic-model to project the lifetime clinical and economic consequences of different clinical management strategies for CUP. The model was parameterized using follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources...
March 29, 2016: Pharmacogenomics Journal
Barakat El-Alfy, Ayman M Ali, Sallam I Fawzy
Comminuted diaphyseal fractures in the pediatric age group represent a major orthopedic problem. It is associated with a high incidence of complications and poor outcomes because of the instability and difficulty in treatment. The aim of this study was to evaluate the efficacy of combined external skeletal fixation and flexible intramedullary nails in reconstruction of comminuted diaphyseal fracture in skeletally immature patients. Combined external fixator and elastic stable intramedullary nails were used in the management of 27 pediatric patients (15 males and 12 females) with unstable comminuted diaphyseal fractures of the tibia and femur...
September 2016: Journal of Pediatric Orthopedics. Part B
Lyndsey A Darrow, Alyx C Groth, Andrea Winquist, Hyeong-Moo Shin, Scott M Bartell, Kyle Steenland
BACKGROUND: Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers. OBJECTIVES: We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease. METHODS: Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information...
August 2016: Environmental Health Perspectives
Andrea Winquist, Andrew Grundstein, Howard H Chang, Jeremy Hess, Stefanie Ebelt Sarnat
PURPOSE: Extreme heat events will likely increase in frequency with climate change. Heat-related health effects are better documented among the elderly than among younger age groups. We assessed associations between warm-season ambient temperature and emergency department (ED) visits across ages in Atlanta during 1993-2012. METHODS: We examined daily counts of ED visits with primary diagnoses of heat illness, fluid/electrolyte imbalances, renal disease, cardiorespiratory diseases, and intestinal infections by age group (0-4, 5-18, 19-64, 65+years) in relation to daily maximum temperature (TMX) using Poisson time series models that included cubic terms for TMX at single-day lags of 0-6 days, controlling for maximum dew-point temperature, time trends, week day, holidays, and hospital participation periods...
May 2016: Environmental Research
Radhika Dhingra, Lyndsey A Darrow, Mitch Klein, Andrea Winquist, Kyle Steenland
INTRODUCTION: Perfluorooctanoic acid (PFOA), a suspected endocrine disruptor, is a bio-persistent chemical found at low levels in the serum of nearly all U.S. residents. Early menopause has been positively associated with serum PFOA in prior cross-sectional studies. METHODS: We conducted a longitudinal analysis of age at menopause among women, aged ≥40 years, (N=8759) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels via contaminated drinking water...
April 2016: Environmental Research
Nahid Punjani, Eric Winquist, Nicholas Power
INTRODUCTION: Extragonadal germ cell tumours (GCTs) have been described arising in midline structures. Although primary retroperitoneal extragonadal GCTs (RPGCTs) comprise 30% to 40% of these, their existence as a genuine disease has been questioned. Our study evaluated clinicopathological findings to examine this question in RPGCT patients at our centre. METHODS: Data from 414 men between 1980 and 2014 treated at London Health Sciences Centre with chemotherapy for testicular GCTs were reviewed retrospectively...
November 2015: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Radhika Dhingra, Cathy Lally, Lyndsey A Darrow, Mitch Klein, Andrea Winquist, Kyle Steenland
INTRODUCTION: Perfluorooctanoic acid (PFOA) is an environmentally persistent chemical found at low-levels in the serum of almost all U.S. residents. Chronic kidney disease (CKD) has been positively associated with serum PFOA in prior cross-sectional studies and in one occupational mortality study, while other investigations have found no association between kidney function and PFOA. METHODS: We conducted a longitudinal analysis of chronic kidney disease among adults, aged ≥20 years, (N=32,254) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels from contaminated drinking water...
February 2016: Environmental Research
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