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Susan M Perkins, Peter Bacchetti, Cynthia S Davey, Christopher J Lindsell, Madhu Mazumdar, Robert A Oster, Peter N Peduzzi, David M Rocke, Kyle D Rudser, Mimi Kim
Given the increasing level and scope of biostatistics expertise needed at academic health centers today, we developed best practices guidelines for biostatistics units to be more effective in providing biostatistical support to their institutions, and in fostering an environment in which unit members can thrive professionally. Our recommendations focus on the key areas of: 1) funding sources and mechanisms; 2) providing and prioritizing access to biostatistical resources; and 3) interacting with investigators...
2016: American Statistician
Thomas D Pollard
No abstract text is available yet for this article.
October 18, 2016: Biophysical Journal
Henrik Oster, Etienne Challet, Volker Ott, Emanuela Arvat, E Ronald de Kloet, Derk-Jan Dijk, Stafford Lightman, Alexandros Vgontzas, Eve Van Cauter
Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has been long recognized that this 24-h rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus...
October 17, 2016: Endocrine Reviews
Jason Brazelton, Robert A Oster, Brandi McCleskey, Jessica Fuller, Jill Adamski, Marisa B Marques
Thrombotic thrombocytopenic purpura (TTP) has >90% mortality without therapeutic plasma exchange (TPE). Despite TPE, approximately 10% of patients still die, presumably from cardiac ischemia. We sought clinical or laboratory parameters associated with death by reviewing the records of all patients hospitalized with acquired TTP in our institution for 10 years, and collect demographics and results for hemoglobin, platelet count, creatinine, lactate dehydrogenase, transaminases, total bilirubin, creatinine kinase (CK), CK-MB, and troponin I...
September 26, 2016: Journal of Clinical Apheresis
Gerry Oster, Sean D Sullivan, Mehul R Dalal, Mahmood R Kazemi, Maria Rojeski, Carol H Wysham, Jennifer Sung, Bryan Johnstone, Anna M G Cali, L J Wei, Louise Traylor, Henry Anhalt, Michelle Hull, John Van Vleet, Luigi F Meneghini
OBJECTIVE: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. STUDY DESIGN AND METHODS: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA)...
October 3, 2016: Postgraduate Medicine
Rebecca Dumbell, Alexei Leliavski, Olga Matveeva, Christopher Blaum, Anthony H Tsang, Henrik Oster
The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component BMAL1 leads to ablation of behavioural and physiological rhythms, hypocortisolism, impaired ACTH and behavioural stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context...
October 3, 2016: Endocrinology
Lisa L Weyandt, Danielle R Oster, Marisa E Marraccini, Bergljot Gyda Gudmundsdottir, Bailey A Munro, Emma S Rathkey, Alison McCallum
Prescription stimulants, including methylphenidate (e.g., Ritalin) and amphetamine compounds (e.g., dextroamphetamine; Adderall), have been approved by the U.S. Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD) and are classified by the United States Drug Enforcement Administration as Schedule II medications because of their high potential for abuse and dependence (Drug Enforcement Administration, U.S. Department of Justice, 2015). Despite the potential health and judicial consequences, misuse of prescription stimulants, typically defined as taking stimulants without a valid prescription, or use of stimulants other than as prescribed, has become a serious problem in the United States and abroad, especially on college campuses...
October 2016: Experimental and Clinical Psychopharmacology
Christiane Koch, Manuela S Bartlang, Jana Thabea Kiehn, Lisa Lucke, Nadine Naujokat, Charlotte Helfrich-Förster, Stefan O Reber, Henrik Oster
In modern societies, the risk of developing a whole array of affective and somatic disorders is associated with the prevalence of frequent psychosocial stress. Therefore, a better understanding of adaptive stress responses and their underlying molecular mechanisms is of high clinical interest. In response to an acute stressor each organism can either show passive freezing or active fight-or-flight behavior, with activation of sympathetic nervous system and the hypothalamus-pituitary-adrenal (HPA) axis providing the necessary energy for the latter by releasing catecholamines and glucocorticoids (GC)...
September 22, 2016: Journal of Endocrinology
Isa Kolbe, Jana Husse, Gabriela Salinas, Thomas Lingner, Mariana Astiz, Henrik Oster
The circadian master pacemaker in the suprachiasmatic nucleus (SCN) orchestrates peripheral clocks in various organs and synchronizes them with external time, including those in adipose tissue, which displays circadian oscillations in various metabolic and endocrine outputs. Because our knowledge about the instructive role of the SCN clock on peripheral tissue function is based mainly on SCN lesion studies, we here used an alternative strategy employing the Cre/loxP system to functionally delete the SCN clock in mice...
September 20, 2016: Journal of Biological Rhythms
Yuko Tsuruta, Laura Q Rogers, Helen Krontiras, William E Grizzle, Andrew D Frugé, Robert A Oster, Heidi R Umphrey, Lee W Jones, Maria Azrad, Wendy Demark-Wahnefried
INTRODUCTION: Obesity is a known risk factor for postmenopausal breast cancer and is associated with poorer prognosis for premenopausal and postmenopausal patients; however, the aetiological mechanisms are unknown. Preclinical studies support weight loss via caloric restriction and increased physical activity as a possible cancer control strategy, though few clinical studies have been conducted. We undertook a feasibility trial among women recently diagnosed with stage 0-II breast cancer hypothesising that presurgical weight loss would be feasible, safe and result in favourable changes in tumour markers and circulating biomarkers...
September 15, 2016: BMJ Open
Ronald E Goldstein, Suruchi Lamba, Nathaniel C Lawson, Preston Beck, Robert A Oster, John O Burgess
OBJECTIVES: To measure microleakage around class V composite restorations after piezoelectric ultrasonic scaling and sonic toothbrushing. METHODS: 3 mm × 2 mm × 1.5 mm boxes were prepared on buccal and lingual surfaces of extracted molars centered on the cementum-enamel junction. Half the preparations were beveled (0.5 mm). Preparations were restored with composite and polished. Restorations on one side of the teeth were either traced with an ultrasonic scaler (60 seconds, n = 16) or brushed in a sonic toothbrushing machine (2 hours, n = 16)...
September 9, 2016: Journal of Esthetic and Restorative Dentistry
Joshua E Allen, C Leah B Kline, Varun V Prabhu, Jessica Wagner, Jo Ishizawa, Neel Madhukar, Avital Lev, Marie Baumeister, Lanlan Zhou, Amriti Lulla, Martin Stogniew, Lee Schalop, Cyril Benes, Howard L Kaufman, Richard S Pottorf, B Rao Nallaganchu, Gary L Olson, Fahd Al-Mulla, Madeleine Duvic, Gen Sheng Wu, David T Dicker, Mala K Talekar, Bora Lim, Olivier Elemento, Wolfgang Oster, Joseph Bertino, Keith Flaherty, Michael L Wang, Gautam Borthakur, Michael Andreeff, Mark Stein, Wafik S El-Deiry
ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that is currently in Phase II clinical trials in multiple advanced cancers. Since the discovery of ONC201 as a p53-independent inducer of TRAIL gene transcription, preclinical studies have determined that ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL...
September 1, 2016: Oncotarget
Julie Colin, Lynn Gregory-Pauron, Marie-Claire Lanhers, Thomas Claudepierre, Catherine Corbier, Frances T Yen, Catherine Malaplate-Armand, Thierry Oster
Lipids are the fundamental structural components of biological membranes. For a long time considered as simple barriers segregating aqueous compartments, membranes are now considered as dynamic interfaces providing a molecular environment favorable to the activity of membrane-associated proteins. Interestingly, variations in membrane lipid composition, whether quantitative or qualitative, play a crucial role in regulation of membrane protein functionalities. Indeed, a variety of alterations in brain lipid composition have been associated with the processes of normal and pathological aging...
September 1, 2016: Biochimie
Carmen C Canavier, Rebekah C Evans, Andrew M Oster, Eleftheria K Pissadaki, Guillaume Drion, Alexey S Kuznetsov, Boris Samuel Gutkin
This review addresses the current state of single cell models of the firing pattern of midbrain dopamine neurons, and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single compartment models. We also use morphologically realistic multi-compartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism...
August 31, 2016: Journal of Neurophysiology
Mohammad H Rahbar, Aisha S Dickerson, Chul Ahn, Rickey E Carter, Manouchehr Hessabi, Christopher J Lindsell, Paul J Nietert, Robert A Oster, Brad H Pollock, Leah J Welty
PURPOSE: To learn the size, composition, and scholarly output of biostatistics, epidemiology, and research design (BERD) units in U.S. academic health centers (AHCs). METHOD: Each year for four years, the authors surveyed all BERD units in U.S. AHCs that were members of the Clinical and Translational Science Award (CTSA) Consortium. In 2010, 46 BERD units were surveyed; in 2011, 55; in 2012, 60; and in 2013, 61. RESULTS: Response rates to the 2010, 2011, 2012, and 2013 surveys were 93...
August 30, 2016: Academic Medicine: Journal of the Association of American Medical Colleges
Bailey A Munro, Lisa L Weyandt, Marisa E Marraccini, Danielle R Oster
The nonmedical use of prescription stimulants (NMUPS) is a prevalent issue among college students. The primary reason college students report NMUPS is for academic enhancement i.e., to perform better on schoolwork/tests and focus better in class. Executive functioning (EF), which includes abilities that allow for planning, cognitive flexibility, self-regulation, and goal-directed behavior, are potential mechanisms underlying academic performance. Preliminary research has revealed that college students with EF deficits are more likely to have educational difficulties and take part in risky behavior...
August 15, 2016: Addictive Behaviors
Lacrecia J Britton, Gabriela R Oates, Robert A Oster, Staci T Self, Robert B Troxler, Wynton C Hoover, Hector H Gutierrez, William T Harris
OBJECTIVE: The clinical benefit of newborn screening (NBS) for cystic fibrosis (CF) has been primarily nutritional, with less overt respiratory impact. Identification of risk factors for infant CF lung disease could facilitate targeted interventions to improve pulmonary outcomes. METHODS: This retrospective study evaluated socioeconomic information, clinical data, and results from routine infant pulmonary function testing (iPFT) of infants diagnosed with CF through NBS (N = 43) at a single CF center over a 4-year period (2008-2012)...
November 2016: Pediatric Pulmonology
Padmini Rangamani, Michael G Levy, Shahid Khan, George Oster
Transient spine enlargement (3- to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Moshe Mittelman, Kalman Filanovsky, Yishai Ofran, Hanna Rosenbaum, Pia Raanani, Andrei Braester, Neta Goldschmidt, Ilya Kirgner, Yair Herishanu, Chava Perri, Martin Ellis, Howard S Oster
Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days). Response was evaluated according to IWG criteria. Totally, 25 patients enrolled, with an average of 76...
October 2016: Annals of Hematology
Laura L Dover, Robert A Oster, Andrew M McDonald, Derek A DuBay, Thomas N Wang, Rojymon Jacob
BACKGROUND: The ideal adjuvant therapy for resected cholangiocarcinoma remains controversial. National guidelines stratify recommendations based on margin status, though few studies are currently available for reference. METHODS: Data was abstracted on all patients with definitive resections of cholangiocarcinoma at our institution between 2000 and 2013. Adjuvant chemoradiation consisted of 45 Gy delivered to elective nodal regions and 50.4-54 Gy to the surgical bed with concurrent fluoropyrimidine-based chemotherapy...
October 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
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