Digital Commons Network^™

The Effects Of Nicotine In The Neonatal Quinpirole Rodent Model Of Psychosis: Neural Plasticity Mechanisms And Nicotinic Receptor Changes, Daniel J. Peterson, W. Drew Gill, John M. Dose, Donald B. Hoover, James R. Pauly, Elizabeth D. Cummins, Katherine C. Burgess, Russell W. Brown

Pharmaceutical Sciences Faculty Publications

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1–21. Animals were given …

Single-Trait And Multi-Trait Genome-Wide Association Analyses Identify Novel Loci For Blood Pressure In African-Ancestry Populations, Jingjing Liang, Thu H. Le, Digna R. Velez Edwards, Bamidele O. Tayo, Kyle J. Gaulton, Jennifer A. Smith, Yingchang Lu, Richard A. Jensen, Guanjie Chen, Lisa R. Yanek, Karen Schwander, Salman M. Tajuddin, Tamar Sofer, Wonji Kim, James Kayima, Colin A. Mckenzie, Ervin Fox, Michael A. Nalls, J. Hunter Young, Yan V. Sun, Jacqueline M. Lane, Sylvia Cechova, Jie Zhou, Hua Tang, Myriam Fornage, Solomon K. Musani, Heming Wang, Juyoung Lee, Adebowale Adeyemo, Albert W. Dreisbach, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10⁻⁸) for either systolic and …

Impact Of Ibrutinib Dose Adherence On Therapeutic Efficacy In Patients With Previously Treated Cll/Sll., Paul M Barr, Jennifer R Brown, Peter Hillmen, Susan O'Brien, Jacqueline C Barrientos, Nishitha M Reddy, Steven Coutre, Stephen P Mulligan, Ulrich Jaeger, Richard R Furman, Florence Cymbalista, Marco Montillo, Claire Dearden, Tadeusz Robak, Carol Moreno, John M Pagel, Jan A Burger, Samuel Suzuki, Juthamas Sukbuntherng, George Cole, Danelle F James, John C Byrd

Articles, Abstracts, and Reports

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. …

A Serosurvey Of Selected Cystogenic Coccidia In Spanish Equids: First Detection Of Anti-Besnoitia Spp. Specific Antibodies In Europe, Daniel Gutiérrez-Expósito, Ignacio García-Bocanegra, Daniel K. Howe, Antonio Arenas-Montes, Michelle R. Yeargan, Sallyanne L. Ness, Luis M Ortega-Mora, G. Álvarez-García

Veterinary Science Faculty Publications

Background: Equine besnoitiosis, caused by Besnoitia bennetti, and equine protozoal myeloencephalitis (EPM), caused by Sarcocystis neurona and Neospora hughesi are relevant equine diseases in the Americas that have been scarcely studied in Europe. Thus, a serosurvey of these cystogenic coccidia was carried out in Southern Spain. A cross-sectional study was performed and serum samples from horses (n = 553), donkeys (n = 85) and mules (n = 83) were included. An in-house enzyme-linked immunosorbent assay (ELISA) was employed to identify a Besnoitia spp. infection and positive results were confirmed by an a posteriori western blot. For Neospora …

Impact Of Sublethal Exposure To A Pyrethroid-Neonicotinoid Insecticide On Mating, Fecundity And Development In The Bed Bug Cimex Lectularius L. (Hemiptera: Cimicidae), Sydney E. Crawley, Jennifer R. Gordon, Katelyn A. Kowles, Michael F. Potter, Kenneth F. Haynes

Entomology Faculty Publications

Sublethal exposure to an insecticide may alter insect feeding, mating, oviposition, fecundity, development, and many other life history parameters. Such effects may have population-level consequences that are not apparent in traditional dose-mortality evaluations. Earlier, we found that a routinely used combination insecticide that includes a pyrethroid and a neonicotinoid (Temprid^® SC) had deleterious effects on multiple bed bug (Cimex lectularius, L.) behaviors. Here, we demonstrate that sublethal exposure impacts physiology and reproduction as well. We report that sublethal exposure to Temprid SC has variable aberrant effects on bed bugs depending on the strain, including: a reduction in …

Ccr4 Is A Determinant Of Melanoma Brain Metastasis., Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz

Articles, Abstracts, and Reports

We previously identified the chemokine receptor CCR4 as part of the molecular signature of melanoma brain metastasis. The aim of this study was to determine the functional significance of CCR4 in melanoma brain metastasis. We show that CCR4 is more highly expressed by brain metastasizing melanoma cells than by local cutaneous cells from the same melanoma. Moreover, we found that the expression of CCR4 is significantly higher in paired clinical specimens of melanoma metastases than in samples of primary tumors from the same patients. Notably, the expression of the CCR4 ligands, Ccl22 and Ccl17 is upregulated at the earliest stages …

Online Neural Monitoring Of Statistical Learning., Laura J Batterink, Ken A Paller

Brain and Mind Institute Researchers' Publications

The extraction of patterns in the environment plays a critical role in many types of human learning, from motor skills to language acquisition. This process is known as statistical learning. Here we propose that statistical learning has two dissociable components: (1) perceptual binding of individual stimulus units into integrated composites and (2) storing those integrated representations for later use. Statistical learning is typically assessed using post-learning tasks, such that the two components are conflated. Our goal was to characterize the online perceptual component of statistical learning. Participants were exposed to a structured stream of repeating trisyllabic nonsense words and a …

Sex-Specific Associations Of Maternal Birthweight With Offspring Birthweight In The Omega Study., Collette N Ncube, Amelia R Gavin, Michelle A Williams, Chunfang Qiu, Tanya K Sorensen, Daniel A Enquobahrie

Articles, Abstracts, and Reports

PURPOSE: We investigated nonlinear and offspring sex-specific associations of maternal birthweight (BW) with offspring BW among participants of the Omega study, a pregnancy cohort.

METHODS: Maternal BW was modeled as a continuous variable, linear spline and binary variable indicating low birthweight (LBW;≥2500 grams). Offspring BW was modeled as a continuous and binary variable in regression models. Nonlinearity was assessed using likelihood ratio tests (LRTs) in marginal linear spline models.

RESULTS: For every 100-gram increase of maternal BW, offspring BW increased by 22.29 (95% CI: 17.57, 27.02) or 23.41 (95% CI: 6.87, 39.96) grams among mothers with normal BW or born …

Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim

Department of Cancer Biology Faculty Papers

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that …

Contextual Factors And Sexual Risk Behaviors Among Young, Black Men, Jamal Jones, Laura F. Salazar, Richard A. Crosby

Health, Behavior & Society Faculty Publications

Young Black men (YBM), aged 13 to 24 years, face a disproportionate burden of sexually transmitted infections (STIs). STI acquisition among YBM is due to incorrect and inconsistent condom use and is exacerbated by multiple sexual partners. Sexual and reproductive health is influenced by a complex interaction of biological, psychological, and social determinants that contribute to increased risk for STI acquisition. However, there are key social determinants of sexual health that play a major role in adolescent sexual risk-taking behaviors: gender norms, environment, peers, and families as well as a desire to impregnate a woman. Associations between contextual factors (risky …

Restriction Spectrum Imaging Improves Risk Stratification In Patients With Glioblastoma., A P Krishnan, R Karunamuni, K M Leyden, T M Seibert, R L Delfanti, J M Kuperman, H Bartsch, P Elbe, A Srikant, A M Dale, Santosh Kesari, D E Piccioni, J A Hattangadi-Gluth, N Farid, C R Mcdonald, N S White

Articles, Abstracts, and Reports

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.

MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, …

Application Of Fluoroquinolone Resistance Score In Management Of Complicated Urinary Tract Infections, Ansal Shah, Julie Ann Justo, P Brandon Bookstaver, Joseph Kohn, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively …

Tuberculosis And Risk Of Acute Myocardial Infarction: A Propensity Score-Matched Analysis, Moises A. Huaman, Richard J. Kryscio, Carl J. Fichtenbaum, David Henson, Elizabeth G. Salt, Timothy R. Sterling, Beth A. Garvy

Biostatistics Faculty Publications

Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with …

A Pilot Investigation Of Acute Inhibitory Control Training In Cocaine Users, Joseph L. Alcorn, Erika Pike, William W. Stoops, Joshua A. Lile, Craig R. Rush

Behavioral Science Faculty Publications

Background—Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals.

Methods—Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using …

Odd Symptom Network During Preschool, Tess E. Smith, Christine A. Lee, Michelle M. Martel, Marni E. Axelrad

Psychology Faculty Publications

Several different conceptualizations of Oppositional Defiant Disorder (ODD) symptoms have been proposed, including one undivided set of symptoms (DSM-IV-TR; APA 2000); two domains of symptoms subdivided into affective and behavioral; and three domains of symptoms subdivided as angry/irritable, argumentative/defiant, and spiteful. The current study utilizes a novel approach to examining the division of ODD symptoms through use of network analysis. Participants were 109 preschoolers (64 male) between the ages of three and six (M = 4.34 years, SD = 1.08) and their parents and teachers/caregivers, who provided ratings of ODD symptoms. Results are consistent with one-, two-, and three- …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

The Interactive Effect Of Diabetes Family Conflict And Depression On Insulin Bolusing Behaviors For Youth., Genevieve Maliszewski, Susana R. Patton, L Kurt Midyett, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Adherence to type 1 diabetes management declines as children enter adolescence. For youth, psychosocial variables including mood and interpersonal relationships play a large role in diabetes maintenance. The current study assessed the unique and interactive roles diabetes family conflict and depression have on insulin bolusing behaviors for youth ages 10-16 years.

METHODS: Ninety-one youth-parent dyads completed a survey assessing family conflict and depression. Mean daily blood glucose levels, mealtime insulin bolus scores ( BOLUS), and glycated hemoglobin (HbA1c) were collected from the medical record as outcome variables.

RESULTS: Parent-reported diabetes-related family conflict and youths' endorsed depression both significantly predicted …

A Novel Method Of Measuring Fractional Exhaled Nitric Oxide In Tracheostomized Ventilator-Dependent Children., Vydehi R. Murthy, Hugo Escobar, Michael Norberg, Charisse I. Lachica, Linda L. Gratny, Ashley K. Sherman, William E Truog, Winston M. Manimtim

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The lower airway concentration of fractional exhaled nitric oxide (FENO) is unknown in children with chronic lung disease of infancy who have tracheostomy for long-term mechanical ventilation. We aimed to evaluate an online method of measuring FENO in a cohort of ventilator-dependent children with a tracheostomy and to explore the relationship between the peak FENO concentration (FENO peak) and the degree of respiratory support using the respiratory severity score.

METHODS: We conducted a prospective cross-sectional study in 31 subjects who were receiving long-term respiratory support through a tracheostomy. We measured the FENO peak and FENO plateau concentration from the …

A Phase Ib/Ii Study Of Cabozantinib (Xl184) With Or Without Erlotinib In Patients With Non-Small Cell Lung Cancer., Heather A Wakelee, Scott Gettinger, Jeffrey Engelman, Pasi A Jänne, Howard J. West, Deepa S Subramaniam, Joseph Leach, Michael Wax, Yifah Yaron, Dale R Miles, Primo N Lara

Articles, Abstracts, and Reports

PURPOSE: Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.

METHODS: This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent …

Antibiotic Prophylaxis Is Associated With Subsequent Resistant Infections In Children With An Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection., Sibani Das, Amanda L. Adler, Arianna Miles-Jay, Matthew P. Kronman, Xuan Qin, Scott J. Weissman, C A. Burnham, Alexis Elward, Jason G. Newland, Rangaraj Selvarangan, Kaede V. Sullivan, Theoklis Zaoutis, Danielle M. Zerr

Manuscripts, Articles, Book Chapters and Other Papers

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 …

Incidence Of Cns Tumors In Appalachian Children, Bin Huang, Alice Luo, Eric B. Durbin, Ellen Lycan, Thomas Tucker, Quan Chen, Craig Horbinski, John L. Villano

Markey Cancer Center Faculty Publications

Determine whether the risk of astrocytomas in Appalachian children is higher than the national average. We compared the incidence of pediatric brain tumors in Appalachia versus non-Appalachia regions, covering years 2000–2011. The North American Association of Central Cancer Registries (NAACCR) collects population-based data from 55 cancer registries throughout U.S. and Canada. All invasive primary (i.e. non-metastatic tumors), with age at diagnosis 0–19 years old, were included. Nearly 27,000 and 2200 central nervous system (CNS) tumors from non-Appalachia and Appalachia, respectively comprise the cohorts. Age-adjusted incidence rates of each main brain tumor subtype were compared. The incidence rate of pediatric CNS …

Sonoelastography Of The Common Flexor Tendon Of The Elbow With Histologic Agreement: A Cadaveric Study., Andrea S Klauser, Mathias J Pamminger, Ethan J. Halpern, Mohamed M H Abd Ellah, Bernhard Moriggl, Mihra S Taljanovic, Christian Deml, Judith Sztankay, Guenter Klima, Leonhard Gruber, Werner R Jaschke

Department of Radiology Faculty Papers

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or …

Bk Channels Mediate Synaptic Plasticity Underlying Habituation In Rats., Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O Poulter, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, …

Potential Deaths Averted And Serious Adverse Events Incurred From Adoption Of The Sprint (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen In The United States: Projections From Nhanes (National Health And Nutrition Examination Survey), Adam P. Bress, Holly Kramer, Rasha Khatib, Srinivasan Beddhu, Alfred K. Cheung, Rachel Hess, Vinod K. Bansal, Guichan Cao, Jerry Yee, Andrew E. Moran, Ramon Durazo-Arvizu, Paul Muntner, Richard S. Cooper

Nephrology Articles

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal ofmellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults.

METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to …

Functional Human Grin2b Promoter Polymorphism And Variation Of Mental Processing Speed In Older Adults, Yang Jiang, Ming Kuan Lin, Gregory A. Jicha, Xiuhua Ding, Sabrina L. Mcilwrath, David W. Fardo, Lucas S. Broster, Frederick A. Schmitt, Richard J. Kryscio, Robert H. Lipsky

Behavioral Science Faculty Publications

We investigated the role of a single nucleotide polymorphism rs3764030 (G > A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reaction times) in older age. Twenty-eight older adults (ages 65-86) from a well-characterized longitudinal cohort were recruited and performed a modified delayed match-to-sample task. The rs3764030 polymorphism was …

Discovery And Fine-Mapping Of Adiposity Loci Using High Density Imputation Of Genome-Wide Association Studies In Individuals Of African Ancestry: African Ancestry Anthropometry Genetics Consortium, Maggie C. Y. Ng, Mariaelisa Graff, Yingchang Lu, Anne E. Justice, Poorva Mudgal, Ching-Ti Liu, Kristin Young, Lisa R. Yanek, Mary F. Feitosa, Mary K. Wojczynski, Kristin Rand, Jennifer A. Brody, Brian E. Cade, Latchezar Dimitrov, Qing Duan, Xiuqing Guo, Leslie A. Lange, Michael A. Nalls, Hayrettin Okut, Salman M. Tajuddin, Bamidele O. Tayo, Sailaja Vedantam, Jonathan P. Bradfield, Guanjie Chen, Wei-Min Chen, Alessandra Chesi, Marguerite R. Irvin, Badri Padhukasahasram, Jennifer A. Smith, Wei Zheng, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Genome-wide association studies (GWAS) have identified > 300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHR_adjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHR_adjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified …

The Effects Of A Hpv Educational Intervention Aimed At Collegiate Males On Knowledge, Vaccine Intention, And Uptake, Mary A. Knudtson

Evidence-Based Practice Project Reports

Human Papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States (US). In 2013, approximately 6% of 19 to 26-year-old males had received at least one dose of the HPV vaccine (Richman, Maddy, Torres, & Goldberg, 2016). Currently there is no known cure for HPV, however a prophylactic vaccination provides an efficacious method for protection against HPV related diseases. The purpose of the evidence-based project was to provide a HPV educational intervention to collegiate males and examine the effects of HPV knowledge, intention to vaccinate, and receipt of vaccination. The Health Belief Model was selected to …

Population Effect Model Identifies Gene Expression Predictors Of Survival Outcomes In Lung Adenocarcinoma For Both Caucasian And Asian Patients, Guoshuai Cai, Feifei Xiao, Chao Cheng, Yafang Li, Christopher I. I. Amos, Michael L. Whitfield

Dartmouth Scholarship

Background: We analyzed and integrated transcriptome data from two large studies of lung adenocarcinomas on distinct populations. Our goal was to investigate the variable gene expression alterations between paired tumor-normal tissues and prospectively identify those alterations that can reliably predict lung disease related outcomes across populations. Methods: We developed a mixed model that combined the paired tumor-normal RNA-seq from two populations. Alterations in gene expression common to both populations were detected and validated in two independent DNA microarray datasets. A 10-gene prognosis signature was developed through a l1 penalized regression approach and its prognostic value was evaluated in a third …

Within-Person Associations Of Young Adolescents' Physical Activity Across Five Primary Locations: Is There Evidence Of Cross-Location Compensation?, Jordan A. Carlson, Tarrah B. Mitchell, Brian E. Saelens, Vincent S. Staggs, Jacqueline Kerr, Lawrence D. Frank, Jasper Schipperijn, Terry L. Conway, Karen Glanz, Jim E. Chapman, Kelli L. Cain, James F. Sallis

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Youth are active in multiple locations, but it is unknown whether more physical activity in one location is associated with less in other locations. This cross-sectional study examines whether on days with more physical activity in a given location, relative to their typical activity in that location, youth had less activity in other locations (i.e., within-person associations/compensation).

METHODS: Participants were 528 adolescents, ages 12 to 16 (M = 14.12, SD = 1.44, 50% boys, 70% White non-Hispanic). Accelerometer and Global Positioning System devices were used to measure the proportion of time spent in moderate-to-vigorous physical activity (MVPA) in five …

Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., Gaia Andreoletti, Valentina Shakhnovich, Kathy Christenson, Tracy Coelho, Rachel Haggarty, Nadeem A. Afzal, Akshay Batra, Britt-Sabina Petersen, Matthew Mort, R Mark Beattie, Sarah Ennis

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort …