Digital Commons Network^™

Non-Invasive Mri And Spectroscopy Of Mdx Mice Reveal Temporal Changes In Dystrophic Muscle Imaging And In Energy Deficits., Christopher R. Heier, Alfredo D. Guerron, Alexandru Korotcov, Stephen Lin, Heather Gordish-Dressman, Stanley Fricke, Raymond W. Sze, Eric P. Hoffman, Paul Wang, Kanneboyina Nagaraju

Genomics and Precision Medicine Faculty Publications

In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging …

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …

Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

BACKGROUND: Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

METHODS: We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

RESULTS: In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …

The Role Of Positive Alcohol Expectancies In Underage Binge Drinking Among College Students, Nicole M Mcbride, Blake Barrett, Kathleen A. Moore, Lawrence Schonfeld

Mental Health Law & Policy Faculty Publications

Objective: This study explored associations between positive alcohol expectancies, and demographics, as well as academic status and binge drinking among underage college students. Participants: A sample of 1,553 underage college students at 3 public universities and 1 college in the Southeast who completed the Core Alcohol and Drug Survey in the Spring 2013 semester. Methods: A series of bivariate analyses and logistic regression models were used to examine associations between demographic and academic status variables as well as positive alcohol expectancies with self-reported binge drinking. Positive alcohol expectancies were examined in multivariable models via 2 factors derived from principal component …

Identification Of Threshold Concepts For Biochemistry, Jennifer Loertscher, David Green, Jennifer E. Lewis, Sara Lin, Vicky Minderhout

Chemistry Faculty Publications

Threshold concepts (TCs) are concepts that, when mastered, represent a transformed understanding of a discipline without which the learner cannot progress. We have undertaken a process involving more than 75 faculty members and 50 undergraduate students to identify a working list of TCs for biochemistry. The process of identifying TCs for biochemistry was modeled on extensive work related to TCs across a range of disciplines and included faculty workshops and student interviews. Using an iterative process, we prioritized five concepts on which to focus future development of instructional materials. Broadly defined, the concepts are steady state, biochemical pathway dynamics and …

Induction Of A Type I Interferon Signature In Normal Human Monocytes By Gadolinium-Based Contrast Agents: Comparison Of Linear And Macrocyclic Agents., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between …

Plagiarism Of Ideas. Benjamin Rush And Charles Caldwell--A Student-Mentor Dispute, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Programmable Folding Of Fusion Rna In Vivo And In Vitro Driven By Prna 3wj Motif Of Phi29 Dna Packaging Motor, Dan Shu, Emil F. Khisamutdinov, Le Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

Misfolding and associated loss of function are common problems in constructing fusion RNA complexes due to changes in energy landscape and the nearest-neighbor principle. Here we report the incorporation and application of the pRNA-3WJ motif of the phi29 DNA packaging motor into fusion RNA with controllable and predictable folding. The motif included three discontinuous ∼18 nucleotide (nt) fragments, displayed a distinct low folding energy (Shu D et al., Nature Nanotechnology, 2011, 6:658–667), and folded spontaneously into a leading core that enabled the correct folding of other functionalities fused to the RNA complex. Three individual fragments dispersed at any …

The Effects Of Sex-Steroids And Menstrual Cycle/Oestrous Phases On Knee Ligament Laxity In Humans And Rodents / Firouzeh Dehghan, Firouzeh Dehghan

Student Works (2010-2019)

The incidence of non-contact knee injury was reported higher in female than male. In female, the occurrence of this injury was related to different phases of the menstrual cycle. In view of this, we investigated the followings: (i) changes in knee laxity in rodent model under different sex-steroid influence; (ii) mechanisms underlying changes in knee laxity, which involves differential expression of relaxin receptors and (iii) correlation between knee laxity and serum levels of sex-steroids and relaxin at different phases of the menstrual cycle. In first part of the study, ovariectomized WKY rats were divided into different treatment groups (n=6 per …

Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation, Y Yan, Ashley L. Hein, Asserewou Etekpo, Katrina M. Burchett, Chi Lin, Charles A. Enke, Surinder K. Batra, Kenneth Cowan, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest …

Planning-Related Motor Processes Underlie Mental Practice And Imitation Learning., Patric Bach, Bassem Khalaf Allami, Mike Tucker, Rob Ellis

School of Psychology

It is still controversial whether mental practice-the internal rehearsal of movements to improve later performance-relies on processes engaged during physical motor performance and, if so, which processes these are. We report data from 5 experiments, in which participants mentally practiced complex rhythms with either feet or hands while using the same or different body parts to respond to unrelated sounds. We found that responses were impaired for those body parts that were concurrently used in mental practice, suggesting a binding of body-part-specific motor processes to action plans. This result was found when participants mentally trained to memorize the rhythms, to …

E5501: Phase Ii Study Of Topotecan Sequenced With Etoposide/Cisplatin, And Irinotecan/Cisplatin Sequenced With Etoposide For Extensive-Stage Small-Cell Lung Cancer., Taofeek K. Owonikoko, Joseph Aisner, Xin Victoria Wang, Suzanne E. Dahlberg, Eric H. Rubin, Suresh S. Ramalingam, Murugesan Gounder, Paul Gregory Rausch, Rita S. Axelrod, Md, Joan H. Schiller

Department of Medical Oncology Faculty Papers

PURPOSE: Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC).

METHODS: Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO …

Potential Role Of Orexin And Sleep Modulation In The Pathogenesis Of Alzheimer's Disease, Jee Hoon Roh, Hong Jiang, Mary Beth Finn, Floy R. Stewart, Thomas E. Mahan, John R. Cirrito, Ashish Heda, B. Joy Snider, Mingjie Li, Masashi Yanagisawa, Luis De Lecea, David M. Holtzman

Open Access Publications

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. …

Phonitalia: A Phonological Lexicon For Italian., Jeremy Goslin, Claudia Galluzzi, Cristina Romani

School of Psychology

In this article, we present the first open-access lexical database that provides phonological representations for 120,000 Italian word forms. Each of these also includes syllable boundaries and stress markings and a comprehensive range of lexical statistics. Using data derived from this lexicon, we have also generated a set of derived databases and provided estimates of positional frequency use for Italian phonemes, syllables, syllable onsets and codas, and character and phoneme bigrams. These databases are freely available from phonitalia.org. This article describes the methods, content, and summarizing statistics for these databases. In a first application of this database, we also demonstrate …

Implementation Of Fourier Transform Infrared Spectroscopy For The Rapid Typing Of Uropathogenic Escherichia Coli., S. E. Dawson, T. Gibreel, N. Nicolaou, H. Alrabiah, Y. Xu, R. Goodacre, M. Upton

School of Biomedical Sciences

In this paper, we demonstrate that Fourier transform infrared (FT-IR) spectroscopy is able to discriminate rapidly between uropathogenic Escherichia coli (UPEC) of key lineages with only relatively simple sample preparation. A total of 95 bacteria from six different epidemiologically important multilocus sequence types (ST10, ST69, ST95, ST73, ST127 and ST131) were used in this project and principal component-discriminant function analysis (PC-DFA) of these samples produced clear separate clustering of isolates, based on the ST. Analysis of data using partial least squares-discriminant analysis (PLS-DA), incorporating cross-validation, indicated a high prediction accuracy of 91.19% for ST131. These results suggest that FT-IR spectroscopy …

Patient-Centered Appointment Scheduling Using Agent-Based Simulation., Ayten Turkcan, Tammy Toscos Phd, Brad N Doebbeling

Health Services and Informatics Research

Enhanced access and continuity are key components of patient-centered care. Existing studies show that several interventions such as providing same day appointments, walk-in services, after-hours care, and group appointments, have been used to redesign the healthcare systems for improved access to primary care. However, an intervention focusing on a single component of care delivery (i.e. improving access to acute care) might have a negative impact other components of the system (i.e. reduced continuity of care for chronic patients). Therefore, primary care clinics should consider implementing multiple interventions tailored for their patient population needs. We collected rapid ethnography and observations to …

Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies, Prue Cormie, Suzanne K. Chambers, Robert U. Newton, Robert A. Gardiner, Nigel Spry, Dennis R. Taaffe, David Joseph, M Akhlil Hamid, Peter Chong, David Hughes, Kyra Hamilton, Daniel A. Galvão

Research outputs 2014 to 2021

Background: Despite being a critical survivorship care issue, there is a clear gap in current knowledge of the optimal treatment of sexual dysfunction in men with prostate cancer. There is sound theoretical rationale and emerging evidence that exercise may be an innovative therapy to counteract sexual dysfunction in men with prostate cancer. Furthermore, despite the multidimensional aetiology of sexual dysfunction, there is a paucity of research investigating the efficacy of integrated treatment models. Therefore, the purpose of this study is to: 1) examine the efficacy of exercise as a therapy to aid in the management of sexual dysfunction in men …

A Comparison Of Aphasia Therapy Outcomes Before And After A Very Early Rehabilitation Programme Following Stroke, Erin Godecke, Natalie A. Ciccone, Andrew S. Granger, Tapan Rai, Deborah West, Angela Cream, Jade Cartwright, Graeme J. Hankey

Research outputs 2014 to 2021

Background Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. Aims To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke) and again at follow-up (6 months). Methods & Procedures This study compared two cohorts from successive studies conducted in four Australian acute/sub-acute hospitals. The studies had near identical recruitment, blinded assessment and data-collection protocols. The Very Early Rehabilitation (VER) cohort (N = 20) had mild-severe aphasia and received up to 20 1-h sessions …

The Complete Genome Sequence Of Escherichia Coli Ec958: A High Quality Reference Sequence For The Globally Disseminated Multidrug Resistant E. Coli O25b:H4-St131 Clone., Brian M. Forde, Zakour Nl Ben, Mitchell Stanton-Cook, Minh Duy Phan, Makrina Totsika, Kate M. Peters, Kok Gan Chan, Mark A. Schembri, Mathew Upton, Scott A. Beatson

School of Biomedical Sciences

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific …

Learning To Pronounce First Words In Three Languages: An Investigation Of Caregiver And Infant Behavior Using A Computational Model Of An Infant., Ian S. Howard, Piers Messum

School of Engineering, Computing and Mathematics

Words are made up of speech sounds. Almost all accounts of child speech development assume that children learn the pronunciation of first language (L1) speech sounds by imitation, most claiming that the child performs some kind of auditory matching to the elements of ambient speech. However, there is evidence to support an alternative account and we investigate the non-imitative child behavior and well-attested caregiver behavior that this account posits using Elija, a computational model of an infant. Through unsupervised active learning, Elija began by discovering motor patterns, which produced sounds. In separate interaction experiments, native speakers of English, French and …

Benthic And Pelagic Pathways Of Methylmercury Bioaccumulation In Estuarine Food Webs Of The Northeast United States, Celia Y. Chen, Mark E. Borsuk, Deenie M. Bugge, Terill Hollweg

Dartmouth Scholarship

Methylmercury (MeHg) is a contaminant of global concern that bioaccumulates and bioamagnifies in marine food webs. Lower trophic level fauna are important conduits of MeHg from sediment and water to estuarine and coastal fish harvested for human consumption. However, the sources and pathways of MeHg to these coastal fisheries are poorly known particularly the potential for transfer of MeHg from the sediment to biotic compartments. Across a broad gradient of human land impacts, we analyzed MeHg concentrations in food webs at ten estuarine sites in the Northeast US (from the Hackensack Meadowlands, NJ to the Gulf of Maine). MeHg concentrations …

Novel Roles For Actin In Mitochondrial Fission, Anna L. Hatch, Pinar S. Gurel, Henry N. Higgs

Dartmouth Scholarship

Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial …

Empirical Models Of Scalp-Eeg Responses Using Non-Concurrent Intracranial Responses, Komalpreet Kaur, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

Objective- This study presents inter-subject models of scalp-recorded electroencephalographic (sEEG) event-related potentials (ERPs) using intracranially recorded ERPs from electrocorticography and stereotactic depth electrodes in the hippocampus, generally termed as intracranial EEG (iEEG).

Approach- The participants were six patients with medically-intractable epilepsy that underwent temporary placement of intracranial electrode arrays to localize seizure foci. Participants performed one experimental session using a brain-computer interface matrix spelling paradigm controlled by sEEG prior to the iEEG electrode implantation, and one or more identical sessions controlled by iEEG after implantation. All participants were able to achieve excellent spelling accuracy using sEEG, four of the participants …

Self-Regulating Smoking And Snacking Through Physical Activity., Hwajung Oh, Adrian H. Taylor

Peninsula Medical School

OBJECTIVE: Emotional snacking contributes to weight gain after smoking cessation. Exercise acutely reduces cravings for cigarettes and snack food. This study examined if different exercise intensities acutely reduces snack and cigarette cravings and attentional bias (AB) to video clips of snacks and cigarettes among abstinent smokers. METHODS: Abstinent smokers (and snackers; N = 23) randomly did 15 mins of moderate and vigorous cycling and a passive control in a cross-over design. Visual initial AB (IAB) and maintained AB (MAB) were assessed pre- and after treatment while watching paired snacking/neutral or smoking/neutral video clips. Desire to snack and smoke were assessed …

A Biological, Latent Variable Model Of Health (Earlybird 68)., Michael E. Hyland, Alison N. Jeffery, Terence J. Wilkin

School of Psychology

OBJECTIVE: To determine whether factor analysis of a set of health-related biomarkers provides evidence of an underlying common dimension of variation, and to explore the relationship between this dimension of variation with positive and negative affect. METHOD: Twelve health-related metabolic, immune and body-composition biomarkers at ages 5, 7, 9, 11, 14 and 16years were obtained from the EarlyBird longitudinal cohort of 347 children and supplemented by positive affect (PA) and negative affect (NA) measured at age 16years. RESULTS: At each age, principal factor analysis revealed that nine of the 12 biomarkers consistently loaded on the first extracted factor, accounting for …

Evaluating The Application Of Research-Based Guidance To The Design Of An Emergency Preparedness Leaflet., E. Hellier, J. Edworthy, L. Newbold, K. Titchener, M. Tucker, E. Gabe-Thomas

School of Psychology

UNLABELLED: Guidelines for the design of emergency communications were derived from primary research and interrogation of the literature. The guidelines were used to re-design a nuclear emergency preparedness leaflet routinely distributed to households in the local area. Pre-test measures of memory for, and self-reported understanding of, nuclear safety information were collected. The findings revealed high levels of non-receipt of the leaflet, and among those who did receive it, memory for safety advice was poor. Subjective evaluations of the trial leaflet suggested that it was preferred and judged easier to understand than the original. Objective measures of memory for the two …

English-Learning One- To Two-Year-Olds Do Not Show A Consonant Bias In Word Learning., Caroline Floccia, Thierry Nazzi, Luche C Delle, Silvana Poltrock, Jeremy Goslin

School of Psychology

Following the proposal that consonants are more involved than vowels in coding the lexicon (Nespor, Peña & Mehler, 2003), an early lexical consonant bias was found from age 1;2 in French but an equal sensitivity to consonants and vowels from 1;0 to 2;0 in English. As different tasks were used in French and English, we sought to clarify this ambiguity by using an interactive word-learning study similar to that used in French, with British-English-learning toddlers aged 1;4 and 1;11. Children were taught two CVC labels differing on either a consonant or vowel and tested on their pairing of a third …

Mediofrontal Event-Related Potentials In Response To Positive, Negative And Unsigned Prediction Errors., Thomas D. Sambrook, Jeremy Goslin

School of Psychology

Reinforcement learning models make use of reward prediction errors (RPEs), the difference between an expected and obtained reward. There is evidence that the brain computes RPEs, but an outstanding question is whether positive RPEs ("better than expected") and negative RPEs ("worse than expected") are represented in a single integrated system. An electrophysiological component, feedback related negativity, has been claimed to encode an RPE but its relative sensitivity to the utility of positive and negative RPEs remains unclear. This study explored the question by varying the utility of positive and negative RPEs in a design that controlled for other closely related …

Using Forced Choice To Test Belief Bias In Syllogistic Reasoning., Dries Trippas, Michael F. Verde, Simon J. Handley

School of Psychology

In deductive reasoning, believable conclusions are more likely to be accepted regardless of their validity. Although many theories argue that this belief bias reflects a change in the quality of reasoning, distinguishing qualitative changes from simple response biases can be difficult (Dube, Rotello, & Heit, 2010). We introduced a novel procedure that controls for response bias. In Experiments 1 and 2, the task required judging which of two simultaneously presented syllogisms was valid. Surprisingly, there was no evidence for belief bias with this forced choice procedure. In Experiment 3, the procedure was modified so that only one set of premises …

Development Of A Prototype Lateral Flow Immunoassay (Lfi) For The Rapid Diagnosis Of Melioidosis., Raymond L. Houghton, Dana E. Reed, Mark A. Hubbard, Michael J. Dillon, Hongjing Chen, Bart J. Currie, Mark Mayo, Derek S. Sarovich, Vanessa Theobald, Direk Limmathurotsakul, Gumphol Wongsuvan, Narisara Chantratita, Sharon J. Peacock, Alex R. Hoffmaster, Brea Duval, Paul J. Brett, Mary N. Burtnick, David P. Aucoin

Peninsula Medical School

Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis. Isolation of B. pseudomallei from clinical samples is the "gold standard" for the diagnosis of melioidosis; results can take 3-7 days to produce. Alternatively, antibody-based tests have low specificity due to a high percentage of seropositive individuals in endemic areas. There is a clear need to develop a rapid point-of-care antigen detection assay for the diagnosis of melioidosis. Previously, we employed In vivo Microbial Antigen Discovery (InMAD) to identify potential B. pseudomallei diagnostic biomarkers. The B. pseudomallei capsular polysaccharide (CPS) and numerous protein antigens were identified as potential …