Digital Commons Network^™

Ultra High-Resolution Gene Centric Genomic Structural Analysis Of A Non-Syndromic Congenital Heart Defect, Tetralogy Of Fallot., Douglas C. Bittel, Xin-Gang Zhou, Nataliya Kibiryeva, Stephanie Fiedler, James E. O'Brien, Jennifer A. Marshall, Shihui Yu, Hong-Yu Liu

Manuscripts, Articles, Book Chapters and Other Papers

Tetralogy of Fallot (TOF) is one of the most common severe congenital heart malformations. Great progress has been made in identifying key genes that regulate heart development, yet approximately 70% of TOF cases are sporadic and nonsyndromic with no known genetic cause. We created an ultra high-resolution gene centric comparative genomic hybridization (gcCGH) microarray based on 591 genes with a validated association with cardiovascular development or function. We used our gcCGH array to analyze the genomic structure of 34 infants with sporadic TOF without a deletion on chromosome 22q11.2 (n male = 20; n female = 14; age range of …

Predicting The Risk Of Suicide By Analyzing The Text Of Clinical Notes, Chris Poulin, Brian Shiner, Paul Thompson, Linas Vepstas, Yinong Young-Xu, Benjamin Goertzel, Bradley Watts, Laura Flashman, Thomas Mcallister

Dartmouth Scholarship

We developed linguistics-driven prediction models to estimate the risk of suicide. These models were generated from unstructured clinical notes taken from a national sample of U.S. Veterans Administration (VA) medical records. We created three matched cohorts: veterans who committed suicide, veterans who used mental health services and did not commit suicide, and veterans who did not use mental health services and did not commit suicide during the observation period (n = 70 in each group). From the clinical notes, we generated datasets of single keywords and multi-word phrases, and constructed prediction models using a machine-learning algorithm based on a …

Investigating The Early Stages Of Person Perception: The Asymmetry Of Social Categorization By Sex Vs. Age, Jasmin Cloutier, Jonathan B. Freeman, Nalini Ambady

Dartmouth Scholarship

The wealth of information provided by facial cues presents challenges to our understanding of these early stages of person perception. The current study aimed to uncover the dynamics of processing multiply categorizable faces, notably as a function of their gender and age. Using a modified four-choice version of a mouse-tracking paradigm (which assesses the relative dominance of two categorical dimensions), the relative influence that sex and age have on each other during categorization of infant, younger adult, and older adult faces was investigated. Results of these experiments demonstrate that when sex and age dimensions are simultaneously categorized, only for infant …

Development Of A Personalized Decision Aid For Breast Cancer Risk Reduction And Management, Elissa M. Ozanne, Rebecca Howe, Zehra Omer, Laura J. Esserman

Dartmouth Scholarship

Background: Breast cancer risk reduction has the potential to decrease the incidence of the disease, yet remains underused. We report on the development a web-based tool that provides automated risk assessment and personalized decision support designed for collaborative use between patients and clinicians. Methods: Under Institutional Review Board approval, we evaluated the decision tool through a patient focus group, usability testing, and provider interviews (including breast specialists, primary care physicians, genetic counselors). This included demonstrations and data collection at two scientific conferences (2009 International Shared Decision Making Conference, 2009 San Antonio Breast Cancer Symposium). Results: Overall, the evaluations were favorable. …

Assessments Of Empathy In Medical School Admissions: What Additional Evidence Is Needed?, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

The Association for the Study of Medical Education (ASME) sponsored a symposium on the theme of Examin-ing the Evidence with Regard to Character, Personality and Values in Medical School Selection which was held on October 14, 2013 at the University of Sheffield Medical School in the United Kingdom. I was invited to speak about credibility issues related to personality assessments in health profession educations. To my pleasant surprise, I found the European audience receptive (more than their counterparts in the United States) to the idea of using personality assess-ments in admission decisions. There seems to be a hesita-tion among leaders …

Revealing Variations In Perception Of Mental States From Dynamic Facial Expressions: A Cautionary Note, Elisa Back, Timothy R. Jordan

All Works

Although a great deal of research has been conducted on the recognition of basic facial emotions (e.g., anger, happiness, sadness), much less research has been carried out on the more subtle facial expressions of an individual's mental state (e.g., anxiety, disinterest, relief). Of particular concern is that these mental state expressions provide a crucial source of communication in everyday life but little is known about the accuracy with which natural dynamic facial expressions of mental states are identified and, in particular, the variability in mental state perception that is produced. Here we report the findings of two studies that investigated …

The Mammalian Neocortex New Pyramidal Neuron: A New Conception, Miguel Marín-Padilla

Dartmouth Scholarship

The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex …

The Association Of Plasma Biomarkers With Computed Tomography-Assessed Emphysema Phenotypes, Brendan J. Carolan, Grant Hughes, Jarrett Morrow, Craig P. Hersh, Wanda K. O'Neal, Stephen I. Rennard, Sreekumar G. Pillai, Paula Belloni, Debra A. Cockayne, Alejandro P. Comellas, Meilan Han, Rachel L. Zemans, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema.

METHODS: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ …

Randomized Study Of The Safety, Pharmacokinetics, And Bronchodilatory Efficacy Of A Proprietary Glycopyrronium Metered-Dose Inhaler In Study Patients With Chronic Obstructive Pulmonary Disease, Stephen I. Rennard, Charles Fogarty, Colin Reisner, Carlos Fernandez, Tracy Fischer, Michael Golden, Earl St Rose, Patrick Darken, Gregory Tardie, Chadwick Orevillo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions. Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.

METHODS: In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of …

Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and …

Roflumilast And Dyspnea In Patients With Moderate To Very Severe Chronic Obstructive Pulmonary Disease: A Pooled Analysis Of Four Clinical Trials, Stephen I. Rennard, Shawn X. Sun, Stavros Tourkodimitris, Paul Rowe, Udo M. Goehring, Dirk Bredenbröker, Peter M.A. Calverley

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Breathlessness is a predominant symptom of chronic obstructive pulmonary disease (COPD), making it a valuable outcome in addition to lung function to assess treatment benefit. The phosphodiesterase-4 inhibitor roflumilast has been shown to provide small but significant improvements in dyspnea, as measured by the transition dyspnea index (TDI), in two 1-year studies in patients with severe to very severe COPD.

PATIENTS AND METHODS: To provide a more comprehensive assessment of the impact of roflumilast on dyspnea, post hoc analyses of four 1-year roflumilast studies (M2-111, M2-112, M2-124, and M2-125) in patients with moderate to very severe COPD were conducted. …

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 …

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% …

Factors Associated With Diabetes-Related Distress: Implications For Diabetes Self-Management., Jana L. Wardian Phd, Fei Sun

Journal Articles: Hospital Medicine

As 7.8% of the U.S. population is affected by diabetes, health care providers are tasked with providing resources to assist patients toward self-management. Psychosocial issues have an effect on diabetes self-care. Diabetes-related distress is associated with self-management and lower A1C. This cross-sectional study seeks to understand how demographic factors, psychological orientations, support, and diabetes management behaviors predict diabetes-related distress. This study uses data from 267 adults with Type 2 diabetes. The Diabetes Distress Scale (DDS) is a 17-item scale measuring diabetes-related distress including emotional distress, physician-related distress, regimen distress, and interpersonal distress. Hierarchical regression was conducted in four stages. The …

Health Care Avoidance Among Rural Populations: Results From A Nationally Representative Survey, Angela M. Spleen, Eugene J. Lengerich, Fabian T. Camacho, Robin C. Vanderpool

Health, Behavior & Society Faculty Publications

BACKGROUND: Previous research suggests that certain populations, including rural residents, exhibit health care avoidant behaviors more frequently than other groups. Additionally, health care avoidance is related to sociodemographics, attitudes, social expectations, ability to pay for care, and prior experiences with providers. However, previous studies have been limited to specific geographic areas, particular health conditions, or by analytic methods.

METHODS: The 2008 Health Information Trends Survey (HINTS) was used to estimate the magnitude of health care avoidance nationally and, while controlling for confounding factors, identify groups of people in the United States who are more likely to avoid health care. Chi-square …

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 …

Enhancing The Care Navigation Model: Potential Roles For Health Sciences Librarians, Jeffrey T. Huber, Robert M. Shapiro Ii, Heather J. Burke, Aaron Palmer

Information Science Faculty Publications

This study analyzed the overlap between roles and activities that health care navigators perform and competencies identified by the Medical Library Association's (MLA's) educational policy statement. Roles and activities that health care navigators perform were gleaned from published literature. Once common roles and activities that health care navigators perform were identified, MLA competencies were mapped against those roles and activities to identify areas of overlap. The greatest extent of correspondence occurred in patient empowerment and support. Further research is warranted to determine the extent to which health sciences librarians might assume responsibility for roles and activities that health care navigators …

Mobile Delivery Of Treatment For Alcohol Use Disorders: A Review Of The Literature, Andrew Quanbeck, Ming-Yuan Chih, Andrew Isham, David H. Gustafson

Health and Clinical Sciences Faculty Publications

Several systems for treating alcohol-use disorders (AUDs) exist that operate on mobile phones. These systems are categorized into four groups: text-messaging monitoring and reminder systems, text-messaging intervention systems, comprehensive recovery management systems, and game-based systems. Text-messaging monitoring and reminder systems deliver reminders and prompt reporting of alcohol consumption, enabling continuous monitoring of alcohol use. Text-messaging intervention systems additionally deliver text messages designed to promote abstinence and recovery. Comprehensive recovery management systems use the capabilities of smart-phones to provide a variety of tools and services that can be tailored to individuals, including in-the-moment assessments and access to peer discussion groups. Game-based …

Primary Stroke In A Woman With Sickle Cell Anemia Responsive To Hydroxyurea Therapy., Samir K. Ballas, Ubaldo E. Martinez-Outshoorn, Michael P. Savage

Cardeza Foundation for Hematologic Research

The most common cause of stroke in children with sickle cell anemia is infarction due to ischemia. In adults, however, stroke is most commonly hemorrhagic in nature. Other causes of stroke in patients with sickle cell disease are very rare. In this short communication, we describe a woman with sickle cell anemia responsive to hydroxyurea (HU) therapy who had primary stroke due to paradoxical embolization caused by a large atrial septal defect. Successful management of the stroke included surgical closure of the defect with trans-esophageal echocardiographic guidance. To the best of our knowledge, this is the first patient with sickle …

Cultural Responses To Pain In Uk Children Of Primary School Age: A Mixed-Methods Study., Pary M. Azize, Ruth Endacott, Allegra Cattani, Ann Humphreys

School of Nursing and Midwifery

Pain-measurement tools are often criticized for not addressing the influence of culture and ethnicity on pain. This study examined how children who speak English as a primary or additional language discuss pain. Two methods were used in six focus group interviews with 34 children aged 4-7 years: (i) use of drawings from the Pediatric Pain Inventory to capture the language used by children to describe pain; and (ii) observation of the children's placing of pain drawings on red/amber/green paper to denote perceived severity of pain. The findings demonstrated that children with English as an additional language used less elaborate language …

Thinking In Circuits: Toward Neurobiological Explanation In Cognitive Neuroscience., Friedemann Pulvermüller, Max Garagnani, Thomas Wennekers

School of Engineering, Computing and Mathematics

Cognitive theory has decomposed human mental abilities into cognitive (sub) systems, and cognitive neuroscience succeeded in disclosing a host of relationships between cognitive systems and specific structures of the human brain. However, an explanation of why specific functions are located in specific brain loci had still been missing, along with a neurobiological model that makes concrete the neuronal circuits that carry thoughts and meaning. Brain theory, in particular the Hebb-inspired neurocybernetic proposals by Braitenberg, now offers an avenue toward explaining brain-mind relationships and to spell out cognition in terms of neuron circuits in a neuromechanistic sense. Central to this endeavor …

Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …

Extending The Indications Of Flow Diversion To Small, Unruptured, Saccular Aneurysms Of The Anterior Circulation., Nohra Chalouhi, Md, Robert M Starke, Steven Yang, Cory D Bovenzi, Stavropoula Tjoumakaris, David Hasan, L. Fernando Gonzalez, Robert H. Rosenwasswer Md, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

BACKGROUND AND PURPOSE: Flow diverters are currently indicated for treatment of large and complex intracranial aneurysms. The purpose of this study was to determine whether the indications of flow diversion can be safely extended to unruptured, small, saccular aneurysms (<10 >mm) of the anterior circulation.

METHODS: Forty patients treated with the pipeline embolization device (PED) were matched in a 1:4 fashion with 160 patients treated with stent-assisted coiling based on patient age, sex, aneurysm location, and aneurysm size. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared.

RESULTS: The rate of periprocedural complications was 5% in the PED …

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 …

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 …

Qualified Doctor And Medical Students' Use Of Resources For Accessing Information: What Is Used And Why?, Nicola Brennan, Sarah Edwards, Narcie Kelly, Alice Miller, Lucy Harrower, Karen Mattick

Peninsula Medical School

BACKGROUND: Learning to access information using resources such as books and search engines is an important and fast changing challenge for doctors and medical students. Many resources exist to support evidence-based clinical decision-making, but a wide range of factors influences their use. OBJECTIVE: To explore qualified doctor and medical students' use of resources for accessing information and to determine what is used and why. METHODS: A stratified sample of 46 participants was recruited in Devon, UK. Participants kept a self-report diary of resources used over a week. The diaries were then used to stimulate recall within a semi-structured interview. Diary …

Development Of A Medical Academic Degree System In China, Lijuan Wu, Youxin Wang, Xiaoxia Peng, Manshu Song, Xiuhua Guo, Hugh Nelson, Wei Wang

Research outputs 2014 to 2021

Context: The Chinese government launched a comprehensive healthcare reform to tackle challenges to health equities. Medical education will become the key for successful healthcare reform. Purpose:We describe the current status of the Chinese medical degree system and its evolution over the last 80 years. Content: Progress has been uneven, historically punctuated most dramatically by the Cultural Revolution. There is a great regional disparity. Doctors with limited tertiary education may be licensed to practice, whereas medical graduates with advanced doctorates may have limited clinical skills. There are undefined relationships between competing tertiary training streams, the academic professional degree, and the clinical …

General Practitioners' Experiences Of Bereavement Care And Their Educational Support Needs: A Qualitative Study, Moira O'Connor, Lauren J. Breen

Research outputs 2014 to 2021

Background: General Practitioners (GPs) are well-positioned to provide grief support to patients. Most GPs view the provision of bereavement care as an important aspect of their role and the GP is the health professional that many people turn to when they need support. We aimed to explore GPs' understandings of bereavement care and their education and professional development needs in relation to bereavement care. Methods. An in-depth qualitative design was adopted using a social constructionist approach as our aims were exploratory and applied. Nineteen GPs (12 women and 7 men) living in Western Australia were interviewed; 14 were based in …

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 …