Digital Commons Network^™

The Odyssey Of Tavr From Concept To Clinical Reality, Alain G Cribier

The Texas Heart Institute Journal

No abstract provided.

A Dedicated Binding Mechanism For The Visual Control Of Movement., Alexandra Reichenbach, David W Franklin, Peter Zatka-Haas, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

The human motor system is remarkably proficient in the online control of visually guided movements, adjusting to changes in the visual scene within 100 ms [1-3]. This is achieved through a set of highly automatic processes [4] translating visual information into representations suitable for motor control [5, 6]. For this to be accomplished, visual information pertaining to target and hand need to be identified and linked to the appropriate internal representations during the movement. Meanwhile, other visual information must be filtered out, which is especially demanding in visually cluttered natural environments. If selection of relevant sensory information for online control …

Quantitative Relaxometry And Diffusion Mri For Lateralization In Mts And Non-Mts Temporal Lobe Epilepsy., Ali R Khan, Maged Goubran, Sandrine De Ribaupierre, Robert R Hammond, Jorge G Burneo, Andrew G Parrent, Terry M Peters

Robarts Imaging Publications

We developed novel methodology for investigating the use of quantitative relaxometry (T1 and T2) and diffusion tensor imaging (DTI) for lateralization in temporal lobe epilepsy. Patients with mesial temporal sclerosis confirmed by pathology (N=8) and non-MTS unilateral temporal lobe epilepsy (N=6) were compared against healthy controls (N=19) using voxel-based analysis restricted to the anterior temporal lobes, and laterality indices for each MRI metric (T1, T2, fractional anisotropy (FA), mean diffusivity, axial and radial diffusivities) were computed based on the proportion of significant voxels on each side. The diffusivity metrics were the most lateralizing MRI metrics in MTS and non-MTS subsets, …

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

Anthropomorphic Breast Phantoms With Physiological Water, Lipid, And Hemoglobin Content For Near-Infrared Spectral Tomography, Kelly E. Michaelsen, Venkataramanan Krishnaswamy, Adele Shenoy, Emily Jordan, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

Breast mimicking tissue optical phantoms with sufficient structural integrity to be deployed as stand-alone imaging targets are developed and successfully constructed with biologically relevant concentrations of water, lipid, and blood. The results show excellent material homogeneity and reproducibility with inter- and intraphantom variability of 3.5 and 3.8%, respectively, for water and lipid concentrations ranging from 15 to 85%. The phantoms were long-lasting and exhibited water and lipid fractions that were consistent to within 5% of their original content when measured 2 weeks after creation. A breast-shaped three-compartment model of adipose, fibroglandular, and malignant tissues was created with water content ranging …

The International Society Of Physical And Rehabilitation Medicine: The Way Forward - Ii., Marta Imamura, Christoph Gutenbrunner, Gerold Stucki, Jianan Li, Jorge Lains, Walter Frontera, John Olver, Levent Özçakar, Joel Delisa, Linamara Rizzo Battistella, John L. Melvin

Department of Rehabilitation Medicine Faculty Papers

This paper reports on recent changes and future plans concerning the International Society of Physical and Rehabilitation Medicine. Issues discussed are its structural organization, collaboration and recognition, liaison with the World Health Organization , work in strengthening science, and its future agenda.

A Review Of The Global Literature On Dental Therapists, David A. Nash, Jay W. Friedman, Kavita R. Mathu-Muju, Peter G. Robinson, Julie Satur, Susan Moffat, Rosemary Kardos, Edward C. M. Lo, Anthony H. H. Wong, Nasruddin Jaafar, Jos Van Den Heuvel, Prathip Phantumvanit, Eu Oy Chu, Rahul Naidu, Lesley Naidoo, Irving Mckenzie, Eshani Fernando

Oral Health Science Faculty Publications

OBJECTIVE: Access to adequate oral health care is deficient in many parts of the world. Many countries are now using dental therapists to increase access, particularly for children. To inform the discussion on dental therapists in the workforce, particularly in the United States, the W.K. Kellogg Foundation funded a review of the global literature to identify as many documents as possible related to the practice of dental therapists since the establishment of the School Dental Service in New Zealand in 1921.

METHODS: Consultants in each of the countries considered to have a substantive literature on dental therapists were …

A Novel In Vivo Model For Evaluating Functional Restoration Of A Tissue-Engineered Salivary Gland., Swati Pradhan-Bhatt, Daniel A Harrington, Randall L Duncan, Mary C Farach-Carson, Xinqiao Jia, Robert L Witt

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: To create a novel model for development of a tissue-engineered salivary gland from human salivary gland cells that retains progenitor cell markers useful for treatment of radiation-induced xerostomia.

STUDY DESIGN: A three-dimensional (3D) hyaluronic acid (HA)-based hydrogel scaffold was used to encapsulate primary human salivary gland cells and to obtain organized acini-like spheroids. Hydrogels were implanted into rat models, and cell viability and receptor expression were evaluated.

METHODS: A parotid gland surgical resection model for xenografting was developed. Salivary cells loaded in HA hydrogels formed spheroids and in vitro were implanted in the three-fourths resected parotid bed of athymic …

Managing The Innovation Supply Chain To Maximize Personalized Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient's molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application …

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 …

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

Spatial Frequency Analysis Of Anisotropic Drug Transport In Tumor Samples, Stewart Russell, Kimberley S. Samkoe, Jason R. Gunn, P Jack Hoopes, Thienan A. Nguyen, Milo J. Russell, Robert R. Alfano, Brian W. Pogue

Dartmouth Scholarship

Directional Fourier spatial frequency analysis was used on standard histological sections to identify salient directional bias in the spatial frequencies of stromal and epithelial patterns within tumor tissue. This directional bias is shown to be correlated to the pathway of reduced fluorescent tracer transport. Optical images of tumor specimens contain a complex distribution of randomly oriented aperiodic features used for neoplastic grading that varies with tumor type, size, and morphology. The internal organization of these patterns in frequency space is shown to provide a precise fingerprint of the extracellular matrix complexity, which is well known to be related to the …

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 …

Prioritizing Protein Complexes Implicated In Human Diseases By Network Optimization., Yong Chen, Thibault Jacquemin, Shuyan Zhang, Rui Jiang

College of Science & Mathematics Departmental Research

BACKGROUND: The detection of associations between protein complexes and human inherited diseases is of great importance in understanding mechanisms of diseases. Dysfunctions of a protein complex are usually defined by its member disturbance and consequently result in certain diseases. Although individual disease proteins have been widely predicted, computational methods are still absent for systematically investigating disease-related protein complexes.

RESULTS: We propose a method, MAXCOM, for the prioritization of candidate protein complexes. MAXCOM performs a maximum information flow algorithm to optimize relationships between a query disease and candidate protein complexes through a heterogeneous network that is constructed by combining protein-protein interactions …

Detection Of Temporal Lobe Epilepsy Using Support Vector Machines In Multi-Parametric Quantitative Mr Imaging., Diego Cantor-Rivera, Ali R Khan, Maged Goubran, Seyed M Mirsattari, Terry M Peters

Robarts Imaging Publications

The detection of MRI abnormalities that can be associated to seizures in the study of temporal lobe epilepsy (TLE) is a challenging task. In many cases, patients with a record of epileptic activity do not present any discernible MRI findings. In this domain, we propose a method that combines quantitative relaxometry and diffusion tensor imaging (DTI) with support vector machines (SVM) aiming to improve TLE detection. The main contribution of this work is two-fold: on one hand, the feature selection process, principal component analysis (PCA) transformations of the feature space, and SVM parameterization are analyzed as factors constituting a classification …

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 …

Primary Microrna Processing Assay Reconstituted Using Recombinant Drosha And Dgcr8., Ian Barr, Feng Guo

Natural Sciences and Mathematics | Faculty Scholarship

In animals, the Microprocessor complex cleaves primary transcripts of microRNAs (pri-miRNAs) to produce precursor microRNAs in the nucleus. The core components of Microprocessor include the Drosha ribonuclease and its RNA-binding partner protein DiGeorge critical region 8 (DGCR8). DGCR8 has been shown to tightly bind an Fe(III) heme cofactor, which activates its pri-miRNA processing activity. Here we describe how to reconstitute pri-miRNA processing using recombinant human Drosha and DGCR8 proteins. In particular, we present the procedures for expressing and purifying DGCR8 as an Fe(III) heme-bound dimer, the most active form of this protein, and for estimating its heme content.

Differential Responding By Rhesus Monkeys (Macaca Mulatta) And Humans (Homo Sapiens) To Variable Outcomes In The Assurance Game, Audrey E. Parrish, Sarah F. Brosnan, Bart J. Wilson, Michael J. Beran

Economics Faculty Articles and Research

Behavioral flexibility in how one responds to variable partner play can be examined using economic coordination games in which subjects play against a variety of partners and therefore may need to alter their behavior to produce the highest payoff. But how do we study this behavioral flexibility once players have settled on a response? Here, we investigated how responding by rhesus monkeys (Macaca mulatta) and humans (Homo sapiens) playing a computerized single-player version of a coordination game, the Assurance game, changed as a function of the variable responses (Stag/Hare) generated by multiple simulations (SIMs). We were interested in whether individuals …

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 …

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 …

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 …

Association Of Ataxia Telangiectasia Mutated (Atm) Gene Mutation/Deletion With Rhabdomyosarcoma, Peilin Zhang, Kunjan S. Bhakta, Pier Lorenzo Puri, Robert Newbury, James Feramisco, Jean Wang

Faculty & Staff Scholarship

No abstract provided.

The Reliability Of An Adolescent Dietary Pattern Identified Using Reduced-Rank Regression: Comparison Of A Ffq And 3 D Food Record, Geeta Appannah, Gerda K. Pot, Therese A. O'Sullivan, Wendy H. Oddy, Susan A. Jebb, Gina L. Ambrosini

Research outputs 2014 to 2021

Despite the increasing use of dietary patterns (DP) to study diet and health outcomes, relatively few studies have examined the reliability of DP using different dietary assessment methods. Reduced-rank regression (RRR) is an emerging statistical method that incorporates a priori information to characterise DP related to specific outcomes of interest. The aim of the present study was to compare DP identified using the RRR method in a FFQ with those in a 3 d food record (FR). Participants were 783 adolescents from the Western Australian Pregnancy (Raine) Cohort Study who completed both a FFQ and FR at 14 years of …

Specific Intracellular Uptake Of Herceptin-Conjugated Cdse/Zns Quantum Dots Into Breast Cancer Cells, Seung-Jin Han, Pierson Rathinaraj, Soo-Young Park, Young-Kyoo Kim, Joon Hyung Lee, Inn-Kyu Kang, Jong-Sik Moon, Jeffrey G. Winiarz

Chemistry Faculty Research & Creative Works

Herceptin, a typical monoclonal antibody, was immobilized on the surface of CdSe/ZnS core-shell quantum dots (QDs) to enhance their specific interactions with breast cancer cells (SK-BR3). the mean size of the core-shell quantum dots (28 nm), as determined by dynamic light scattering, increased to 86 nm after herceptin immobilization. the in vitro cell culture experiment showed that the keratin forming cancer cells (KB) proliferated well in the presence of herceptin-conjugated QDs (QD-Her, 5 nmol/mL), whereas most of the breast cancer cells (SK-BR3) had died. to clarify the mechanism of cell death, the interaction of SK-BR3 cells with QD-Her was examined …

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 …

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 …

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 …

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 …

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 …

A Proto-Architecture For Innate Directionally Selective Visual Maps., Sv Adams, Cm Harris

School of Psychology

Self-organizing artificial neural networks are a popular tool for studying visual system development, in particular the cortical feature maps present in real systems that represent properties such as ocular dominance (OD), orientation-selectivity (OR) and direction selectivity (DS). They are also potentially useful in artificial systems, for example robotics, where the ability to extract and learn features from the environment in an unsupervised way is important. In this computational study we explore a DS map that is already latent in a simple artificial network. This latent selectivity arises purely from the cortical architecture without any explicit coding for DS and prior …