Medicine and Health Sciences Commons^™

Estimating Patient-Centered And Community-Centered Treatment Effects: Examples From Medical Care And Public Health, Glen P. Mays

Health Management and Policy Presentations

Health services researchers face growing clinical and policy imperatives for estimating how the effectiveness of medical and public health interventions vary across patients, population groups, and community settings. Recent advances in local instrumental variables estimation techniques allow for the estimation of person-specific and community-specific treatment effects in the presence of unobserved heterogeneity. This presentation explores examples from both medicine and public health following the local IV methods developed by Basu et al. (2013).

Derivation Of An Analytical Solution To A Reaction-Diffusion Model For Autocatalytic Degradation And Erosion In Polymer Microspheres, Ashlee N. Ford Versypt, Paul D. Arendt, Daniel W. Pack, Richard D. Braatz

Pharmaceutical Sciences Faculty Publications

A mathematical reaction-diffusion model is defined to describe the gradual decomposition of polymer microspheres composed of poly(D,L-lactic-co-glycolic acid) (PLGA) that are used for pharmaceutical drug delivery over extended periods of time. The partial differential equation (PDE) model treats simultaneous first-order generation due to chemical reaction and diffusion of reaction products in spherical geometry to capture the microsphere-size-dependent effects of autocatalysis on PLGA erosion that occurs when the microspheres are exposed to aqueous media such as biological fluids. The model is solved analytically for the concentration of the autocatalytic carboxylic acid end groups of the polymer chains that comprise the microspheres …

Chronic Ldh Elevation After Left Ventricular Assist Device Implantation, Hesham R. Omar, Navin Rajagopalan, Maya Guglin

The VAD Journal

A 61-year-old woman who underwent HeartMate II left ventricular assist device placement for non-ischemic cardiomyopathy developed elevated lactate dehydrogenase within two weeks after implantation. After eight months of observation and several hospital admissions during which there was no evidence of pump thrombosis, she presented with clinically manifest hemolysis. During pump exchange there was notable pannus formation on the inflow cannula of the left ventricular assist device. The pannus around the inflow likely existed for several months, limiting the flow and creating a low-grade hemolysis and this low flow state stimulated thrombus formation triggering gross hemolysis. Thoratec analysis of the pump …

Chronic Hemodialysis In A Patient With Left Ventricular Assist Device., Amr Idris, Georges Lolay, Ana L. Castellanos, Navin Rajagopalan, Maya Guglin

The VAD Journal

Renal dysfunction in the setting of heart failure is a common medical problem. This dysfunction can range from reversible ischemic changes to renal failure requiring renal replacement therapy. Patients who are candidates for mechanical circulatory support with left ventricular assistant device (LVAD) pose unique challenge with respect to receiving dialysis. We present a 47 year old patient who required renal replacement therapy peri-implantation of LVAD for management of acute on chronic kidney disease, and was discharged for chronic hemodialysis in an outpatient setting. In this report we highlight the challenges of managing volume overload in patients with impaired renal function …

Phases Of Su(3) Gauge Theories With Fundamental Quarks Via Dirac Spectral Density, Andrei Alexandru, Ivan Horváth

Anesthesiology Faculty Publications

We propose that, in SU(3) gauge theories with fundamental quarks, confinement can be inferred from spectral density of the Dirac operator. This stems from the proposition that its possible behaviors are exhausted by three distinct types (Fig. 1). The monotonic cases are standard and entail confinement with valence chiral symmetry breaking (A) or the lack of both (C,C’). The bimodal (anomalous) option (B) was frequently regarded as an artifact (lattice or other) in previous studies, but we show for the first time that it persists in the continuum limit, and conclude that it informs of a nonconfining …

Foundational Public Health Services And Health System Reform, Glen P. Mays

Health Management and Policy Presentations

The Institute of Medicine's 2012 report on public health financing recommended a national initiative to identify the components and costs of a "minimum package" of public health programs and infrastructure that should be available in every U.S. community. In response, efforts are now underway to reach consensus on a set of "Foundational Public Health Services" for the nation, and to identify resource requirements for implementing these services. This presentation reviews existing research on the current availability of Foundational Public Health Services across the U.S. and the health and economic effects attributable to these services. We also review progress on ongoing …

Fundamentals Of Economic Evaluation For Public Health, Glen P. Mays, Cezar Mamaril

Health Management and Policy Presentations

This workshop provides an overview of the design and implementation of economic evaluation studies of public health programs and policies. Strategies for integrating economic evaluation principles, measurement strategies, analytic approaches, and results into the routine operations of public health agencies are examined.

Summary Of Proposed Updates To The National Health Security Preparedness Index For 2015-2016, Glen P. Mays, Michael T. Childress, Pierre Martin Dominique Zephyr, Christopher R. Bollinger, Anna Goodman Hoover

Health Management and Policy Reports

This report describes proposed updates in methodology and measures for the 2015-16 release of the National Health Security Preparedness Index

Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings …

Applying Failure Modes And Effects Analysis To Public Health Models: The Breathe Easy At Home Program, Johnna S. Murphy, Margaret Reid, Amanda Ali, Laura Harrington, Megan Sandel

Frontiers in Public Health Services and Systems Research

Failure Modes and Effects Analysis (FMEA) is a structured process used to identify and prioritize risks by ranking them based on severity, occurrence, and detectability. Historically, FMEA has been used within industries, including automotive and health care. This project explored the adaption of the FMEA template to a small public health program designed to improve asthma outcomes. The Breathe Easy at Home (BEAH) program is a multi-sector partnership that uses a web-based system to link clinical sites with housing code inspections and enforcement for patients with asthma.

In July and August 2014, an FMEA was conducted to uncover risks within …

Economic Evaluation Of Fungal Meningitis Outbreak Response In New River Valley: Local Health Department Perspective, Kaja M. Abbas, Nargesalsadat Dorratoltaj, Margaret L. O’Dell, Paige Bordwine, Thomas M. Kerkering, Kerry J. Redican

Frontiers in Public Health Services and Systems Research

Background: The multi-state fungal meningitis outbreak started in September 2012 in Tennessee. The cause of the outbreak was injection of contaminated lots of methylprednisolone acetate used in epidural spinal injections. Roanoke and New River Valley were the epicenter of this outbreak in Virginia, with two clinical centers having administered the contaminated injections to their patients. New River Health District, in coordination with hospitals, and state and federal agencies, deployed its resources to control the local impact of the outbreak.

Purpose: The objective of this study was to conduct an economic evaluation of the fungal meningitis outbreak response in New River …

Implementation Of Electronic Disease Reporting Systems By Local Health Departments, Gulzar H. Shah, Karmen Williams, Bushra G. Shah

Frontiers in Public Health Services and Systems Research

Background: Electronic disease reporting systems (EDRSs) are imperative for local health departments (LHDs) operating in the post-H1N1 and evidence-based public health practice era. Studies regarding functionality and factors responsible for variation in implementation are important but rare.

Purpose: This primary objective for this study was to provide evidence regarding the level to which LHDs have implemented electronic disease reporting systems and factors associated with variation in implementation of electronic disease reporting systems.

Methods: A quantitative analysis was performed of the 2013 Profile of Local Health Departments Survey conducted by the National Association of County and City Health Officials (NACCHO). The …

Impact Of Organizational Networks On The Cost Of Core Services In Ohio’S Local Health Departments, Jason E. Orcena, Michael Petros, Patrick M. Bernet

Frontiers in Public Health Services and Systems Research

Introduction: Although several studies have linked population size to the cost of service delivery in local health departments, none have looked at the network position of the LHD. This study expands the understanding of how the position of an LHD in Ohio’s local health department network affects its expenditures in providing core, or nonclinical, services.

Methods: In 2014, 44% (55 of 124 eligible) of Ohio’s health officers responded to the PARTNER survey, a web-based network analysis program, with the analysis completed by the spring of 2015. Network data were then included in a regression analysis of the Core Plus-Scale model …

Measuring Changes In Local Surveillance And Investigation Capacity, Christine A. Bevc, Mary V. Davis, Anna P. Schenck

Frontiers in Public Health Services and Systems Research

Background: The outbreak of Ebola virus disease in West Africa and confirmation of the first cases in the United States highlight the need for robust and responsive public health surveillance system. With a 25% decline in funding since 2007, the impact on local surveillance capacities has not previously been described.

Purpose: The Surveillance & Investigation domain of the Local Health Department Preparedness Capacities Survey (PCAS) was reweighted to reflect the national profile of LHDs. Changes in subdomain performance of capacities and the effect of population size on subdomain capacity performance were examined over time.

Methods: Participating LHDs (n=208) …

Evidence For The Involvement Of Sphingosine-1-Phosphate In The Homing And Engraftment Of Hematopoietic Stem Cells To Bone Marrow, Mateusz Adamiak, Sylwia Borkowska, Marcin Wysoczynski, Malwina Suszynska, Magda Kucia, Gregg Rokosh, Ahmed Abdel-Latif, Janina Ratajczak, Mariusz Z. Ratajczak

Internal Medicine Faculty Publications

The α-chemokine stromal-derived factor 1 (SDF-1), which binds to the CXCR4 receptor, directs migration and homing of CXCR4⁺ hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) stem cell niches. Nevertheless, it is also known that CXCR4^-/- fetal liver-derived hematopoietic stem cells engraft into BM and that blockade of CXCR4 by its antagonist AMD3100 does not prevent engraftment of HSPCs. Because of this finding of SDF-1-CXCR4-independent BM homing, the unique role of SDF-1 in HSPC homing has recently been challenged. While SDF-1 is the only chemokine that chemoattracts HSPCs, other chemoattractants for these cells have recently been described, including …

Increased Expression Of Fatty Acid Synthase Provides A Survival Advantage To Colorectal Cancer Cells Via Upregulation Of Cellular Respiration, Yekaterina Y. Zaytseva, Jennifer W. Harris, Mihail I. Mitov, Ji Tae Kim, D. Allan Butterfield, Eun Young Lee, Heidi L. Weiss, Tianyan Gao, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN), a lipogenic enzyme, is upregulated in colorectal cancer (CRC). Increased de novo lipid synthesis is thought to be a metabolic adaptation of cancer cells that promotes survival and metastasis; however, the mechanisms for this phenomenon are not fully understood. We show that FASN plays a role in regulation of energy homeostasis by enhancing cellular respiration in CRC. We demonstrate that endogenously synthesized lipids fuel fatty acid oxidation, particularly during metabolic stress, and maintain energy homeostasis. Increased FASN expression is associated with a decrease in activation of energy-sensing pathways and accumulation of lipid droplets in CRC cells …

Inner Synovial Membrane Footprint Of The Anterior Elbow Capsule: An Arthroscopic Boundary, Srinath Kamineni, Abdo Bachoura, Koichi Sasaki, Danielle Reilly, Kate N. Harris, Anthony Sinai, Andrew Deane

Orthopaedic Surgery and Sports Medicine Faculty Publications

Introduction. The purpose of this study is to describe the inner synovial membrane (SM) of the anterior elbow capsule, both qualitatively and quantitatively. Materials and Methods. Twenty-two cadaveric human elbows were dissected and the distal humerus and SM attachments were digitized using a digitizer. The transepicondylar line (TEL) was used as the primary descriptor of various landmarks. The distance between the medial epicondyle and medial SM edge, SM apex overlying the coronoid fossa, the central SM nadir, and the apex of the SM insertion overlying the radial fossa and distance from the lateral epicondyle to lateral SM edge along the …

A Case Study Of The Impediments To The Commercialization Of Research At The University Of Kentucky, Nathan L. Vanderford, Elizabeth Marcinkowski

Markey Cancer Center Faculty Publications

The commercialization of university-based research occurs to varying degrees between academic institutions. Previous studies have found that multiple barriers can impede the effectiveness and efficiency by which academic research is commercialized. This case study was designed to better understand the impediments to research commercialization at the University of Kentucky via a survey and interview with three successful academic entrepreneurs. The study also garnered insight from the individuals as to how the commercialization process could be improved. Issues with commercialization infrastructure; a lack of emphasis, at the university level, on the importance of research commercialization; a void in an entrepreneurial culture …

Truncating Mutation In The Autophagy Gene Uvrag Confers Oncogenic Properties And Chemosensitivity In Colorectal Cancers, Shanshan He, Zhen Zhao, Yongfei Yang, Douglas O'Connell, Xiaowei Zhang, Soohwan Oh, Binyun Ma, Joo-Hyung Lee, Tian Zhang, Bino Varghese, Janae Yip, Sara Dolatshahi Pirooz, Ming Li, Yong Zhang, Guo-Min Li, Sue Ellen Martin, Keigo Machida, Chengyu Liang

Toxicology and Cancer Biology Faculty Publications

Autophagy-related factors are implicated in metabolic adaptation and cancer metastasis. However, the role of autophagy factors in cancer progression and their effect in treatment response remain largely elusive. Recent studies have shown that UVRAG, a key autophagic tumour suppressor, is mutated in common human cancers. Here we demonstrate that the cancer-related UVRAG frameshift (FS), which does not result in a null mutation, is expressed as a truncated UVRAG^FS in colorectal cancer (CRC) with microsatellite instability (MSI), and promotes tumorigenesis. UVRAG^FS abrogates the normal functions of UVRAG, including autophagy, in a dominant-negative manner. Furthermore, expression of UVRAG^FS can …

Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander

Gill Heart & Vascular Institute Faculty Publications

Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.

Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma …

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA^m-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …

Amphiphilic Tobramycin Analogues As Antibacterial And Antifungal Agents, Sanjib K. Shrestha, Marina Y. Fosso, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C₁₂ and C₁₄ chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter …

Appalachian Research Day: Come Sit On The Porch, Frances J. Feltner, Beth Bowling, Wayne Noble

Center of Excellence in Rural Health Presentations

Rural Appalachian communities in eastern Kentucky suffer from some of the Nation’s most concerning health disparities. Community-based research can be an effective way to address health disparities by identifying problems and sharing innovative solutions. However, challenges exist in recruiting and retaining research participants in rural populations that can often be difficult to reach. Partnerships between researchers and communities are essential to the success of the research process, particularly translation of findings back into the community

Assessment Of Accelerometers For Measuring Upper-Extremity Physical Activity, Elizabeth Lawinger, Timothy L. Uhl, Mark Abel, Srinath Kamineni

Physical Therapy Faculty Publications

Objective: The overarching goal of this study was to examine the use of triaxial accelerometers in measuring upper-extremity motions to monitor upper-extremity-exercise compliance. There were multiple questions investigated, but the primary objective was to investigate the correlation between visually observed arm motions and triaxial accelerometer activity counts to establish fundamental activity counts for the upper extremity.

Study Design: Cross-sectional, basic research.

Setting: Clinical laboratory.

Participants: Thirty healthy individuals age 26 ± 6 y, body mass 24 ± 3 kg, and height 1.68 ± 0.09 m volunteered.

Intervention: Participants performed 3 series of tasks: activities of …

The Cestode Community In Northern Fur Seals (Callorhinus Ursinus) On St. Paul Island, Alaska, Tetiana A Kuzmina, Jesús S. Hernández-Orts, Eugene T. Lyons, Terry R Spraker, Vadym V. Kornyushyn, Roman Kuchta

Veterinary Science Faculty Publications

The diversity and ecology of cestodes from the northern fur seals, Callorhinus ursinus (NFS), were examined using newly collected material from 756 humanely harvested subadult males between 2011 and 2014. NFSs were collected from five different haul-outs on St. Paul Island, Alaska. A total of 14,660 tapeworms were collected with a prevalence of 98.5% and intensity up to 107 cestodes per host (mean intensity 19.7 ± 16.5 SD). Three species of tapeworms were found: Adenocephalus pacificus (Diphyllobothriidea) was the most prevalent (prevalence 97.4%), followed by Diplogonoporus tetrapterus (49.7%), and 5 immature specimens of Anophryocephalus cf. ochotensis (Tetrabothriidea) (0.5%). Most of …

Sleeping While Driving, Joav Merrick, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

4e-Bp1 As An Oncotarget, Qing-Bai She

Markey Cancer Center Faculty Publications

No abstract provided.

Chemically Related 4,5-Linked Aminoglycoside Antibiotics Drive Subunit Rotation In Opposite Directions, Michael R. Wasserman, Arto Pulk, Zhou Zhou, Roger B. Altman, John C. Zinder, Keith D. Green, Sylvie Garneau-Tsodikova, Jamie H. Doudna Cate, Scott C. Blanchard

Pharmaceutical Sciences Faculty Publications

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of …

Pp2a Inhibitors Arrest G2/M Transition Through Jnk/Sp1-Dependent Down-Regulation Of Cdk1 And Autophagy-Dependent Up-Regulation Of P21, Fei-Ran Gong, Meng-Yao Wu, Meng Shen, Qiaoming Zhi, Ze-Kuan Xu, Rong Wang, Wen-Jie Wang, Yang Zong, Zeng-Liang Li, Yadi Wu, Binhua P. Zhou, Kai Chen, Min Tao, Wei Li

Markey Cancer Center Faculty Publications

Protein phosphatase 2A (PP2A) plays an important role in the control of the cell cycle. We previously reported that the PP2A inhibitors, cantharidin and okadaic acid (OA), efficiently repressed the growth of cancer cells. In the present study, we found that PP2A inhibitors arrested the cell cycle at the G2 phase through a mechanism that was dependent on the JNK pathway. Microarrays further showed that PP2A inhibitors induced expression changes in multiple genes that participate in cell cycle transition. To verify whether these expression changes were executed in a PP2A-dependent manner, we targeted the PP2A catalytic subunit (PP2Ac) using siRNA …

Reversal Of Aging-Related Neuronal Ca2+ Dysregulation And Cognitive Impairment By Delivery Of A Transgene Encoding Fk506-Binding Protein 12.6/1b To The Hippocampus, John C. Gant, Kuey-Chu Chen, Inga Kadish, Eric M. Blalock, Olivier Thibault, Nada M. Porter, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Brain Ca(2+) regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca(2+)-dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca(2+) channel activity and ryanodine receptor (RyR)-mediated Ca(2+) release, but underlying molecular mechanisms are poorly understood. Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca(2+) release in cardiomyocytes, declines in hippocampus of aged rats and Alzheimer's disease subjects. Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments neuronal Ca(2+) responses. …