Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Sepsis: Do The Clinical Criteria Support The Medical Coding?, April M. Insco

Theses and Dissertations (ETD)

Background: Sepsis is a condition that can be very costly and very deadly. Diagnosing sepsis can be challenging as there is not one specific test that will identify whether a patient has sepsis and there are varying opinions as to the true definition of sepsis. The definition of sepsis used for this research is a combination of System Inflammatory Response Syndrome (SIRS) with an identified infection. Medical Coders must review the documentation provided in a medical record to accurately assign an ICD-10-CM code. Administrative data is then used to provide statistical information for research purposes. When coded data is not …

Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling, Mingqi Li

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) is aggressive but cannot be treated with hormone therapy or molecular therapy due to the lack of a target. Chemotherapy is a systemic treatment that works by attacking rapidly growing cells, which is initially more effective for TNBC patients than those individuals with the hormone receptor-positive breast cancer. However, patients with TNBC tend to develop resistance to chemo drugs, called chemoresistance. After years of effort, the signaling pathways involved in TNBC chemoresistance are gradually revealed, including the nuclear factor-kappa B (NF-kB) pathway. Transcription factor NF-kB is widely involved in cancer development and progression, and its …

Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib

Theses and Dissertations (ETD)

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …

The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle

Theses and Dissertations (ETD)

CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia in patients without Down syndrome (non-DS-AMKL) and is associated with an event free survival of only 8% even with high intensity chemotherapy and stem cell transplant in first remission. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified …

A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer

Theses and Dissertations (ETD)

Real-world conversations are often accompanied by some sort of interference that challenges the clarity of the speaker’s message, causing listeners to exert more effort to understand speech. Previous research has demonstrated that when listening to speech becomes difficult, various regions of the brain are recruited beyond those which engage during optimal listening conditions. However, the neural correlates that underly listening effort are not fully understood. Importantly, the pupillary response can be used to index listening effort, such that pupil size increases with increasing cognitive demand. I proposed that pupillometry can be used to characterize the cortical response, such that changes …

Predictors Of Hyperkalemia And Outcomes Of Dyskalemia In Us Veterans With Advanced Chronic Kidney Disease Transitioning To Dialysis, Ankur Dashputre

Theses and Dissertations (ETD)

Background: The kidneys play a crucial role in maintaining homeostasis of serum potassium levels (K+). Patients with advanced chronic kidney disease (CKD) are at a higher risk of experiencing dyskalemia events (i.e. hyper- and hypokalemia; especially the former) and thus future adverse outcomes. Currently, there is a dearth of literature on prediction models for hyperkalemia and the effects of dyskalemia on outcomes such as incidence of ischemic stroke and short-term hospital/emergency room (ER) utilization in an advanced CKD population transitioning to dialysis. Objectives: Using a nationally representative sample of US veterans with advanced CKD transitioning to dialysis, in the pre-dialysis …

Targeting Protein Degradation To Uncover Novel Oncoprotein Drivers Of Acute Leukemia, Fatemeh Keramatnia

Theses and Dissertations (ETD)

Acute Lymphoblastic Leukemia (ALL), the most common childhood cancer and the second most common acute leukemia in adults, arises from clonal expansion of undifferentiated lymphoid precursor cells in bone marrow. Despite the extensive knowledge on its cytogenetic and molecular biology, ALL treatment remains highly challenging especially after relapse. Conventional chemotherapy has shown significant improvement in overall survival rates of pediatric patients up to 90%, however, treatment failure due to ALL relapse occurs in 15-20% of the cases. On the other hand, adults and elderly patients with ALL are considered difficult to treat populations with the 5-year overall survival of 30–40%. …

The Relationship Of Child Health And Parenting Stress To Child Neurocognitive Development, Nancy Alise Farrell

Theses and Dissertations (ETD)

Problem. Although the United States rates high in economic resources, the neurocognitive development (NCD) of children falls behind many other developed nations. Levels of parenting stress may be linked to sociodemographic factors such as the high incidence of poverty in children or health disparities in children, which in turn may affect NCD in children. Using the data from an observational, longitudinal cohort study of a diverse population could provide information related to parenting stress, child health, and related factors to guide and support interventions with families and policies to improve child NCD. Aims. The overall aim of this study was …

Immunomodulatory Roles Of The Lysosomal Sialidase Neuraminidase 1, Leigh Ellen Fremuth

Theses and Dissertations (ETD)

Background Sialic acids are key sugar moieties located at the non-reducing terminals of glycan chains on glycoproteins and glycolipids. By virtue of their location, they influence the functions and biochemical properties of the macromolecules they are bound to. Removal of sialic acids in mammalian cells is carried out by four sialidases, which are differentially expressed and localized in distinct subcellular compartments. Neuraminidase 1 (NEU1), the most abundant and ubiquitous of the four sialidases, functions primarily in the acidic environment of the lysosomes, but can hydrolyze substrates at the plasma membrane, at least in certain cell types. The enzyme initiates the …

Developing Deep-Learning Methods For Diagnosis And Prognosis Of Pediatric Progressive Diseases Using Modern Imaging Techniques, Mahdieh Shabanian

Theses and Dissertations (ETD)

Purpose and Rationale. Central nervous system manifestations form a significant burden of disease in young children. There have been efforts to correlate the neurological disease state in tuberous sclerosis complex (TSC) neurological disease state with imaging findings is a standard part of patient care. However, such analysis of neuroimaging is time- and labor-intensive. Automated approaches to these tasks are needed to improve speed, accuracy, and availability. Automated medical image analysis tools based on 3D/2D deep learning algorithms can help improve the quality and consistency of image diagnosis and interpretation for cognitive disorders in infants. We propose to automate neuroimaging analysis …

Identifying The Molecular Cause Of Extreme Endoplasmic Reticulum Dilation In Pediatric Osteosarcoma And Its Relationship To The Disease, Rachael Wood

Theses and Dissertations (ETD)

Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology …

Ecology Of Hantaviruses In Rodent Reservoirs And Their Early Innate Immune Responses In Human Model Systems, Evan Peter Williams

Theses and Dissertations (ETD)

The spillover of zoonotic RNA viruses is responsible for a great deal of the disease outbreaks in human populations. These spillover events are set to continue due to anthropogenic and environmental changes that impact the distribution of these viruses. The viruses in the family Hantaviridae are classified as one of these emerging zoonotic RNA viruses. The spillover of the viruses in this family are responsible for two severe human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These viruses are distributed across the globe and are responsible for a large number of human disease cases with …

Examination Of Antiviral Resistance In Venezuelan Equine Encephalitis Virus, Jasper Lee

Theses and Dissertations (ETD)

Venezuelan equine encephalitis virus (VEEV) is a New World Alphavirus that causes Venezuelan equine encephalitis (VEE), which is characterized by a febrile illness that can progress to neurological disease and death. While no major outbreaks of VEE have occurred since 1995, VEEV is a virus of concern as, in addition to its spread through mosquitos, it can be aerosolized and used as a bioweapon. Unfortunately, there are currently no FDA-approved vaccines or antivirals against VEEV. Efforts have been made to discover small molecules with an inhibitory effect on VEEV, but the potential for emergence of antiviral resistance to these compounds …

Responding To The Pandemic: A Multicountry Study On Social-Political Factors And Health Outcomes Of Covid-19, Lan Yao

Theses and Dissertations (ETD)

Introduction. Coronavirus Disease 2019 (COVID-19) poses a major global threat to human beings, which has caused devastating consequences of population health, political, and economic crises in many countries. This dissertation was composed of three research activities to study the following aims: (1) review the existing literature focusing on political factors and health outcomes of COVID-19; (2) assess the relationship between democracy and case fatality rate of COVID-19 by controlling for the effect of age, comorbidity, health expenditure, healthcare workforce, and population density; and (3) identify the trajectory pattern cases peak days, deaths peak days, and peak periods.

Methods. We accessed …

Evaluation And Feasibility Of A Head Positioning Intervention In Patients With Intraparenchymal Hemorrhage, Wendy L. Dusenbury

Theses and Dissertations (ETD)

Stroke caused by intraparenchymal hemorrhage (IPH) is most commonly the result of hypertension-induced blood vessel rupture in the brain and is associated with devastating disability and high rates of death. To date, no intervention has improved outcomes in IPH stroke patients; however, head elevation may be one of the most important first steps to promote clinical stability in the hyperacute stage of IPH stroke because of the risk of increased intracranial pressure (ICP) in these patients. Nursing research completed in the late 1970s and early 1980s in patients with increased ICP due to traumatic brain injury showed that elevating the …

Iatrogenic Electrocautery Damage And Cellular-Based Corrosion Of Total Joint Arthroplasty Biomaterials, Kirsten Carol Miller

Theses and Dissertations (ETD)

Introduction. The number of patients undergoing a Primary Total Knee Arthroplasty (PTKA) has been increasing steadily each year. Of those PTKA patients, 20% report long-term pain and/or some functional deficit. Cobalt-Chromium-Molybdenum (CoCrMo) alloy is one of the most used materials in Total Joint Arthroplasty (TJA) implants due the material’s high strength, high corrosion resistance, and biocompatibility. The release of metal ions and potential occurrence of metallosis in TJA has been shown to be detrimental to the longevity of the implant. The mechanisms leading to this increase in metal ion concentrations have been up for debate, with some believing it is …

Near-Field Electrospinning And Characterization Of Biodegradable Small Diameter Vascular Grafts, William E. King Iii

Theses and Dissertations (ETD)

The ideal “off the shelf” tissue engineering, small-diameter (< 6 mm inner diameter (ID)) vascular graft hinges on designing a template that facilitates transmural ingrowth of capillaries to regenerate an endothelized neointimal surface. Previous traditionally electrospun (TES) approaches to create bioresorbable vascular grafts lack the pore sizes required to facilitate transmural capillary ingrowth required for successful in situ neovascular regeneration. Therefore, the ability to create scaffolds with program-specific architectures independent of fiber diameter via the relatively recent sub-technique of near-field electrospinning (NFES) represents a promising solution to create tissue engineering vascular grafts. These programmed large pore sizes are anticipated to promote in situ regeneration and improve the outcomes as well as the quality of life of patients with arterial disease.

In this dissertation, we manufactured via NFES as well as characterized biodegradable polydioxanone (PDO) small-diameter vascular grafts. Chapter 1 introduces the need for off-the-shelf, small-diameter vascular grafts to facilitate in situ regeneration, the process and pore size limitations of TES vascular grafts, and the promising use of NFES to develop precisely tailored PDO vascular grafts. Chapter 2 describes the process of NFES and details the current progress in NFES of biomedical polymers as well as the major limitations that exist in the field. Chapters 3, 4, and 5 contain primary research …

Feasibility And Acceptability Of Using Mobile Health Apps In Underserved Patients With Diabetes, Jieyu Luo

Theses and Dissertations (ETD)

Introduction. Diabetes mellitus is a condition with a growing morbidity and mortality burden. An estimated 30 million adults currently live with diabetes, with each individual spending over $9500 annually on medical care. The successful management of diabetes is a lifelong endeavor. This involves balancing a variety of factors including diet, medications, and glucose monitoring. It has been well established that successful control of diabetes depends largely upon patients’ daily lifestyle habits and activities. Not all patients, however, have the resources necessary for effective diabetes management. Health disparities lead to a higher rate of diabetes development in minority and poor populations. …

Early Diagnosis Of Alzheimer’S Disease In The Primary Care Setting, Raymond R. Romano

Theses and Dissertations (ETD)

The burden of Alzheimer’s disease (AD) affects not just the individual but also families, providers, and society. Early recognition and diagnosis of AD may reduce cost by reducing interaction with the health care system, earlier initiation of treatment, and prolonging time to long- term care. Primary care providers, the first contact for diagnosis of patients with AD, are not fulfilling the potential of early diagnosis for a variety of reasons. Biomarkers of AD emerge on average 15 to 20 years before clinical diagnosis, yet currently established biomarkers are not easily available in the primary care setting. A growing body of …

Audiovisual Integration During Novel Word Learning Among School-Aged Children With Cochlear Implants, Kristen Elizabeth Thompson Thornton

Theses and Dissertations (ETD)

Objective. It is well established that being able to see someone’s mouth move as they speak boosts speech perception for children with cochlear implants (CIs). Thus, children with CIs are often instructed to orient themselves toward the person they are listening to, to gain access to visual speech cues. Children with CIs who are better “audiovisual integrators,” or those who experience an auditory-visual (AV) enhancement effect (higher performance for AV information than auditory-alone (AO) or visual-alone (VO)), are more likely to have better speech and language outcomes after receiving their CI than children with poorer AV integration skills. While AV …

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

Design, Development And Evaluation Of Dual Drug Nanomedicine For Non-Small Cell Lung Cancer, Elham Hatami

Theses and Dissertations (ETD)

Resistance to conventional chemotherapy is a big challenge in the treatment of cancer including non-small cell lung cancer (NSCLC). A combination of natural chemo sensitizer agents with chemotherapy offers unique advantages over monotherapy alone. However, free unbound drugs, (in combination or as a single agent), lack tumor-targeted accumulation and therefore can be easily eliminated from the patient body. Moreover, some drugs are hydrophobic, and their organic solvents cause in vivo toxicity, thereby limiting their capability in clinical translation. Herein, dual loaded biocompatible and biodegradable nanoparticles (NPs) using Gemcitabine (Gem)a pyrimidine nucleoside antimetabolite and Gambogic acid (GA) (a highly hydrophobic chemo …

A Dynamic Ankle Orthosis For Alleviating Mechanical Foot And Ankle Pain, Preserving Joint Motion, And Restoring Patient Function, Chloe Ly Chung

Theses and Dissertations (ETD)

Over two million Americans visit the doctor each year for foot and ankle pain stemming from a degenerative condition or injury. Standard of care ankle-foot orthoses have been shown to effectively manage pain symptoms of the lower limb, but they can also significantly hinder joint motion and limit function. The Dynamic Ankle Orthosis (DAO) was created with the intent to alleviate pain using an offloading mechanism without interfering with natural joint motion. This dissertation presents the development, benchtop validation, functional assessment, and clinical evaluation of this novel treatment option for patients suffering from acute and chronic foot and ankle pain.A …

Cellular Corrosion Of Cocrmo Total Knee Implants: Understanding Underlying Mechanisms Through Retrieval Analysis And Simulated Inflammatory Conditions, Griffin Heise

Theses and Dissertations (ETD)

Introduction. Total joint arthroplasty is considered one of the most beneficial aspects of modern orthopedic surgery. Due to the increase in population, obesity rates, and medical advances, total joint replacements have become more commonplace in the United States. Recently, a unique type of damage has been investigated in cobalt-chrome (CoCr) implants that remains poorly understood and highly controversial. Originally, it was believed that this damage type was caused by inflammatory cells directly attacking the metal surface, leading to damage of the oxide layer. However, damage caused by electrocautery tools has shown identical characteristics, leading some to believe this is the …

Validation Testing Of A Synthetic Spine And Upgraded Protocol For A Biomechanical Evaluation Of A Lumbar Spinal Orthosis, Daniel Hoyer

Theses and Dissertations (ETD)

Low back pain (LBP) is highly prevalent in all walks of life. Standard conservative treatment methods may work for some, but others go on to have spinal injections, opioids, or surgical procedures to alleviate pain. The Distractive and Mobility-Enabling Orthosis (DMO) was developed to meet the need for a conservative, drug-free treatment method. In this research, the low back support test protocol for evaluating DMO success was upgraded with a new synthetic lumbar spine model. The latest generation of the DMO project was then evaluated using the new system in a laboratory setting and on a pilot physical therapy patient.First, …

Joint Coordination Variability In Anterior Cruciate Ligament Reconstructed Subjects During Stair Ambulation Using A Vector Coding Technique, Bryan R. Simrak

Theses and Dissertations (ETD)

Anterior cruciate ligament (ACL) rupture is a common injury, with an estimated incidence of 120,000 to 200,000 per year in the United States. ACL reconstruction surgery is the standard treatment for this injury to restore knee joint stability and function. While surgical reconstruction has been shown to restore laxity of the knee, current literature lacks consensus on return to normal knee joint kinematics following surgery. Additionally, re-injury is a major risk for those who return to sports activity after reconstruction surgery. Dynamical systems methods for quantifying joint coordination variability have been explored as a method for detecting differences between ACL …

Effective Measures Of Weight Gain Five Years Post-Kidney Transplantation, Tara Calico Cherry

Theses and Dissertations (ETD)

BACKGROUND: Weight gain is commonly observed post-kidney transplantation and is associated with unfavorable health outcomes, such as graft loss, new onset diabetes, and cardiovascular disease. The purpose of this study was to determine the most effective measure for assessing body composition after kidney transplantation.

DESIGN: The study was a descriptive correlational follow-up study from a single kidney transplant site.

SUBJECTS: A total of 45 eligible patients from a 2007-2011 parent study were selected, ages of 37 to 78.

MEASUREMENTS: Body composition was obtained 5–8 years posttransplant via anthropometric measures (waist circumference, body mass index, and dual energy X-ray …

Failure Of Primary Total Knee Arthroplasty: Establishing A Baseline For Retrieval Analysis Using Well-Functioning Necropsy Specimens, Meredith Perkins

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee. While many patients have positive functional and pain outcomes following primary TKA, a subset of patients have suboptimal outcomes, such as unexplained pain or aseptic loosening of the implant components necessitating revision of the index procedure. The understanding of the exact etiology of these suboptimal outcomes of primary TKA is in its infancy. In order to elucidate the etiology of failure in primary TKAs, a baseline for the factors contributing to arthroplasty failure and dissatisfaction must first be established. The purpose of this study …

Retrieval Analysis Of Necropsy Total Hip Replacements: Considerations Beyond The Implant, Julie Alyse Lowell

Theses and Dissertations (ETD)

Introduction. Total hip arthroplasty (THA) surgery is one of the most commonly performed and successful orthopedic procedures in the United States. More than 300,000 primary THAs and 40,000 revision THAs performed in the United States every year. While the need for revision surgeries can stem from a variety of causes, there have been, to the author’s knowledge, no studies attempting to correlate the concentrations of certain inflammatory cytokines to metal ion concentrations found in the tissue surrounding the implant, amount of polyethylene wear, or strength of the interface of the modular taper. The purpose of this study was to begin …

Habituation And Dishabituation In The Olfactory Bulb: From Neural Responses To Behavior, Mary Cameron Ogg

Theses and Dissertations (ETD)

Habituation and dishabituation modulate the neural resources and behavioral significance allocated to incoming stimuli across the sensory systems. The purpose of the research presented in this dissertation was to characterize these processes in the mouse olfactory bulb (OB) and to determine if OB acetylcholine (ACh) has a role in physiological and behavioral olfactory dishabituation. Calcium imaging was used to determine the timecourse and magnitude of habituation in different parts of the OB during and after a prolonged odor presentation. Widefield imaging of the dendritic, or glomerular, response of OB output cells demonstrated that prolonged odor input habituates glomerular responses during …