Medicine and Health Sciences Commons^™

Advanced Microstructural Characterization Of Functionally Graded Dental Ceramic Material For Materials-Informed Finishing, Angani Vigneswaran

Theses and Dissertations--Manufacturing Systems Engineering

Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) has gained popularity as the choice of material for dental prosthetics. Ivoclar Vivadent’s IPS e.max ZirCAD Prime dental ceramic incorporates a unique gradient technology that varies the yttria content over the thickness of the material. The top layer is composed of 5Y-TZP which is desired for its optical properties while the bottom layer is composed of a much stronger 3Y-TZP. In between the two layers, 5Y-TZP and 3Y-TZP are mixed to form a transition layer. Varying the amount of yttria allows for more esthetically pleasing translucency in the visible areas of the restoration without compromising …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Towards A Holistic Risk Model For Safeguarding The Pharmaceutical Supply Chain: Capturing The Human-Induced Risk To Drug Quality, Heather R. Campbell

Theses and Dissertations--Pharmacy

Counterfeit, adulterated, and misbranded medicines in the pharmaceutical supply chain (PSC) are a critical problem. Regulators charged with safeguarding the supply chain are facing shrinking resources for inspections while concurrently facing increasing demands posed by new drug products being manufactured at more sites in the US and abroad. To mitigate risk, the University of Kentucky (UK) Central Pharmacy Drug Quality Study (DQS) tests injectable drugs dispensed within the UK hospital. Using FT-NIR spectrometry coupled with machine learning techniques the team identifies and flags potentially contaminated drugs for further testing and possible removal from the pharmacy. Teams like the DQS are …

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

Atv Dynamics And Pediatric Rider Safety, James T. Auxier Ii

Theses and Dissertations--Biomedical Engineering

It has been observed through numerous academic and governmental agency studies that pediatric all-terrain vehicle ridership carries significant risk of injury and death. While no doubt valuable to safety, the post-hoc approach employed in these studies does little to explain the why and how behind the risk factors. Furthermore, there has been no prolonged, widespread, organized, and concerted effort to reconstruct and catalog the details and causes of the large (20,000+) number of ATV-related injuries that occur each year as has been done for road-based motor vehicle accidents. This dissertation takes the opposite approach from a meta-analysis and instead examines …

Tolerance Intervals For Time Series Models And Specifying Trimming/Winsorizing Cutoffs, Kedai Cheng

Theses and Dissertations--Statistics

Confidence intervals are used to capture a parameter of interest, usually a mean or a quantile, at a specified confidence level. Prediction intervals are another practical interval that aim at making sound predictions of future values with some confidence. Although these are useful inference tools, neither of them gives people a plausible range of the sampled population. Tolerance intervals are such an inference tool that captures a specified proportion of the sampled population at a predetermined confidence level. In this dissertation, tolerance intervals for an autoregressive process with order p are constructed. In addition, a method of utilizing tolerance interval …

Knee Joint Loading Following Anterior Cruciate Ligament Reconstruction: Link To Patient Reported Outcomes And A Novel Method To Monitor With Wearable Sensors, Alex Spencer

Theses and Dissertations--Kinesiology and Health Promotion

Recovery from anterior cruciate ligament reconstruction (ACLR) commonly results in undesirable physical and patient-reported outcomes (PROs). Identification of modifiable factors such as knee contact force (KCF) early in rehabilitation that can improve these outcomes is important due to the rapid decrease in function, quality of life, and joint health in this population. Additionally, if noninvasive measurement of KCFs outside of a traditional laboratory were possible, clinicians could optimize patient treatment with personalized care. Therefore, there are two primary aims to this thesis: 1) quantify the link between KCF and PROs which measure pain, ability to perform activities of daily living, …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

A Brain-Computer Interface For Closed-Loop Sensory Stimulation During Motor Training In Patients With Tetraplegia, Sarah Helen Thomas

Theses and Dissertations--Biomedical Engineering

Normal movement execution requires proper coupling of motor and sensory activation. An increasing body of literature supports the idea that incorporation of sensory stimulation into motor rehabilitation practices increases its effectiveness. Paired associative stimulation (PAS) studies, in which afferent and efferent pathways are activated in tandem, have brought attention to the importance of well-timed stimulation rather than non-associative (i.e., open-loop) activation. In patients with tetraplegia resulting from spinal cord injury (SCI), varying degrees of upper limb function may remain and could be harnessed for rehabilitation. Incorporating associative sensory stimulation coupled with self-paced motor training would be a means for supplementing …

Calibrated Short Tr Recovery Mri For Rapid Measurement Of Brain-Blood Partition Coefficient And Correction Of Quantitative Cerebral Blood Flow, Scott William Thalman

Theses and Dissertations--Biomedical Engineering

The high prevalence and mortality of cerebrovascular disease has led to the development of several methods to measure cerebral blood flow (CBF) in vivo. One of these, arterial spin labeling (ASL), is a quantitative magnetic resonance imaging (MRI) technique with the advantage that it is completely non-invasive. The quantification of CBF using ASL requires correction for a tissue specific parameter called the brain-blood partition coefficient (BBPC). Despite regional and inter-subject variability in BBPC, the current recommended implementation of ASL uses a constant assumed value of 0.9 mL/g for all regions of the brain, all subjects, and even all species.

The …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Improving Safety Performance Of Highway Maintenance Crews Through Pre-Task Safety Toolbox Talks, Zamaan Al-Shabbani

Theses and Dissertations--Civil Engineering

The dangerous work environment in the construction industry and the inherent high risks associated with construction work make it the focus of safety training and regulations. Highway construction and maintenance has unique hazards but seemingly less directly applicable safety standards, regulations, and programs. Department of Transportation (DOT) employees working in highway maintenance are exposed to a variety of unique hazards specifically associated with their work and not relating to the adjacent traffic. Yet, highway construction and maintenance work has not received sufficient attention in terms of safety research and programs. The lack of safety training and education in highway construction …

Connecting The Pieces: How Low Back Pain Alters Lower Extremity Biomechanics And Shock Attenuation In Active Individuals, Alexa Johnson

Theses and Dissertations--Rehabilitation Sciences

Low back pain in collegiate athletes has been reported at a rate of 37% from a wide array of sports including soccer, volleyball, football, swimming, and baseball. Whereas, in a military population the prevalence of low back pain is 70% higher than the general population. Compensatory movement strategies are often used as an attempt to reduce pain. Though compensatory movement strategies may effectively reduce pain, they are often associated with altered lower extremity loading patterns. Those who suffer from chronic low back pain tend to walk and run slower and with less trunk and pelvis coordination and variability. Individuals with …

Adrenergic Stimulation In Acute Hyperglycemia: Effects On Cellular And Tissue Level Murine Cardiac Electrophysiology, Sridevi Thyagarajan

Theses and Dissertations--Biomedical Engineering

Cardiovascular complications associated with elevated levels of glucose in the blood (Hyperglycemia, HG) is a growing health concern. HG is known to be associated with a variety of cardiovascular morbidities including higher incidence of electrical disturbances. Although effects of chronic HG have been widely investigated, electrophysiological effects of acute hyperglycemia are relatively less known. Further, hyperglycemic effects on adrenergic response is not widely investigated. We used excised ventricular tissues from mice to record trans-membrane potentials during a variety of pacing protocols to investigate cellular/tissue level electrophysiological effects of acute hyperglycemia and adrenergic stimulation (1µM Isoproterenol, a β-adrenergic agonist). A custom …

Interactive Clinical Event Pattern Mining And Visualization Using Insurance Claims Data, Zhenhui Piao

Theses and Dissertations--Computer Science

With exponential growth on a daily basis, there is potentially valuable information hidden in complex electronic medical records (EMR) systems. In this thesis, several efficient data mining algorithms were explored to discover hidden knowledge in insurance claims data. The first aim was to cluster three levels of information overload(IO) groups among chronic rheumatic disease (CRD) patient groups based on their clinical events extracted from insurance claims data. The second aim was to discover hidden patterns using three renowned pattern mining algorithms: Apriori, frequent pattern growth(FP-Growth), and sequential pattern discovery using equivalence classes(SPADE). The SPADE algorithm was found to be the …

Multimodal Noncontact Diffuse Optical Reflectance Imaging Of Blood Flow And Fluorescence Contrasts, Daniel Irwin

Theses and Dissertations--Biomedical Engineering

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

Understanding The Thermodynamics And Oral Absorption Potential Of Pharmaceutical Amorphous Solid Dispersions, Nico Setiawan

Theses and Dissertations--Pharmacy

Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such …

Design And Analysis Of A 3d-Printed, Thermoplastic Elastomer (Tpe) Spring Element For Use In Corrective Hand Orthotics, Kevin Thomas Richardson

Theses and Dissertations--Mechanical Engineering

This thesis proposes an algorithm that determine the geometry of 3D-printed, custom-designed spring element bands made of thermoplastic elastomer (TPE) for use in a wearable orthotic device to aid in the physical therapy of a human hand exhibiting spasticity after stroke. Each finger of the hand is modeled as a mechanical system consisting of a triple-rod pendulum with nonlinear stiffness at each joint and forces applied at the attachment point of each flexor muscle. The system is assumed quasi-static, which leads to a torque balance between the flexor tendons in the hand, joint stiffness and the design force applied to …

Design And Analysis Of Curcumin Conjugated Poly(Beta-Amino Ester) Networks For Controlled Release In Oxidative Stress Environments, Carolyn T. Jordan

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress, the imbalance of free radical generation with antioxidant defenses, leads to cellular inflammation, apoptosis and cell death. This compromised environment results in debilitating diseases, such as oral mucositis (OM), atherosclerosis, and ischemia/reperfusion injury. Antioxidant therapeutics has been a proposed strategy to ameliorate these imbalances and maintain homeostatic environments. However, the success of these approaches, specifically curcumin, has been limited due to characteristics such as hydrophobicity and high reactivity when released as bolus doses to contest to oxidative stress induced diseases. The development of a controlled release system to aid in protection of the antioxidant capacity of curcumin, as …

Investigation Of Environmental Cadmium Sources In Eastern Kentucky, Elizabeth Maher

Theses and Dissertations--Mining Engineering

Utilizing data collected by the University of Kentucky Lung Cancer Research Initiative (LCRI), this study investigated potential mining-related sources for the elevated levels of cadmium in Harlan and Letcher counties. Statistical analyses for this study were conducted utilizing SAS. A number of linear regression models and logarithmic models were used to evaluate the significance of the data. The linear regression models consisted of both simple and multivariate types, with the simple models seeking to establish significance between the potential sources and urine cadmium levels and the multivariate models seeking both to identify any statistically significant linear relationships between source types …

Mammogram And Tomosynthesis Classification Using Convolutional Neural Networks, Xiaofei Zhang

Theses and Dissertations--Computer Science

Mammography is the most widely used method of screening for breast cancer. Traditional mammography produces two-dimensional X-ray images, while advanced tomosynthesis mammography produces reconstructed three-dimensional images. Due to high variability in tumor size and shape, and the low signal-to-noise ratio inherent to mammography, manual classification yields a significant number of false positives, thereby contributing to an unnecessarily large number of biopsies performed to reduce the risk of misdiagnosis. Achieving high diagnostic accuracy requires expertise acquired over many years of experience as a radiologist.

The convolutional neural network (CNN) is a popular deep-learning construct used in image classification. The convolutional process …

Age-Related Differences In The Lumbopelvic Kinematics During The Trunk Motions In The Anatomical Planes, Milad Vazirian

Theses and Dissertations--Biomedical Engineering

Management and control of the low back pain as an important health problem in the industrial societies necessitates to investigate how the risk of this disease is affected by aging. Since the abnormalities of the lumbopelvic kinematics are related to the existence or risk of low back injuries, the objective of this dissertation was set to find the age-related differences in lumbopelvic kinematics when performing basic trunk motions reaching to range of motion in different anatomical planes.

A cross-sectional study was designed where sixty asymptomatic individuals between 20–70 years old with no confounding health condition, no current or previous highly …

Validation, Optimization, And Image Processing Of Spiral Cine Dense Magnetic Resonance Imaging For The Quantification Of Left And Right Ventricular Mechanics, Gregory J. Wehner

Theses and Dissertations--Biomedical Engineering

Recent evidence suggests that cardiac mechanics (e.g. cardiac strains) are better measures of heart function compared to common clinical metrics like ejection fraction. However, commonly-used parameters of cardiac mechanics remain limited to just a few measurements averaged over the whole left ventricle. We hypothesized that recent advances in cardiac magnetic resonance imaging (MRI) could be extended to provide measures of cardiac mechanics throughout the left and right ventricles (LV and RV, respectively).

Displacement Encoding with Stimulated Echoes (DENSE) is a cardiac MRI technique that has been validated for measuring LV mechanics at a magnetic field strength of 1.5 T but …

Properties And Optimization Of Respiratory Navigator Gating For Spiral Cine Dense Cardiac Mri, Sean Michael Hamlet

Theses and Dissertations--Electrical and Computer Engineering

Cardiac magnetic resonance (MR) imaging can non-invasively assess heart function. Displacement encoding with stimulated echoes (DENSE) is an advanced cardiac MR imaging technique that measures tissue displacement and can be used to quantify cardiac mechanics (e.g. strain and torsion). When combined with clinical risk factors, cardiac mechanics have been shown to be better predictors of mortality than traditional measures of heart function.

End-expiratory breath-holds are typically used to minimize respiratory motion artifacts. Unfortunately, requiring subjects to breath-hold introduces limitations with the duration of image acquisition and quality of data acquired, especially in patients with limited ability to hold their breath. …

Biventricular Finite Element Modeling And Quantification Of 3d Langragian Strains And Torsion Using Dense Mri, Zhanqiu Liu

Theses and Dissertations--Mechanical Engineering

Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Development And Application Of Gadolinium Free Cardiac Magnetic Resonance Fibrosis Imaging For Multiscale Study Of Heart Failure In Patients With End Stage Renal Disease, Tori A. Stromp

Theses and Dissertations--Physiology

Cardiac magnetic resonance (CMR) is a powerful tool to noninvasively image ventricular fibrosis. Late gadolinium enhancement (LGE) CMR identifies focal and, with T1 mapping, diffuse fibrosis. Despite prevalent cardiac fibrosis and heart failure, patients with end stage renal disease (ESRD) are excluded from LGE. Absence of a suitable diagnostic has limited the understanding of heart failure and obstructed development of therapies in the setting of ESRD. A quantitative, gadolinium free fibrosis detection method could overcome this critical barrier, propelling the advancement of diagnostic, monitoring, and therapy options. This project describes the development of a gadolinium free CMR technique and application …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemo-Radiation Therapy Outcomes, Lixin Dong

Theses and Dissertations--Biomedical Engineering

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis …

Surface Functionalized Magnetic Nanoparticles For Cancer Therapy Applications, Robert J. Wydra

Theses and Dissertations--Chemical and Materials Engineering

Despite recent advances, cancer remains the second leading cause of deaths in the United States. Magnetic nanoparticles have found various applications in cancer research as drug delivery platforms, enhanced contrast agents for improved diagnostic imaging, and the delivery of thermal energy as standalone therapy. Iron oxide nanoparticles absorb the energy from an alternating magnetic field and convert it into heat through Brownian and Neel relaxations. To better utilize magnetic nanoparticles for cancer therapy, surface functionalization is essential for such factors as decreasing cytotoxicity of healthy tissue, extending circulation time, specific targeting of cancer cells, and manage the controlled delivery of …