Engineering Commons^™

Influence Of Material Properties On Granules Prepared By Dry Co-Rotating Twin Screw Extrusion And Counterrotating Batch Mixing, Afstathios Steve Pafiakis

Dissertations

Recently, the pharmaceutical industry has shown interest in continuous granulating technology because of the flexibility it offers as an option that bypasses the costly scale-up process associated with batch manufacturing. However, the granulation mechanism(s) using twin screw co-rotating hot melt extrusion (HME) has not been fully explored, and it is not yet well understood. This leads to costly experiments during development and process reliability problem in commercial manufacturing. The main objective of this dissertation is to increase the mechanistic understanding of the twin screw granulation process of systems containing an active pharmaceutical ingredient (API) and a polymer excipient. This is …

Hydrophobically Modified Isosorbide Dimethacrylates As Biomaterials For Bisphenol A Free Dental Fillings, Bilal Marie

Dissertations

Amalgam and Bisphenol A glycerolate dimethacrylate (BisGMA) are the main dental filling materials in use today. Because of the negative perception of amalgam and its lower esthetic appeal, as well as the desire to replace the endocrine disruptor Bisphenol A, which is the building block of BisGMA, there has been a critical need to search for safer alternatives to these dental filling materials.

Isosorbide is a sugar-based molecule generally recognized as safe. It has been extensively studied as a replacement to the Bisphenol A core in various materials. However, isosorbide is extremely hygroscopic, and water uptake in dental fillings causes …

Multi-Stage Stochastic Optimization And Reinforcement Learning For Forestry Epidemic And Covid-19 Control Planning, Sabah Bushaj

Dissertations

This dissertation focuses on developing new modeling and solution approaches based on multi-stage stochastic programming and reinforcement learning for tackling biological invasions in forests and human populations. Emerald Ash Borer (EAB) is the nemesis of ash trees. This research introduces a multi-stage stochastic mixed-integer programming model to assist forest agencies in managing emerald ash borer insects throughout the U.S. and maximize the public benets of preserving healthy ash trees. This work is then extended to present the first risk-averse multi-stage stochastic mixed-integer program in the invasive species management literature to account for extreme events. Significant computational achievements are obtained using …

Stochastic Programming And Agent-Based Simulation Approaches For Epidemics Control And Logistics Planning, Xuecheng Yin

Dissertations

This dissertation addresses the resource allocation challenges of fighting against infectious disease outbreaks. The goal of this dissertation is to formulate multi-stage stochastic programming and agent-based models to address the limitations of former literature in optimizing resource allocation for preventing and controlling epidemics and pandemics. In the first study, a multi-stage stochastic programming compartmental model is presented to integrate the uncertain disease progression and the logistics of resource allocation to control a highly contagious infectious disease. The proposed multi-stage stochastic program, which involves various disease growth scenarios, optimizes the distribution of treatment centers and resources while minimizing the total expected …

Towards Quality By Design (Qbd) Of Pharmaceutical Oral Films Loaded With Poorly Watersoluble Drugs, Eylul Cetindag

Dissertations

Oral films are an emerging drug delivery dosage form with numerous advantages such as ease of handling, the possibility to circumvent the first-pass metabolism, better patient compliance, capability for continuous manufacturing, and as a platform for personalized medicine. As films are different from other final dosages by their dimensions and their matrix form, further research is required to better understand the impact of excipient and drug on product performance to assure a consistent and good quality product. Therefore, this dissertation aims to contribute towards the processability and manufacturability of films by examining the impact of the materials and processes. First, …

Exploring Fused Deposition Modeling (Fdm) Three-Dimensional Printing Tablet Design Options For Pharmaceutical Dosage Forms, Guluzar Gorkem Buyukgoz

Dissertations

This dissertation examines the use of Fused Deposition Modeling (FDM) based three-dimensional (3D) printing approach for developing patient-specific dosage forms and addressing related technical challenges in such drug delivery systems. The first main objective is to explore pharmaceutical tablet design options using novel FDM 3D printing technology as the drug delivery platform such that drug form and tablet properties are tailored by considering patient age-specific formulations and dissolution control. Of the five different design options, two proposed options meet the main objective of providing similar drug release, whereas the popular option of fixed drug concentration but differing tablet size could …

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space …

Developmental And Sex Modulated Neurological Alterations In Autism Spectrum Disorder, Azeezat Azeez

Dissertations

Autism Spectrum Disorder (ASD) was first described in 1943 by Dr. Leo Kranner in a case study published in The Nervous Child. It is a neurodevelopment disorder, with a range of clinical symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), used by clinicians to diagnose mental disorders, a child needs to have persistent social deficits, language impairments, and repetitive behaviors, that cannot be explained by neurological damage or intellectual disability. It is known that children diagnosed with ASD are often are developmentally delayed therefore alterations in the typical developmental trajectory should be a major factor in …

Modelling In Vitro Dissolution And Release Of Sumatriptan Succinate From Polyvinylpyrrolidone-Based Microneedles Aided By Iontophoresis, James Paul Ronnander

Dissertations

A novel dissolving microneedle array system is developed to investigate permeation of a sumatriptan succinate formulations through the skin aided by iontophoresis. Three formulations consisting of hydrophilic, positively charged drug molecules encapsulated in a water-soluble biologically suitable polymer, polyvinylpyrrolidone (PVP), have been accepted by the U.S. Food and Drug Administration (FDA). The microneedle systems are fabricated with 600 pyramid-shaped needles, each 500 µm tall, on a 0.785-cm² circular array. In vitro transdermal studies with minipig skin and vertical Franz diffusion cells show > 68% permeation of sumatriptan over a 24-hour period. A combination of microneedle and electrical current density ranging …

Roles Of Surfactant And Binary Polymers On Dissolution Enhancement Of Bcs Ii Drugs From Nanocomposites And Amorphous Solid Dispersions, Md Mahbubur Rahman

Dissertations

Drug nanocomposites and amorphous solid dispersions (ASDs) are two major formulation platforms used for the bioavailability enhancement of BCS Class II drugs. The major drawback of nanocomposites is their inability to attain high drug supersaturation during in vitro (<50% relative supersaturation) and in vivo dissolution. On the other hand, formulating an amorphous solid dispersion (ASD) with high drug loading (>20%) that releases drug rapidly, while generating and maintaining high supersaturation over at least three hours is challenging. The goal of this thesis is to develop a fundamental understanding of the impact of anionic surfactants–polymers on in vitro drug release from nanocomposites and ASDs, while addressing the above challenges. To achieve this goal, the following objectives are set: (1) compare griseofulvin …

A Multimodal Approach To Investigate Brain Reorganization After Spinal Cord Injury Using Functional Magnetic Resonance Imaging And Functional Near-Infrared Spectroscopy, Keerthana Deepti Karunakaran

Dissertations

Traumatic Spinal Cord Injury (SCI) results in structural and functional neurological changes at both the brain and the level of the spinal cord. Anatomical studies indicate decreased grey matter volume in sensorimotor and non-sensorimotor regions of the cortex following SCI; whereas, neurophysiological findings mostly report altered functional activity in the sensorimotor nodes of the cortex, subcortex, and cerebellum. Therefore, it is currently unknown whether tissue atrophy observed in non-motor related areas has any concomitant functional consequences. Furthermore, the neural underpinnings of adaptive neuroplasticity after SCI is not well-defined in the current literature. Hence, this dissertation is a pioneer study investigating …

High-Performance Learning Systems Using Low-Precision Nanoscale Devices, Nandakumar Sasidharan Rajalekshmi

Dissertations

Brain-inspired computation promises a paradigm shift in information processing, both in terms of its parallel processing architecture and the ability to learn to tackle problems deemed unsolvable by traditional algorithmic approaches. The computational capability of the human brain is believed to stem from an interconnected network of 100 billion compute nodes (neurons) that interact with each other through approximately 10¹⁵ adjustable memory junctions (synapses). The conductance of synapses is modifiable allowing the network to learn and perform various cognitive functions. Artificial neural networks inspired by this architecture have demonstrated even super-human performance in many complex tasks.

Computational systems based …

Submandibular Mechanical Stimulation Of Upper Airway Muscles To Treat Obstructive Sleep Apnea, Ferhat Erdogan

Dissertations

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during …

Compressive Sensing Framework For Mass Spectrometry Data Analysis, Khalfalla Ahmad Kh. Awedat

Dissertations

Mass Spectrometry (MS) data is ideal for identifying unique bio-signatures of diseases. However, the high dimensionality of MS data hinders any promising MS-based proteomics development. The goal of this dissertation is to develop an accurate classification tool by employing compressive sensing (CS). Not only can CS significantly reduce MS data dimensionality, but it also will allow for full reconstruction of original data. The framework developed in this work is based on using L2 and a mixed L2-L1 norms, allowing an overdetermined system to be resolved. The results show that the L2- based algorithm with regularization terms has a better performance …

Effects Of Expected Service Life Exposures On The Functional Properties And Impact Performance Of An American Football Helmet Outer Shell Material, David E. Krzeminski

Dissertations

The purpose of this dissertation is to gain a greater scientific understanding of the changes in functional material properties and impact performance of an American football helmet outer shell material under expected service life exposures. The research goals are to (i) quantify chemical, physical, thermal, and mechanical degradation of an American football outer shell material under expected environmental conditions and (ii) develop a linear drop test impact protocol to employ expected on-field impact conditions to American football helmet components and a plaque-foam (i.e., shell-liner) surrogate. Overall, a step-wise progression of analysis was demonstrated to concurrently quantify and understand changes in …

Transient Cardiovascular Hemodynamics In A Patient-Specific Arterial System, Jr Rodward Hewlin

Dissertations

The ultimate goal of the present study is to aid in the development of tools to assist in the treatment of cardiovascular disease. Gaining an understanding of hemodynamic parameters for medical implants allow clinicians to have some patient-specific proposals for intervention planning. In the present study a full cardiovascular experimental phantom and digital phantom (CFD model) was fabricated to study: (1) the effects of local hemodynamics on global hemodynamics, (2) the effects of transition from bed-rest to upright position, and (3) transport of dye (drug delivery) in the arterial system. Computational three dimensional (3-D) models (designs A, B, and C) …

Fluorine Containing Uv-Curable Materials For Advanced Transport Applications, James Thomas Goetz

Dissertations

The characterization of structure, thermal, gas transport, and free volume properties of two unique UV cured polymeric systems are studied and reported. In the initial pursuit of waterproof high water vapor transport membranes, it became apparent that the UV curing of fluorinated materials yielded routes to develop unique materials that fundamentally challenge conventional models for free volume and light gas transport behavior. UV-curing provides a means to rapidly “lock-in” morphologies that are accessible in the small molecule, monomer phase but rapidly become kinetically inaccessible when constraints such as covalent bonding and cross linking limit motion in the polymer system. This …

Processing And Characterization Of Innovative Magnesium Alloys For Biodegradable Orthopaedic Implants, Christopher E. Smith

Dissertations

There is a need for innovation in medical implant devices through novel biomaterials that will improve the quality of life. The first step in the creation of a foundation of knowledge and technology to improve these implant devices is through the creation of new alloys with the capabilities of biodegradation and bioabsorption without a toxic effect that will pass through FDA regulatory procedures. In this study, unique heat treatment processing techniques coupled with innovation in elemental alloying produced distinctive magnesium (Mg) based alloy systems. The MgZnCa system was used as the underpinning system where four groups of novel alloys were …

Numerical And Experimental Investigation Of Orthopaedic Fracture Fixation, Bipinchandra Patel

Dissertations

Poor bone fracture fixation leads to malunion, delayed union, non-union, or infection. These malunited fractures affect a bone’s ability to carry loads. Patient outcomes regarding fixation quality can be affected by the healing environment and human factors such as bone quality and surgeons’ perception. Furthermore, the stiffness and strength of the screw-plate construct affect the healing environment. Therefore, this dissertation investigates the stiffness and strength of the non-locking (conventional) and locking (fixed angle) type screw-plate constructs and the factors that contribute to them, such as screw-plate interface, screw design, bone density, cortical bone thickness and load orientation. Additionally, the surgeon’s …

Effect Of Doping On Β-Tricalcium Phosphate Bioresorbable Bulk Material And Thin Film Coatings, Suhaila Abdalla

Dissertations

Magnesium has emerged as a revolutionary biodegradable metal for use as an orthopedic material, it has several advantages over the permanent metallic materials currently in use, including eliminating the effects of stress shielding, improving biocompatibility and degradation properties, thus removing the requirement of a second surgery for implant removal. Due to the rapid degradation of magnesium, it is necessary to control the corrosion rates of the materials to match the rates of bone healing. This dissertation reports on the effect of doping on the properties of β-tricalcium phosphate (β-TCP). It also reports on its application as a thin film coating …

Assessment Of Neck And Shoulder Muscle Coactivations And The Effect On The Musculoskeletal System, Regina Derria Pope-Ford

Dissertations

Musculoskeletal disorders (MSDs) constitute one of the most important occupational health issues in healthcare workers who are susceptible to upper extremity disorders. Yet MSDs in the healthcare professions have not been studied extensively beyond the lower back. The focus population for this research is the field of dentistry where neck and shoulder disorders have been documented to have a high prevalence. Though quantitative data has been collected, many prior studies have focused on self-reported information. The goal of this research is to provide insight into the inter-relationship of muscles in the upper extremities. One way to accomplish this is to …

A Mathematical Modeling Framework For Phlebotomist Scheduling And Blood Draw Assignments In Laboratory Medicine, Laquanda T. Leaven

Dissertations

Laboratory services in healthcare delivery systems play a vital role in inpatient care. Studies have shown that laboratory data affects approximately 65% of the most critical decisions on admission, discharge, and medication. Laboratory testing accounts for approximately 10% of hospital billing. Reducing laboratory costs would contribute to reducing total healthcare cost, which is one of the major goals for the U.S. healthcare delivery system. This research focuses on improving the performance of the hospital laboratory in a large hospital system. The intention of this study is to identify and then optimize the most critical stage to improve the entire laboratory …

A Study To Determine The Influence Of Workload On Nursing Personnel, Supreeta G. Amin

Dissertations

The alarming number of adverse medical events and associated costs have placed immense importance toward the safety and health of both patients and medical personnel. A shrinking nurse workforce, an aging patient and nursing population coupled with a mismatch between hospital demands and the available nursing staff have created a situation detrimental to both patient and nursing personnel. Long working hours, working more than one job, low staffing ratios, high patient acuity, minimal social support, low experience level, complicated equipment, complex procedures and varying workload are some factors that may have a negative impact on the quality of care provided …