Purpose: Due to the neurological aspects of Parkinson’s Disease (PD) and the sensitivity of eye movements to neurological issues, eye tracking has the potential to be an objective biomarker with higher accuracy in diagnosis than current clinical standards. Currently when PD is diagnosed clinically, there is an accuracy of 74% when diagnosed by a general practitioner and 82% when diagnosed by a movement disorder specialist. This study was designed to: 1. Assess eye movements as a potential biomarker for Parkinson’s Disease. 2. Determine if eye movements can distinguish between Parkinson’s Disease and commonly confounded movement disorders with parkinsonian symptoms. 3. Determine if the eye movements of Rapid Eye Movement Behavior Disorder (RBD) patients who will likely convert to PD are distinguishable from healthy controls and if RBD patients have eye movements with similar features to PD. Methods: The eye movements of 160 subjects (43 healthy controls, 63 PD, 31 REM Behavior Disorder, and 22 Other Parkinsonisms) were recorded at 500 Hz and analyzed. Each subject performed five eye tracking tasks that included reflexive saccades, inhibition of reflexive saccades, predictive saccades, and reading. Based on an analysis of selected eye movement measurement parameters, a multivariable logistic regression model was developed that compared: PD vs. Control, PD vs. “Other”, PD vs RBD, and Control vs RBD. The resulting predictive model was then assessed for accuracy, sensitivity, and specificity. Results: After screening, the most statistically significant predictors that were included in the final multivariate model were: Site, Sex, Age, Age squared, UPDRS Score, mean absolute fixation velocity (Horizontal Step Task), saccadic duration, average saccadic velocity, and mean fixation velocity (Predictive Task). The model predicted with an accuracy of: 92% for Controls, 88% for PD, 86% for RBD, and 68% for Other Parkinsonisms. The model was best at distinguishing between PD and Other Parkinsomisms with an accuracy of 89% and RBD and Controls with an accuracy of 88%. Conclusion: This research found that specific combinations of eye tracking parameters from simple tasks can be used to distinguish between PD and commonly confounded movement disorders with parkinsonism symptoms. The model’s ability to distinguish between groups indicates that in a confirmatory study we should have relatively high accuracy in discriminating between groups. This model is able to accurately distinguish Controls from RBDs, however due to an insufficient number of follow-up visits to date, the current study is unable to confirm if the RBDs tested will convert to PD. With such high error rates in diagnosing PD clinically, this model is a potentially beneficial and could serve as an easy screening tool to add to the suite of diagnostic tests and improve clinician’s ability to diagnose accurately.

Skin cancer is a prevalent disease that globally affects 2-3 million people per year [1]. This number is expected to grow tenfold as depletion of the ozone layer contributes to harsher rays reaching Earth’s surface [2]. A common way to protect against those ultraviolet waves is to apply sunscreen, however, recent reports call into question the safety of some active ingredients as they can enter through the skin into the bloodstream [3]. This thesis aims to investigate an alternative solution that uses bovine sphingomyelin (BSM) as photoprotective solution against UV irradiation. In order to evaluate the effectiveness of BSM against UV radiation, p21 intensity was measured on a monolayer of keratinocytes, as the intensity directly correlates to cell damage. Additionally, fluorescent sphingomyelin (FSM) was added as a treatment because it was created to be an analog to BSM and allowed for visualization of sphingomyelin within the cell. Differences in p21 intensities were observed with BSM and FSM showing a reduced p21 intensity compared to the no sphingomyelin case. FSM helped locate sphingomyelin within the cell and a mechanism was proposed for how it reduces cell damage. Lastly, high variation was seen between experimental designs. Further measures were needed to reduce this intra-subject standard deviation, so additional experimental parameters were tested such as min/max intensity values, cell count, and nucleus circularity to explain this variation.

A well documented laboratory setup, leech preparation process, and bio-potential data recording process are needed. Repeatability and quality data recordings are essential and thus dictate the requirements of the laboratory setup and processes listed above. Advances in technology have both helped and hindered this development. While very precise equipment is required to record the low voltage bio-potentials, noisy electronic equipment and wires surrounding the work area provide high levels of interference. Proper laboratory setup and data recording processes, however, limit the unwanted interference. Quality data can only be recorded from a properly handled and prepared leech subject. Proper setup and procedures result in quality recordings which lend a clean signal for furthering the understanding of nerve functionality. The electrophysiology lab at California Polytechnic State University in San Luis Obispo is an example of a proven lab setup for high quality signal capture.

A greater understanding of bone materials would be beneficial in creating more accurate computer models and in the making of biomedical products involving bone. This study set out to determine whether cortical and trabecular bone are two separate materials, or whether they are the same material with a variance in porosity. To answer this question, samples were taken from different sections of the equine metacarpus, underwent densitometry analysis and were statistically analyzed. The majority of results suggest that the material is the same between varying densities of bone and thus the same between cortical and trabecular bone. These particular results are consistent with current standard practices. However, in several instances specifically regarding high porosity trabecular bone, a variance in density was found likely indicating a combination of differences in both material and architecture. Further studies should be done with specific focus on material variances to high porosity trabecular bone to improve the accuracy of computer models and general knowledge.

A new detection reagent that could possibly augment or replace antibodies research and diagnosis methods are aptamers. Aptamers are ssDNA, RNA or polypeptide constructs that function like active antibodies. Antibodies and aptamers both specifically bind to selected target molecules, and as such they enable the detection or targeting of the presence or absence of a specific antigen. In order to ensure that ssDNA aptamers perform similarly to antibodies, anti-VEGF-A polyclonal antibody and anti-VEGF-A ssDNA aptamer were evaluated against vascular endothelial growth factor A (VEGF-A) using Surface Plasmon Resonance (SPR). It was hypothesized that the anti-VEGF-A aptamer had the same, if not better, binding kinetics than the anti-VEGF-A polyclonal antibody, and as such offers an ideal replacement for use in in field, real-time testing assays. SPR revealed that both the polyclonal antibody and ssDNA aptamer bound the target antigen, VEGF-A. Additionally, from the SPR kinetic analysis, the anti-VEGF-A aptamer had KD values of 20-28 nM and the anti-VEGF-A antibody had KD values of 16-127 uM. The binding efficacy of the aptamer was several orders of magnitude better than that of the antibody. The aptamer was also stable in solution for a longer amount of time than the antibody, which denatured in solution after two weeks.

Impedance spectroscopy (IS) is an important tool for cell detection and characterization in medical and food safety applications. In this thesis, the Cal Poly Biofluidics Lab’s impedance spectroscopy system was re-evaluated and optimized for single-cell impedance spectroscopy. To evaluate the IS system, an impedance spectroscopy bioMEMS chip was fabricated in the Cal Poly Microfabcrication lab, software was developed to run IS experiments, and studies were run to validate the system. To explore IS optimization, Maxwell’s mixture theorem and the Schwartz-Christoffel transform were used to calculate an analytic impedance solution to the co-planar electrode system,a novel volume fraction to account for the non-uniformity of the electric field was developed to increase the accuracy of the analytic solution and to investigate the effect of cell position on the impedance spectrum, a software program was created to allow easy access to the analytic solution, and FEA models were developed to compare to the analytic solution and to investigate the effect of complex device geometry.

Transfemoral amputees around the world experience increased difficulty in climbing stairs due to lack of muscle, balance, and other factors. The loss of a lower limb greatly diminishes the amount of natural force generation provided that is necessary to propel oneself up stairs. This study investigated possible solutions to the problem of stair ascension for transfemoral amputees by the means of designing and developing an externally attachable device to a prosthesis. The number of amputations from military service has greatly increased since 2008, which shows there is a clear need for assistive devices (Wenke, Krueger, & Ficke, 2012). With the number of amputations rising and no current externally attachable products on the market to aid in stair ascension for transfemoral amputees, the need for this specific device has become more prominent. Research, previous work, and preliminary testing provided a basis for design and development of a new prototype. Bench top testing was conducted to review concepts in the prototype and provide data for further modifications. Results from testing of previous work, as well as testing of new concepts and modifications, provided a framework for designing a new externally attachable device for assistance in stair ascension. A new prototype was then designed, manufactured, and tested with bench models as well as real-time testing with amputees. Success of the device’s performance was based on bench top results and feedback from amputees, noting both the advantages and shortcomings of the new prototype. Testing provided results and feedback that the device was well built and functioned properly, but did not perform satisfactorily, particularly in the categories of force generation and balance.

The purpose of this research is to determine if it is possible to validate the new 1D method for measuring pulse wave velocity in the aorta in vivo and estimate compliance. Arterial pressure and blood flow characterize the traveling of blood from the heart to the arterial system and have played a significant role in the evaluation of cardiovascular diseases. Blood vessel distensibility can give some information on the evolution of cardiovascular disease. A patient’s aorta cannot be explanted to measure compliance; therefore we are using a flow phantom model to validate the 1D pulse wave velocity technique to estimate compliance.

As implantable medical devices are being used more often to treat medical problems for which pharmaceuticals don’t suffice, it is important to understand their interactions with commonly used medical modalities. The interactions between medical implants and Magnetic Resonance Imaging machines have proven to be a risk for patients with implants. Implanted medical devices with elongated metallic components can create harmful levels of local heating in a Magnetic Resonance Imaging (MRI) environment [1]. The heating of a biological medium under MRI is monitored via the Specific Absorption Rate (SAR). SAR, defined as power absorbed per unit mass (W/kg), can be calculated as , where σ is electrical conductivity of the medium in units of , |E| is the magnitude of the applied electric field in units of , and ρ is the density of the medium in units of . For continuous, uniform power deposition this can be measured experimentally as a rise in temperature over time (∆T/t), where c is the specific heat capacity of the medium in units of. To understand the SAR induced in-vivo, a phantom (Figure 2.10) is used to conduct in-vitro experiments, as it provides a controllable and repeatable experimental setup. In order to experiment in the phantom, an understanding of the background SAR distribution and in turn the exposure field distribution of the phantom is required as per the ASTMF2182-09 standard [2]. In this work, the background SAR distribution of an ASTM standard torso phantom is measured and studied via fiber optic thermometry. The measurements are compared with an electromagnetic model simulated via FDTD, demonstrating agreement between 10-25%. A custom exposure and data collection setup (including oscilloscope, function generator, RF amplifier, directional coupler, and Neoptix Omniflex Fiber Optic Thermometry system) was integrated and automated using NI LabView. The purpose of this thesis is to map the field distribution in a torso phantom under RF exposure from a 64 MHz MRI RF Birdcage, compare the results to an electromagnetic simulation, and finally conclude the accuracy of this method for field measurements in a standard torso phantom. Understanding the capabilities and accuracy of the fiber optic thermometry method will ultimately allow researchers to successfully apply this method to monitor background fields in their respective experimental setups (related to MRI implant heating) and understand its limitations.

The purpose of this study is to further quantify adult ovine ovariectomized bone for new remodeling characteristics to obtain a better understanding of how remodeling is occurring and the effectiveness of this animal model for the study of postmenopausal osteoporosis. Postmenopausal osteoporosis is a major health concern and animal models to test new treatment options are needed. The ovine model is a good option because the ewes undergo Haversian remodeling, are a large sized animal, and have a similar hormone profile to humans. Ewes, however, do not undergo a natural menopause, so an ovariectomy surgery was conducted in the sheep to simulate the decreased levels in estrogen. Columbia-Rambouillet sheep were used in this study: some that have been ovariectomized as a model for postmenopausal osteoporosis and some that underwent a sham surgery to serve as a control. The sheep were sacrificed 12 months post operatively in the month of August, so the seasonal effects of remodeling were accounted for. The left radius was then processed into microradiographs of 6 regional cortical beams, where the cranial (tensile side) and caudal (compressive side) anatomical sections were analyzed in this study to determine regional differences in remodeling. Previous students’ theses have analyzed the similar samples for basic bone remodeling histology measurements, resulting in some significant seasonal, anatomical, and treatment differences. However, most of the results showed no particular increase in the amount of remodeled area for the ovariectomized sheep compared to the sham sheep, even though an ovariectomy is believed to cause a burst of remodeling in bone due to the decreased levels in estrogen. In this study, a new repeatable method was developed that further examines secondary bone by quantifying the extent to which secondary osteons encroach on previously-existing secondary osteons. Encroached and unencroached secondary osteons were quantified using two different methods: a point count method that measured the percentage of the area the encroached and unencroached secondary osteons inhabited and an osteon count method that measured the number of encroached and unencroached secondary osteons per area. These raw measurements were calculated into 18 parameters and 2-way repeated measures ANOVAs were run to determine the effects of surgery and anatomical region on each of the bone remodeling parameters. The results found significant effects from estrogen deletion which were different depending on if the bone region was predominately in compression or tension. The ovariectomy surgery caused an increase in remodeling, which was mostly confined on the compressive side to areas that have been previously remodeled, but on the tensile side, bone remodeling expanded into areas that used to be primary bone. The new secondary osteons, as a result of the ovariectomy surgery, were larger than in the control animals. There however, was not an increase in porosity from the ovariectomy surgery, which is one of the main characteristics of osteoporosis. The model could be further studied to determine what sheep are doing that prevents them from losing bone and that knowledge could be greatly beneficial for human treatment plans of postmenopausal osteoporosis.