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Can Startle Elicit Sequential Movements in Highly Trained Individuals?

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Most daily living tasks consist of pairing a series of sequential movements, e.g., reaching to a cup, grabbing the cup, lifting and returning the cup to your mouth. The process by which we control and mediate the smooth progression of

Most daily living tasks consist of pairing a series of sequential movements, e.g., reaching to a cup, grabbing the cup, lifting and returning the cup to your mouth. The process by which we control and mediate the smooth progression of these tasks is not well understood. One method which we can use to further evaluate these motions is known as Startle Evoked Movements (SEM). SEM is an established technique to probe the motor learning and planning processes by detecting muscle activation of the sternocleidomastoid muscles of the neck prior to 120ms after a startling stimulus is presented. If activation of these muscles was detected following a stimulus in the 120ms window, the movement is classified as Startle+ whereas if no sternocleidomastoid activation is detected after a stimulus in the allotted time the movement is considered Startle-. For a movement to be considered SEM, the activation of movements for Startle+ trials must be faster than the activation of Startle- trials. The objective of this study was to evaluate the effect that expertise has on sequential movements as well as determining if startle can distinguish when the consolidation of actions, known as chunking, has occurred. We hypothesized that SEM could distinguish words that were solidified or chunked. Specifically, SEM would be present when expert typists were asked to type a common word but not during uncommon letter combinations. The results from this study indicated that the only word that was susceptible to SEM, where Startle+ trials were initiated faster than Startle-, was an uncommon task "HET" while the common words "AND" and "THE" were not. Additionally, the evaluation of the differences between each keystroke for common and uncommon words showed that Startle was unable to distinguish differences in motor chunking between Startle+ and Startle- trials. Explanations into why these results were observed could be related to hand dominance in expert typists. No proper research has been conducted to evaluate the susceptibility of the non-dominant hand's fingers to SEM, and the results of future studies into this as well as the results from this study can impact our understanding of sequential movements.

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2018-05

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Characterization and Optimization of Ion-Sensitive Field Effect Transistors for Rapid Personalized Diagnostics

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The growth of the medical diagnostic industry in the past several decades has largely been due to the creation and iterative optimization of bio sensors. Recent pushes towards value added as well as preventative health care has made point of

The growth of the medical diagnostic industry in the past several decades has largely been due to the creation and iterative optimization of bio sensors. Recent pushes towards value added as well as preventative health care has made point of care devices more attractive to health care providers. Rapid detection for diseases and cancers is done with a bio sensor, which a broad term used to describe an instrument which uses a bio chemical reaction to detect a chemical compound with the use of a bio recognition event in addition to a signal detection event. The bio sensors which are presented in this work are known as ion-sensitive field effects transistors (ISFETs) and are similar in function to a metal oxide field effect transistor (MOSFET). These ISFETs can be used to sense pH or the concentration of protons on the surface of the gate channel. These ISFETs can be used for certain bio recognition events and this work presents the application of these transistors for the quantification of tumor cell proliferation. This includes the development of a signal processing and acquisition system for the long term assessment of cellular metabolism and optimizing the system for use in an incubator. This thesis presents work done towards the optimization and implementation of complementary metal\u2014oxide\u2014semiconductor (CMOS) ISFETs as well as remote gate ISFETs for the continuous assessment of tumor cell extracellular pH. The work addresses the challenges faced with the fabrication and optimization of these sensors, which includes the mitigation of current drift with the use of pulse width modulation in addition to issues encountered with fabrication of electrodes on a quartz substrate. This work culminates in the testing of an autonomous system with mammary tumor cells as well as the assessment of cell viability in an incubator over extended periods. Future applications of this work include the creation of a remote gate ISFET array for multiplexed detection as well as the implementation of ISFETs for bio marker detection via an immunoassay.

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2017-05

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Startle can evoke individuated movements of the fingers; implications for neural control

Description

Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that

Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that hand movements are susceptible to SEM. Interestingly, only coordinated movements of the hand (grasp) but not individuated movements of the finger (finger abduction) were susceptible. It was suggested that this resulted from different neural mechanisms involved in each task; however it is possible this was the result of task familiarity. The objective of this study was to evaluate a more familiar individuated finger movement, typing, to determine if this task was susceptible to SEM. We hypothesized that typing movements will be susceptible to SEM in all fingers. These results indicate that individuated movements of the fingers are susceptible to SEM when the task involves a more familiar task, since the electromyogram (EMG) latency is faster in SCM+ trials compared to SCM- trials. However, the middle finger does not show a difference in terms of the keystroke voltage signal, suggesting the middle finger is less susceptible to SEM. Given that SEM is thought to be mediated by the brainstem, specifically the reticulospinal tract, this suggest that the brainstem may play a role in movements of the distal limb when those movements are very familiar, and the independence of each finger might also have a significant on the effect of SEM. Further research includes understanding SEM in fingers in the stroke population. The implications of this research can impact the way upper extremity rehabilitation is delivered.

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2016-12

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Utilization of Nanoparticles for Identifying Fibrin Deposition in Neural Tissue

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The main objective of this research is to develop and characterize a targeted contrast agent that will recognize acute neural injury pathology (i.e. fibrin) after traumatic brain injury (TBI). Single chain fragment variable antibodies (scFv) that bind specifically to fibrin

The main objective of this research is to develop and characterize a targeted contrast agent that will recognize acute neural injury pathology (i.e. fibrin) after traumatic brain injury (TBI). Single chain fragment variable antibodies (scFv) that bind specifically to fibrin have been produced and purified. DSPE-PEG micelles have been produced and the scFv has been conjugated to the surface of the micelles; this nanoparticle system will be used to overcome limitations in diagnosing TBI. The binding and imaging properties will be analyzed in the future to determine functionality of the nanoparticle system in vivo.

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2014-05

DEVELOPMENT OF A BIOSENSOR FOR RAPID DIAGNOSIS OF NAVAJO NEUROHEPATOPATHY

Description

MPV17-related hepatocerebral mitochondrial DNA depletion syndrome, previously known as Navajo Neurohepatopathy (NNH), is a rare genetic disease affecting Navajo children of the American Southwest. These children can suffer from several severe symptoms like brain damage and liver disease, and a

MPV17-related hepatocerebral mitochondrial DNA depletion syndrome, previously known as Navajo Neurohepatopathy (NNH), is a rare genetic disease affecting Navajo children of the American Southwest. These children can suffer from several severe symptoms like brain damage and liver disease, and a diagnosis leads to death by age 10, on average. The only known effective therapy for NNH is a liver transplant. Currently, the disease is diagnosed through a lengthy and expensive process of gene sequencing, but oftentimes patients with the most severe forms of NNH deteriorate quickly; thus a rapid diagnostic would be beneficial to beginning the transplant process as early as possible. Here, Tentacle Probes, a novel technology to detect genetic mutations, were proposed to rapidly and accurately diagnose NNH. Because of Tentacle Probes' double binding site kinetics, they can detect mutations more accurately than other types of genetic probes. Probes specific to the NNH mutation were designed for use with a real-time polymerase chain reaction (PCR) detection platform. Initial synthetic DNA testing of Tentacle Trobes showed capable differentiation between mutated and non-mutated samples. However, experiments to validate those results at Phoenix Children's Hospital before moving to patient samples showed that test viability decreased over time. Efforts to diagnose the issues that led to decreased viability suggested four possible explanations that are as follows (in order of decreasing likelihood): first, undesired products from improper PCR primer design was supported by double bands in DNA gel electrophoresis; second, DNA may have degraded over time or due to repeated cycles of freezing and thawing stock solutions, and this was supported by smeared DNA gel electrophoresis; third, probe degradation, specifically of the fluorescent reporter, is possible; finally, contaminants that inhibit the PCR reaction may have been introduced. A combination of these factors may also have caused the change in assay viability. As a result of these most likely possibilities, new primers were designed and steps suggested to return viability to the assay. Thus, the various limitations and requirements for this Tentacle Probe diagnostic have been identified, and as assay development continues following the promising initial results achieved, we are confident that a rapid method if diagnosing NNH is on its way to help the children afflicted with this devastating disease receive timely access to treatment.

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Date Created
2016-05

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Markov Chain Monte Carlo (MCMC) Modelling of Diagnostics for Pandemic Planning Using JAGS Package in R

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Markov Chain Monte-Carlo methods are a Bayesian approach to predictive statistics, which takes advantage of prior beliefs and conditions as well as the existing data to produce posterior distributions of relevant parameters. This approach, implementable through the JAGS packaging in

Markov Chain Monte-Carlo methods are a Bayesian approach to predictive statistics, which takes advantage of prior beliefs and conditions as well as the existing data to produce posterior distributions of relevant parameters. This approach, implementable through the JAGS packaging in R, is promising for its impact on the diagnostics space, which is a critical bottleneck for pandemic planning and rapid response. Specifically, these methods provide the means to optimize diagnostic testing, for example, by determining whether it is best to test individuals in a certain locale once or multiple times. This study compares the expected accuracy of single and double testing under two specific conditions, a general and Icelandic test case, in order to ascertain the validity of MCMC methods in this space and inform decisionmakers and future research in the space. Models based on this platform may eventually be tailored to the priors of specific locales. Additionally, the ability to test multiple regimes of real or simulated data while maintaining uncertainty widens the pool of researchers that can impact the space. In future studies, ensemble methods investigating the full range of parameters and their combinations can be studied.

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2020-05

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Startle-evoked movement in multi-jointed, two-dimensional reaching tasks

Description

Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown

Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed with difficulty. While the presence of SEM in the stroke survivor population advances scientific understanding of movement capabilities following a stroke, published studies using the SEM phenomenon only examined one joint. The ability of SEM to generate multi-jointed movements is understudied and consequently limits SEM as a potential therapy tool. In order to apply SEM as a therapy tool however, the biomechanics of the arm in multi-jointed movement planning and execution must be better understood. Thus, the objective of our study was to evaluate if SEM could elicit multi-joint reaching movements that were accurate in an unrestrained, two-dimensional workspace. Data was collected from ten subjects with no previous neck, arm, or brain injury. Each subject performed a reaching task to five Targets that were equally spaced in a semi-circle to create a two-dimensional workspace. The subject reached to each Target following a sequence of two non-startling acoustic stimuli cues: "Get Ready" and "Go". A loud acoustic stimuli was randomly substituted for the "Go" cue. We hypothesized that SEM is accessible and accurate for unrestricted multi-jointed reaching tasks in a functional workspace and is therefore independent of movement direction. Our results found that SEM is possible in all five Target directions. The probability of evoking SEM and the movement kinematics (i.e. total movement time, linear deviation, average velocity) to each Target are not statistically different. Thus, we conclude that SEM is possible in a functional workspace and is not dependent on where arm stability is maximized. Moreover, coordinated preparation and storage of a multi-jointed movement is indeed possible.

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2016-12

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The Making of a COVID Testing Laboratory: Deconstructing the Saliva Sample Collection Process and Preanalytical Standardization

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This thesis project is the result of close collaboration with the Arizona State University Biodesign Clinical Testing Laboratory (ABCTL) to document the characteristics of saliva as a test sample, preanalytical considerations, and how the ABCTL utilized saliva testing to develo

This thesis project is the result of close collaboration with the Arizona State University Biodesign Clinical Testing Laboratory (ABCTL) to document the characteristics of saliva as a test sample, preanalytical considerations, and how the ABCTL utilized saliva testing to develop swift COVID-19 diagnostic tests for the Arizona community. As of April 2021, there have been over 130 million recorded cases of COVID-19 globally, with the United States taking the lead with approximately 31.5 million cases. Developing highly accurate and timely diagnostics has been an important need of our country that the ABCTL has had tremendous success in delivering. Near the start of the pandemic, the ABCTL utilized saliva as a testing sample rather than nasopharyngeal (NP) swabs that were limited in supply, required highly trained medical personnel, and were generally uncomfortable for participants. Results from literature across the globe showed how saliva performed just as well as the NP swabs (the golden standard) while being an easier test to collect and analyze. Going forward, the ABCTL will continue to develop high quality diagnostic tools and adapt to the ever-evolving needs our communities face regarding the COVID-19 pandemic.

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2021-05