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ABSTRACT Billions of dollars are spent annually on urine specimen collection and analysis as they are critical clinical components vital to human health. The mid-stream clean catch (MSCC) process is the gold standard of ambulatory urine specimen collection for clinical diagnosis of urinary tract infections (UTI).

ABSTRACT Billions of dollars are spent annually on urine specimen collection and analysis as they are critical clinical components vital to human health. The mid-stream clean catch (MSCC) process is the gold standard of ambulatory urine specimen collection for clinical diagnosis of urinary tract infections (UTI). The MSCC process is over 60 years old and is plagued by ridiculously high specimen contamination rates. The MSCC has resisted numerous attempts aimed at improving it. The purpose of this study was to determine if utilizing the concepts of Human Systems Engineering (HSE) could improve the urine specimen collection process. HSE concepts were not only targeted toward the problems, they were also used in the quest to develop effective solutions. Results obtained demonstrate that HSE concepts, when applied to urine specimen collection, can and do make a difference in terms of specimen quality and patient satisfaction. One low cost easily implemented targeted HSE-informed intervention effort resulted in a specimen contamination rate reduction of 16.6%. A second targeted HSE-informed intervention involving the redesign of the specimen cup, its instruction set, and additional sign placement made it three times less likely for participants to provide a contaminated MSCC sample. The redesigned specimen cup automatically captures and isolates an initial void sample from an MSCC sample, both derived from one continuously provided patient specimen. Clinical utility comes in the form of improved MSCC specimen quality and a separated initial void available for analysis using Nucleic Acid Amplification Testing (NAAT) or other test protocols. Capturing and isolating both an initial void and an MSCC at the same time allows for a more complete diagnostic workup utilizing a higher quality MSCC without requiring the patient to follow two different protocols to urinate into two different specimen cups. The redesigned specimen cup also provides for automatic overflow prevention, incorporates a new ergonomic grip, and a saddle adapter that provides affordances for both women and men in terms of urine capture and the reduced likelihood of urinating on one’s self.
ContributorsWallace, David (Author) / Gutzwiller, Robert S (Thesis advisor) / Branaghan, Russell J (Committee member) / Cooke, Nancy J (Committee member) / Hall, Rick (Committee member) / Arizona State University (Publisher)
Created2021
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Description
In classification applications, such as medical disease diagnosis, the cost of one type of error (false negative) could greatly outweigh the other (false positive) enabling the need of asymmetric error control. Due to this unique nature of the problem, traditional machine learning techniques, even with much improved accuracy, may not

In classification applications, such as medical disease diagnosis, the cost of one type of error (false negative) could greatly outweigh the other (false positive) enabling the need of asymmetric error control. Due to this unique nature of the problem, traditional machine learning techniques, even with much improved accuracy, may not be ideal as they do not provide a way to control the false negatives below a certain threshold. To address this need, a classification algorithm that can provide asymmetric error control is proposed. The theoretical foundation for this algorithm is based on Neyman-Pearson (NP) Lemma and it is complemented with sample splitting and order statistics to pick a threshold that enables an upper bound on the number of false negatives. Additionally, this classifier addresses the imbalance of the data, which is common in medical datasets, by using Hellinger distance as the splitting criterion. This eliminates the need of sampling methods, which add complexity and the need for parameter selection. This approach is used to create a novel tree-based classifier that enables asymmetric error control. Applications, such as prediction of the severity of cardiac arrhythmia, require classification over multiple classes. The NP oracle inequalities for binary classes are not immediately applicable for the multiclass NP classification, leading to a multi-step procedure proposed in this dissertation to extend the algorithm in the context of multiple classes. This classifier is used in predicting various forms of cardiac disease for both binary and multi-class classification problems with not only comparable accuracy metrics but also with full control over the number of false negatives. Moreover, this research allows us to pick the threshold for the classifier in a data adaptive way. This dissertation also shows that this methodology can be extended to non medical applications that require classification with asymmetric error control.
ContributorsBokhari, Wasif (Author) / Bansal, Ajay (Thesis advisor) / Zhang, Yu (Committee member) / Yang, Yezhou (Committee member) / Bahadur, Faisal (Committee member) / Arizona State University (Publisher)
Created2021
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Stroke occurs when the blood supply to part of the brain is interrupted or reduced, preventing brain tissue from getting oxygen and nutrients, thus causing brain cells to die. Stroke is the 5th leading cause of death in the United States and is one of the major causes of disability.

Stroke occurs when the blood supply to part of the brain is interrupted or reduced, preventing brain tissue from getting oxygen and nutrients, thus causing brain cells to die. Stroke is the 5th leading cause of death in the United States and is one of the major causes of disability. Conventional therapy is a form of stroke rehabilitation generally consisting of physical and occupational therapy. It focuses on customized exercises based on the patient’s feedback. Physical therapy includes exercises such as weight bearing (affected arm), vibration of affected muscle and gravity-eliminated movement of affected arm. Overall physical therapy aims at strengthening muscle groups and aides in the relearning process. Occupational aspect of conventional therapy includes activities of daily living (ADL) such as dressing, self-feeding, grooming and toileting. Overall occupational therapy focuses on improving the daily activities performed by individuals. In comparison to conventional therapy, robotic therapy is relatively newer therapy. It uses robotic devices to perform repetitive motions and delivers high dosage and high intensity training to stroke patients. Based on the research studies reviewed, it is known that neuroplasticity in stroke patients is linked to interventions which are high in dosage, intensity, repetition, difficulty, salience. Peer-reviewed literature suggests robotic therapy might be a viable option for recovery in stroke patients. However, the extent to which robotic therapy may provide greater benefits than conventional therapy remains unclear. This thesis addresses the key components of a study design for comparing the efficacy of robotic therapy relative to conventional therapy to improve upper limb sensorimotor function in stroke survivors. The study design is based on an extensive review of the literature of stroke clinical trials and robotic therapy studies, analyses of the capabilities of a robotic therapy device (M2, Fourier Intelligence), and pilot data collected on healthy controls to create a pipeline of tasks and analyses to extract biomarkers of sensorimotor functional changes. This work has laid the foundation for a pilot longitudinal study that will be conducted at the Barrow Neurological Institute, Phoenix, AZ, where conventional and robotic therapy will be compared in a small cohort of stroke survivors.
ContributorsThomas, Lovein (Author) / Santello, Marco (Thesis advisor) / Kleim, Jeffrey (Committee member) / Maruyama, Trent (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Interictal spikes - transient bursts of neuronal depolarization observed between epileptic seizures - are typically regarded as a sign of epilepsy and have been used in the localization of seizure onsets. Interictal spikes are thought to arise primarily from large excitatory postsynaptic potentials (EPSPs), although not much is known about

Interictal spikes - transient bursts of neuronal depolarization observed between epileptic seizures - are typically regarded as a sign of epilepsy and have been used in the localization of seizure onsets. Interictal spikes are thought to arise primarily from large excitatory postsynaptic potentials (EPSPs), although not much is known about the precise role they play in epilepsy. Here the in vivo spatiotemporal dynamics of sequences of interictal spikes in a small (4mm x 4mm) patch of the cortex of a patient with intractable epilepsy is studied. In conjunction with this, the impact on action potential generation and firing of local voltage changes due to paroxysmal depolarizations similar to interictal spikes was also evaluated in vitro using resected neural tissue from an epileptic human neocortex. Sequences of interictal spikes were found to consistently propagate in a direction-specific manner across the neocortex. In addition to this, bursts of action potentials from the ex vivo samples underwent variable degrees of depolarization-induced inactivation. Intracellular recordings in neocortical slices of human brain tissue confirmed that bursts of inactivated action potentials occurred during spontaneous paroxysmal depolarization shifts. These ex vivo findings showed inactivated action potentials being generated by large depolarizations. The results suggest the existence of an aberrantly strong synchronization among neuronal populations in the epileptic cortex, triggered or enhanced by interictal spike depolarization and propagation. This supports a key element in the hypothesis that interictal spikes, and the associated alteration of action potential firing patterns, may alter the electrical environment of the brain and contribute to the progression of the underlying idiopathic seizure disorder.
ContributorsFoli, Crispin (Author) / Greger, Bradley B. G. (Thesis advisor) / Tsakalis, Konstantinos K.T. (Committee member) / Muthuswamy, Jitendran J.M. (Committee member) / Arizona State University (Publisher)
Created2021
Description
Contaminated aerosols and micro droplets are easily generated by infected hosts through sneezing, coughing, speaking and breathing1-3 and harm humans’ health and the global economy. While most of the efforts are usually targeted towards protecting individuals from getting infected,4 eliminating transmissions from infection sources is also important to prevent disease

Contaminated aerosols and micro droplets are easily generated by infected hosts through sneezing, coughing, speaking and breathing1-3 and harm humans’ health and the global economy. While most of the efforts are usually targeted towards protecting individuals from getting infected,4 eliminating transmissions from infection sources is also important to prevent disease transmission. Supportive therapies for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pneumonia such as oxygen supplementation, nebulizers and non-invasive mechanical ventilation all carry an increased risk for viral transmission via aerosol to healthcare workers.5-9 In this work, I study the efficacy of five methods for self-containing aerosols emitted from infected subjects undergoing nebulization therapies with a diverse spectrum on Non-Invasive Positive Pressure Ventilator (NIPPV) with oxygen delivery therapies. The work includes five study cases: Case I: Use of a Full-Face Mask with biofilter in bilevel positive airway pressure device (BiPAP) therapy, Case II: Use of surgical mask in High Flow Nasal Cannula (HFNC) therapy, Case III: Use of a modified silicone disposable mask in a HFNC therapy, Case IV: Use of a modified silicone disposable mask with a regular nebulizer and normal breathing, Case V: Use of a mitigation box with biofilter in a BiPAP. We demonstrate that while cases I, III and IV showed efficacies of 98-100%; cases II and V, which are the most commonly used, resulted with significantly lower efficacies of 10-24% to mitigate the dispersion of nebulization aerosols. Therefore, implementing cases I, III and IV in health care facilities may help battle the contaminations and infections via aerosol transmission during a pandemic.
ContributorsShyamala Pandian, Adithya (Author) / Forzani, Erica (Thesis advisor) / Patel, Bhavesh (Committee member) / Xian, Xiaojun (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Magnetic resonance imaging (MRI) is a noninvasive imaging modality, which is used for many different applications. The versatility of MRI is in acquiring high resolution anatomical and functional images with no use of ionizing radiation. The contrast in MR images can be engineered by two different mechanisms with imaging parameters

Magnetic resonance imaging (MRI) is a noninvasive imaging modality, which is used for many different applications. The versatility of MRI is in acquiring high resolution anatomical and functional images with no use of ionizing radiation. The contrast in MR images can be engineered by two different mechanisms with imaging parameters (TR, TE, α) and/or contrast agents. The contrast in the former is influenced by the intrinsic properties of the tissue (T1, T2, ρ), while the contrast agents change the relaxation rate of the protons to enhance contrast. Contrast agents have attracted a lot of attention because they can be modified with targeting groups to shed light on some physiological and biological questions, such as the presence of hypoxia in a tissue. Hypoxia, defined as lack of oxygen, has many known ramifications on the outcome of therapy in any condition. Hence its study is very important. The standard gold method to detect hypoxia, immunohistochemical (IHC) staining of pimonidazole, is invasive; however, there are many research groups focused on developing new and mainly noninvasive methods to investigate hypoxia in different tissues.Previously, a novel nitroimidazole-based T1 contrast agent, gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI ), has been synthesized and characterized on subcutaneous prostate and lung tumor models. Here, its efficacy and performance on traumatic brain injuries and brain tumors are studied. The pharmacokinetic properties of the contrast agent the perfusion properties of brain tumors are investigated. These results can be used in personalized therapies for more effective results for patients. Gadolinium (Gd), which is a strongly paramagnetic heavy metal, is routinely and widely used as an MR contrast agent by chelation with a biocompatible ligand which is typically cleared through the kidneys. While widely used, there are serious concerns for patients with impaired kidney function, as well as recent studies showed Gd accumulation in the bone and brain. Iron as a physiological ion is also capable of generating contrast in MR images. Here synthesis and characterization of an iron-based hypoxia targeting contrast agent is proposed to eliminate Gd-related complications and provide a cheaper and more economical alternative contrast agent to detect hypoxia.
ContributorsMoghadas, Babak (Author) / Kodibagkar, Vikram D (Thesis advisor) / Beeman, Scott (Committee member) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Turner, Gregory (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Systematic Reviews (SRs) aim to synthesize the totality of evidence for clinical practice and are important in making clinical practice guidelines and health policy decisions. However, conducting SRs manually is a laborious and time-consuming process. This challenge is growing due to the increase in the number of databases to search

Systematic Reviews (SRs) aim to synthesize the totality of evidence for clinical practice and are important in making clinical practice guidelines and health policy decisions. However, conducting SRs manually is a laborious and time-consuming process. This challenge is growing due to the increase in the number of databases to search and the papers being published. Hence, the automation of SRs is an essential task. The goal of this thesis work is to develop Natural Language Processing (NLP)-based classifiers to automate the title and abstract-based screening for clinical SRs based on inclusion/exclusion criteria. In clinical SRs, a high-sensitivity system is a key requirement. Most existing methods for SRs use binary classification systems trained on labeled data to predict inclusion/exclusion. While previous studies have shown that NLP-based classification methods can automate title and abstract-based screening for SRs, methods for achieving high-sensitivity have not been empirically studied. In addition, the training strategy for binary classification has several limitations: (1) it ignores the inclusion/exclusion criteria, (2) lacks generalization ability, (3) suffers from low resource data, and (4) fails to achieve reasonable precision at high-sensitivity levels. This thesis work presents contributions to several aspects of the clinical systematic review domain. First, it presents an empirical study of NLP-based supervised text classification and high-sensitivity methods on datasets developed from six different SRs in the clinical domain. Second, this thesis work provides a novel approach to view SR as a Question Answering (QA) problem in order to overcome the limitations of the binary classification training strategy; and propose a more general abstract screening model for different SRs. Finally, this work provides a new QA-based dataset for six different SRs which is made available to the community.
ContributorsParmar, Mihir Prafullsinh (Author) / Baral, Chitta (Thesis advisor) / Devarakonda, Murthy (Thesis advisor) / Riaz, Irbaz B (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Motor skill learning is important to rehabilitation, sports, and many occupations. When attempting to learn or adapt a motor skill, some individuals learn slower or less compared to others despite the same amount of motor practice. This dissertation aims to understand the factors that contributed to such variability in motor

Motor skill learning is important to rehabilitation, sports, and many occupations. When attempting to learn or adapt a motor skill, some individuals learn slower or less compared to others despite the same amount of motor practice. This dissertation aims to understand the factors that contributed to such variability in motor learning, and thereby identify viable methods to enhance motor learning. Behavioral evidence from our lab showed that visuospatial ability is positively related to the extent of motor learning. Neuroimaging studies suggest that motor learning and visuospatial processes share common frontoparietal neural structures, and that this visuospatial-motor relationship may be more pronounced in the right hemisphere compared to the left. Thus, the overall objective of this dissertation is to determine if aspects of motor learning (such as the rate and extent of skill acquisition) may be modifiable through neuromodulation of the right frontoparietal network. In Aim 1, anodal transcranial direct current stimulation (tDCS) was used to test whether modulating the right parietal area affects visuospatial ability and motor skill acquisition. A randomized, three-arm design was used, which added a no-tDCS control group to the double-blinded sham-control protocol to address placebo effects. No tDCS treatment effect was observed, likely due to low statistical power to detect any treatment effects as the study is still ongoing. However, the current results revealed a unique finding that the placebo effect of tDCS was stronger than its treatment effect on motor learning, with implications that tDCS and motor studies should measure and control for placebo effects. In Aim 2, right frontoparietal connectivity during resting-state EEG was estimated via alpha band imaginary coherence to test whether it correlated with visuospatial performance and motor skill acquisition. As a preliminary step towards leveraging the frontoparietal network for EEG-neurofeedback applications, this work found that alpha imaginary coherence was positively correlated with visuospatial function, but not with motor skill acquisition during a limited dose of motor practice (only 5 trials). This work establishes a premise for developing frontoparietal alpha IC-based neurofeedback for cognitive training in rehabilitation, while warranting future studies to test the relationship between alpha IC and motor learning with a more extensive motor training regimen.
ContributorsWang, Peiyuan (Author) / Schaefer, Sydney Y (Thesis advisor) / Buneo, Christopher A (Committee member) / Abbas, James (Committee member) / Lohse, Keith R (Committee member) / Wyckoff, Sarah N (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique that offers a unique ability to provide the spatial distribution of relevant biochemical compounds (metabolites). The ‘spectrum’ of information provided by MRSI is used as biomarkers for the differential diagnosis of several diseases such as cancer or neurological disorders. Treatment responsive

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique that offers a unique ability to provide the spatial distribution of relevant biochemical compounds (metabolites). The ‘spectrum’ of information provided by MRSI is used as biomarkers for the differential diagnosis of several diseases such as cancer or neurological disorders. Treatment responsive brain tumors can appear similar to non-responsive tumors on conventional anatomical MR images, earlier in the therapy, leading to a poor prognosis for many patients. Biomarkers such as lactate are particularly of interest in the oncological studies of solid tumors to determine their energy metabolism, blood flow, and hypoxia. Despite the capability of nearly all clinical MRI scanners to perform MRSI only limited integration of MRSI into routine clinical studies has occurred to date. The major challenges affecting its true potential are the inherently long acquisition time, low signal-to-noise (SNR) of the signals, overlapping of spectral lines, or the presence of artifacts. The goal of this dissertation work is to facilitate MRSI in routine clinical studies without affecting the current patient throughput. In this work, the Compressed Sensing (CS) strategy was used to accelerate conventional Point RESolved Spectroscopy (PRESS) MRSI by sampling well below the Shannon-Nyquist limit. Two undersampling strategies, namely the pseudo-random variable density and a novel a priori method was developed and implemented on a clinical scanner. Prospectively undersampled MRSI data was acquired from patients with various brain-related concerns. Spatial-spectral post-processing and CS reconstruction pipeline was developed for multi-channel undersampled data. The fidelity of the CS-MRSI method was determined by comparing the CS reconstructed data to the fully sampled data. Statistical results showed that the a priori approach maintained high spectral fidelity compared to the fully sampled reference for an 80% reduction in scan time. Next, an improvement to the CS-MRSI reconstruction was achieved by incorporating coil sensitivity maps as support in the iterative process. Further, a CS-MRSI-based fast lactate spectroscopic imaging method was developed and implemented to achieve complete water and fat suppression for accurate spatial localization and quantification of lactate in tumors. In vitro phantoms were developed, and the sequence was tested to determine the efficacy of CS-MRSI for low SNR signals, the efficacy of the CS acceleration was determined with statistical analysis.
ContributorsBikkamane Jayadev, Nutandev (Author) / Kodibagkar, Vikram (Thesis advisor) / Chang, John (Committee member) / Robison, Ryan (Committee member) / Smith, Barbara (Committee member) / Sohn, Sung-Min (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Point-of-Care diagnostics is one of the most popular fields of research in bio-medicine today because of its portability, speed of response, convenience and quality assurance. One of the most important steps in such a device is to prepare and purify the sample by extracting the nucleic acids, for which small

Point-of-Care diagnostics is one of the most popular fields of research in bio-medicine today because of its portability, speed of response, convenience and quality assurance. One of the most important steps in such a device is to prepare and purify the sample by extracting the nucleic acids, for which small spherical magnetic particles called magnetic beads are often used in laboratories. Even though magnetic beads have the ability to isolate DNA or RNA from bio-samples in their purified form, integrating these into a microfluidic point-of-need testing kit is still a bit of a challenge. In this thesis, the possibility of integrating paramagnetic beads instead of silica-coated dynabeads, has been evaluated with respect to a point-of-need SARS-CoV-2 virus testing kit. This project is a comparative study between five different sizes of carboxyl-coated paramagnetic beads with reference to silica-coated dynabeads, and how each of them behave in a microcapillary chip in presence of magnetic fields of different strengths. The diameters and velocities of the beads have been calculated using different types of microscopic imaging techniques. The washing and elution steps of an extraction process have been recreated using syringe pump, microcapillary channels and permanent magnets, based on which those parameters of the beads have been studied which are essential for extraction behaviour. The yield efficiency of the beads have also been analysed by using these to extract Salmon DNA. Overall, furthering this research will improve the sensitivity and specificity for any low-cost nucleic-acid based point-of-care testing device.
ContributorsBiswas, Shilpita (Author) / Christen, Jennifer B (Thesis advisor) / Ozev, Sule (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2021