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Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the

Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the cells of multicellular organisms which arises when the cell is subjected to an unusual amount of stress. Since this default phenotype is similar across cell types and even organisms, it seems it must be an evolutionarily ancestral phenotype. We take a phylostratigraphical approach, but systematically add species divergence time data to estimate gene ages numerically and use these ages to investigate the ages of genes involved in cancer. We find that ancient disease-recessive cancer genes are significantly enriched for DNA repair and SOS activity, which seems to imply that a core component of cancer development is not the regulation of growth, but the regulation of mutation. Verification of this finding could drastically improve cancer treatment and prevention.
ContributorsOrr, Adam James (Author) / Davies, Paul (Thesis director) / Bussey, Kimberly (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
Magnetic resonance imaging (MRI) data of metastatic brain cancer patients at the Barrow Neurological Institute sparked interest in the radiology department due to the possibility that tumor size distributions might mimic a power law or an exponential distribution. In order to consider the question regarding the growth trends of metastatic

Magnetic resonance imaging (MRI) data of metastatic brain cancer patients at the Barrow Neurological Institute sparked interest in the radiology department due to the possibility that tumor size distributions might mimic a power law or an exponential distribution. In order to consider the question regarding the growth trends of metastatic brain tumors, this thesis analyzes the volume measurements of the tumor sizes from the BNI data and attempts to explain such size distributions through mathematical models. More specifically, a basic stochastic cellular automaton model is used and has three-dimensional results that show similar size distributions of those of the BNI data. Results of the models are investigated using the likelihood ratio test suggesting that, when the tumor volumes are measured based on assuming tumor sphericity, the tumor size distributions significantly mimic the power law over an exponential distribution.
ContributorsFreed, Rebecca (Co-author) / Snopko, Morgan (Co-author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / WPC Graduate Programs (Contributor) / School of Accountancy (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Speech nasality disorders are characterized by abnormal resonance in the nasal cavity. Hypernasal speech is of particular interest, characterized by an inability to prevent improper nasalization of vowels, and poor articulation of plosive and fricative consonants, and can lead to negative communicative and social consequences. It can be associated with

Speech nasality disorders are characterized by abnormal resonance in the nasal cavity. Hypernasal speech is of particular interest, characterized by an inability to prevent improper nasalization of vowels, and poor articulation of plosive and fricative consonants, and can lead to negative communicative and social consequences. It can be associated with a range of conditions, including cleft lip or palate, velopharyngeal dysfunction (a physical or neurological defective closure of the soft palate that regulates resonance between the oral and nasal cavity), dysarthria, or hearing impairment, and can also be an early indicator of developing neurological disorders such as ALS. Hypernasality is typically scored perceptually by a Speech Language Pathologist (SLP). Misdiagnosis could lead to inadequate treatment plans and poor treatment outcomes for a patient. Also, for some applications, particularly screening for early neurological disorders, the use of an SLP is not practical. Hence this work demonstrates a data-driven approach to objective assessment of hypernasality, through the use of Goodness of Pronunciation features. These features capture the overall precision of articulation of speaker on a phoneme-by-phoneme basis, allowing demonstrated models to achieve a Pearson correlation coefficient of 0.88 on low-nasality speakers, the population of most interest for this sort of technique. These results are comparable to milestone methods in this domain.
ContributorsSaxon, Michael Stephen (Author) / Berisha, Visar (Thesis director) / McDaniel, Troy (Committee member) / Electrical Engineering Program (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
In this paper, I will show that news headlines of global events can predict changes in stock price by using Machine Learning and eight years of data from r/WorldNews, a popular forum on Reddit.com. My data is confined to the top 25 daily posts on the forum, and due to

In this paper, I will show that news headlines of global events can predict changes in stock price by using Machine Learning and eight years of data from r/WorldNews, a popular forum on Reddit.com. My data is confined to the top 25 daily posts on the forum, and due to the implicit filtering mechanism in the online community, these 25 posts are representative of the most popular news headlines and influential global events of the day. Hence, these posts shine a light on how large-scale social and political events affect the stock market. Using a Logistic Regression and a Naive Bayes classifier, I am able to predict with approximately 85% accuracy a binary change in stock price using term-feature vectors gathered from the news headlines. The accuracy, precision and recall results closely rival the best models in this field of research. In addition to the results, I will also describe the mathematical underpinnings of the two models; preceded by a general investigation of the intersection between the multiple academic disciplines related to this project. These range from social to computer science and from statistics to philosophy. The goal of this additional discussion is to further illustrate the interdisciplinary nature of the research and hopefully inspire a non-monolithic mindset when further investigations are pursued.
Created2016-12
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Description

Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT,

Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT, is an alternative to continuous ADT that improves the patient’s quality of life while testosterone levels recover between cycles. In this paper,we explore the response of intermittent ADT to metastasized prostate cancer by employing a previously clinical data validated mathematical model to new clinical data from patients undergoing Abiraterone therapy. This cell quota model, a system of ordinary differential equations constructed using Droop’s nutrient limiting theory, assumes the tumor comprises of castration-sensitive (CS) and castration-resistant (CR)cancer sub-populations. The two sub-populations rely on varying levels of intracellular androgen for growth, death and transformation. Due to the complexity of the model,we carry out sensitivity analyses to study the effect of certain parameters on their outputs, and to increase the identifiability of each patient’s unique parameter set. The model’s forecasting results show consistent accuracy for patients with sufficient data,which means the model could give useful information in practice, especially to decide whether an additional round of treatment would be effective.

ContributorsBennett, Justin Klark (Author) / Kuang, Yang (Thesis director) / Kostelich, Eric (Committee member) / Phan, Tin (Committee member) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into

Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.

ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description
In the age of information, collecting and processing large amounts of data is an integral part of running a business. From training artificial intelligence to driving decision making, the applications of data are far-reaching. However, it is difficult to process many types of data; namely, unstructured data. Unstructured data is

In the age of information, collecting and processing large amounts of data is an integral part of running a business. From training artificial intelligence to driving decision making, the applications of data are far-reaching. However, it is difficult to process many types of data; namely, unstructured data. Unstructured data is “information that either does not have a predefined data model or is not organized in a pre-defined manner” (Balducci & Marinova 2018). Such data are difficult to put into spreadsheets and relational databases due to their lack of numeric values and often come in the form of text fields written by the consumers (Wolff, R. 2020). The goal of this project is to help in the development of a machine learning model to aid CommonSpirit Health and ServiceNow, hence why this approach using unstructured data was selected. This paper provides a general overview of the process of unstructured data management and explores some existing implementations and their efficacy. It will then discuss our approach to converting unstructured cases into usable data that were used to develop an artificial intelligence model which is estimated to be worth $400,000 and save CommonSpirit Health $1,200,000 in organizational impact.
ContributorsBergsagel, Matteo (Author) / De Waard, Jan (Co-author) / Chavez-Echeagaray, Maria Elena (Thesis director) / Burns, Christopher (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Computer Science and Engineering Program (Contributor)
Created2022-05
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Description
The purpose of this thesis is to accurately simulate the surface brightness in various spectral emission lines of the HH 901 jets in the Mystic Mountain Formation of the Carina Nebula. To accomplish this goal, we gathered relevant spectral emission line data for [Fe II] 12660 Å, Hα 6563 Å,

The purpose of this thesis is to accurately simulate the surface brightness in various spectral emission lines of the HH 901 jets in the Mystic Mountain Formation of the Carina Nebula. To accomplish this goal, we gathered relevant spectral emission line data for [Fe II] 12660 Å, Hα 6563 Å, and [S II] 6720 Å to compare with Hubble Space Telescope observations of the HH 901 jets presented in Reiter et al. (2016). We derived the emissivities for these lines from the spectral synthesis code Cloudy by Ferland et al. (2017). In addition, we used WENO simulations of density, temperature, and radiative cooling to model the jet. We found that the computed surface brightness values agreed with most of the observational surface brightness values. Thus, the 3D cylindrically symmetric simulations of surface brightness using the WENO code and Cloudy spectral emission models are accurate for jets like HH 901. After detailing these agreements, we discuss the next steps for the project, like adding an external ambient wind and performing the simulations in full 3D.
ContributorsMohan, Arun (Author) / Gardner, Carl (Thesis director) / Jones, Jeremiah (Committee member) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05