Doctor of Philosophy

dissertationThe primary objective of cancer registries is to capture clinical care data of cancer populations and aid in prevention, allow early detection, determine prognosis, and assess quality of various treatments and interventions. Furthermore, the role of cancer registries is paramount in supporting cancer epidemiological studies and medical research. Existing cancer registries depend mostly on humans, known as Cancer Tumor Registrars (CTRs), to conduct manual abstraction of the electronic health records to find reportable cancer cases and extract other data elements required for regulatory reporting. This is often a time-consuming and laborious task prone to human error affecting quality, completeness and timeliness of cancer registries. Central state cancer registries take responsibility for consolidating data received from multiple sources for each cancer case and to assign the most accurate information. The Utah Cancer Registry (UCR) at the University of Utah, for instance, leads and oversees more than 70 cancer treatment facilities in the state of Utah to collect data for each diagnosed cancer case and consolidate multiple sources of information.Although software tools helping with the manual abstraction process exist, they mainly focus on cancer case findings based on pathology reports and do not support automatic extraction of other data elements such as TNM cancer stage information, an important prognostic factor required before initiating clinical treatment. In this study, I present novel applications of natural language processing (NLP) and machine learning (ML) to automatically extract clinical and pathological TNM stage information from unconsolidated clinical records of cancer patients available at the central Utah Cancer Registry. To further support CTRs in their manual efforts, I demonstrate a new approach based on machine learning to consolidate TNM stages from multiple records at the patient level

Deep Learning in Cardiology

The medical field is creating large amount of data that physicians are unable to decipher and use efficiently. Moreover, rule-based expert systems are inefficient in solving complicated medical tasks or for creating insights using big data. Deep learning has emerged as a more accurate and effective technology in a wide range of medical problems such as diagnosis, prediction and intervention. Deep learning is a representation learning method that consists of layers that transform the data non-linearly, thus, revealing hierarchical relationships and structures. In this review we survey deep learning application papers that use structured data, signal and imaging modalities from cardiology. We discuss the advantages and limitations of applying deep learning in cardiology that also apply in medicine in general, while proposing certain directions as the most viable for clinical use.Comment: 27 pages, 2 figures, 10 table

Adverse Drug Event Detection, Causality Inference, Patient Communication and Translational Research

Adverse drug events (ADEs) are injuries resulting from a medical intervention related to a drug. ADEs are responsible for nearly 20% of all the adverse events that occur in hospitalized patients. ADEs have been shown to increase the cost of health care and the length of stays in hospital. Therefore, detecting and preventing ADEs for pharmacovigilance is an important task that can improve the quality of health care and reduce the cost in a hospital setting. In this dissertation, we focus on the development of ADEtector, a system that identifies ADEs and medication information from electronic medical records and the FDA Adverse Event Reporting System reports. The ADEtector system employs novel natural language processing approaches for ADE detection and provides a user interface to display ADE information. The ADEtector employs machine learning techniques to automatically processes the narrative text and identify the adverse event (AE) and medication entities that appear in that narrative text. The system will analyze the entities recognized to infer the causal relation that exists between AEs and medications by automating the elements of Naranjo score using knowledge and rule based approaches. The Naranjo Adverse Drug Reaction Probability Scale is a validated tool for finding the causality of a drug induced adverse event or ADE. The scale calculates the likelihood of an adverse event related to drugs based on a list of weighted questions. The ADEtector also presents the user with evidence for ADEs by extracting figures that contain ADE related information from biomedical literature. A brief summary is generated for each of the figures that are extracted to help users better comprehend the figure. This will further enhance the user experience in understanding the ADE information better. The ADEtector also helps patients better understand the narrative text by recognizing complex medical jargon and abbreviations that appear in the text and providing definitions and explanations for them from external knowledge resources. This system could help clinicians and researchers in discovering novel ADEs and drug relations and also hypothesize new research questions within the ADE domain

Exploration and adaptation of large language models for specialized domains

Large language models have transformed the field of natural language processing (NLP). Their improved performance on various NLP benchmarks makes them a promising tool—also for the application in specialized domains. Such domains are characterized by highly trained professionals with particular domain expertise. Since these experts are rare, improving the efficiency of their work with automated systems is especially desirable. However, domain-specific text resources hold various challenges for NLP systems. These challenges include distinct language, noisy and scarce data, and a high level of variation. Further, specialized domains present an increased need for transparent systems since they are often applied in high stakes settings. In this dissertation, we examine whether large language models (LLMs) can overcome some of these challenges and propose methods to effectively adapt them to domain-specific requirements. We first investigate the inner workings and abilities of LLMs and show how they can fill the gaps that are present in previous NLP algorithms for specialized domains. To this end, we explore the sources of errors produced by earlier systems to identify which of them can be addressed by using LLMs. Following this, we take a closer look at how information is processed within Transformer-based LLMs to better understand their capabilities. We find that their layers encode different dimensions of the input text. Here, the contextual vector representation, and the general language knowledge learned during pre-training are especially beneficial for solving complex and multi-step tasks common in specialized domains. Following this exploration, we propose solutions for further adapting LLMs to the requirements of domain-specific tasks. We focus on the clinical domain, which incorporates many typical challenges found in specialized domains. We show how to improve generalization by integrating different domain-specific resources into our models. We further analyze the behavior of the produced models and propose a behavioral testing framework that can serve as a tool for communication with domain experts. Finally, we present an approach for incorporating the benefits of LLMs while fulfilling requirements such as interpretability and modularity. The presented solutions show improvements in performance on benchmark datasets and in manually conducted analyses with medical professionals. Our work provides both new insights into the inner workings of pre-trained language models as well as multiple adaptation methods showing that LLMs can be an effective tool for NLP in specialized domains

OCD as a Dynamical Disease and the Familial Context of Ritual Rigidity: A Nonlinear Dynamics Perspective

Comparatively few studies of obsessive compulsive disorder (OCD) have addressed the interpersonal dynamical patterns within families that could exacerbate or quell symptom severity in the ill relatives or hypothesize other roles for familial variables. Furthermore, the extant studies have relied primarily upon linear models. Methodological limitations of linear models, such as assuming that change occurs as the result of unidirectional influences and that the scores obtained for each variable are independent of each other are at variance with temporal, dynamic phenomena and have restricted the empirical investigations of the dynamics of OCD. The current study investigated whether OCD could be considered a dynamical disease such that the complex rhythmic processes that are the norm for living things would be replaced by relatively constant dynamics or by periodic dynamics. Determining whether OCD could be a dynamical disease could improve our current treatment strategies or lead to the development of new treatment strategies, by finding ways to best control or alter the dynamics of the family system and determining when the best time for change could take place. To accomplish this, this study analyzed both the occurrence of rituals as they transpired over time and the influence the family may have had upon the spatiotemporal structure of symptoms. This information was obtained by using the time-diary method and comparing the time-series of 17 clinical cases with 16 matched controls. Comparisons of nonlinear regression parameters and Lyapunov exponents revealed that OCD exhibited a low-dimensional deterministic structure. The average nonlinear model (R2 = 0.32) explained more than 10 times the variance of its linear counterpart (R2 = 0.03). Family reactions and emotional responses accounted for only a very modest increase in the variance explained by the nonlinear regression model or in the amount of turbulence. Family reactions and emotional responses do little to make the rituals go away, but instead may strengthen the dynamics. Finally, significant rank order correlations were found between the R2 for each logbook and Lyapunov exponents with symptom severity and family reactions. Theoretical and practical implications of the results are discussed, including implications for treatment

Effects of Diversity and Neuropsychological Performance in an NFL Cohort

Objective: The aim of this study was to examine the effect of ethnicity on neuropsychological test performance by comparing scores of white and black former NFL athletes on each subtest of the WMS. Participants and Methods: Data was derived from a de-identified database in South Florida consisting of 63 former NFL white (n=28, 44.4%) and black (n=35, 55.6%) athletes (Mage= 50.38; SD= 11.57). Participants completed the following subtests of the WMS: Logical Memory I and II, Verbal Paired Associates I and II, and Visual Reproduction I and II. Results: A One-Way ANOVA yielded significant effect between ethnicity and performance on several subtests from the WMS-IV. Black athletes had significantly lower scores compared to white athletes on Logical Memory II: F(1,61) = 4.667, p= .035, Verbal Paired Associates I: F(1,61) = 4.536, p = .037, Verbal Paired Associates: II F(1,61) = 4.677, p = .034, and Visual Reproduction I: F(1,61) = 6.562, p = .013. Conclusions: Results suggest significant differences exist between white and black athletes on neuropsychological test performance, necessitating the need for proper normative samples for each ethnic group. It is possible the differences found can be explained by the psychometric properties of the assessment and possibility of a non-representative sample for minorities, or simply individual differences. Previous literature has found white individuals to outperform African-Americans on verbal and non-verbal cognitive tasks after controlling for socioeconomic and other demographic variables (Manly & Jacobs, 2002). This highlights the need for future investigators to identify cultural factors and evaluate how ethnicity specifically plays a role on neuropsychological test performance. Notably, differences between ethnic groups can have significant implications when evaluating a sample of former athletes for cognitive impairment, as these results suggest retired NFL minorities may be more impaired compared to retired NFL white athletes

Distinguishing Performance on Tests of Executive Functions Between Those with Depression and Anxiety

Objective: To see if there are differences in executive functions between those diagnosed with Major Depressive Disorder (MDD) and those with Generalized Anxiety Disorder (GAD).Participants and Methods: The data were chosen from a de-identified database at a neuropsychological clinic in South Florida. The sample used was adults diagnosed with MDD (n=75) and GAD (n=71) and who had taken the Halstead Category Test, Trail Making Test, Stroop Test, and the Wisconsin Card Sorting Test. Age (M=32.97, SD=11.75), gender (56.7% female), and race (52.7% White) did not differ between groups. IQ did not differ but education did (MDD=13.41 years, SD=2.45; GAD=15.11 years, SD=2.40), so it was ran as a covariate in the analyses. Six ANCOVAs were run separately with diagnosis being held as the fixed factor and executive function test scores held as dependent variables. Results: The MDD group only performed worse on the Category Test than the GAD group ([1,132]=4.022, p\u3c .05). Even though both WCST scores used were significantly different between the two groups, both analyses failed Levene’s test of Equality of Error Variances, so the data were not interpreted. Conclusions: Due to previous findings that those diagnosed with MDD perform worse on tests of executive function than normal controls (Veiel, 1997), this study wanted to compare executive function performance between those diagnosed with MDD and those with another common psychological disorder. The fact that these two groups only differed on the Category Test shows that there may not be much of a difference in executive function deficits between those with MDD and GAD. That being said, not being able to interpret the scores on the WCST test due to a lack of homogeneity of variance indicates that a larger sample size is needed to compare these two types of patients, as significant differences may be found. The results of this specific study, however, could mean that the Category Test could be used in assisting the diagnosis of a MDD patient

The Effect of Ethnicity on Neuropsychological Test Performance of Former NFL Athletes

Objective: To investigate the effect of ethnicity on neuropsychological test performance by specifically exploring differences between white and black former NFL athletes on subtests of the WAIS-IV. Participants and Methods: Data was derived from a de-identified database in Florida consisting of 63 former NFL athletes (Mage=50.38; SD=11.57); 28 white and 35 black. Participants completed the following subtests of the WAIS-IV: Block Design, Similarities, Digit Span, Matrix Reasoning, Arithmetic, Symbol Search, Visual Puzzles, Coding, and Cancellation. Results: One-Way ANOVA yielded a significant effect between ethnicity and performance on several subtests. Black athletes had significantly lower scaled scores than white athletes on Block Design F(1,61)=14.266, p\u3c.001, Similarities F(1,61)=5.904, p=.018, Digit Span F(1,61)=8.985, p=.004, Arithmetic F(1,61)=16.07, p\u3c.001 and Visual Puzzles F(1,61)=16.682, p\u3c .001. No effect of ethnicity was seen on performance of Matrix Reasoning F(1,61)=2.937, p=.092, Symbol Search F(1,61)=3.619, p=.062, Coding F(1,61)=3.032, p=.087 or Cancellation F(1,61)=2.289, p=.136. Conclusions: Results reveal significant differences between white and black athletes on all subtests of the WAIS-IV but those from the Processing Speed Scale and Matrix Reasoning. These findings align with previous literature that found white individuals to outperform African-Americans on verbal and non-verbal tasks after controlling for socioeconomic and demographic variables (Manly & Jacobs, 2002). These differences may also be a reflection of the WAIS-IV’s psychometric properties and it is significant to consider the normative sample used may not be appropriate for African-Americans. This study highlights the need for future research to identify how ethnicity specifically influences performance, sheds light on the importance of considering cultural factors when interpreting test results, and serves as a call to action to further understand how and why minorities may not be accurately represented in neuropsychological testing