Medicine and Health Sciences Commons^™

Humanizing Affordable Housing: A Public Health Centered Approach To Affordable Housing, Eiman Mohamed

Graduate School of Architecture & Urban Design Theses & Dissertations

This thesis focuses on exploring housing as a determinant of health; thus, the aim is to investigate the historical and current influence of housing design and city planning on occupant health and population health in metropolitan cities. The thesis will primarily examine how housing affects the health of low-income individuals. Historically and presently, this demographic has been disproportionately affected by health issues stemming from overcrowding, substandard housing design, declining neighborhood conditions, and environmental inequities. The goal is to discern the dimensions and standards for healthy housing against which designers and planners can define health outcomes. By acknowledging the factors that …

Role Of Integrase-Pp2a Interaction In Human T-Cell Leukemia Virus Type-1 Replication And Pathogenesis, Shayna Turbin

Senior Honors Papers / Undergraduate Theses

Human T-cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes multiple disorders, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 retroviral integrase binds to the regulatory B’56γ subunit of the host cell Protein Phosphatase 2A (PP2A). Integrase contains a highly conserved LxxIxE motif that is essential for binding, which increases integration efficiency and facilitates HTLV-1 hijack of host cell machinery. We aim to understand how mutations introduced in the highly conserved binding site can affect viral particle production and infectivity. We transfected 729B human lymphoblastoid cells and 293T cells with mutant and wildtype virus. Mutations L213A, …

Integrating Health Equity Into Implementation Science To Advance Chronic Disease Prevention And Control, Callie Walsh-Bailey

Brown School Theses and Dissertations

Marginalized populations are inequitably burdened by chronic diseases such as diabetes, heart disease, obesity, and cancer. The goal of health equity work is to ensure all people have a fair and just opportunity to achieve optimal health. Implementation science has made health equity a greater focus and priority in recent years. There has been a proliferation of guidance on what implementation science needs to do to advance equity. However, the field currently lacks specific, actionable guidance on how to integrate equity. The overarching goal of this dissertation is to synthesize conceptual and theoretical underpinnings regarding health equity and bring them …

Projecting, Persuading, & Protecting: A Mixed Methods Analysis Of Adult Children’S Predictions Of Parents’ Quality-Of-Life Valuations In Serious Illness States, Jessica Hahne

Arts & Sciences Electronic Theses and Dissertations

Older adults often face complex serious illness decisions and involve their adult children as shared or surrogate decision makers. However, previous research asking family members to predict older adults’ treatment preferences in serious illness situations typically shows poor concordance with older adults’ actual preferences. In the current mixed methods analysis, we surveyed older adults (n = 38) on their health state valuations in five serious illness scenarios. Two of their adult children (n = 76) predicted their parent’s preferences. Families also participated in a semi-structured conversation to discuss their preferences and predictions.

Quantitative analyses showed that parents’ average valuations were …

Automatic Cardiac Mri Image Segmentation And Mesh Generation, Ziyuan Li

McKelvey School of Engineering Theses & Dissertations

Segmenting and reconstructing cardiac anatomical structures from magnetic resonance (MR) images is essential for the quantitative measurement and automatic diagnosis of cardiovascular diseases [1]. However, manual evaluation of the time-series cardiac MRI (CMRI) obtained during routine clinical care are laborious, inefficient, and tends to produce biased and non-reproducible results [2]. This thesis proposes an end-to-end pipeline for automatically segmenting short-axis (SAX) CMRI images and generating high-quality 2D and 3D meshes suitable for finite element analysis. The main advantage of our approach is that it can not only work as a stand-alone pipeline for the automatic CMR image segmentation and mesh …

Characterization Of Subcellular Functional Domains In The Vesicular Glutamate Transporter 3-Expressing Retinal Amacrine Cell Using Correlative Light And Electron Microscopy, Karl Friedrichsen

Arts & Sciences Electronic Theses and Dissertations

The following work seeks to better understand how neurons process multiple streams of information within the branches of their dendritic arbors. We use correlated light and electron microscopy to capture both live subcellular calcium responses and detailed morphology and synaptic connectivity in a unique retinal amacrine cell in order to directly study the relationship between structure and function. The vesicular glutamate transporter 3-expressing amacrine cell (VG3) selectively integrates and segregates visual information within its arbor branches and provides multiple target neuron types with appropriate excitatory or inhibitory synaptic inputs. By reconstructing VG3 arbor branches, synapses, and connected cell types, we …

The Effect Of Spinal Cord Stimulation And Video Games Training On Body-Machine Interface Control, Jie Fei

McKelvey School of Engineering Theses & Dissertations

Damage to the spinal cord causes long-lasting loss of motor and sensory function, and currently, there is no ‘cure’ for paralysis. However, even people with severe spinal cord injuries (SCI) have some residual mobility. Studies have shown that transcutaneous electrical spinal cord stimulation (tSCS) combined with functional training targeting residual mobility can further improve the motor function of individuals with SCI. In this study, we present a technical framework that aims to enhance rehabilitation outcomes by targeting residual mobility through a motor training-based approach. Our technical framework centers around a non-invasive body-machine interface (BoMI) that relies on the use of …

Feature Selection From Clinical Surveys Using Semantic Textual Similarity, Benjamin Warner

McKelvey School of Engineering Theses & Dissertations

Survey data collected from human subjects can contain a high number of features while having a comparatively low quantity of examples. Machine learning models that attempt to predict outcomes from survey data under these conditions can overfit and result in poor generalizability. One remedy to this issue is feature selection, which attempts to select an optimal subset of features to learn upon. A relatively unexplored source of information in the feature selection process is the usage of textual names of features, which may be semantically indicative of which features are relevant to a target outcome. The relationships between feature names …

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …

Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan

Arts & Sciences Electronic Theses and Dissertations

The survival of a species is inextricably linked to its ability to successfully navigate and interact with its surroundings, whether to seek safety from predators or gain sustenance from prey. Both functions are performed by mice, guided by vision, and rely on intricate processing in the retina and subcortical targets in the brain. This dissertation addresses how specific features of the visual environment and specific retinal ganglion cell circuits that sample a particular space in the visual environment are used to guide efficient predation in mice.Recent studies have begun to link the ability to detect, track, and ultimately capture prey …

The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan

Arts & Sciences Electronic Theses and Dissertations

The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …

Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer

Arts & Sciences Electronic Theses and Dissertations

The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …

The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland

Arts & Sciences Electronic Theses and Dissertations

The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …

Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones

Arts & Sciences Electronic Theses and Dissertations

K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …

Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard

Arts & Sciences Electronic Theses and Dissertations

The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …

Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy

Arts & Sciences Electronic Theses and Dissertations

Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …

Genetic And Transcriptomic Aspects Of Major Depressive Disorder: In Vivo Functional Assays Of Risk-Associated Variation, Candidate Disease Cell Types, And Their Pharmacologic And Sex Interactions, Bernard Mulvey

Arts & Sciences Electronic Theses and Dissertations

Major depressive disorder (MDD) is a debilitating illness that affects hundreds of millions globally, with substantial personal, medical, economic, and societal consequences. While depression occurs more commonly in females, the biology of the brain and sex underlying this skewed prevalence remains unclarified. This body of work explores two aspects of how biological sex may influence the brain at the level of gene expression: through intrinsic sex differences and through sex-mediated effects of depression risk genetics.

The monoamine hypothesis of depression suggests that modulatory neurotransmitters including serotonin and norepinephrine constitute a key axis in development of MDD. Large-scale studies of MDD …

Trauma Exposures Across The Life Course For Individuals Who Experience Incarceration, Maria Morrison

Brown School Theses and Dissertations

The U.S. incarcerates more people than any other country in the world, with 2.2 million people currently behind bars, 60% of whom are people of color. At the same time, there is an unprecedented political consensus to develop strategies for reducing the incarcerated population and safely returning the majority of incarcerated individuals to society. While there has been a substantial research focus on the potential of this population to commit acts of violence post-release, this tells only half the story. This dissertation hopes to provide a more complete picture of the role of violence in the lives of individuals released …

The Cost Of Child Support: Policy Design And Father Identity, Lara Markovitz

Brown School Theses and Dissertations

Child support policy is one of the key forces in the lives of families in the U.S., where 1 in 4 children and half of African American children live apart from their fathers (Carlson et al., 2017; Grall, 2020; U.S. Census Bureau, 2014). Most unmarried fathers of newborns express a strong desire and commitment to their children (Carlson & McLanahan, 2002; England & Edin, 2007). However, by the time their children turn five, fathers'; involvement (caregiving and time, provision of child support) diminishes greatly (Turner & Waller, 2017). This decrease in father involvement among low-income NRFs is thought to be …

Evaluation And Clinical Implementation Of A Dual-Energy Ct Stopping-Power Ratio Mapping Technique For Proton-Therapy Treatment Planning, Maria Jose Medrano Matamoros

McKelvey School of Engineering Theses & Dissertations

Proton radiotherapy has the potential to treat tumors with better conformal dose distribution than competing modalities when the rapid dose falloff at the end of the proton-beam range is correctly aligned to the edge of the clinical target volume (CTV). However, its clinical potential is dependent on the accurate localization of the Bragg-peak position from predicted stopping-power ratio maps. The method that is most commonly used in today’s clinical practice for predicting stopping-power ratio (SPR) consists of a stoichiometric calibrationtechnique based on single-energy CT (SECT) for direct estimation of patient-specific SPR distribution from vendor-reconstructed Hounsfield Unit (HU) images. Unfortunately, this …

Salience Coding In The Basal Forebrain And The Heterogeneous Underpinnings Underlying Novelty Computations, Kaining Zhang

McKelvey School of Engineering Theses & Dissertations

Humans and animals are consistently learning from the environment by interacting with it and getting feedback from their actions. In the environment, some objects are more important than others, because they are associated with reward, uncertainty, surprise, or novelty etc. These objects are salient to the animal. Salient objects attract attention and orientation, increase arousal, facilitate learning and memory, and affect reinforcement learning and credit assignment. However, the neural basis to support these effects is still not fully understood.We first studied how the basal forebrain, one of the principal sources of modulation of the neocortex, encodes salience events. We found …

Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene

Arts & Sciences Electronic Theses and Dissertations

Alzheimer’s disease (AD) is the leading cause of dementia and is pathologically defined by the aggregation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Rare heritable mutations within the genes for amyloid precursor protein (APP) and presenilin 1 (PSEN1), and presenilin 2 (PSEN2) cause early onset AD and account for approximately 1% of AD cases. While the majority of AD cases are late-onset (LOAD), which is defined by a markedly more complex genetic architecture that is comprised of many genetic risk factors that influence AD through multiple cellular pathways. The advent of deep sequencing analyses have allowed for the identification …

Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales

Arts & Sciences Electronic Theses and Dissertations

Endogenous analgesic pathways embody a potential target for the development for chronic pain therapies. Previous studies have demonstrated the role of the ventrolateral periaqueductal gray (vlPAG) in descending pain modulation. It has been proposed that tonic GABAergic neurotransmission at the level of the vlPAG serves to inhibit efferent excitatory projections that mediate descending analgesia. Disinhibition of these projection neurons allows subsequent activation of rostral ventromedial medulla (RVM) neurons that inhibit nociception at the level of the spinal cord. However, lack of cell-type specificity in these studies has prevented the determination of the role of specific subsets of vlPAG neurons in …

Validation, Categorizing, And Prediction Of Upper Limb Outcomes After Stroke, Jessica Barth

Arts & Sciences Electronic Theses and Dissertations

The incidence and costs of stroke in the United States are projected to rise over the next decade because of the aging population. Declining stroke mortality over the past few decades means that more people survive stroke and live with physical, cognitive, and emotional disability. Stroke remains one of the leading causes of disability in the United States because very few survivors experience a full recovery of their upper limb. Upper limb recovery after stroke is critical to performing activities of daily living and physical and occupational therapies are one of the only treatment options to address these challenges. The …

Identifying Contextual And Structural Factors Contributing To Organizational Sustainability In Pediatric Healthcare, Sara Malone

Arts & Sciences Electronic Theses and Dissertations

Every year, millions of children seek health care for acute and emergent needs. However, evidence-based care is not currently delivered to every child. Even when teams implement care discoveries designed to improve outcomes, they are often not sustained over time. All children should receive care that is in accord with current evidence-based guidelines, and those evidence-based practices must be effectively maintained over time. It is imperative to understand how to sustain care improvements in the clinical setting. Sustainability capacity allows us to understand the organizational factors that ensure care delivery over time. While there has been an increased focus on …

Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough

Arts & Sciences Electronic Theses and Dissertations

The overall goal of this dissertation is to gain a better understanding of how current Alzheimer disease pathologic progression models interact with sources of individual-level variation in pathology to influence overall disease progression in a clinically meaningful way. Many sources of variation, both internal (e.g., genetic mutations, heterogeneity of tau pathology) and external (e.g., diet and exercise, sleep quality), are known to influence disease progression and symptom onset in AD. With the advent of therapies that have shown successful reduction of amyloid load in trials and the rapid progression of anti-tau therapies, we hypothesize that a better understanding of how …

Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold

Arts & Sciences Electronic Theses and Dissertations

Brain circuits are shaped and maintained by active use. We blocked use of motor circuits in three adult participants by constraining the dominant upper extremity in a cast for two weeks, causing loss of strength and fine motor function. Daily resting-state functional magnetic resonance imaging (rs-fMRI) collected for 42-64 days before, during and after casting revealed two sets of changes in brain function. First, large, spontaneous pulses of activity occurred in the disused motor circuits. Pulses showed a consistent pattern of propagation through the disused circuits— occurring earliest in the dorsal anterior cingulate cortex (dACC) and supplementary motor area (SMA), …

Cancer Survivors’ Participation In Meaningful Life Activities, A Mixed Methods Approach, Allison Jean L'Hotta

Arts & Sciences Electronic Theses and Dissertations

A new cancer diagnosis dramatically impacts an individual’s daily life. While data describing cancer-related symptoms (e.g. fatigue) and impairments (e.g. weakness) are abundant, there remains limited data detailing the impact of cancer on survivors’ daily life participation. Advancement in participation research is challenged by the lack of a universally accepted definition of participation and a standard approach to measurement. Previous research evaluating participation among cancer survivors is limited by small sample sizes, cross-sectional data including only a single disease group, and assessing participation exclusively among individuals who have completed active cancer treatment. The purpose of the presented dissertation was to …

Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu

Arts & Sciences Electronic Theses and Dissertations

Protein inclusions such as β-amyloid, tau, α-synuclein, and TDP-43 are considered the pathologic hallmarks of many neurodegenerative diseases. These proteins are prone to misfold, aggregate, and template new aggregates. Accumulating evidence suggests that those proteins in their high-molecular-weight forms can serve as a "seed", spread through an interconnected brain network, and induce new inclusions. Therefore, it is essential to understand the mechanism of proteopathic seeding. In this dissertation, we performed a whole genomic CRISPR-Cas9 KO screening to identify gene modifiers of αS seeding. Within the screening, we found several hits of endolysosomal function and trafficking, including VCP. VCP is a …

Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira

Arts & Sciences Electronic Theses and Dissertations

At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …