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Principal Component Analysis-Based Anatomical Motion Models For Use In Adaptive Radiation Therapy Of Head And Neck Cancer Patients, Mikhail Aleksandrovich Chetvertkov

Wayne State University Dissertations

Purpose: To develop standard and regularized principal component analysis (PCA) models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients, assess their potential use in adaptive radiation therapy (ART), and to extract quantitative information for treatment response assessment.

Methods: Planning CT (pCT) images of H&N patients were artificially deformed to create “digital phantom” images, which modeled systematic anatomical changes during Radiation Therapy (RT). Artificial deformations closely mirrored patients’ actual deformations, and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and synthetic …

Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model, Bing Xu

Wayne State University Dissertations

The aim of this study was to elucidate the expression and functions of interleukin (IL)-24 and suppressor of cytokine signaling 3 (SOCS3), and their regulatory relationship in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by the infection, and this upregulation was dampened by flagellin pretreatment. Time course studies revealed that IL-24 expression was markedly elevated, followed by a subsidence and second elevation, a pattern shared with SOCS3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression, and suppressed SOCS3, IL-1β, IL-1RN, and …

An Examination Of Quality Of Life Of Parents Of Adult Children Diagnosed With Autism Spectrum Disorder, Christina Noel Marsack

Wayne State University Dissertations

Previous research on parental caregivers has focused primarily on caregivers of individuals with intellectual and developmental disabilities, rather than focusing specifically on parents of adult children diagnosed with autism spectrum disorder (ASD). Most research on ASD has centered on parents of young children with this diagnosis, but not on parents of adult children with ASD. Understanding the experiences of parents caring for adult children with ASD is important given the increase in the prevalence of individuals with ASD and the lack of information regarding parents of adult children with ASD. A nonexperimental, quantitative, correlational design was used to examine effects …

Essays On Healthy Aging From The Perspective Of A Health Production Function, Nasim Baghban Ferdows

Wayne State University Dissertations

This dissertation examines the determinants of healthy aging among older adults using Grossman’s framework of a health production function. Healthy aging is produced using a variety of inputs, including some determined in early life, such as health and socioeconomic status as a child, others determined in young adulthood, such as education, others determined in mid-life, such as household wealth, and still others determined in later-life, such as current health habits. A production function for healthy aging is estimated using nationally representative data from the 2010 Health and Retirement Study on non-institutionalized seniors, and positing a simultaneous equations mediation model, recognizing …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …

Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price

Wayne State University Dissertations

While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation.

Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow.

A 36×43×2 cm3 phantom with 255 known landmarks …

Fear Of Alzheimer's Disease And Its Role In Memory Monitoring And Control, Annalise Marie Rahman

Wayne State University Dissertations

Introduction: Fear of Alzheimer’s disease (FAD), or Anticipatory Dementia, is a healthy adult’s misinterpretation of everyday memory failures as indicators of developing dementia. The current study investigated the construct of FAD and aimed to contextualize FAD within the Health Belief Model through development of a new scale, the Anticipatory Dementia Index (ADI). The study also assessed the relationship between FAD and metacognitive monitoring and metacognitive control.

Methods: 94 cognitively-intact community-dwelling older adults with and without a history of family history of AD completed questionnaires regarding their subjective memory complaints, state and trait anxiety, depression, and multiple measures of FAD, including …

Identifying Mechanisms Of Resistance And Potential Therapeutic Targets For Pediatric Acute Myeloid Leukemia, John Timothy Caldwell

Wayne State University Dissertations

Acute myeloid leukemia (AML) is a potentially devastating disease that can affect people of all ages. While there are certain patient groups that typically have favorable outcomes, in the pediatric population, overall survival (OS) is approximately 70%, leaving much progress to be made. Children with Down syndrome (DS) have a substantially elevated risk for developing AML, especially of the megakaryocytic phenotype (AMKL).

Patients with DS AMKL almost universally harbor a mutation in the gene encoding the GATA1 transcription factor, resulting in the translation of a short-form protein GATA1s, which has been shown to contribute to chemotherapy sensitivity. In contrast, in …

Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish

Wayne State University Dissertations

Breast cancer is the most common cancer and the second leading

cause of cancer death in women. While ER-positive breast cancer subtypes are initially

well-managed by targeted therapies targeting estrogen signaling, many women are

suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients

who were previously successfully treated with anti-estrogen therapies worsens

overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of

a tumor may allow for the possibility …