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Subclonal Evolution Of Chronic Lymphocytic Leukemia After Allogeneic T Cell Therapies, Haven Garber

Dissertations and Theses (Open Access)

Subclonal evolution of chronic lymphocytic leukemia after allogeneic T-cell therapies

Haven Garber, MD

Advisory Professor: Jeffrey Molldrem, MD

Intratumoral genetic heterogeneity describes the molecular differences among subclones within a tumor and is a major barrier to effective therapy in many solid and liquid cancers, including chronic lymphocytic leukemia (CLL). Rare, treatment-resistant subclones can expand to compose relapsed disease during tumor evolution. Examination of malignant evolution in the context of specific treatment provides insight into the molecular lesions that mediate therapeutic response and resistance. Both chemotherapy and targeted therapy were shown to precipitate CLL subclonal evolution. We hypothesized that allogeneic T-cell …

Reversal Of Neurodegeneration By Engineered Monocytes In Alzheimer’S Disease, Chao-Hsien Chen

Dissertations and Theses (Open Access)

The health challenges posed by Alzheimer’s disease (AD) continue to grow as societies age worldwide. Accumulation of Tau-associated pathology correlates with clinical cognitive deterioration in AD. Resident myeloid cells within the central nervous system (CNS) have a limited capacity to uptake and degrade Tau; however, the resulting secretion of proinflammatory cytokines only acts to accelerate neurodegeneration. Therapeutic antibodies can reduce the neurotoxic oligomeric form of Tau (o-Tau), but in doing so they also aggravate inflammation. Attenuating mutation of the antibody Fc region can silence inflammation but also eliminates its capacity to mediate o-Tau clearance by CNS myeloid cells. Thus, there …

A Pharmacological Strategy Against African Sleeping Sickness, Wahaj Zuberi

Dissertations and Theses (Open Access)

Trypanosoma brucei is a parasitic eukaryote and is the causal agent of the disease known as African sleeping sickness, transmitted via the bite of a tsetse fly. If left untreated, the parasite ultimately crosses the blood-brain eventually leading to death. Currently there are 5 approved drugs used to treat it, each with toxic side effects and effective at specific disease stages. A more effective and less toxic drug candidate is highly sought after. The essential enzyme, dUTPase, is an excellent drug target in the parasite while utilizing S. cerevisiae as a model system.

dUTPase is essential in T. brucei (tbdUTPase), …

Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero

Dissertations and Theses (Open Access)

ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT

Rosa M. Santana Carrero, B.S.

Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.

Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …

Micrornas Associated With Melanoma Inflammation And Response To Pd-1 Inhibition, Robert Szczepaniak Sloane

Dissertations and Theses (Open Access)

Melanoma is an aggressive malignancy of melanocytes with historically poor outcomes. Melanoma therapy has improved markedly over the past decade with advances in molecularly targeted agents and immunotherapies. Immune checkpoint inhibitors achieve T-cell mediated anti-tumor efficacy by blocking engagement of inhibitory checkpoints on T-cells to overcome immunosuppressive signals from tumor cells and the broader microenvironment. Despite these advances, there are a significant proportion of patients who do not benefit from existing immunotherapy strategies making it a priority to identify and target the mechanisms that confer resistance to therapy. We demonstrate that microRNAs are accurate markers of microenvironment composition with prognostic …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations and Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Fibroblast Heterogeneity In Pancreatic Cancer Immunity, Josephine Darpolor

Dissertations and Theses (Open Access)

Fibroblasts are a unique cell type defined by their mesenchymal phenotype and exclusion from epithelial, immune, and endothelial cell subsets. Although well studied in wound healing, cancer associated fibroblasts (CAFs) are incredibly heterogeneous, leading to contradictions as to the roles CAFs play in the tumor microenvironment (TME). CAFs were thought to be a barrier to treatment of pancreatic ductal adenocarcinoma (PDAC). However, general stromal targeting strategies have largely failed in the clinic likely due to the heterogeneity of CAFs in the TME. Therefore, our groups and others have worked to unravel the heterogeneity of CAFs in PDAC. In the works …

“A Climate Of Lawlessness”: Upholding A Government’S Affirmative Duty To Protect The Environment Using Deshaney’S Special Relationship Exception, Katherine G. Horner

Journal of Law and Policy

The Industrial Revolution introduced an era of exceptional technological advances. However, it also led to rampant environmental pollution and degradation. The proliferation of toxic pollutants in the air, water and soil has led us to the precipice of an unimaginable future; a future defined by climate change. This Note argues for the use of the special relationship exception, affirmed by the Supreme Court in DeShaney v. Winnebago, in environmental litigation in order to uphold governments’ affirmative duty to protect the environment. As federal and state governments have the sole power to regulate environmental pollution and enforce environmental protections, individuals are …

Providing Head Start Services Amid A Global Pandemic: A Mixed Methods Explanatory Study Of Capacity, Resources, And Support, Kelly L. Vigants

Dissertations

The COVID-19 pandemic altered education in dramatic ways including immediate building closures and the implementation of virtual instruction. In March of 2020, Michigan faced a statewide shutdown on all non-essential travel as Michiganders were ordered to “Stay Home. Stay Safe.” Head Start began to provide remote services to families and students. Head Start lead teachers were charged with using virtual methods to teach their students. With little direction in the beginning and many unknowns, Head Start lead teachers used innovative methods to promote family engagement.

This study used a mixed method, explanatory sequential design to evaluate the most effective methods …

Is Media Assistance Obsolete? A Practice-Based Perspective On The Potential For Digital Technologies To Achieve Media Development Goals In Sub-Saharan Africa, Daire Higgins

Doctoral

The area of media assistance is not a widely known part of the Development Aid sector, even though it has been in existence since after World War II and has grown significantly since then as part of the development agenda. Media Assistance has been included in the strategies of Western and non Western donors as part of their overseas Aid programmes in many regions, supporting journalism and media with the objectives of contributing to accountability, transparency, governance and ultimately, democracy. This thesis examines the impact on the Media Assistance sector of the arrival of digital technologies into the ‘information ecosystems’ …

Genotypic And Phenotypic Characterization, Antibiotic Resistance And Virulence Patterns Of Staphylococcus Aureus Isolated Form Goat Mastitis, Yasser Kamel

Mansoura Veterinary Medical Journal

Objective: To determine the phenotypic and genotypic characterization of the virulence and antimicrobial susceptibility of S. aureus. Design: Descriptive study Samples:175 raw goat milk samples Procedures: A total of 87 S. aureus strains was isolated from goat with mastitis in north-west cost of Egypt. PCR technique was used to detect genes coding some virulence and antimicrobial properties while phenotypic antimicrobial susceptibility was determined by the disc diffusion method. Results: Most S. aureus isolates were resistant to amoxycillin (89.7%), penicillin G (88.5%), and ampicillin (86%) while were less resistant to other members of β-lactam group as cefoxitin (17.2%) and ceftriaxone (10.3%).The …

Longitudinally Extensive Transverse Myelitis: A Sub-Saharan Conundrum, Antonina Obayo, Sylvia Mbugua, Sayed Karar

Internal Medicine, East Africa

Spinal cord schistosomiasis is a rare, underdiagnosed manifestation of schistosomiasis. We present the case of a 36-year-old male who presented to our institution with a one-week history of low back pain with rapidly progressive lower limb weakness, loss of sensation, and flaccid paraparesis. An MRI of the spine showed a longitudinally extensive transverse myelitis from T6 to L1, with enhancement at the cauda equina region. Further review of the images and serological tests eventually led to diagnosis of spinal schistosomiasis. He was treated with praziquantel and high-dose steroids, with minimal improvement in his symptoms.

Effect Of A Mobile Phone Intervention For Female Sex Workers On Unintended Pregnancy In Kenya (Whisper Or Shout): A Cluster-Randomised Controlled Trial, Frances H. Ampt, Megan S. C. Lim, Paul A. Agius, Kelly L'Engle, Griffins Manguro, Caroline Gichuki, Peter Gichangi, Walter Jaoko, Marleen Temmerman, Stanley Luchters

Obstetrics and Gynaecology, East Africa

Background: Female sex workers in low-income and middle-income countries face high risks of unintended pregnancy. We developed a 12-month, multifaceted short messaging service intervention (WHISPER) for female sex workers in Kenya who had the potential to become pregnant, to improve their contraceptive knowledge and behaviours. The aim of this study was to assess the effectiveness of the intervention to reduce the incidence of unintended pregnancy among sex workers in Kenya compared with an equal-attention control group receiving nutrition-focused messages (SHOUT).

Methods: Our two-arm, cluster-randomised controlled trial was done in sex-work venues in two subcounties of Mombasa, Kenya (Kisauni and Changamwe). …

Impact Of A Pharmacist-Driven Methicillin-Resistant Staphylococcus Aureus Nasal Swab Protocol On The De-Escalation Of Empiric Vancomycin In The Setting Of Community Acquired Pneumonia, Grether Hernandez Gama, Winifred Pardo, Wilbert Fuerte, James Adefisoye

All Publications

No abstract provided.

Pathology Findings And Correlation With Body Condition Index In Stranded Killer Whales (Orcinus Orca) In The Northeastern Pacific And Hawaii From 2004 To 2013, Stephen A. Raverty, Judy St. Leger, Dawn P. Noren, Kathy Burek Huntington, David S. Rotstein, Francis M.D. Gulland,, Deborah A. Duffield, Multiple Additional Authors

Biology Faculty Publications and Presentations

Understanding health and mortality in killer whales (Orcinus orca) is crucial for management and conservation actions. We reviewed pathology reports from 53 animals that stranded in the eastern Pacific Ocean and Hawaii between 2004 and 2013 and used data from 35 animals that stranded from 2001 to 2017 to assess association with morphometrics, blubber thickness, body condition and cause of death. Of the 53 cases, cause of death was determined for 22 (42%) and nine additional animals demonstrated findings of significant importance for population health. Causes of calf mortalities included infectious disease, nutritional, and congenital malformations. Mortalities in sub-adults were …

Fundamental Studies Of Nanomaterial-Mediated Photothermal Effects And Novel Applications In Visual Quantitative Disease Diagnoses, Wan Zhou

Open Access Theses & Dissertations

Infectious diseases and cancers frequently cause public health concerns and high burdens on health care globally. Early diagnosis of these diseases can provide an important guide on prevention, treatment, and prognosis in clinical practice. However, current laboratory diagnostic methods, such as nucleic acid- and protein-based detection methods, require sophisticated infrastructure, expensive and bulky instrumentation, well-trained personnel, and time-consuming processes, which significantly leads to high cost of detection assays and limit their wide accessibility, especially in low-resource settings. To address these issues, we have developed multiple simple, low-cost, and visual quantitative diagnostic methods based on nanomaterial-mediated photothermal effects for the detection …

Privacy In Multigenerational Homes Before And Amidst Covid-19, Jennifer Luque

Electronic Theses and Dissertations

Multigenerational households in the United States are more prevalent now than they have been in the last forty years. In part, aging, illness, job loss, saving money, and even tradition are factors that contribute to the idea of multiple generations living together in one home. Given the health of the individuals, size of the home, and number of dedicated bedrooms and bathrooms, living multigenerational can have both positive and adverse effects. Many family groups fall into the category of multigenerational living. However, this study investigates the relationships between adults and senior family members in terms of privacy in the home. …

Ac Electrokinetic Effect Of V-Electrode Pattern On Microfluids, Mohammad Salman Parvez

Theses and Dissertations

Electrokinetics has been used for guiding, pumping, and manipulating microfluidic particles for many years in the field of Biomedical, Microbiology, Chemistry, Medicine, and other fields of research, which makes it a ubiquitous tool for the multidisciplinary research on microfluidics. Between these two Alternating Current (AC) Electrokinetics have been proven to be more feasible for the researcher than the other one. In this research, we have investigated AC Electrokinetics and s effect on a new electrode configuration called V-electrode pattern. The V-electrode has been inspired and modified from the previous research work on the Orthogonal Electrode Pattern. In this research, this …

Drone Utilization In A Pandemic And Beyond: Finding The Balance Between Public Safety And Privacy, Editorial Team

Journal of Drone Law and Policy

No abstract provided.

Scale‐Dependent Effects Of Host Patch Traits On Species Composition In A Stickleback Parasite Metacommunity, Daniel I. Bolnick, Emlyn J. Resetarits, Kimberly Ballare, Yoel E. Stuart, William E. Stutz

Biology: Faculty Publications and Other Works

A core goal of ecology is to understand the abiotic and biotic variables that regulate species distributions and community composition. A major obstacle is that the rules governing species distributions can change with spatial scale. Here, we illustrate this point using data from a spatially nested metacommunity of parasites infecting a metapopulation of threespine stickleback fish from 34 lakes on Vancouver Island, British Columbia. Like most parasite metacommunities, the composition of stickleback parasites differs among host individuals within each host population, and differs between host populations. The distribution of each parasite taxon depends, to varying degrees, on individual host traits …

Behavioral And Enhanced Perinatal Intervention (B-Epic): A Randomized Trial Targeting Tobacco Use Among Opioid Dependent Pregnant Women, Amanda Fallin-Bennett, Michelle R. Lofwall, Teresa M. Waters, Paul Nuzzo, Janine Barnett, Letitia Ducas, Andrea Mccubbin, Niraj R. Chavan, Lisa Blair, Kristin Ashford

Nursing Faculty Publications

Background

Opioid use during pregnancy is a significant public health issue. The standard of care for treating opioid use disorder during pregnancy includes medications for opioid disorder (MOUD). However, tobacco use often goes unaddressed among pregnant women on MOUD. In 2018, our team received a National Institute on Drug Abuse (NIDA) funded R34 to conduct a three year-randomized trial to test the feasibility of a novel tobacco intervention for pregnant women receiving MOUD.

Aims

The aims of this study are: (1) to determine the impact of the B-EPIC intervention on maternal tobacco use and stage of change; (2) to determine …

Statistical Models For The Analysis Of Complex Data, Stefani Mokalled

All Dissertations

This dissertation focuses on developing statistical models to analyze complex data. The motivating applications in this work include infectious disease screening, engineering, and public health problems. Chapters 2 and 3 take a frequentist approach to modeling and parameter estimation while Chapters 4 and 5 proceed with Bayesian methods. Maximum likelihood estimation is implemented in a case of missing data through latent variables (Chapter 2) as well as by embedding a finite element model within the likelihood framework (Chapter 3). Two Markov Chain Monte Carlo (MCMC) algorithms are applied to estimate parameters and fit regression models using data obtained from a …

Regional Disparities In Healthy Eating And Nutritional Status In South Korea: Korea National Health And Nutrition Examination Survey 2017, Jounghee Lee, Jaesin Sa

BACKGROUND/OBJECTIVES: Concerns about regional disparities in heathy eating and nutritional status among South Korean adults are increasing. This study aims to identify the magnitude of regional disparities in diet and nutritional status among Korean adults who completed the 2017 Korea National Health and Nutrition Examination Survey (KNHANES).

SUBJECTS/METHODS: The participants were a nationally representative sample of Korean adults aged 19 years and older from the 2017 KNHANES (n = 6,126). We employed the svy commands in STATA to accommodate the complex survey design. The relative concentration index (RCI), absolute concentration index (ACI) and index of disparity were used to measure …

Existence And Stability Of The Doubly Nonlinear Anisotropic Parabolic Equation, Huashui Zhan, Zhaosheng Feng

School of Mathematical & Statistical Sciences Faculty Publications

In this paper, we are concerned with a doubly nonlinear anisotropic parabolic equation, in which the diffusion coefficient and the variable exponent depend on the time variable t. Under certain conditions, the existence of weak solution is proved by applying the parabolically regularized method. Based on a partial boundary value condition, the stability of weak solution is also investigated.

Community Acquired Pneumonia Antibiotic Treatment Length: Summary, Children's Mercy Kansas City

Clinical Critically Appraised Topics

No abstract provided.

“Fetch M’Dear”: Healers, Midwives, Witches, And Conjuring Women In Select Ya And Toni Morrison Novels, Diane Mallett-Birkitt

Electronic Theses and Dissertations

Accusations and persecution of witchcraft have been embedded in global culture for centuries. For as long as these persecutions have occurred, women have found themselves accused most frequently. Older women with herbal knowledge were often called on to assist with childbirth or termination of pregnancies and this “secret knowledge” often led them to be suspected of supernatural abilities, often of a satanic nature. Intrigued by these wise women who appeared to have mysterious powers and a penchant for arousing the ire of men in the legal, medical, and religious communities, I began to notice their frequent appearance in novels. Does …

Taxes As Pandemic Controls, Ashley C. Craig, James R. Hines Jr.

Articles

Tax policy can play important roles in limiting the spread of communicable disease and in managing the economic fallout of a pandemic. Taxes on business activities that bring workers or customers into close contact with each other offer efficient alternatives to broad regulatory measures, such as shutdowns, that have been effective but enormously costly. Corrective taxation also helps raise the revenue required to cover elevated government expenditure during a pandemic. Moreover, the restricted consumer choice that accompanies a pandemic reduces the welfare cost of raising tax revenue from higher-income taxpayers, making it a good time for deficit closure. Current U.S. …

Reducing Infant Catheterization In The Emergency Department Through Clean-Catch Urine Collection., Amanda E Mulcrone, Manas Parikh, Fahd A Ahmad

2020-Current year OA Pubs

OBJECTIVE: Our emergency department (ED) traditionally relied on urethral catheterization to obtain urine cultures when evaluating infants for urinary tract infections (UTIs). Catheterization is associated with adverse effects, and recent studies have demonstrated clean-catch urine methods can be successfully used to obtain urine cultures. We pursued a quality improvement (QI) initiative aimed at decreasing the frequency of urethral catheterizations in our ED by using an established clean-catch technique to obtain infant urine cultures.

METHODS: We implemented a clean-catch urine collection method, which we entitled "Bladder Massage," for infants 0-6 months of age needing a urine culture in our ED. Exclusions …

Copper And Cobalt Metal Conjugation Enhances Flaviviral Replication, And Denv/Zikv Caused Thrombocytopenia Suppresses Integrin Signaling, Shovan Dutta

Biomedical Sciences Theses & Dissertations

Vector control is a global concern, and effective strategies have been on the way. Among the many different strategies, insect repellents to protect us from blood-feeding arthropods are very common. Food processing or preservatives in food expose us to several chemicals associated with insect repellents, insecticides, and pesticides. Using metallic conjugation with plant extracts or essential oils has become a widespread strategy to increase their efficacy. But it is worth it to be aware that some of those metallic compounds like Cobalt or Copper upon conjugation with thiosemicarbazone ligands derived from Citral and 2-acetylethiazole at the center coordination enhance both …

No-Cost Flu Clinics, Madyson Shands

Capstone Projects and Master's Theses

Thousands of people go each year without access to flu vaccinations. In consideration of the current pandemic, there was a need for vaccinations in order to limit the possibility of a double pandemic. The Visiting Nurses Association (VNA), Community services is a non-profit organization that provides services that range from immunization to wellness programs. The community service department strives to connect with the community and construct programs that will assess their needs. The project consists of no-cost flu clinics working with agencies within the Monterey community. Interim is a transitional housing center for adults with mental illnesses. There was a …