LYMPHOCYTE-SPECIFIC TYROSINE KINASE EXPRESSION IN OVARIAN CANCER: A VALUABLE PROGNOSTIC INDICATOR

Cellular immune response, specifically tumor infiltrating lymphocytes (TILs), has been correlated to survival in epithelial ovarian cancer; however, specific gene expression patterns for this response remain poorly understood. The objective of this research was to investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC). To do so, a panel of immune related gene expression was evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA) and validated in an independent cohort of ovarian tumors. Based on the strong association with survival, the cohort was grouped into LCK (lymphocyte specific tyrosine kinase) high and non-LCK high tumors and profiles of gene expression and clinical information were obtained. We demonstrate that mRNA upregulation of LCK was correlated with the strongest improvement in survival of the genes investigated. When compared to previously validated metrics such as cytolytic activity score (CYT), LCK proved to be a more discerning prognosticator across tumor types available in the TCGA. In ovarian cancer, correlated gene enrichments were notable for chemokine and immunoglobin complex related genes, ie B cell related transcripts. Therefore, this research shows that LCK is a biomarker of prognostic and biological importance, potentially due to its ability to capture the genomic signature of cooperative T and B cell interaction. This provides essential support for further investigation into the role of tumor infiltrating B cells (TIL-B) and tertiary lymphoid structures (TLS), from which insights into this cooperation can be drawn. As ovarian cancer is the leading cause of death from gynecologic malignancy, such insights have the potential to not only offer important prognostic information but also may provide novel therapeutic approaches to the treatment of this deadly disease

Why She Didn\u27t Just Leave: The Effect of Nuisance Ordinances on Domestic Violence

Municipalities throughout the country have adopted nuisance ordinances to recruit landlords in assisting with crime control. Nuisance ordinances are municipality-level policies that sanction landlords if police are frequently called to respond to a landlord’s tenants. To avoid a fine, landlords must abate tenants whose conduct was considered a nuisance under the municipality’s ordinance; most often, this abatement process involves evicting the tenant. Little research has evaluated the impact of nuisance ordinances on innocent tenants – particularly, female victims of domestic violence. Because domestic violence is seldom excluded from the list of nuisance activities considered under the ordinances, legal advocates have warned that the threat of eviction associated with nuisance ordinances could discourage domestic violence victims from reporting their abuse to the police. This thesis contributes the first econometric analysis of the effect of nuisance ordinances on domestic violence reporting and incidence. The variation in nuisance ordinance enactment across municipalities and over time provides the framework to identify the causal effect of nuisance ordinances on domestic violence using a difference-in-differences strategy. I find that nuisance ordinance enactment leads to a 16.5-23.2 percent reduction in domestic violence-related 911 calls for assistance and a 0.4-0.7 percentage point increase in self-reported domestic violence incidence in California. Nationwide, I also find nuisance ordinance enactment is associated with a statistically significant increase in online search activity related to domestic violence as a proxy for domestic violence incidence. These results suggest that nuisance ordinances have the unintended consequence of discouraging domestic violence victims from reporting their abuse, thereby allowing the incidence of domestic violence to persist

Alternative Schooling Strategy Brief

Although there is little overall research on alternative schooling due in part to the widely disparate types of alternative school programs, there is program evaluation and anecdotal support for their effectiveness for some students. These programs are commonplace, and must be considered a part of the effort to keep students, particularly students with behavioral needs in school. There is anecdotal evidence that these programs can be beneficial to students who would otherwise not participate and complete a school program

Quantifying and understanding the distribution of hosts, parasites, and their interactions in freshwater ecosystems

This dissertation investigates the ecology and distribution of amphibians, parasites, and their interactions within aquatic ecosystems. Throughout my dissertation, I use quantitative tools and field observations to examine the factors limiting distributions of amphibians and their parasites across both temporal and spatial scales. In my first chapter, I tracked the assembly of parasite communities as they colonized larval amphibian hosts in 10 different ponds over the course of a summer. This work indicated that the attributes of individual hosts or species do not strongly influence parasite community composition and instead, site-level heterogeneity is important in structuring parasite diversity. For my second chapter, I evaluated the stability and distribution of amphibian species across a broader temporal scale – an entire decade. My focus in this chapter was on the response of different amphibian species to a severe drought event. I found that amphibian species experienced strong declines during drought, but that native species recovered more quickly than exotic species. Building on that analysis, and the finding that some amphibian species were more difficult to monitor than others, my third chapter investigated the use of environmental DNA (eDNA) to improve amphibian monitoring programs. I found that eDNA analysis enhanced the detection of threatened amphibian species, and that more generally, eDNA approaches can effectively complement (but not replace) routine field surveys. Finally, for my fourth chapter, I used network analysis to evaluate temporal variation in host-parasite interactions over seven years. I found that despite having life history strategies that could promote stability, parasite communities were highly dynamic and that their fluctuations were independent of their host communities. Throughout my dissertation, I leverage multiple approaches and frameworks to advance understanding of amphibian and parasite ecology. Together, these studies show that freshwater communities and their interactions exhibit high seasonal and interannual variation, and that dispersal, landscape connectivity, and hydroperiod are important targets for future research into the management of both amphibians and their diseases

Extending self-determination theory’s dual-process model to a new tripartite model to explain diminished functioning

In a three-study investigation, we pursued three purposes: (1) extend self-determination theory’s dual-process model to a new tripartite model—to recognize that environmental conditions sometimes render a psychological need dormant; (2) better explain adolescents’ diminished functioning; and (3) develop the Three States Questionnaire (TSQ). In Study 1, 402 high schoolers reported the satisfied, frustrated, and dormant state of their psychological needs (autonomy, competence, and relatedness) during classroom instruction to develop the TSQ. In Study 2, 320 high schoolers reported their satisfied, frustrated, and dormant states as well as 17 indicators of their effective, defiant, and diminished classroom functioning. The TSQ showed excellent psychometric properties, and the predictive power of the tripartite model was superior to that of the dual-process model in the prediction of all five indicators of diminished functioning (e.g., disengagement). In Study 3, 457 high schoolers’ perceived teachers’ motivating styles (supporting, controlling, and neglecting) predicted their three need states (satisfied, frustrated, and dormant), which predicted the quality of their classroom functioning (effective, defiant, and diminished). Overall, the dormant state was distinct from the other two states, it uniquely explained diminished functioning, and the tripartite model out-predicted the dual-process model

The Gathering Storm: Infectious Diseases and Human Rights in Burma

Documents how decades of repressive rule, civil war, and poor governance in Burma have contributed to the spread of HIV/AIDS, tuberculosis, malaria, and other infectious diseases

The effect of chewing gum on physiological and self-rated measures of alertness and daytime sleepiness

The proposition that chewing gum can improve alertness was investigated via both physiological and self-rated measures. The Pupillographic Sleepiness Test (PST) provided a measure of pupillary unrest (PUI); a physiological index of daytime sleepiness. Chewing gum reduced the extent of sleepiness as measured by both PUI and self-rated sleepiness. Specifically, in comparison with sham chewing and no chewing controls, the chewing gum condition significantly limited the increase in pupillary unrest following the 11-minute PST within a darkened laboratory: a finding indicating moderation of the daytime sleepiness increase for the chewing gum condition. In addition, there was some evidence that chewing gum (relative to the no-chewing condition only) moderated the increase in a self-rated measure of sleepiness (Stanford Sleepiness Scale). However, there was no evidence that chewing gum moderated the decrease in self-rated alertness (Bond-Lader Visual Analogue Mood Scale). Although the precise mechanism underpinning the effect of chewing gum is unclear, the reduction in daytime sleepiness may be underpinned via heightened cerebral activity following the chewing of gum or the arousing effects of mint flavour