Pancreatic ductal adenocarcinoma (PDAC) is a formidable cancer with low survival rates, influenced by a hypoxic tumor microenvironment rich in cancer-associated fibroblasts (CAFs) which contribute to tumor progression and therapeutic resistance. This paper proposes a novel approach to PDAC treatment by identifying the effects of HIF2a inhibition. Leveraging Belzutifan, an FDA-approved HIF2a inhibitor, this paper aims to assess the mechanism by which Belzutifan can effectively target myofibroblastic CAFs in the PDAC tumor stroma. By conducting a literature review and integrating findings from preliminary in vitro experiments using PDAC organoid/immune/CAF cell co-cultures, I aim to explore the changes in gene expression and signaling pathways. This will include assessing the impact on immune cell recruitment and activation through advanced molecular techniques. The findings are anticipated to advance our comprehension of PDAC pathophysiology and highlight potential therapeutic avenues, offering a promising shift in PDAC treatment strategies.

In an effort to preserve and to provide access to their collections of black and white film negatives, many institutions (museums, libraries, archives, etc) are digitizing these collections. Several international committees were formed to define the needed image quality and created digitization guidelines with specifics for different material types to ensure that collection materials are properly documented and digitally preserved. Current practices for digitizing black and white negatives involve many different technologies, most of which incorporate broad-band "white" light sources. To assist with black and white film digitization image quality improvement efforts and standardizations, the author explores the benefits of utilizing a camera sensor without a color filter array and differing narrow-band light sources to mitigate image degradation caused by diffraction and chromatic change of focus. This thesis demonstrates that utilizing this technique enhances the optical resolution, or modulation transfer function, of the imaging setup with minimal drawbacks as is discussed in this thesis.

We present the characterization of a prototype Tunable All-Reflective Spatial Heterodyne Spectrometer (TARSHS), a novel extension of the already-existing and successfully flight-demonstrated All-Reflective Spatial Heterodyne Spectrometer (ARSHS) design. ARSHS is recognized for its high resolving power (R > 105), wide field of view (FOV), and unique optical design that is especially well-suited for UV-visible remote sensing of faint and extended planetary and astrophysical targets. However, ARSHS utility is limited by a fixed and narrow bandpass. TARSHS overcomes this limitation by incorporating motor-driven rotation stages into the instrument pilot mirrors, enabling rapid selection between many different bandpass centers across a broad spectral range. This tunability significantly enhances the instrument’s versatility and potential science return per flight without sacrificing the high R and FOV that are characteristic of base ARSHS design. The TARSHS prototype reported below, assembled primarily with commercial-grade components, demonstrated a resolving power of R = 30,000 across an operable range of 400 – 700 nm. Stable, reliable tuning and minimal degradation across its tunable range were found, supporting its readiness for higher technology readiness levels (TRL). This study outlines the optical configuration, operational mechanics, and prototype results, establishing TARSHS as a robust, cost-effective tool for space-based spectroscopy. Future efforts should focus on miniaturization and environmental validation for deployment on robotic missions.

Experiments have been conducted in a blowdown wind tunnel at Mach 2.1 and Mach 3.0 to study swept shock boundary layer interactions (SBLIs) generated by impinging, oblique shocks on a fully turbulent boundary layer. The overall goal of this work is to determine the effect of increasing the aspect ratio of the SBLI by comparing results to similar experiments conducted in a smaller wind tunnel. Shock sweep angles of 20 and 40 degree are tested at each Mach number. The quasi-infinite region is increased by increasing the aspect ratio of the shock generator from 2.33 in previous studies to 2.75 in the current study. To isolate the effect of sweep, a fixed inviscid pressure rise normal to the sweep angle of Cpn is used for each case. The mean flow topology is studied using three methods: infrared thermography, mean pressure measurements, and oil flow visualization. Mean flow results from each of the three techniques show good agreement and are able to identify salient features of the SBLI. The Stanton number distribution from infrared thermography accurately provides the location of the initial pressure rise and separation via a local minima and maxima in the Stanton number distribution. Mean pressure results also validate the locations of the initial pressure rise and separation locations determined from infrared thermography results. Oil flow shows the local skin friction direction on the SBLI surface and offers the most conclusive separation and reattachment locations, but also allows for the visualization of the initial pressure rise. The initial pressure rise and separation locations for all three methods align well, validating the use of infrared thermography to identify these salient features of the SBLI. A local maxima of the Stanton number distribution is seen in both separated and attached SBLIs. Therefore, heat flux data can be used to aid in determining the location of the separation for the SBLI, but does not offer conclusive results for whether the flow has separated or remains attached. Further, the Stanton number distribution is not sufficient in determining a precise location of reattachment if the flow has separated. Oil flow visualization offers the most conclusive results when determining separation and reattachment. Previous results from a smaller aspect ratio interaction show that separation exhibits conical similarity for 20 degree sweep in Mach 2.3 flow. However, oil flow visualization at Mach 2.1 for the larger aspect ratio interaction investigated here exhibits cylindrical behavior. This suggests that the SBLI aspect ratio influences the mean flow topology in that lower aspect ratios promote conical similarity. Comparison of the 40 degree sweep cases for the two different aspect ratio tests show similar structures, but Mach 3.0 results require further analysis since oil flow offers the most accurate reattachment location but was unable to be obtained for these tests.

This Doctor of Nursing Practice (DNP) project aimed to train nurses and other healthcare professionals at the Tripler Army Medical Center (TAMC) psychiatric inpatient unit in mindfulness-based breathing techniques via brief educational intervention. The goal of the project was to enhance stress management and increase their intention to continue using the method in the future.This quality improvement project, employed a descriptive study design. Participation was voluntary, with nurses and healthcare workers providing informed consent. Data was collected through pretest and posttest surveys administered via Qualtrics software, which was also used for analysis. A total of 23 participants completed the pretest, and 26 completed the posttest survey. The results revealed a significant shift in participants' attitudes toward mindfulness-based interventions. Participants demonstrated a heightened interest in and willingness to engage in mindfulness practices, indicating a growing awareness of the benefits of these techniques in managing stress and promoting well-being among healthcare professionals. This positive shift in attitude highlighted an evolving perception of mindfulness programs within the healthcare community.

Water distribution systems (WDS) are one of the most vulnerable components of water infrastructure systems. After the events of 9/11, there was increased concern regarding the potential for the deliberate introduction of chemical agents that may affect public health. Later, these concerns moved towards accidental water quality incidents produced by, for example, cross-connections and low-pressure events. In either case, Surveillance Response Systems (SRS) were formulated to protect water quality by make prompt detection and confirmation of contamination events. The overall objective of this dissertation is to develop a decision framework capable of making a timely detection, confirmation and forecasting of a contamination event in WDS. The fulfilment of this objective relied on the use of confirmatory sampling locations (CSLs) as a way to overcome the limitations of traditional water quality monitoring, which includes the high cost of sensors and limited detection capabilities due to the lack of contaminant-specific sensors. Based on previous research that provided a foundation to identify the best individual CSL using an entropy metric derived from information theory, this dissertation proposed the Updating Greedy Algorithm (UGA) to identify a set of \emph{multiple} CSLs in real-time. The UGA used an approximation to the entropy metric and a greedy heuristic to identify the set of CSLs. When tested on a small network, the UGA results were almost identical to the solutions achieved by a Genetic Algorithm using an exact formulation of the entropy metric, but in orders of magnitude less time. As the number of CSLs increased, the placements were spatially very similar (similar hydraulic paths), which may lead to a potential overlap of information across the CSL. To enable the implementation of the UGA in real-sized networks, the UGA was extended into a cluster-based optimization approach in order to reduce the solution space. The clustering algorithm grouped the network nodes based upon similarities in hydraulic connectivity. Each cluster was then assigned a representative sampling unit within each cluster to be used as a potential CSL. Two types of sampling units were used: i) the centroids of the cluster and ii) the location within the cluster that maximized information gain. The use of the clusters and sampling units were proposed to reduce the computational burden of the algorithm while maintaining a similar set of spatially distributed potential CSL. Ultimately, this approach was tested on a large network, and was shown capable of generating optimal solutions within an amount of time consistent with real-time application (1 hour). Finally, the reduction of information overlap was investigated through the introduction of the Multi-Objective Updating Greedy Algorithm (MUGA). The MUGA incorporated D-optimality, a correlation metric, to increase the spatial distribution of CSLs across the network while maximizing the amount of information gained from the samples. The trade-off between Information Gain and D-Optimality showed that the information gain tended to place CSLs along similar hydraulic paths, reinforcing existing connections, whereas the maximization of D-Optimality placed CSLs in unexplored hydraulic paths, creating new connections. The MUGA was tested in a large network using the clustering approach previously developed. The MUGA approach was shown to be computational efficient, and able to achieve good results (relative to Genetic Algorithm solutions). Overall, the addition of the D-optimality was capable of spatially distribution the CSLs and, at lower weights, was able to help avoid some local minima when using the Information Gain as a single objective. Overall, the deployment of CSLs provides useful information to characterize a contamination event, that enhances detection, confirmation and forecasting capabilities of SRS. These methodologies must be efficient enough to provide good solutions in at a time frame useful for real-time application. This research developed an approximation to the exact solution for information gain, a clustering approach to reduce the solution space of large networks, a greedy heuristic placement algorithm, and a multi-objective placement algorithm that that were shown capable of generating good CSL solutions in less than an hour -- often in seconds for the single objective placement. Further research may explore the response of the proposed approaches under diverse characteristics of a contamination event (varying injection locations and times), as well as considering demand uncertainty. Finally, as some contaminants may remain undetected, the inclusion of alternate data sources (e.g., public health data) may be integrated to enhance detection capabilities of SRS.

This study utilizes Positive Youth Development (PYD) and resilience frameworks as a lens to examine the transition experiences for youth with disabilities who experience and exit foster care through secondary analysis of data collected from a statewide needs assessment, Fostering Positive Outcomes: Assessing transition needs and supports for youth with disabilities in foster care (FPO Project). Secondary analysis of data from the multi-mixed methods approach of the FPO project (group concept mapping, surveys, focus group and interview data) was conducted with application of Lerner et al (2015) Five C Model + Contribution (i.e., Six Cs) indicators of PYD – competence, confidence, character, connection, caring, and contribution. Utilizing a bioecological perspective, this study centers the voices of youth with lived experience to examine resiliency and positive development to answer the following research questions: 1) How are the Six Cs of positive youth development expressed in describing the foster care transition experiences of youth with disabilities? 2) How do multiple systems of support affect the Six Cs of positive youth development for youth with disabilities transitioning from foster care? Findings from this study highlight the complexities, challenges and opportunities for disabled youth experiencing foster care to thrive in adulthood. Each of the PYD indicators, the Six Cs, were described as primarily absent in this population’s transition experiences and may appear in different ways for this specific population. Potential new pathways for PYD were identified that encompass the unique experiences and developmental processes among youth with disabilities in foster care. Findings were translated to propose an adapted Six C model with expanded definitions to make each indicator more applicable and inclusive of this population, as well as help guide the development of interventions specific to this population for positive adaptation. One of the most notable findings based on interactions across the Six Cs is the emergence of self-determination as a major theme which may be a unique indicator of “thriving” among youth with disabilities in foster care. Moreover, youth at this intersection engage with multiple systems of support related to child welfare, disability, education, vocation, and health. Findings indicate gatekeeping, stigma and biases, and staffing and provider issues associated with policies and practices of these systems pose significant barriers to PYD. This study’s findings give rise to implications for the PYD model and resilience, and further scholarship needed in this area, as well as implications for practice and policy with recommendations for interventions through a multi-pronged ecological approach to improve outcomes for youth with disabilities who experience foster care. This study helps to address the gap in the scholarship regarding youth with disabilities who experience foster care and the explicit use of relational developmental frameworks through innovative methods with an under studied, marginalized, and hard to reach population.

This dissertation examines the association between sexual victimization among college womenand individual- and campus-level factors using a nationally representative dataset. Specifically, it explores whether a higher proportion of same-sex and same-race peers provides a protective buffer against sexual victimization. The study controls for known risk factors, such as class standing, sexual orientation, and living situation, and investigates how institutional characteristics like enrollment size and student body composition influence the likelihood of victimization and formal reporting. Key findings reveal that first-year and sophomore students are less likely to report victimization than seniors, non-heterosexual women face a higher risk for attempted rape and sexual coercion, and students living in sorority housing or off-campus are more vulnerable to certain forms of sexual exploitation. Additionally, a higher percentage of same-race peers is associated with a lower likelihood of attempted sexual coercion. These findings contribute to the growing literature on sexual exploitation in higher education, highlighting the need for larger and more comprehensive datasets to fully capture the complexity of campus-level influences on sexual exploitation. Understanding these relationships is critical for developing more effective prevention strategies.

Purpose: The purpose of this Doctor of Nursing Practice (DNP) project was to assess the effectiveness of an educational intervention designed to enhance psychiatric staff knowledge and willingness to implement an evidence-based aggression screening tool, the Dynamic Appraisal of Situational Aggression (DASA), during patient admissions. The project also aimed to identify barriers and facilitators to the integration of structured aggression screening into clinical practice.Background: Aggression in psychiatric settings posed significant risks to patient and staff safety. Evidence-based tools like the DASA had been shown to improve the identification of aggression risk and promote proactive interventions. Despite these benefits, implementation was often hindered by knowledge gaps, resistance to change, and systemic barriers. Addressing these challenges through targeted educational initiatives improved staff preparedness and fostered safer environments. Methods: A single-group pretest-posttest design was utilized to evaluate the impact of the educational intervention on staff knowledge of the DASA tool. The intervention included a structured presentation emphasizing the operational use of the tool and the importance of mitigating personal bias. Due to limited staff availability, only the director of risk management participated in both the pretest and posttest. Quantitative data from knowledge assessments were analyzed, and qualitative feedback from the participant was thematically analyzed to identify implementation barriers and perceptions. Results: The participant demonstrated consistent pretest and posttest scores of 8/10, indicating a high baseline knowledge level but no measurable improvement. Qualitative data collected revealed key themes, including confusion regarding tool sequencing, corporate barriers to implementation, and the perceived feasibility of the DASA tool when adequately supported by leadership and training. These findings emphasized the need for systemic changes and enhanced educational efforts. Conclusions: This project highlighted the potential of targeted educational interventions to improve aggression screening practices in psychiatric settings. While limited by sample size, the findings underscored the importance of leadership engagement, ongoing training, and policy adjustments to facilitate the integration of structured tools like the DASA. Future efforts should focus on addressing systemic barriers, expanding training initiatives, and conducting multi-site evaluations to validate these findings and enhance scalability.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the US as well as the third most common cause of cancer-related death. Standard treatment includes surgical resection and adjuvant chemotherapy with multidrug regimens such as FOLFOX (Folinic Acid, 5-Fluorouracil, Oxaliplatin). However, due to high heterogeneity in colon tumors, patient response is variable and tools to predict drug response are few. Additionally, resistance, which can lead to recurrence and metastasis, is not uncommon. As such, there is a need for improved treatment options, better methods for predicting drug response, and better understanding of resistance mechanisms in CRC. Here, we introduce a host of new methodologies to phenotypically characterize CRC with the long term goals of better understanding chemotherapy resistance and creating actionable clinical tools that can model and predict individual tumors’ drug response. We have curated a set of colon tumor organoids, titled the Heterogeneity Library, that represents a variety of CRC subtypes. We used our newly designed phenotypic profiling pipeline, which leverages DAPI, pAKT, CD44v9, and H2AX, to characterize a FOLFOX-induced, PI3K/AKT-driven survival signature originally identified in our transcriptomic data. Unbiased subpopulation analysis confirms a cohort of cells with high PI3K/AKT signaling, high DNA damage, and high levels of stem cell markers across organoids. We believe that cells increasingly upregulate survival signaling, including extracellular matrix components and growth factor receptors, which all activate AKT, which in turn leads to a protective, resistant phenotype. Ultimately, we posit the observed FOLFOX dose-dependent increases in the fraction of these resistant cells across tumor types is a combination of adaptation down this proposed Resistance Trajectory in combination with a selection process whereby susceptible cells are readily eliminated, leaving the increasingly mesenchymal progenitor- and stem-like cells to expand despite FOX exposure. Finally, we endeavored to target this resistant population by treating organoid monolayers with a combination of FOLFOX and Dactolisib, the PI3K/mTOR dual inhibitor, which exhibited significant synergy across organoids. Even the most FOLFOX-resistant organoid – made up almost entirely of the previously described highly damaged, AKT-driven, stem-like resistant cells – demonstrated increased FOLFOX efficacy when also treated with Dactolisib. We hope that with further validation, the novel contributions of this dissertation can be developed into actionable tools for use from bench to bedside.