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Examining the Effect of Predictability on Eye Movement During Story Reading in Neurotypical Adults and People with Aphasia
No full textThere is a current need to improve and expand options for reading intervention that support people with post-stroke aphasia. The present study used pre-existing eye tracking data, which tracked the reading behaviors of people with aphasia and neurotypical adults during story reading. The objectives of this analysis were to compare the eye movement patterns of each participant group, and to retrospectively describe an effect of a word predictability measure (surprisal) on eye movement across groups during story reading. Analysis revealed that people with aphasia had longer gaze durations and total fixation durations compared to neurotypical adults, which is consistent with previous findings of group effects in sentence-level stimuli. The positive effect of surprisal on probability of first pass fixation also aligns with previous studies of predictability and eye movement, but the negative effect of surprisal on probability of first pass regression, gaze duration, and total fixation duration contradicts much of the previous evidence on predictability effects. Additionally, no interactions of group and surprisal were found in this dataset, suggesting that neurotypical adults and people with aphasia respond similarly to the predictability of words during reading. While these findings could be attributable to the design of the original experiment or the current analysis approach, it is also possible that these findings are unlocking reading behaviors not previously shown in predictability literature. The current findings have the potential to inform future interventions for acquired reading impairment in post-stroke aphasia
Insights from Sc-RNA Analysis: Immunomodulation and Neutrophils in Periodontitis
No full textThis thesis explores the complex interplay of immunomodulation and neutrophil dynamics within the context of periodontal disease (PD), a chronic inflammatory condition characterized by the degradation of tooth-supporting tissues and microbial imbalance. Central to the pathogenesis of PD are the interactions between various components of the immune system, including innate and adaptive immune cells, cytokines, chemokines, and lipid mediators. Neutrophils are fundamental to the innate immune response in the periodontal environment, serving as the first responders to pathogenic challenges and the overseers of homeostasis. This thesis investigates the therapeutic potential of neutrophil modulation in PD through the local sustained delivery of the chemokine CCL2, encapsulated within biodegradable PLGA microspheres. Utilizing the established murine ligature-induced periodontitis model, this study provides a multifaceted assessment of periodontal health. Parameters such as bone integrity, gene expression profiles, neutrophil cluster dynamics, osteoclastic activity, and the structural organization of the periodontal ligament were evaluated to analyze the effectiveness of the intervention. Advanced single-cell RNA sequencing was employed to unravel the complex gene expression landscape of periodontal neutrophils, uncovering distinct phenotypic subsets and pathways that could potentially guide disease progression or therapeutic resolution. Furthermore, the thesis investigates the nuanced interplay between neutrophils and macrophages, revealing a complex network of interactions crucial for periodontal disease outcomes. By integrating these cellular and molecular insights, the thesis underscores the translational potential of targeting immune pathways to combat PD. The strategic modulation of neutrophils presents a novel avenue for intervention, aiming to rebalance the periodontal microenvironment and halt disease progression. This research endeavors to extend beyond the current paradigms of PD treatment, advocating for the development of targeted immunomodulatory therapies that can effectively restore and preserve periodontal health. This study stands as a testament to the promise of precision medicine in dentistry, with the potential to revolutionize periodontal therapy and improve patient outcomes
Computational approaches for characterization and prioritization of human genetic variants
No full textProtein-coding and non-protein-coding genetic variants both play essential roles in contributing to human diseases. Therefore, better approaches for characterizing and prioritizing genetic variants can advance our understanding of the genetic causes of disease and contribute to the design of diagnostic and therapeutic strategies. In this dissertation, I explore both coding and non-coding genetic variants and report on new computational methods for their annotation and prioritization.
First, I developed a disease-specific approach for prioritizing non-coding variants. Integrating tissue-specific functional genomics data with non-coding disease-associated variants from the NHGRI-EBI GWAS catalog allowed me to design a model for disease-specific variant prioritization. This approach outperformed other variant-prioritization approaches, yielded interpretable and sensible associations between tissues and diseases, and enabled the calculation of disease similarities and the identification of biologically meaningful disease groups.
Next, I further improved this disease-specific approach by combining disease-associated variants across different disease terms, in order to enable information sharing. Through a systematic evaluation of all pairs of disease terms in the GWAS catalog, I discovered that combining variants from related diseases improved the performance of variant prioritization.
Additionally, I found that suitable disease pairs for combination could be quickly identified using the disease similarity we derived previously.
Finally, I focused on a specific type of protein-coding variant that introduces a premature termination codon (PTC) and can lead to mRNA non-sense mediated decay (NMD). Since not all PTC-causing variants trigger NMD, I contributed to the development of a software tool called "aenmd" that annotates whether such a variant is predicted to trigger NMD, or not (NMD escape). Applying aenmd to coding variants from the GWAS Catalog identified disease terms that were enriched with NMD-escaping and NMD-triggering variants, respectively.
Altogether, my thesis presents novel approaches for effectively characterizing and prioritizing protein-coding and non-protein-coding genetic variants in the context of human diseases. The tools I developed will contribute to improved annotation and understanding of genetic variants; they also can assist geneticists in the discovery of genetic factors contributing to human diseases, thereby ultimately facilitating the development of more efficacious diagnostic strategies and therapeutic interventions
Multiphysics Investigations of Emerging Direct Air and Ocean Carbon Capture Technologies
No full textThis thesis aims to advance the diverse fields of carbon removal through the experimental and computational applications of available and emerging materials and processes. Current oceanic and terrestrial carbon dioxide removal strategies span a wide range of technologies supported by biological and nonbiological mechanisms. This thesis organizes the current industry strategies for carbon dioxide removal and expands upon those featuring membrane and solid adsorbent separation mechanisms. First, a literature review organizes the landscape of carbon dioxide removal by analyzing each strategy and its energy costs and infrastructural requirements for deployment. A comparison of these strategies, their current and future challenges, and potential benefits is offered. This review highlights the elevated costs of certain nonbiological carbon dioxide removal strategies and motivates research on membrane- and adsorbent-based carbon separation mechanisms. Second, an investigation is conducted on the feasibility of using membrane-encapsulation of CO solvents to remove dissolved unionized carbon dioxide from seawater. This investigation involved a series of lab-scale experiments that guided the development of 0D and 1D computational models. These computational models then informed a preliminary techno-economic assessment, which found that the economic feasibility of microencapsulated solvents for ocean carbon dioxide removal was limited. The investigation concluded that the financial viability of this strategy is more realistic when seawater pH is lowered by 2-3 orders of magnitude, suggesting the need for advanced membrane coatings development to realize this end. Finally, an investigation is conducted using hierarchically structured metal-organic frameworks (MOFs) as core-shell pellets for atmospheric carbon dioxide removal in the presence of ambient humidity. This highly collaborative MOF investigation combined experimental adsorption isotherm data with computationally derived theoretical selectivity and diffusivity values into a 2D parametric simulation of a core-shell MOF pellet. This model included five distinct variants of the (Zr)UiO-67 MOF and parameterized the pellet's shell thickness, ambient humidity levels, and carbon dioxide concentrations to arrive at optimized operation conditions. This investigation found that the pellet's shell was most effective at separating water from carbon dioxide before reaching the pellet's core when the shell MOF's linker had a more hydrophilic character. A thicker pellet shell increased the degree of separation between these two gases but also necessarily led to extended CO saturation times and reduced capacity. This study concludes with the need for more comprehensive experimental and computational research to facilitate simulation accuracy and reliability. Furthermore, continued efforts to replicate this work will enable the establishment of best-use cases for such hierarchically structured materials in the carbon removal sector
Digital Transformation and Innovation in Health Insurance
No full textDigital transformation holds public health significance by enabling health insurance companies to utilize data-informed decisions to enhance their member services and monitor health disparities for optimized well-being interventions. UPMC Insurances Division as the largest health insurer in western Pennsylvania constantly innovates to provide quality care, lower costs, and smooth experiences with better outcomes for its members. HealthPlaNET and Consumer Innovation, the clinical population health/care management software and digital strategy teams respectively of UPMC Health Plan, represent the “center-edge” of digital transformation in improving and addressing user needs outside of core reimbursement experiences. My role as an Extended Administrative Resident in these teams contributed to this transformation through three projects that developed proprietary strategic improvements across pharmacy; aging in place; and virtual assistant features, as well as data analysis to curate key visualizations for future iterative innovations
Pittsburgh City Theatre Young Playwrights Program 2022-2023 Evaluation Report
No full textThe Young Playwrights’ Program is an annual grant-funded arts educational program for middle and high school students and teachers offered by City Theatre, located in Pittsburgh’s South Side area. The program consists of in-school workshops for students and professional development sessions for teachers in collaboration with residential teaching artists contracted by City Theatre. Students also have the opportunity to develop their own playscripts and submit them to be produced into productions for the Young Playwrights’ Festival in the fall. City Theatre emphasizes the public health significance of youth arts by offering them a platform to empower their unique voices, creating a safe, inclusive environment that helps build community, and providing a space for students to celebrate differences and build self-efficacy. Results indicated that overall satisfaction of the program was positive across students, teachers, and teaching artists. Additionally, City Theatre continues to offer the Young Playwrights’ Program to students who have limited exposure of professional development opportunities in performance arts. General recommendations to improve program implementation include: (1) continue to target schools with higher rates of disparities and/or minority group populations, (2) provide opportunities for teachers to collaborate and share best practices, and (3) improve collaboration efforts between teaching artists and students
Promoting Medication Safety Through Pharmacy-Led Medication Reconciliation
No full textThis essay presents a literature and health policy review focusing on promoting medication safety through pharmacy-led medication reconciliation. Medication reconciliation plays a pivotal role in promoting medication safety through mitigating medication errors, discrepancies, and adverse drug events, which has been a great public health prevalence. Although there is promising evidence that pharmacy-led medication reconciliation may improve accuracy and enhance best practices due to pharmacists’ expertise in medication management, pharmacists are not as integrated in medication reconciliation practices as they should be. This paper will highlight the
need for systemic change in further integrating pharmacy-led medication reconciliation practices to enhance medication safety. Structured into three main sections: reviewing the evidence on the effectiveness of pharmacy-led medication reconciliation, describing the current health policy landscape, which outlines the policy levers that may be used to expand the use of pharmacy-led practices, and a discussion of health system implementation that may constrain the uptake of pharmacy-led medication reconciliation
The Association Between Oral and Systemic Conditions using the Staging and Grading Diagnosis of Periodontitis
No full textSeveral studies have suggested an association between oral infection, especially periodontitis with systemic diseases due to the release of inflammatory mediators like C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin 1 and 6, prostaglandins E2 (PGE2) and matrix metalloproteinases (MMP). Periodontitis is a multifactorial inflammatory condition and one of the most common diseases in the oral cavity. Previous studies have shown the associations between periodontitis and different systemic conditions. However, most of the studies exploring the association between periodontal health and overall health were conducted using the 1999 American Academy of Periodontology (AAP) classification. In 2017 the American Association of Periodontology and the European Federation of Periodontology (EEP) created a new classification for periodontitis diagnosis which includes the rate of progression and the inclusion of diabetes and smoking status as modifying factors influencing the diagnosis. Guided by the available literature and by identified gaps related to the association between systemic and oral health, our research focused on determining the associations between the new staging and grading diagnosis of periodontitis created by the AAP/EEP in 2017 and systemic diseases. We leveraged a cohort of research participants recruited as part of the Dental Registry and DNA Repository (DRDR) at the University of Pittsburgh, School of Dental Medicine to conduct epidemiologic and candidate gene analyses to identify these associations with the most common comorbidities reported at the DRDR. Our study design consists of association studies, including phenotypic and genotypic analysis. We also aimed
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to determine if a genetic variant that has been found to overlap between periodontitis and conditions such as cardiovascular disease and cancers (rs1333048 in ANRIL) is associated with highly characterized oral infection phenotypes in a population from Pittsburgh undergoing regular dental treatment. We have selected a cohort from the (DRDR) and defined the diagnosis of periodontitis according to stages and grades, using the updated criteria. We found a potential link between periodontitis stages 3 and 4, cancer, and asthma. In addition to that, we found an association between the rs1333048 in ANRIL in participants with periodontitis in stages 3 and 4
Computational Investigation of Potential Negative Allosteric Modulator (NAM) Binding Sites for Cannabinoid CB2 Receptor
No full textThe aim of this project is to predict the residues in site C of cannabinoid receptor 2 (CB2) that could play an important role in TM17-1 NAM binding. Prediction of the important binding sites for allosteric modulator (AM) binding is significant as the information from this study could prove to be helpful in the design of future AM drugs. Allosteric modulators have several advantages over drugs targeting the orthosteric or active site, including the ceiling effect, which prevents drug overdoses, biased signaling, and greater specificity to the receptor, which in combination reduces the chance of adverse reactions occurring. We used a combination of molecular docking and structural protein analyses to predict the residues for allosteric modulator binding in site C for TM17-1 NAM binding. Based on the computational studies conducted, we showed that Tyr70, Arg131, Leu 243, and Ser 303 potentially have significant interactions with TM17-1 in site C of the CB2 receptor. Site-directed mutagenesis will be used in future studies to validate our hypothesis. We hypothesize that TM17-1 may act as a CB2 NAM by preventing Tyr70, and Arg131 in CB2 from forming key interactions with Gαi, thus preventing CB2 agonist modulation of this pathway
Bias Against Black Women: A Review of the Effects of Bias Within the Healthcare Setting
No full textBlack women have historically suffered from unequal treatment throughout the healthcare system when compared to their White counterparts, and they continue to face varying forms of opposition when seeking care across healthcare settings. Specifically, Black women are dying at higher rates, not establishing relationships with physicians, and receiving insufficient pain management. Factors contributing to this unequal treatment include implicit bias, lack of resources, insufficient research, and the teaching of inaccurate medical studies. This essay focuses on bias's impact on the care rendered to Black women. Bias refers to the tendency to favor one group over another. Bias can be both implicit and explicit. Implicit bias can be defined as an individual unintentionally using generalizations about a particular group that result in categorizations that are rooted in bias. Explicit bias is based on a person's conscious thoughts and behaviors.
Implicit bias can be hard to identify because when you ask someone a straight-out bias question, they will likely respond in opposition to the intended bias. Explicit bias is an outward expression of biased viewpoints. However, these individuals may not realize that they are perpetuating their unconscious generalization to others. In the end, it will be apparent that clinicians’ biases create unwelcoming environments for Black women to seek help. Bias can be mitigated if healthcare systems address the bias their providers may perpetuate. Some ways in which hospitals can help to resolve some of the bias within the healthcare setting include increasing the quality of care given to Black women, holding training for providers to learn how to communicate with their patients effectively, and teaching them how to listen actively. Moreover, there needs to be hospital standards that address the varying treatment being given to Black patients versus White patients. Hospitals must implement ways to help providers identify and resolve their biases