Reverse QMRA As a Decision Support Tool: Setting Acceptable Concentration Limits for Pseudomonas Aeruginosa and Naegleria Fowleri

Opportunistic premise plumbing pathogens such as Pseudomonas aeruginosa and Naegleria fowleri are a growing concern in building water systems because of their potential risks to human health. The aim of this study is to determine the critical concentrations of P. aeruginosa and N. fowleri in water that are associated with meaningful public health risks. To determine these concentrations, a reverse quantitative microbial risk assessment (QMRA) was conducted. Environmental concentrations of P. aeruginosa and N. fowleri corresponding to the risk target of 1 micro- disability-adjusted life year (DALYs) per person per year and 1∗10−4 annual risks of illness were calculated for several applicable exposure scenarios. To calculate the concentration of P. aeruginosa, cleaning contact lenses with potentially contaminated tap water in the absence of an appropriate cleaning solution was considered. For N. fowleri, two exposure scenarios, recreational exposure (swimming), and nasal cleansing (via the use of a Neti pot or similar device) were considered. Critical mean concentrations of P. aeruginosa were obtained (mean concentration 0.30 CFU/L to 0.33 CFU/L) for the two experimentally measured and drop volume exposure methods based on the DALY approach. The highest critical concentration for P. aeruginosa was found to be 33.41 CFU/L with a 95% confidence interval of [2.03,117.70] for the drop measurement exposure method using the 10-4 annual risk target. For N. fowleri, based on the DALY approach, critical concentrations were 1.08 N. fowleri/L for swimming and 0.02 N. fowleri/L for Neti pot use scenario. Considering the heat inactivation, the critical concentration limits for P. aeruginosa using the DALY approach and the 10-4 annual risk target approach were found 0.55 CFU/L and 54.57 CFU/L, respectively based on the measured scenario. For N. fowleri, the 10-4 annual risk target approach resulted in 20.95 N. fowleri/L and the DALY approach resulted in 0.02 N. fowleri/L for the Neti pot scenario. Sensitivity analysis was performed for all the exposure scenarios. For P. aeruginosa, N50 and alpha (α) contributed the most and contact rates the least to the variability and uncertainty of the estimates for all the scenarios. For N. fowleri, N50 and contact rates contributed the most and α the least to the variability and uncertainty to calculate the concentrations for all the scenarios. The QMRA framework implemented in this research can be used to incorporate more information regarding opportunistic pathogens to inform management decisions, and to prioritize the best intervention regarding estimated reduction in infections caused by opportunistic pathogens.M.S., Environmental Engineering -- Drexel University, 201

Funding Arts Organizations and Social Justice

The arts and social justice are historically interconnected, but current research demonstrates how arts and culture organizations connect funding models to these practices. Funding for the arts sector has been studied as well as research about how the arts affects social justice. My research examines funding models and methods used by arts and culture organizations who embark on social justice programming. Through a review of the literature and interviews at three arts and culture organizations in the City of Philadelphia, my research uncovers common themes in the sector, specifically in regard to funding. Further, my research explores the intersecting topics associated with funding, including programming, evaluation, and communication with community members and donors. It is the intention of this paper to offer findings and recommendations for the field as we move towards increased engagement in social justice.M.S., Arts Administration -- Drexel University, 201

Utilizing a convolutional neural network to predict HIV-1 Tat biological functions and the impact of Tat genetic variation on neurocognitive impairment

Human immunodeficiency virus type 1 (HIV-1) infections have been associated with neurocognitive impairment. However, this cognitive decline occurs at a rate that is specific to individual patients. Evidence suggests that the protein sequence of HIV-1 Tat may have an impact on this rate. The mutations within Tat can affect the biological function of this viral protein. This study proposes to utilize deep learning techniques to perform inference on amino acid changes and their effects on Tat functions. To predict biological functions consistent with annotations of the Gene Ontology (GO) Consortium, a convolutional neural network (CNN) was developed and trained on more than 500,000 GO-annotated sequences from the Uniprot Knowledgebase. Analysis was performed on various lengths of Tat protein sequences, considering the prevalence of naturally truncated Tat protein sequences in HIV-1-infected patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) cohort. Results of processing truncated Tat subtype B sequences with lengths between 20 and 60 amino acids revealed a decreased sequence similarity with proteins found in the nucleus and an increased sequence similarity with proteins associated with pathogenesis, extracellular regions, and cellular toxicity. With the focus of examining which regions of Tat are responsible for its known biological functions, a windowing strategy was implemented. Using 30-mer windows, there was an increase in sequence v similarity to proteins associated with ribosomal function and translation for the Tat polypeptide region between residues 40 and 80. The CNN achieved an area under the receiver operating curve (AUC) of 0.985 for GO predictions and 0.541 for neurocognitive impairment. The evaluation metric of AUC has been used in several peer-reviewed papers, but it is not an ideal evaluation method. Although some neurocognitive impairment (NCI) prediction AUC scores are fairly high, there is little to no correlation between the predicted and calculated, actual score using Pearson correlation.M.S., Biomedical Science -- Drexel University, 201

Demographic and Socioeconomic Characteristics Associated with Hospital Acquired Clostridium difficile Infections at Hahnemann University Hospital: Identifying Risk Factors For Use of Indications to Receive a Clostridium difficile vaccine and for the Development of a Generalizable Predictive Prevention Tool

Clostridium difficile is a gut colonizing, gram-positive, sporulating, anaerobic bacteria that causes disease when toxins are released, leading to gastrointestinal inflammation and other associated side effects. C. difficile infections (CDIs) have been highly associated with age and length of inpatient hospital stay. Hahnemann University Hospital (HUH) serves a unique population of low income, minority, and young patients in a large, urban, tertiary acute care medical center providing this study a unique population of subjects to further test known risk factors of CDI and determine other potential risk factors that may not have been detected by the Centers for Disease Control and Prevention (CDC). We hypothesized that analysis of this cohort would reveal unique risk factors associated with patient characteristics and socioeconomic factors. Using a cross-sectional analysis of medical records from HUH, collected between 2014 and 2016, we analyzed 682 subjects in a 1:2 case-control ratio. Every lab confirmed Hospital-Acquired CDIs (228 subjects) were collected from medical records and considered as cases. Non-CDI controls (454 subjects) were randomly selected from the general hospital census and frequency matched for age and duration of inpatient visits. In the first aim, I conducted a test of proportions (chi-squared) to find if there are any significant differences between cases and controls by sex, race, ethnicity, where people were referred from, or insurance type--all potential confounders. This analysis demonstrated stark differences in insurance types (private versus nonprivate) between HA-CDI cases; 62% were Non-Private in comparison only 38% controls were Non-Private. CDI cases were more likely to be African American or Black, making up 53% of all HA-CDIs versus 48% of Controls. Just over half of all cases were males, the majority being between the ages of 46 and 64 years of age. Most patients with HA-CDI came from their homes before being admitted to HUH (66 %). These results do not reflect the CDC's findings that people over the age of 65 have a higher risk of developing CDI. Secondly, we analyzed potential environmental risk factors for HA-CDI in the Philadelphia and Southern New Jersey zip codes. In this analysis we collected zip code data on mean population, median household income, median age, household size, race, and education. These analyses showed no significant differences of any specific ecological factors, including neighborhood levels of poverty and education status when compared with Controls. This analysis showed that within Hahnemann's catchment area, HA-CDI risk factors do not reflect national trends but do reflect the local demographics. It also found that whether someone is on private versus non-private health insurance could be an indicator of risk for HA-CDI. In the discussion, I review why HA-CDI surveillance may be most effective at the local level focusing on the demographics of the patient population of that hospital. Risk factors considered to be generalized may not be when a hospital's population is not representative of the U.S. general population.M.S., Biomedical Science -- Drexel University, 201

Method of quantifying wind-driven natural ventilation flowrate and the development of systematic analysis on the relationship between the flowrate and building configuration

It is very challenging to design a building when one is trying to determine the wind-driven ventilation due to the instability of the wind. While a significant amount of research has been carried out to measure and estimate the wind-driven ventilation of buildings in the recent decade, few could systematically quantify the ventilation flowrates in different building types in different wind environments. In order to thoroughly investigate the research gap above, the thesis has been divided into four stages and covered by four related studies. the first stage of the four studies analyzed the relationship between façade opening size and wind-driven airflow rates through small openings by using CFD. Then, for the second stage, a Weibull model fitted wind characteristic study was carried out to try to represent variable wind by a mathematical model. A series of CFD simulation and wind tunnel experiments were conducted for the third stage to establish a methodology to use CFD simulation software carrying out virtual wind tunnel experiments. Finally, for the last stage, by applying the methodology created in the third stage, a series of building façade pressure coefficient simulations were conducted, and wind-driven ventilation of these buildings under historical wind conditions was estimated. To summarize the results of these four related studies, the opening size analysis showed the relationship between the airflow at the building opening, which is driven by the wind, opening size, and wind direction. The investigation revealed the airflow through the opening was mostly driven by the pressure difference, in which wind momentum energy dissipated at the building surface, even while the wind was not perpendicular to the façade. By changing the opening size, it also revealed that the primary driving force of the airflow through opening shifted from pressure to momentum while the opening size was increased. This study provided the threshold of opening size while pressure-driven airflow applied. The next step provided the mathematical model exploration of wind data, which delivered a method to represent wind characteristic data. The study illustrated the inaccuracy of using TMY3 wind data to estimate wind-driven ventilation when comparing to ASOS data. Weibull model fitted into ASOS data showed the potential of using the mathematical model to generate wind data. The thirst step demonstrates the use of a virtual wind tunnel developed to systematically obtain building facade pressure coefficient and the accompanying framework to duplicate this process to fit any building. This virtual wind tunnel analysis was validated against a real wind tunnel experiment (by FIU WoW facility) and the method and framework of acquiring pressure data under different wind conditions via the virtual wind tunnel are expected to generate high-value results for other researchers. Finally, by applying the virtual wind tunnel based data (pressure coefficients), the estimation of wind-driven ventilation rates was calculated for different building and different locations. The calculated flowrates was used in investigating the efficacy and viability of using wind-driven natural ventilation to fulfill current ventilation requirements.Ph.D., Environmental Engineering -- Drexel University, 201

Associations of built and social neighborhood environment variables with pediatric BMI z-score and changes in BMI z-score

Introduction: Child obesity remains a major public health challenge and neighborhood environments could have a significant role in driving the epidemic. However existing evidence on the impact of neighborhoods on child obesity remains inconclusive. I conducted a systematic literature review of longitudinal studies analyzing the associations between built and social neighborhood environment exposures and pediatric weight. I also conducted a cross-sectional and longitudinal study of these exposures’ associations with BMI z-score using geographically linked electronic heath records (EHR) from a large sample of urban-dwelling, predominantly African American children. Methods: The literature search included six databases searched over 2011 to 2017. Thirty-one longitudinal studies met the inclusion criteria. Information on the study populations, exposure and outcome measures, and main results were extracted. To conduct the cross-sectional and longitudinal analyses I used a pediatric integrated EHR database of children residing in Philadelphia from 2007-2016. I used a generalized estimating equation to analyze the cross-sectional associations between built and social neighborhood environment variables with BMI z-score. I also examined synergisms between built and social environment variables. I used a fixed effects model to analyze the associations between a change in the neighborhood environment with a change in BMI z-score. In both analyses I examined whether associations were modified by age, sex, neighborhood SES, or population density. Results: Most longitudinal studies of the relationship between the built and social environment are prospective cohort studies conducted in high income western countries. The literature review showed that higher access to greenness, parks, and physical activity facilities were associated with less weight gain and lower obesity incidence. The literature also showed that increases in crime were associated with increases in BMI and higher obesity incidence. Cross-sectional analyses showed that higher greenness and Walk Score® were associated with lower BMI z-scores. Higher access to healthy food and physical activity facilities was associated with higher BMI z-scores. I did not find synergisms between built and social environment exposures. Longitudinal analyses showed that increases greenness and safety were associated with decreases in BMI z-score. The effects of safety were stronger in younger children than older children. Increases in social cohesion were associated with increases in BMI z-score and this effect was stronger in boys than in girls. Conclusions: Greenness and safety are associated with decreases in weight in children. Further research is needed to understand associations between changes in healthy food stores, physical activity facilities, urban form, and social cohesion with changes in pediatric BMI.Ph.D., Epidemiology -- Drexel University, 201

Characterizing the Induction of Senescence by Tau and Beta-amyloid in Rat Astrocytes

Alzheimer's Disease characterized by cognitive deficits, memory loss and changes in behavior has no cure currently. Beta amyloid and tau are two main proteins that play a significant role in AD. A mutated Amyloid Precursor Protein abnormally cleaved by beta and gamma secretases causes the accumulation of beta amyloid that lead to the characteristic beta amyloid plaques found extracellularly in AD patients. Tau induces its own adverse effects by hyperphosphorylation and forming neurofibrillary tangles. Aging is the primary risk factor for Alzheimer's Disease (AD). Senescence is a hallmark of aging that can a contributing factors in pathology of AD. there are many overlapping consequences of senescence in AD such as oxidative stress, inflammation and DNA damage. Previous results from our lab have shown that there is an increase in the population of senescent astrocytes in AD patients and beta amyloid as the inducer of the program of senescence. Astrocytes have a vital role in regulating homeostasis at the blood brain barrier and hold a strategic position between the neurons and the capillaries. Astrocyte senescence is considered in this thesis as a contributing factor to AD. Tau, the other hallmark of AD may be also play a role in the induction of senescence in astrocytes. In this thesis, we analyzed the roles of tau and beta amyloid in the activation of senescence in rat by the expression SA-beta galactosidase and mitochondrial membrane potential. Our findings support that tau and beta amyloid have different targets that induce senescence in the astrocytes. The combination of beta amyloid and tau as well as beta amyloid by itself, were well characterized by the expression of SA-beta galactosidase and Tau is shown to be implicated in mitochondrial dysfunction.M.S., Biomedical Engineering -- Drexel University, 201

Multiscale Modeling of Thixotropy in Soft Clays

Thixotropy is a material property that describes how a substance can 'soften' upon continues deformation and heal back to the 'thicker' state over time when left to rest. It is also a fundamental soil behavior mechanism that governs multiple time-dependent engineering properties of soft clays (e.g., the evolution of stiffness, strength, and sensitivity over time).While significant understanding of thixotropy of colloid systems has been achieved since the initiation of the field of thixotropy in the early 1920s, current knowledge on soil thixotropy is still based primarily on some pioneering work performed in and prior to the 1960s and, since then, new developments have been scarce and fragmental. Such a paucity of new findings and the disparity in thixotropy research and advancement between colloid science and soil mechanics provide an impetus to this research. Therefore, this project that integrates multiscale computational and experimental efforts is to study soft clay thixotropy. The work done in this study aims to examine and simulate the clay particle-scale development of thixotropy under various environmental conditions (time, water chemistry, and temperature) and at different size scales. This innovative bottom-up multiscale modeling approach serves to understand the physics underlying macroscopic soft clay thixotropic behavior. The overall goal of the project is to create the enabling knowledge on the macroscale mechanical and microscale structural mechanisms of soft clay thixotropy and hence to append some new time-dependent soil behavior to the geotechnical knowledge base. It is to develop an understanding of the micro- to macro-linkage of soft clay thixotropy through the development of a versatile molecular dynamics (MD) simulation tool to accurately duplicate the time-dependent interactions between clay particles and to provide a framework for the study of the three-dimensional mechanical behavior of soft clays. The value of this project stems from three aspects: (1) the geotechnical knowledge base on soil thixotropy will be expanded with new understanding, particularly the effects of physico-chemical factors such as temperature and porewater chemistry; (2) both the macroscale mechanical and microscale structural mechanisms of thixotropic hardening of soft clays will be uncovered via multiscale computational research; and (3) the linkage between quantitative time-dependent clay fabric evolution and macroscale thixotropic processes will be developed. Because soil thixotropy plays an important role in many engineering problems, the project also can generate significant practical impacts to geotechnical engineering, particularly the design and construction of engineering systems involving soft clays. Examples include evaluation of pile and suction caisson setup, design of wind farm foundations, and disposal of dredged materials, among others. Moreover, the multiscale investigation methodology developed through this project can be generalized to other more complex soil research topics and can also serve as a generic approach for other basic research queries.Ph.D., Civil engineering -- Drexel University, 201

Coca-Cola and Corporate Social Responsibility: A Case Study of Sustainable Development in Education in Kenya

The launch of the United Nations Sustainable Development Goals in 2015 included the private sector as a key actor to improve sustainable development across 17 targets, including education. Utilizing a qualitative case-study approach, the research provides insight into the implementation of a Fortune 500 U.S.-based company's investment in sustainable development through exploration of the Coca-Cola Company's corporate social responsibility (CSR) education programs in Kenya and their impact on the beneficiary. The following questions guided this research: a) How does Coca-Cola represent its CSR education activities in public relations materials? b) Who are Coca-Cola's partners for program planning, implementation, and evaluation of CSR education activities in Kenya and what is the value of Coca-Cola's work to these partners? c) What challenges have Coca-Cola partners experienced implementing CSR education activities in Kenya? d) What strategies did Coca-Cola develop to overcome such challenges? e) What challenges or tensions remain and what does this suggest for the futher of CSR in education? Through an exploration of Coca-Cola's partners, specifically those working on water conservation, entrepreneurship, and scholarships, this study illuminates the ways business-society relationships in education can work to overcome structural barriers limiting access to education, such as financial constraints, discriminatory sociocultural beliefs, and gender inequality. The study contributes to the literature on corporate social responsibility, education, and international development.Ed.D., Educational Leadership and Management -- Drexel University, 201

Visual Artist Studios in Philadelphia: A Case Study of Three Studio Facilities

While studio space is essential to an artist’s practice, the quality and availability of this space varies. Inspired by difficulties in finding affordable and convenient space, I set out to better understand what it takes to rent and manage independent studio spaces. Through researching existing visual art studios in Philadelphia, I aimed to find out what makes a studio space successful and determined common needs and challenges of both tenants and management staff running these facilities. Focusing on three studio facilities in Philadelphia – Bok, Crane Arts, and MaKen Studios – I conducted a multiple case study to explore how these facilities are meeting visual artist tenants’ needs, and what a successful independent studio space may look like. Through interviews with management staff and visual artist tenants, as well as a tenant survey, I explored multiple perspectives to better understand common challenges and benefits of these spaces. Most tenants were generally satisfied with their studio situations. However, common tenant needs were identified. The most prominent was the desire for low and stable rent, as well as the need for both private workspace and a space to conduct additional business beyond art making. Most management staffs’ concerns related to the ability to meet tenants’ individual needs, including outfitting spaces and providing appropriate utilities. While some management is more involved than others, the relationships between the staff and tenants are generally positive. Additionally, some external environmental and economic factors affect both management and tenants. However, additional research on neighborhood changes in Philadelphia and the impact of artists on cities needs to be explored to further address this.M.S., Arts Administration -- Drexel University, 201