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Reverse QMRA As a Decision Support Tool: Setting Acceptable Concentration Limits for Pseudomonas Aeruginosa and Naegleria Fowleri
No full textOpportunistic 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
Experimental Verification of Finite Element Computer Modeling of Distal Radius Locking Bridge Plate for Treatment of Distal Radius Fracture
No full textThis study aims to produce experimental data on the mechanical properties and modes of failure of a distal radius locking bridge plate in simulated distal radius fracture (DRF), both independently and screwed to synthetic bone, loaded in a similar loading configuration as reported in patients. These data will be used to validate a finite element analysis (FEA) model of the same fracture fixation construct under similar loading conditions in future studies. Two biomechanical in-vitro experiments were performed using composite radius and fused hand Sawbones to represent patient anatomy. The plate is installed by a registered orthopedic surgeon using a surgical guide provided by the manufacturer. After plate installation, a one-centimeter gap is osteotomized in the metaphysis region and replaced with rubber. A static loading test in a cantilever arrangement was performed on this assembly, as well as on an isolated plate, held in a custom-made jig in which the sample was fixed proximally. The isolated plate showed plastic deformation at 46.5 Newtons, and the assembly deformed at between 65 and 90 Newtons. Plastic deformation is measured using strain and force gages. These tests measure data at one sample per second, and the rate of change of this data can be studied as a correspondence to spring constant. These values can be compared to show consistency and are elucidated below. Confidence in these results is verified by mathematical modeling which approximates the isolated plate as a simply supported beam. In the case of this simplified model, the isolated plate would deform at 27 N. This is a ballpark approximation that shows that measurements are on the right order of magnitude. These data collected give evidence that the experimental setup gives repeatable results in multiple iterations, which are usable for finite element analysis to be conducted in the future.M.S., Mechanical Engineering and Mechanics -- Drexel University, 201
Understanding the Mechanistic Role of Grain Boundaries on the Strength and Deformation of Nanocrystalline Metals using Atomistic Simulations
No full textNanocrystalline (NC) materials, defined structurally by having average grain sizes less than 100nm, exhibit a number of enhanced mechanical properties such as ultrahigh strength, improved wear resistance and greater resistance to fatigue crack initiation compared to coarser grained polycrystalline (PC) materials. NC materials exhibit these improved properties, in part, due to the increased grain boundary (GB) volume fraction. NC materials strength increases with decreasing grain size, known as the Hall-Petch (HP) effect often resulting in a peak strength between 10-20nm. Studies have shown that NC materials strength decreases due to the shift from dislocation-dominant to GB-dominant deformation mechanisms in the plastic flow regime as average grain size decreases below 10-20nm. While the potential improved properties are of interest, the application of NC materials are hindered due to microstructural instability i.e., grain growth to reduce the total energy of the system, thus degrading desired mechanical properties. Numerous studies have looked at avenues to stabilize NC microstructure, namely through thermodynamics and kinetics, alloying has been one significant strategy used to stabilize NC materials. As these processes are used to stabilize NC microstructures to thermally-induce grain growth, they add additional uncertainty as the deformation and GB behavior of pure NC materials are still not fully understood. Experimental work on NC materials is difficult due to the length scale being investigated as it is difficult to manufacture and can be time consuming to analyze with current technology. Atomistic simulations have shown the potential to investigate fundamental behavior at the nanoscale and provide important insight in the mechanisms that drive the mechanical behavior of NC materials. This thesis will use atomistic simulations to study the structure-property relationship of face-centered-cubic (fcc) metals by focusing on GBs to investigate the strength of NC nickel. During the course of this thesis, four aspects that govern NC behavior will be studied, yielding, plasticity, thermal effects, and GB disorder to elucidate deeper insight into the underlying deformation mechanisms that control the strength of FCC NC metals i.e., flow stress, in the grain size regime 6 to 20nm.Ph.D., Mechanical Engineering and Mechanics -- Drexel University, 201
Mapping of a baseball pitch
No full textCurrently Major League Baseball shows the trajectory of a pitch live using its own in house tracking system, Trackman or Pitchf/x (pre 2015). A major issue with this system is that it is only possible to understand the movement of the pitch as it happens live. As of now there is no mathematical model that would show how the new trajectory of the pitch if the speed were increased or if there was more spin. This thesis will attempt to show a mathematical model that would give the general movement of a pitch with only the inputs of the pitches initial velocity as well as its initial spin. This thesis will explore two solutions, the first using Euler angles and the second using quaternions. This thesis will also explore how to determine the aerodynamic forces using pitch data gathered by Major League Baseball.M.S., Mechanical Engineering and Mechanics -- Drexel University, 201
Sex Differences in the Endocannabinoid System: Implications for Stress-Related Psychiatric Disorders
No full textStress-related psychiatric disorders including post-traumatic stress disorder (PTSD), depression, and anxiety are among the most prevalent conditions in the world, and their incidence continues to rise each year. These patient populations are comprised of more women than men and are difficult to treat as the underlying neurobiology is complex, and a diverse array of symptoms present clinically, often in a sex-dependent manner. The dysregulation of the stress-responsive locus coeruleus–norepinephrine (LC-NE) system has been implicated in the onset and progression of many psychiatric diseases, and restoration of LC-NE function is associated with resolved symptoms in cases of successful treatment. Brain endocannabinoids (eCBs) are ubiquitously expressed neurotransmitters involved in the regulation of many physiological processes, including modulating behavioral responses to stress. The LC is a target of eCB action and exerts its influence via the cannabinoid type 1 receptor (CB1r). The eCB system is capable of enhancing or reducing LC responsivity to various physiological and environmental stimuli. Thus, targeting the eCB system may have therapeutic potential in treating stress-related psychiatric disorders, in part, by modulating the LC-NE system. Conventional pharmacological approaches are often only successful in a subpopulation of afflicted individuals. Therefore, the purpose of the present study is to characterize compensatory mechanisms in the eCB system under conditions of NE depletion, a model of symptoms that arise in patient subpopulations that are difficult to treat such as atypical depression. Protein expression levels of a key enzyme in the biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-[alpha] (DGL-[alpha]), as well as two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) were examined in the LC of mice that lack the NE-synthesizing enzyme, dopamine [beta]-hydroxylase (D[beta]H-knockout, KO) and in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), an LC-specific neurotoxin. In D[beta]H-KO mice, DGL-[alpha] expression was significantly increased in both sexes when compared to wildtype (WT). While MGL expression was not altered in either D[beta]H-KO, FAAH expression was significantly reduced in female D[beta]H-KO groups compared to WT. In DSP-4 male rats, DGL-[alpha] expression was significantly increased compared to saline-treated controls, and a similar trend was observed in DSP-4 treated female rats. There were no observed differences in either groups for MGL expression. Meanwhile, FAAH was found to be significantly decreased in DSP-4 treated males and significantly increased in DSP-4 treated females. Thus, the results of these findings suggest increased eCB tone in DSP-4 treated male rats and overall increased turnover in female DSP-4 treated rats. The results indicate that sex-specific strategies may be advantageous for stress-related therapeutics which are aimed at modifying the LC-NE system via the eCB system.M.S., Drug Discovery and Development -- Drexel University, 201
From School to Work: The Role of Self-Efficacy in a Successful Transition—An Instrumental Case Study
No full textThe transition a person makes when they graduate from business school and move into their first professional job is an important moment in a college graduate's life. Many factors play a role in that transition phenomenon. It is important to conduct research in the area of school-to-work transition between post-secondary education and the working world. State funding models have begun tying education dollars to student matriculation and graduation rates instead of simple enrollment rates. The purpose of this research was to explore the perceptions that undergraduate business program graduates have in relation to their education, their personal belief in their own skills and abilities, and how those skills translate into the workplace. This study was designed to explore the self-efficacy levels of recent college graduates related to their experiences with the current system of professional development programs for undergraduate business students. This research employed an instrumental case study consisting of document analyses and semi-structured interviews with recent graduates focused on their transition experience. The study explored self-efficacy, soft skills, professional development curriculum, connection to colleagues, faculty roles, and reported post-graduation outcome results. This research is significant because the results could inform other education leaders about the need of improving post-graduation outcomes for students.Ed.D., Educational Leadership and Management -- Drexel University, 201
Optimization of a Physiology Based Pharmacokinetic Model for Drug Interaction Predictions With Application to Esketamine
No full textOptimization of a Physiology Based Pharmacokinetic Model for Drug Interaction Predictions With Application to Esketamine Introduction: Drug-drug interactions (DDI) are commonly evaluated during development, as is recommended by health authorities. These interactions may alter the pharmacokinetics (PK), the toxicity, and efficacy of the drug. Cytochrome P450 (CYP) enzymes are commonly considered for DDIs as they play a major role in the metabolism of small molecules. However, the perpetrator drugs may interact with other proteins related to the ADME of the victim drug. A PBPK platform is ideal for exploring these interactions as it can take into account many aspects of ADME processes. Method: A PBPK model will be built utilizing an iterative approach. The model was first built for intravenous (IV) esketamine. The oral model expanded on the IV model with only oral processes being optimized. Lastly, DDI was tested for perpetrator drugs, clarithromycin and itraconazole. Results: Using the iterative process allowed for the successful development of a PBPK model describing both IV and oral esketamine. Total error for the final model reduced from 7.33 to 1.22 and from 3.52 to 2.18 for the IV and oral training datasets, respectively. DDI simulations showed an increase in AUC for clarithromycin and itraconazole, showing a lesser effect to itraconazole. AUC ratios were over predicted compared to observed values, but the simulations upheld the difference in effect of the two inhibitors. Conclusion: The modeling process described in the paper, although timely, has many benefits. It decouples the fitting of IV and oral data together, which aids identification of ADME processes and allows use of limited oral data.M.S., Biomedical Engineering -- Drexel University, 201
Pedagogy for a Globalized World: A Case Study of Teacher Perceptions on Preparing Youth for an Interconnected World
No full textAccelerating trends towards global interconnectedness, multi-cultural societies, and challenges to the earth's eco-system are creating the educational imperative to educate youth in international-mindedness and global citizenship. There is concern, however, that public schools in the United States are not adequately preparing youth to work and live effectively in a globalized society. For scholars, helping schools meet this challenge requires providing them with greater conceptual frameworks that clarify the concept of international-mindedness and an effective global pedagogy. This single qualitative case study explores teacher perceptions at an International Baccalaureate World School in the United States. The methodology used for this case study consisted of one-to-one semi-structured interviews, observation, and documentation to explore the phenomenon. Using a conceptual framework developed by Robert Hanvey (1979), the study analyzed the data using In Vivo and Values Coding methods. Among the study group findings was the perception that international-mindedness consists of open-mindedness leading towards the dimensions of perspective awareness, knowledge and appreciation of other cultures, and awareness of the interconnectedness of the world. Key Words: global education, international-mindedness, global perspective education, global citizenship.Ed.D., Educational Leadership and Management -- Drexel University, 201
Effects of Crosslinking and Pro-Inflammatory Signals on Vascularization of Biomaterials In Vivo
No full textCurrent biomaterials used to support the repair and regeneration of damaged or diseased tissues often utilize crosslinked and non-crosslinked collagen, the most prominent protein in the human body. Crosslinked materials can be advantageous due to their increased mechanical strength, slower degradability, and structure that more closely mimics that in human tissues. One major challenge in collagen-based biomaterials is a lack of healthy vascularization after implantation and its integration in the body. Macrophages are one of the primary cells involved in angiogenesis and in response to implanted biomaterials, which suggests that biomaterials can modulate macrophage behavior and may have potential to facilitate enhanced angiogenesis. Previous research has suggested that pro inflammatory M1 macrophages in crosslinked scaffolds initiate angiogenesis, however, the effect of crosslinking and macrophage behavior on vascularization is still poorly understood in vivo. Therefore, the goal of this study was to determine the effects of chemical crosslinking and the release of pro inflammatory, M1-stimulating, interferon gamma (IFNg) on macrophage behavior and blood vessel infiltration into the scaffolds and within the scaffold cross-section edges in vivo. Following pilot studies to optimize methods for blood vessel measurements, the work for this thesis come from 2 studies, one of which is a repeat of the other (n=6 mice total, 3 mice for each study). One scaffold from each group (non-crosslinked collagen control scaffold, non-crosslinked collagen scaffold with adsorbed IFNg, crosslinked collagen scaffold, and crosslinked collagen scaffold with IFNg) was implanted subcutaneously into the dorsal region of 8-week-old, C57BL/6J male mice. After 14 days, the mice were perfused with anti-mCD31 via a tail-vein injection to visualize blood vessels, and then sacrificed. Scaffolds were then explanted from the mice and processed for cryo-sectioning and staining. Blood vessels within the scaffolds and within the scaffold cross-section edges from each group were manually counted from z-stack images and averaged per mouse. Measurements of the furthest distances that the blood vessels traveled into each scaffold cross-section were also acquired. One cross section from the Disc Center range and one cross-section from each of the Disc Edge ranges were randomly selected per group per mouse to analyze for both studies. Results from both studies showed that crosslinking changed the effects of IFNg compared to non-crosslinked scaffolds. IFNg decreased vascularization within non-crosslinked scaffolds and increased vascularization within crosslinked scaffolds. In scaffolds without IFNg, vascularization was increased in non-crosslinked scaffolds, but decreased in crosslinked scaffolds compared to scaffolds with IFNg. These results suggest that complex interactions between scaffold properties and immunomodulatory drugs affect macrophage behavior. These results also suggest that the immune response can be controlled to affect desired vascularization.M.S., Biomedical Science -- Drexel University, 201
"Remember When?": How Emerging Adults Reflect On, Share, and Make Sense of Photos on Social Media
No full textCurrent technology makes it possible for billions of photos to be taken and shared every day. Many of these photos will collect virtual dust, while others will become cherished digital mementos – objects kept in memory of a person or event. Photos are one of the most central artifacts for supporting reminiscence across the life course. People often keep memorable photos as nostalgic reminders of their past, share them with others to support collective reminiscence, and display them in their homes to reinforce family bonds and personal identities. However, photography has changed with the advent of Smartphones and social media, and we know relatively little about how people identify, manage, and share digital mementos at different stages in their life course with modern technologies, the functions they serve, and the types of content that people come to cherish out of their increasingly massive personal digital archives. One group of stakeholders that fall into a specific life stage, and who may benefit from access to digital mementos, is emerging adults. Emerging adulthood occurs between the ages of 18 and 25, and it has five defining features as identified by Arnett: identity exploration, instability, self-focus, possibilities, and feeling in-between. Since nostalgia and reminiscence serve important self-oriented, social, and adaptive functions across the life course, emerging adults may use and benefit from access to digital mementos during their transition to adulthood. In this dissertation, I explore the roles that photographic digital mementos serve in the lives of emerging adults in college in three phases, which include a descriptive survey on photo-sharing, interviews aided by virtual tours of social media, and a mixed-methods experimental survey. In the first phase of my research, I draw on my survey on photo-sharing with 138 participants, and 23 semi-structured interviews and virtual tours with college students, to examine how and why they reminisce about and share photographic digital mementos. I explore when and why participants reminisce, what kinds of photos become shareable mementos, how they are shared, and the functions these serve in the context of emerging adulthood. I find that the participants seek out digital mementos to buffer against feelings of loneliness and stress, share them to bond over shared experiences, affirm relationships, reconnect with others, and reveal information about themselves to new friends. Digital mementos are also valued because they support impression management and provide a positive resource for reflecting on and exploring identities. Perhaps most importantly, humorous photos are cherished for their social value – something rarely explored in the reminiscence literature – and ephemeral, chat-based sharing platforms like Snapchat have promoted new forms of collective reminiscence and joking that enable people to build and maintain relationships as well as feel like they belong to a group. In the second phase of my research, I conducted a mixed-methods, experimental survey with 132 first and second year college students to explore the narratives that emerging adults develop when writing and reflecting on nostalgic photos, to understand what kinds of photos prompt nostalgia and how emerging adults make sense of them. In this survey, I identify whether reflecting on such photos promotes social and psychological well-being in the forms of increased perceptions of social capital and self-continuity. The third phase of my research explores the roles that digital mementos and nostalgia play in the transition to college and adulthood by synthesizing findings across my interviews. My findings suggest that nostalgia and digital mementos play an important role in the transition to adulthood because they are used to socially, emotionally, and cognitively navigate changing relationships and identities during this life stage. My research expands our understanding of nostalgia in the context of emerging adulthood and digital technologies, identifies different ways that social media affordances influence how young adults collectively and personally engage with their past content, and suggests how design can support meaningful social and personal engagement with digital mementos.Ph.D., Information Studies -- Drexel University, 201