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Kinetics and Mechanics of Blood Clot Contraction
Get PDFThrombotic conditions such as heart attacks and strokes are leading causes of death and disability worldwide. Clot contraction, which is the volume shrinkage of the blood clot, has been implicated to play a role in hemostasis, wound healing, and the restoration of blood flow past otherwise obstructive thrombi. Despite these clinical implications, clot contraction is the least studied area of the coagulation process, which can be largely attributed to a previous lack of methodology. To address this need, we developed a novel optical tracking system that allows for the quantitative assessment of clot contraction. These studies revealed that clot contraction is a three-phase process that can be differently affected by platelets, fibrin, and erythrocytes. Platelet count and function have the ability to enhance the extent of clot contraction while increased erythrocytes and fibrin dampen the extent of clot contraction. We developed a three-element active poroviscoelastic model to improve the understanding of how composition of the clot, particularly the presence of erythrocytes, affects the process of clot contraction. We determined that erythrocytes influence clot contraction through both a tensile and compressive resistance, which resulted in a decrease in the extent of contraction coupled with an apparently paradoxical increase in generation of contractile force. The knowledge that blood composition can influence clot contraction coupled with the clinical importance of thrombotic conditions such as stroke and heart attack revealed a need for studies of clot contraction in patients with (pro)-thrombotic conditions. We examined clot contraction in the blood of patients with ischemic stroke, sickle cell disease, and deep vein thrombosis. Interestingly, in all three pathologies we have observed a significant reduction in the extent of clot contraction. With respect to ischemic stroke and deep vein thrombosis, this reduction in clot contraction correlates with a lower platelet count and platelet dysfunction. Whereas, the reduction in contraction in sickle cell disease patients can be attributed to their increased erythrocyte rigidity. Ultimately after a clot is formed it needs to be resolved, which occurs through the enzymatic process of fibrinolysis. Here we examined influence of clot contraction on rate of physiologic or internal fibrinolysis and clinical thrombolysis or external fibrinolysis. Interestingly, clot contraction enhanced the rate of internal fibrinolysis while decreasing the rate of external fibrinolysis. Collectively, these findings provide new information about basic mechanisms of clot contraction and point to its importance with respect to thrombotic conditions, and have the potential to lead to the development of diagnostic assays or therapeutic targets.Ph.D., Biomedical Science -- Drexel University, 201
Elevating the Arts City: A Study of Place Marketing in Three Philadelphia Arts Organizations
Get PDFAs arts organizations face the challenge of attracting emerging audiences in a competitive market, they are tasked with setting themselves apart with strategic marketing techniques that will sustain their organization. One technique is place marketing, which incorporates an organization’s location into the marketing storytelling to draw audiences to the organization as well as the destination. This study examines three Philadelphia arts organizations that currently use the city to tell their marketing stories to local audiences: Opera Philadelphia, Theatre Exile and the Barnes Foundation. Opera Philadelphia is a 43-year-old performing arts company that incorporated place marketing less than a decade ago. Theatre Exile is a 20-year-old theater company that weaves Philadelphia’s story into each artistic and marketing choice. The Barnes Foundation is a 95-year-old regional landmark established in Merion, Pennsylvania and moved to Philadelphia’s Benjamin Franklin Parkway in 2012. It is only within recent years that the Barnes embraced the city through marketing new audiences. The review of these cases intends to support that the use of place marketing to attract local, emerging audiences, specifically among Philadelphia arts organizations, will enhance a connection to the community and an organization’s own relevance to ultimately influence a city’s position in the arts sector. The paper concludes with recommendations for arts organizations to employ place marketing to their own local communities to elevate their city to a premier arts destination.M.S., Arts Administration -- Drexel University, 201
Rural Public School Educators' Perceptions of the Shared Superintendent's Instructional Leadership
Get PDFShared superintendent agreements in Pennsylvania have emerged as the latest form of school district reorganization. The term "shared superintendent" refers to a superintendent who serves as the chief executive officer of more than one school district. Four school districts have entered into two shared agreements in the last three years in Pennsylvania. This study examines teachers' and principals' perceptions of the shared superintendent's instructional leadership across six rural school districts, engaged in three sharing agreements, in Iowa. Iowa was targeted due to its distinction as the center for superintendent sharing and research. Teachers and principals were asked to rate the instructional leadership capacity of their shard superintendent in the areas of resource provider, instructional resource, communicator, and visible presence. Differences identified between groups and subgroups included special education, "essential", and elementary teachers consistently rating their shared superintendent lower in all areas than their content and secondary area peers. Statistically significant differences were found between the teacher and principal groups in the areas of Resource Provider and Visible Presence. Additionally, years of experience for principals were found to negatively affect principal perceptions, specifically in the Instructional Resource domain. In spite of these differences, the overall perceptions were considered to be positive. These positive perceptions toward the shared superintendent's instructional leadership capacity, coupled with the potential for fiscal savings, make the shared superintendent model a very real and viable possibility for rural school districts considering this in Pennsylvania.Ed.D., Educational Leadership and Management -- Drexel University, 201
Development of a Left Heart Simulator for Prosthetic Valve Evaluation
Get PDFCardiovascular disease is the number one cause of death globally, and many valve diseases contribute to this statistic. Heart valve prostheses have rapidly evolved for both mitral and aortic valves, embodied in both mechanical and bioprosthetic designs. Prosthetic valves undergo extensive in vitro testing to qualify the device’s performance prior to clinical implantation, according to ISO 5840:1. ISO 5840:1 describes the testing requirements for pulse duplication, and currently, device manufacturers utilize academic or commercial pulse duplicators to evaluate their devices. However, both avenues have limitations in quality control or flexibility that bring about the need for a custom pulse duplicator. The objective of this research project was to develop a cardiac pulse duplicator to test mechanical, aortic prosthetic valves in a 3rd party pre-clinical laboratory and validate the benchtop system using ISO criteria. The design incorporated the use of a driving mechanism composed of MTS MiniBionix 858 and a bellow adapted from the TA Electroforce Stent Graft Tester and rigid custom housing to mimic the left ventricle, left atrium, and aorta, reporting pressure as the primary deliverable for analysis. The design was constructed and experimentally validated using criteria from ISO 5840:1, including aortic pressure ranges, peak diastolic differential pressure, systolic and diastolic ratios, motor capacity and tester repeatability. The design conformed with most criteria; however, further work will be needed to implement an additional dashpot component to decrease systolic oscillations.M.S., Biomedical Engineering -- Drexel University, 201
Evaluating School Climate, Teacher Self-Efficacy of Implementation Practices, and Student Outcomes Within a Multi-Tiered Framework of Instruction
Get PDFAs the U.S. Congress continues to increase its demand for accountability and student outcomes, school districts are finding unique ways to meet these challenges in education reform. The Every Student Succeeds Act (ESSA) stresses closing the achievement gap for students who are disadvantaged and have high needs. The act calls for the use of evidence-based intervention models to positively affect student outcomes. Some schools have responded to this challenge by implementing multi-tiered learning strategies that contain the core components as described in the Individuals With Disabilities Education Act (IDEA). Some schools are successful with the use of these multi-tiered learning models, while others are not. Perhaps the difference in success is a result of the influence of other variables found within the learning environment. Research indicates school climate and teacher self-efficacy of implementation practices are major factors in student outcomes and are often the target of school reform. It is easier to evaluate concrete variables that affect the learning environment, and it is more difficult to evaluate and alter those that are abstract and more subjective. However, if schools are able to alter their school climate and change teacher self-efficacy, theoretically, student outcomes would change. This case-study involved an evaluation of school climate as mediating the relationship between teacher self-efficacy and student outcomes in two elementary schools located in an urban New Jersey public school district. Each program was located within the same district and accessed the same multi-tiered learning framework of instruction and RTI consultant, but different student outcomes resulted.Ed.D., Educational Leadership and Management -- Drexel University, 201
Regulation of ACSS2 by O-GlcNAc Transferase in Glioblastoma Cells
No full textO-GlcNAcylation plays an important role in the regulation of various signaling pathways and diseases such as cancer. Many cancers contain elevated O-GlcNAc levels, owed to an increase in O-GlcNAc Transferase (OGT), the enzyme that adds this sugar moiety to proteins. OGT regulates the activity of many pathways, such as those that generate lipid metabolites, which are significantly reduced upon knockdown of OGT. Given OGT’s apparent role in lipid metabolism, we hypothesized that highly lipid-dependent cancers, such as glioblastoma, would be reliant on OGT’s activity. Additionally, glioblastoma has a very poor survival rate, and has been void of significant treatment advances in the last decade, thus research into this disease is desperately needed. Here, we show that O-GlcNAcylation is required for glioblastoma growth, and regulates protein levels of Acetyl-CoA Synthetase 2 (ACSS2), the enzyme that converts acetate to acetyl-CoA, a key precursor of lipid metabolism. Increased O-GlcNAcylation leads to elevated ACSS2 levels and increased phosphorylation on serine 267, a putative cyclin-dependent kinase 5 (CDK5) site. Indeed, we show that CDK5 can phosphorylate ACSS2 in vitro and these two proteins interact both in vitro and in glioblastoma cells in an O-GlcNAc-dependent manner. This phosphorylation event appears to be important in the regulation of ACSS2, as inhibition of CDK5 activity negates OGT’s influence on ACSS2 protein levels. Thus, elevated O-GlcNAcylation increases acetate metabolism through the CDK5-dependent regulation of ACSS2 in brain cancer. This work identifies both OGT and CDK5 as novel therapeutic targets for treating glioblastomas.M.S., Biomedical Studies -- Drexel University, 201
NeuroHub Networking Integration: Time Synchronization Device for Multimodal Brain Imaging and Hyperscanning Research
Get PDFSignificant progress has been made over the last decades in understanding the physiological and neural bases of cognitive processes and behavior. The advent of new and improved sensors enables monitoring the human body and brain activity in natural environments, with cost-effective, mobile and wearable form factor systems. As neuroimaging and brain sensing technologies are further developed, there's an expanding interest for using multiple systems concurrently on i) the same brain: multimodal/hybrid measurements for better identification of neurophysiological markers, and ii) multiple brains: hyperscanning for novel investigations of brain functions during social interactions. Particularly for functional neuroimaging, such as Functional Near Infrared Spectroscopy (fNIRS) and Electroencephalography (EEG), precise time synchronization of experimental events with acquired datasets is necessary for proper analysis and interpretation of results. However, there are currently no standards for interoperability and neuroimaging systems have many different designs and interfaces. Furthermore, it is often cumbersome to come up with a custom solution to each new research setup based on the devices involved. The original NeuroHub, a plug-and-play time synchronization device developed at Drexel University, attempted to alleviate some of the complications associated with custom setups and time synchronization. The original NeuroHub relayed any incoming signal to one of its four serial ports, TTL port, and parallel port, to all other ports on the device and can be connected to multiple sending/listening devices or computers. Although one or more of these legacy ports are present in various neuroimaging systems, modern computing systems require more sophisticated alternatives. This thesis proposes a solution and improvement to the original NeuroHub, by incorporating time synchronization over a network as an information transfer layer. The network solution enables more flexible experimental configurations and expands the compatible plug-and-play system range. Moreover, this new approach eliminates the need for multiple wires, while still being able to service large number of clients. The new NeuroHub is also able to directly interface with typical RS-232 serial ports and offers the best of both worlds - ability to interface with network and legacy hardware ports for complete customizability, flexibility and backward compatibility. The new NeuroHub network module consists of a Raspberry Pi Model 1B fitted with a serial port add-on board. The device transmits any event markers received from either networked or serial ports and relays them to the other opened ports. Verification testing confirmed that the device transmits with 100% accuracy and the latency to send a byte from one computer to the other via the network module was minimal, ranging from sub-millisecond speeds to 7 ms depending on the use of serial ports, baud-rate, and configuration order. The new NeuroHub network module was tested in Brain Compute Interface (BCI) setups using OpenViBE as a stimulus presenter and EEG data recording, with COBI Studio as the fNIRS data recording software to receive markers all through NeuroHub. This simple use case demonstrates the utility of the new NeuroHub for simplification of complex functional neuroimaging, neuroergonomics and BCI research experimental setups.M.S., Biomedical Engineering -- Drexel University, 201
Microglial reactivity and functional deficits following traumatic brain injury in the neonate rat
Get PDFTraumatic brain injury (TBI) is a leading cause of disability in young children as survivors face life-long physical and cognitive impairments. Inflammation, specifically microglia/macrophage activation, has been identified as a target for acute therapeutic intervention for the traumatically-injured adult brain, but it is unclear whether this strategy will be effective in the immature injured brain. Closed head injury in the 11-day-old rat induced robust microglia/macrophage reactivity in multiple brain regions and was associated with neurodegeneration and axonal injury. Additionally, brain-injured animals demonstrated cognitive deficits and motor function impairments at 4 weeks post-injury, mirroring the sustained functional deficits observed in humans. Immediately after injury, intracerebral depletion of microglia/macrophages with clodronate or inhibition of active microglia/macrophages systemically with minocycline decreased the number of total and activated microglia/macrophages in the injured brain. This effect was accompanied by an increase in neurodegeneration at 3 days post-injury, suggestive of a lack of clearance of degenerating cells. Both of these acute manipulations, however, were associated with an increase in microglia/macrophage reactivity and neurodegeneration at 4 weeks post-injury that coincided with hyperactivity (clodronate) or hypoactivity (minocycline) within the injury site. In addition, systemic minocycline administration reversed alterations in cortical activity, deficits in working memory, and impairment of forelimb function that were not associated with neurodegeneration or microglia/macrophage activation. These results are not only suggestive of off-target effects of minocycline, but also emphasize the importance of acute post-injury microglia/macrophage reactivity and the need for a more target-specific anti-inflammatory therapeutic strategy in the developing brain.Ph.D., Neuroscience -- Drexel University, 201
A case study of an instrumental music program and its influence on the culture of a school
Get PDFThe purpose of this case study was to examine how participation in a school-based instrumental music program contributed to the culture of a suburban high school. The questions guiding the research were: (1) How and why are multiple music programs supported by staff, students, parents and the community at this school? (2) What are the benefits of maintaining a music curriculum at the school? A single-site case study was conducted at Bigrock High School, a suburban public school in an area outside a major Mid-Atlantic city. The case study utilized in-depth interviews of students, parents, teachers, school administrator and members of the community as data sources. A content analysis of these interviews provided insight into perceptions and beliefs that stakeholders have about the value of students performing in musical ensembles at this research site. Three strands of literature helped frame the content analysis, namely self-efficacy, social capital, and the implementation of music schools. Findings from this study can provide useful ideas on how schools with fewer resources can benefit from having a music program at their site. This includes investigating programs that support the arts in and outside of schools. Future research can focus on schools with smaller music programs and investigate ideas on becoming larger. Additionally, future research can be centered on the level of musical influence to children whose parents/guardians also played a musical instrument.Ed.D., Educational Leadership and Management -- Drexel University, 201
The Development of an In-situ TEM Technique for Studying Corrosion Behavior as Applied to Zirconium-based Alloys
Get PDFZirconium-based alloys are a commonly used material for nuclear fuel rod cladding, due to its low neutron cross section and good corrosion properties. However, corrosion is still a limiting factor in fuel rod lifespan, which restricts burn up levels, and thus efficiency, that can be achieved. While long-term corrosion behavior has been studied through both reactor and autoclave samples, the oxide nucleation and growth behavior has not been extensively studied. This work develops a new technique to study the initial stages of corrosion in zirconium-based alloys and the microstructural effects on this process by developing an environmental cell system for the TEM. Nanoscale oxidation parameters are developed, as is a new FIB technique to support this method. Precession diffraction is used in conjunction with in-situ TEM to observe the initial stages of corrosion in these alloys, and oxide thickness is estimated using low-loss EELS. In addition, the stress stabilization of tetragonal ZrO2 is explored in the context of sample preparation for TEM. It was found that in-situ environmental TEM using an environmental cell replicates the oxidation behavior observed in autoclaved samples in both oxide structure and phases. Utilizing this technique, it was shown that cracking of the oxide layer in zirconium-based alloys is related to oxide relaxation, and not thermal changes. The effect of secondary phase particles on oxidation behavior did not present significant results, however a new method for studying initial oxidation rates using low-loss EELS was developed.Ph.D., Materials Science and Engineering -- Drexel University, 201