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Description
Sensitivity is a fundamental challenge for in vivo molecular magnetic resonance imaging (MRI). Here, I improve the sensitivity of metal nanoparticle contrast agents by strategically incorporating pure and doped metal oxides in the nanoparticle core, forming a soluble, monodisperse, contrast agent with adjustable T2 or T1 relaxivity (r2 or r1). I first developed a simplified technique to incorporate iron oxides in apoferritin to form "magnetoferritin" for nM-level detection with T2- and T2* weighting. I then explored whether the crystal could be chemically modified to form a particle with high r1. I first adsorbed Mn2+ ions to metal binding sites in the apoferritin pores. The strategic placement of metal ions near sites of water exchange and within the crystal oxide enhance r1, suggesting a mechanism for increasing relaxivity in porous nanoparticle agents. However, the Mn2+ addition was only possible when the particle was simultaneously filled with an iron oxide, resulting in a particle with a high r1 but also a high r2 and making them undetectable with conventional T1-weighting techniques. To solve this problem and decrease the particle r2 for more sensitive detection, I chemically doped the nanoparticles with tungsten to form a disordered W-Fe oxide composite in the apoferritin core. This configuration formed a particle with a r1 of 4,870mM-1s-1 and r2 of 9,076mM-1s-1. These relaxivities allowed the detection of concentrations ranging from 20nM - 400nM in vivo, both passively injected and targeted to the kidney glomerulus. I further developed an MRI acquisition technique to distinguish particles based on r2/r1, and show that three nanoparticles of similar size can be distinguished in vitro and in vivo with MRI. This work forms the basis for a new, highly flexible inorganic approach to design nanoparticle contrast agents for molecular MRI.
ContributorsClavijo Jordan, Maria Veronica (Author) / Bennett, Kevin M (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sherry, A Dean (Committee member) / Wang, Xiao (Committee member) / Yarger, Jeffery (Committee member) / Arizona State University (Publisher)
Created2012
Description
Virtual Patient Simulations (VPS) are web-based exercises involving simulated patients in virtual environments. This study investigates the utility of VPS for increasing medical student clinical reasoning skills, collaboration, and engagement. Many studies indicate that VPS provide medical students with essential practice in clinical decision making before they encounter real life patients. The utility of a recursive, inductive VPS for increasing clinical decision-making skills, collaboration, or engagement is unknown. Following a design-based methodology, VPS were implemented in two phases with two different cohorts of first year medical students: spring and fall of 2013. Participants were 108 medical students and six of their clinical faculty tutors. Students collaborated in teams of three to complete a series of virtual patient cases, submitting a ballpark diagnosis at the conclusion of each session. Student participants subsequently completed an electronic, 28-item Exit Survey. Finally, students participated in a randomized controlled trial comparing traditional (tutor-led) and VPS case instruction methods. This sequence of activities rendered quantitative and qualitative data that were triangulated during data analysis to increase the validity of findings. After practicing through four VPS cases, student triad teams selected accurate ballpark diagnosis 92 percent of the time. Pre-post test results revealed that PPT was significantly more effective than VPS after 20 minutes of instruction. PPT instruction resulted in significantly higher learning gains, but both modalities supported significant learning gains in clinical reasoning. Students collaborated well and held rich clinical discussions; the central phenomenon that emerged was "synthesizing evidence inductively to make clinical decisions." Using an inductive process, student teams collaborated to analyze patient data, and in nearly all instances successfully solved the case, while remaining cognitively engaged. This is the first design-based study regarding virtual patient simulation, reporting iterative phases of implementation and design improvement, culminating in local theories (petite generalizations) about VPS design. A thick, rich description of environment, process, and findings may benefit other researchers and institutions in designing and implementing effective VPS.
ContributorsMcCoy, Lise (Author) / Wetzel, Keith (Thesis advisor) / Ewbank, Ann (Thesis advisor) / Simon, Harvey (Committee member) / Arizona State University (Publisher)
Created2014
Description
Advances in implantable MEMS technology has made possible adaptive micro-robotic implants that can track and record from single neurons in the brain. Development of autonomous neural interfaces opens up exciting possibilities of micro-robots performing standard electrophysiological techniques that would previously take researchers several hundred hours to train and achieve the desired skill level. It would result in more reliable and adaptive neural interfaces that could record optimal neural activity 24/7 with high fidelity signals, high yield and increased throughput. The main contribution here is validating adaptive strategies to overcome challenges in autonomous navigation of microelectrodes inside the brain. The following issues pose significant challenges as brain tissue is both functionally and structurally dynamic: a) time varying mechanical properties of the brain tissue-microelectrode interface due to the hyperelastic, viscoelastic nature of brain tissue b) non-stationarities in the neural signal caused by mechanical and physiological events in the interface and c) the lack of visual feedback of microelectrode position in brain tissue. A closed loop control algorithm is proposed here for autonomous navigation of microelectrodes in brain tissue while optimizing the signal-to-noise ratio of multi-unit neural recordings. The algorithm incorporates a quantitative understanding of constitutive mechanical properties of soft viscoelastic tissue like the brain and is guided by models that predict stresses developed in brain tissue during movement of the microelectrode. An optimal movement strategy is developed that achieves precise positioning of microelectrodes in the brain by minimizing the stresses developed in the surrounding tissue during navigation and maximizing the speed of movement. Results of testing the closed-loop control paradigm in short-term rodent experiments validated that it was possible to achieve a consistently high quality SNR throughout the duration of the experiment. At the systems level, new generation of MEMS actuators for movable microelectrode array are characterized and the MEMS device operation parameters are optimized for improved performance and reliability. Further, recommendations for packaging to minimize the form factor of the implant; design of device mounting and implantation techniques of MEMS microelectrode array to enhance the longevity of the implant are also included in a top-down approach to achieve a reliable brain interface.
ContributorsAnand, Sindhu (Author) / Muthuswamy, Jitendran (Thesis advisor) / Tillery, Stephen H (Committee member) / Buneo, Christopher (Committee member) / Abbas, James (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
ABSTRACT Current federal and state education mandates were developed to make schools accountable for student performance with the rationale that schools, teachers, and students will improve through the administration of high-stakes tests. Public schools are mandated to adhere to three accountability systems: national, state, and local. Additional elements include the recent implementation of the Common Core standards and newly devised state accountability systems that are granted through waivers as an alternative to the accountability mandates in the No Child Left Behind Act NCLB of 2001. Teachers' voices have been noticeably absent from the accountability debates, but as studies show, as primary recipients of accountability sanctions, many teachers withdraw, "burn out," or leave the profession altogether. The present study is based on the premise that teachers are vital to student achievement, and that their perspectives and understandings are therefore a resource for educational reform especially in light of the accountability mandates under NCLB. With that premise as a starting point, this dissertation examines practicing urban teachers' experiences of accountability in culturally and linguistically diverse schools. To fulfill these goals, this qualitative study used individual and focus group interviews and observations with veteran elementary school teachers in an urban Southwestern public school district, to ascertain practices they perceive to be effective. The study's significance lies in informing stakeholders, researchers, and policymakers of practicing teachers' input on accountability mandates in diverse urban schools.
ContributorsGishey, Rhiannon L (Author) / Mccarty, Teresa L (Thesis advisor) / Fischman, Gustavo E (Committee member) / Ikeler, Susan (Committee member) / Arizona State University (Publisher)
Created2013
Description
Public demands for accountability and educational change are at an all-time high. No Child Left Behind set the stage for public accountability of educators and the recently created Race to the Top grant raised the stakes of public school accountability even more with the creation of national standards and assessments as well as public accountability of individual teacher performance based on student test scores. This high-stakes context has placed pressure on local schools to change their instructional practices rapidly to ensure students are learning what they need to in order to perform well on looming Partnership for Assessment of Readiness for College and Careers (PARCC) exams. The purpose of this mixed methods action research study was to explore a shared leadership model and discover the impact of a change facilitation team using the Concerns Based Adoption Model tools on the speed and quality of innovation diffusion at a Title One elementary school. The nine-member change facilitation team received support for 20 weeks in the form of professional development and ongoing team coaching as a means to empower teacher-leaders to more effectively take on the challenges of change. Eight of those members participated in this research. This approach draws on the research on change, learning organizations, and coaching. Quantitative results from the Change Facilitator Stages of Concern Questionnaire were triangulated with qualitative data from interviews, field notes, and Innovation Configuration Maps. Results show the impact on instructional innovation when teacher-leadership is leveraged to support change. Further, there is an important role for change coaches when leading change initiatives. Implications from this study can be used to support other site leaders grappling with instructional innovation and calls for additional research.
ContributorsCruz, Jennifer (Author) / Zambo, Debby (Thesis advisor) / Foulger, Teresa (Committee member) / Tseunis, Paula (Committee member) / Arizona State University (Publisher)
Created2014
Description
The basal ganglia are four sub-cortical nuclei associated with motor control and reward learning. They are part of numerous larger mostly segregated loops where the basal ganglia receive inputs from specific regions of cortex. Converging on these inputs are dopaminergic neurons that alter their firing based on received and/or predicted rewarding outcomes of a behavior. The basal ganglia's output feeds through the thalamus back to the areas of the cortex where the loop originated. Understanding the dynamic interactions between the various parts of these loops is critical to understanding the basal ganglia's role in motor control and reward based learning. This work developed several experimental techniques that can be applied to further study basal ganglia function. The first technique used micro-volume injections of low concentration muscimol to decrease the firing rates of recorded neurons in a limited area of cortex in rats. Afterwards, an artificial cerebrospinal fluid flush was injected to rapidly eliminate the muscimol's effects. This technique was able to contain the effects of muscimol to approximately a 1 mm radius volume and limited the duration of the drug effect to less than one hour. This technique could be used to temporarily perturb a small portion of the loops involving the basal ganglia and then observe how these effects propagate in other connected regions. The second part applied self-organizing maps (SOM) to find temporal patterns in neural firing rate that are independent of behavior. The distribution of detected patterns frequency on these maps can then be used to determine if changes in neural activity are occurring over time. The final technique focused on the role of the basal ganglia in reward learning. A new conditioning technique was created to increase the occurrence of selected patterns of neural activity without utilizing any external reward or behavior. A pattern of neural activity in the cortex of rats was selected using an SOM. The pattern was then reinforced by being paired with electrical stimulation of the medial forebrain bundle triggering dopamine release in the basal ganglia. Ultimately, this technique proved unsuccessful possibly due to poor selection of the patterns being reinforced.
ContributorsBaldwin, Nathan Aaron (Author) / Helms Tillery, Stephen I (Thesis advisor) / Castaneda, Edward (Committee member) / Buneo, Christopher A (Committee member) / Muthuswamy, Jitendran (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Alzheimer's disease (AD) is the most common type of dementia, affecting one in nine people age 65 and older. One of the most important neuropathological characteristics of Alzheimer's disease is the aggregation and deposition of the protein beta-amyloid. Beta-amyloid is produced by proteolytic processing of the Amyloid Precursor Protein (APP). Production of beta-amyloid from APP is increased when cells are subject to stress since both APP and beta-secretase are upregulated by stress. An increased beta-amyloid level promotes aggregation of beta-amyloid into toxic species which cause an increase in reactive oxygen species (ROS) and a decrease in cell viability. Therefore reducing beta-amyloid generation is a promising method to control cell damage following stress. The goal of this thesis was to test the effect of inhibiting beta-amyloid production inside stressed AD cell model. Hydrogen peroxide was used as stressing agent. Two treatments were used to inhibit beta-amyloid production, including iBSec1, an scFv designed to block beta-secretase site of APP, and DIA10D, a bispecific tandem scFv engineered to cleave alpha-secretase site of APP and block beta-secretase site of APP. iBSec1 treatment was added extracellularly while DIA10D was stably expressed inside cell using PSECTAG vector. Increase in reactive oxygen species and decrease in cell viability were observed after addition of hydrogen peroxide to AD cell model. The increase in stress induced toxicity caused by addition of hydrogen peroxide was dramatically decreased by simultaneously treating the cells with iBSec1 or DIA10D to block the increase in beta-amyloid levels resulting from the upregulation of APP and beta-secretase.
ContributorsSuryadi, Vicky (Author) / Sierks, Michael (Thesis advisor) / Nielsen, David (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2014
Description
Recently, a student in a Maricopa County, Arizona area school district drowned during a physical education class, resulting in a heightened awareness of school aquatics safety guidelines. The goal of this study was to use Wenger's idea of nurturing a Community of Practice (CoP) with the existing physical education CoP at GFJRHS (school pseudonym), to examine the current curriculum and enhance the program and safety standards. The study duration was a five-week period; the participants were 7th grade males. This action research addressed the following questions: 1.)To what extent does the new swim curriculum increase students' (a) self-efficacy for swimming, (b) self-efficacy for water safety, (c) perception of swim skills, and (d) perception of water safety skills? 2.) How, and to what extent, do students value different observational learning techniques presented during the swim unit? 3.) To what extent does the new swim curriculum increase students' swimming capabilities? 4.) How does working as a Community of Practice influence implementing an enhanced swim curriculum? 5.) What challenges and improvements do participants report during the enhanced curriculum? A triangulation mixed methods design was used to determine whether observational learning techniques and mini aquatics safety lessons incorporated into the curriculum improved students' swimming ability, self-efficacy, and safety knowledge. Pre-and post-test swim assessments, pre- and post-test surveys, focus group interviews and researcher journal observations provided data for the study. Both quantitative and qualitative data were collected to integrate the strengths of the varied forms of research. Cronbach's coefficient α was computed for the reliability of the survey and a multivariate repeated measures analysis of variance (ANOVA) was conducted to determine whether the new swim curriculum increased students' self-efficacy for swimming, self-efficacy for water safety, perception of swim skills, perception of water safety skills, and swimming capabilities. Results of this study indicated students' self-efficacy and perception of water safety skills increased, students' ability and perception of swimming skills increased, students valued all observational learning techniques, and teachers felt that functioning as a CoP was crucial to the process.
ContributorsJonaitis, Sean (Author) / Wetzel, Keith A (Thesis advisor) / Ewbank, Ann D (Thesis advisor) / Darst, Paul W. (Committee member) / Arizona State University (Publisher)
Created2014
Description
ABSTRACT Education policymakers at the national level have initiated reforms in K-12 education for that past several years that have focused on teacher quality and teacher evaluation. More recently, reforms have included legislation that focuses on administrator quality as well. Included in far-reaching recent legislation in Arizona is a requirement that administrators be evaluated on a standards-based evaluation system that is linked to student outcomes. The end result is an annual summative measure of administrator effectiveness that impacts job retention. Because of this, Arizona administrators have become concerned about rapidly becoming proficient in the new evaluation systems. Administrators rarely have the explicit professional development opportunities they need to collaborate on a shared understanding of these new evaluation systems. This action research study focused on a group of eight administrators in a small urban district grappling with a new, complex, and high-stakes administrator evaluation that is a component of an all-encompassing Teacher Incentive Fund Grant. An existing professional learning time was engaged to assist administrators in lessening their concerns and increasing their understanding and use of the evaluation instrument. Activities were designed to engage the administrators in dynamic, contextualized learning. Participants interacted in a group to interpret the meaning of the evaluation instrument share practical knowledge and support each other's acquisition understanding. Data were gathered with mixed methods. Administrators were given pre-and post-surveys prior to and immediately after this six-week innovation. Formal and informal interviews were conduct throughout the innovation. Additionally, detailed records in the form of meeting records and a researcher journal were kept. Qualitative and quantitative data were triangulated to validate findings. Results identified concerns and understanding of administrators as they attempted to come to a shared understanding of the new evaluation instrument. As a result of learning together, their concerns about the use of the instrument lessened. Other concerns however, remained or increased. Administrators found the process of the Administrator Learning Community valuable and felt their understanding and use of the instrument had increased. Intense concerns about the competing priorities and initiatives led to the administrators to consider a reevaluation of the competing initiatives. Implications from this study can be used to help other administrators and professional development facilitators grappling with common concerns.
ContributorsEsmont, Leah W (Author) / Wetzel, Keith (Thesis advisor) / Ewbank, Ann (Thesis advisor) / McNeil, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to determine the speed of the plane. A clinical example would be that the flow of a patient's breath which could help determine the state of the patient's lungs. This project is focused on the flow-meter that are used for airflow measurement in human lungs. In order to do these measurements, resistive-type flow-meters are commonly used in respiratory measurement systems. This method consists of passing the respiratory flow through a fluid resistive component, while measuring the resulting pressure drop, which is linearly related to volumetric flow rate. These types of flow-meters typically have a low frequency response but are adequate for most applications, including spirometry and respiration monitoring. In the case of lung parameter estimation methods, such as the Quick Obstruction Method, it becomes important to have a higher frequency response in the flow-meter so that the high frequency components in the flow are measurable. The following three types of flow-meters were: a. Capillary type b. Screen Pneumotach type c. Square Edge orifice type To measure the frequency response, a sinusoidal flow is generated with a small speaker and passed through the flow-meter that is connected to a large, rigid container. True flow is proportional to the derivative of the pressure inside the container. True flow is then compared with the measured flow, which is proportional to the pressure drop across the flow-meter. In order to do the characterization, two LabVIEW data acquisition programs have been developed, one for transducer calibration, and another one that records flow and pressure data for frequency response testing of the flow-meter. In addition, a model that explains the behavior exhibited by the flow-meter has been proposed and simulated. This model contains a fluid resistor and inductor in series. The final step in this project was to approximate the frequency response data to the developed model expressed as a transfer function.
ContributorsHu, Jianchen (Author) / Macia, Narciso (Thesis advisor) / Pollat, Scott (Committee member) / Rogers, Bradley (Committee member) / Arizona State University (Publisher)
Created2013