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Designing Multimedia and 3D-Printed Models to Engage Patients Considering Osseointegration
Get PDFApproximately 1 in 150 Americans currently live with limb loss and this number is expected to double by 2050 (Smidt and Bicknell 2024). While most lower limb amputees use a socket prosthesis to connect their residual limb to their prosthetic leg, some individuals develop skin problems that make the socket prosthesis uncomfortable to wear long-term. Osseointegration (OI), the surgical insertion of a metal implant into the bone of the residual limb, provides an alternative to a socket prosthesis. Johns Hopkins holds monthly OI Clinics for amputees who are either considering OI or have begun the process. The clinic lacked patient-focused visuals to represent the OI care pathway, which includes pre-op requirements, post-op rehabilitation, and long-term care. While multimedia forms of patient education are very effective and accessible via the internet, patients continue to benefit from traditional teaching methods used during clinic, such as in-person discussions and brochures. Studies demonstrate that 3D-printed models give patients a better understanding of their anatomy, leading to improved outcomes (Ghazi and Teplitz 2020; Sander et al. 2017).
This thesis utilized a multimodal approach to educating OI patients, with the objective of creating two resources for limb loss patients to learn about OI within and outside of clinical settings. The resources created in this project include (1) a narrative 2D animation and (2) multi-component 3D printed models. The four minute and 49 second animation addresses crucial aspects of the OI care pathway, including evaluation, surgery, rehabilitation, and long-term care of an OI implant. The two 3D printed models, printed at 50% actual size, visually depict a transfemoral leg after stages one and two of osseointegration with the OPRA™ implant. The models were designed for tactile interaction, serving to educate patients about surgical and rehabilitative considerations related to the OPRA™ implant. To understand the impact of these resources on patient engagement and knowledge, an IRB-approved study will be conducted. Using this patient-centric approach to education, it is our goal to empower patients with the knowledge necessary to make informed decisions about their osseointegration journey
Role of Histone Variant MacroH2A1.1 in Regulating Topoisomerase 1 Activity
Get PDFTopoisomerase 1 (TOP1) activity is critical in resolving DNA supercoiling that arises during replication and transcription but frequently causes single-stranded DNA (ssDNA) breaks (SSBs) in cells. Since the aborted TOP1 catalytic cycle is one of the main sources of accumulated SSBs that leads to mutagenesis and cytotoxicity, a sophisticated and coherent regulatory system is indispensable to repair these breaks efficiently to avoid genomic instability. Notably, the induction of DNA breaks caused by TOP1 inhibition has been exploited in cancer therapies to trigger tumor cell death. Previous research showed that these SSBs can be resolved through repair pathways that involve Poly(ADP-ribose)polymerase-1 (PARP1). Since TOP1 activity is non-random and occurs at defined genomic loci, it is crucial to target the repair machinery coping with TOP1-induced SSBs to these specific loci, suggesting a potential role of epigenetic regulation in this process. However, how this is achieved remains largely unexplored. MacroH2A1.1, one of two alternative macroH2A1 splice isoforms, is the only nucleosome building block with the ability to bind the PARP1 product poly(ADP-ribose) (PAR) and has been implicated in transcriptional control as well as DNA double-strand break repair (DSB). By combining the genome-wide mapping of TOP1, macroH2A1.1, and TOP1:DNA cleavage complexes (TOP1cc) with the functional inactivation of macroH2A1.1 or the alteration of its ability to bind PAR, we uncover that macroH2A1.1 creates a TOP1-permissive chromatin environment that facilitates PARP/PAR-dependent repair of DNA lesions induced by TOP1 inhibition. In summary, macroH2A1.1 serves as an epigenetic modulator promoting TOP1-associated genome maintenance, thus protecting it from the mechanical stress induced by DNA supercoiling. Given that TOP1cc induction is a mainstay cancer treatment, the manipulation of macroH2A1.1 splicing may, therefore, present a potential cancer vulnerability
DESIGN OF A SELF-CONSTRUCTED ELECTROCHEMICAL SYSTEM FOR HIGH SENSITIVITY DETECTION OF 9 MAJOR WATER-SOLUBLE VITAMINS AND DEGRADATION PRODUCTS IN MAMMALIAN CELL CULTURE MEDIA
Get PDFVitamins are essential organic substances in cell culture media, and their instability is a key contributor to the media’s variabilities and short shelf life. Many factors can break down vitamins and yield degradation products that compromise cell culture performance. However, real time measuring and controlling their levels is a challenge. In this paper, a low-cost, highly sensitivity, and fast electrochemical sensor has been developed for the purpose of quantifying 9 water soluble vitamins (vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, and vitamin C) and evaluate their performance in cell culture media, thereby guiding effective strategies for vitamin stabilization.
The initial method employs cyclic voltammetry (CV) detection to fingerprint the unique chemical signature of each electroactive water-soluble vitamins using a glassy carbon electrode (GCE). The sensitivity of this technique is evaluated and discussed. A second approach improves the detection performance through the use of a modified glassy carbon electrode with carbon black, differential pulse voltammetry, and square-wave voltammetry (SWV). Results with respect to linearity, precision and accuracy were obtained in the concentration range studied for the vitamins. The third strategy involves designing a self-constructed, low-cost electrode device that is compatible with commercial CE machines, which has the potential to monitor vitamin levels and trace degradation products rapidly and quantitatively.
The successful development of this sensor will analyze spent media and facilitate the implementation of a control system to monitor nutrient levels for driving feeding strategies. This control strategy ensures the maintenance of vitamin levels crucial for robust growth and protein biosynthesis. Additionally, the use of complexing agents to stabilize vitamins will be explored. In the future, continuous refinement of analytical conditions will ensure rapid and accurate measurements and robust control of mammalian cell culture process
Design, Fabrication, and Validation of an Ultra Miniaturized Wireless Multi-Sensor Recording Device for the Freely Flying Bat
Get PDFThe echolocating bat is an invaluable animal model for studying the mechanisms of active sensing and multiple sensor fusion. In addition to echolocation, bats receive other sensory feedback from vestibular, somatosensory, and visual systems during flying. Exploring how the bat brain processes and integrates these multiple sensory inputs and uses them to guide its motor output will greatly promote understanding of one of the most powerful evolutionarily driven biological systems.
To understand these mechanisms in a natural scenario, the first and foremost question is how to robustly and conveniently record various sensory signals from the freely flying bat. Yet, none of the current state-of-the-art recording methods can record all of these sensory inputs without influencing the bat’s natural sensory-motor functions. This thesis tries to address this challenge by proposing the design and fabrication of a complete hardware and software system solution of an ultra-miniaturized wireless multi-sensor recording device that is mounted on the bat’s head and body with minimal impact on its natural flight kinematics. The customized device can integrate real-time synchronized head and body motion tracking (both 3D linear acceleration and 3D angular velocity), echolocation audio tracking, and eye movement tracking altogether on one single miniaturized device while supporting remote wireless configuration and storing data into the SD card. The validation experiments in a practical experiment environment supported the functionality of the proposed customized device. The pilot design in this thesis proves the feasibility of the ultra-miniaturized wireless multi-sensor recording device and also sheds light on the future device improvement for the freely moving animal recording setup
Optimization of Recombinant Protein Production in Different Cell Lines
Get PDFThis thesis addresses the optimization of recombinant protein production in two distinct cellular platforms: insect (Sf9) and mammalian (CHO-S) cell lines. The first part focuses on Sf9 cells and investigates the potential of histone deacetylase inhibitors (HDACi) as alternatives to commercial enhancers for Sf9 baculovirus expression. HDACi is a chemical component that can inhibit the activity of histone deacetylases and promote histone acetylation, leading to a more open chromatin structure at the promoter regions of target genes and an increasement in gene expression. Using the recombinant baculovirus that contribute to the expression of the β-glucuronidase (Gus) gene as a reference, we compared the commercial enhancer and HDACi Sodium Butyrate (NaBu), BML-210, Panobinostat, and curcumin in insect cell platforms. The Gus virus was harvested by transfected Sf9 cells, virus titer was measured by HPLC. After setting up different cell densities and multiplicities of infections, Sf9 cells were infected by the Gus virus and growth curves were built. The results confirmed that Nabu is the relatively most cost-effective alternative to promote protein production. Additionally, the study explores the use of the 96 deep-well plate as a cost-effective and space-saving alternative to the shake flask for Sf9 culture. Growth curves and metabolic analyses confirm the feasibility of U-shaped plates for Sf9 culture and infection tests. The second part focuses on the optimization of recombinant protein production in CHO cells by enhancing the absorption of glutamine and glutamate, which are beneficial to cell growth and productivity. Overexpression of transporter genes SLC38A2 and SLC7A11 is employed to manipulate the glutamine-glutamate metabolic pathway. Comparative experiments confirm that cells overexpressing SLC7A11 and SLC38A exhibit higher glutamate serection compared to those non-transfected cells. These plasmids used were designed by our collaborators from WPI. To set a control condition for the plasmid itself, they designed a plasmid with mScarlet. Despite lower cell densities due to the stress of high gene expression, the increased glutamate secretion suggests a potential for enhanced protein production in CHO cells. Successful transfection is confirmed by fluorescence microscopy to detect GFP or Red fluorescence in the plasmid
MONOCYTE MIGRATION AND MECHANOSENSING IN HEALTH AND THE TUMOR MICROENVIRONMENT
No full textMonocytes and macrophages are pivotal components of the innate immune system and have been extensively investigated regarding their roles in orchestrating immune response under homeostasis, infection and tumorigenesis. As precursors driving the replenishment of tissue macrophages, classical monocytes that mature in the bone marrow and emigrate to the peripheral blood constantly traffic between blood vessels and tissues, a process during which their phenotypes and functionalities are inherently intertwined with biophysical properties or cellular composition of tissue microenvironment. Nevertheless, the cellular behavior of monocytes in the tissue matrix has long been neglected in that they are conventionally classified as macrophages once extravasated, regardless of their differentiation status.
Here, utilizing biomaterials designed to recapitulate physiological tissue conditions including 3D collagen matrices and tunable collagen-coated polyacrylamide gels, I explore the random basal migration and biophysical patterned domain formation of human primary monocytes in health and the tumor microenvironment.
I first unravel that the migration patterns of monocytes and macrophages are qualitatively and quantitatively different, a difference that is accentuated in the presence of cancer cells. This high-motility tumor-associated monocyte (TAMo) is demonstrated to be pro-tumorigenic and induced by secreted IL-6 in the tumor microenvironment mainly from cancer cells and regulated via IL-6/JAK2/STAT3 signaling pathway, which is independent from widely known CCL2 mediated chemotactic cascade. Enhanced migration drives monocyte’s enrichment in tissue matrix that potentially elicits aggregation. In the second part of this dissertation, I illustrate that matrices of physiological (healthy and diseased) stiffnesses can spontaneously trigger monocyte homotypic patterned domain formation via combined over-expression of β2 integrin and ICAM-1 at their surface to promote long-term cell viability. A phenomenological model based on the Turing mechanism and Cahn-Hilliard equation for phase transitions is developed for simulation, which incorporates the β2 integrin-ICAM-1 complex as a local activator and self-inhibitory soluble factors secreted by aggregated monocytes as global inhibitors. Effects of cell seeding density and cell migration on monocyte homotypic patterns are predicted by computational simulations and validated in corresponding experiments. Collectively, these works characterize the migration and mechanosening of monocytes in healthy and cancerous tissue microenvironment
Three Essays on Tax Deductions and Wealth Inequality
No full textThis dissertation examines the impact of various tax policies on economic behavior and outcomes through three interconnected studies. The first chapter investigates the role of the mortgage interest deduction in influencing the racial wealth gap in America. Using a distributed lag model, I examine the distribution of mortgage interest deduction benefits and their impact on wealth accumulation across different racial and wealth groups. I find significant variations in the impact of the mortgage interest deduction, highlighting its role in perpetuating existing wealth inequalities. The findings suggest the need for policy reconsideration, aiming for more inclusive and equitable housing and tax policies to address the racial wealth gap.
The second chapter employs a difference-in-differences model to analyze the impact of inheritances on wealth accumulation, with a particular focus on the disparities between Black and White households in the United States. I find that inheritances significantly enhance wealth for both racial groups, albeit with notable differences in the extent and persistence of these effects. While White households benefit from a substantial immediate increase in wealth following an inheritance, Black households see less pronounced and shorter-lived benefits. This divergence is evident in wealth mobility, where inheritances boost White households' ability to ascend within the wealth distribution more effectively than for Black households.
The third chapter quantifies tax noncompliance by examining the relationship between charitable contributions and reported income across multiple income sources. The result is used to estimate the true income of self-employed individuals which is then incorporated into a structural probit model to assess the impact of taxation on the choice of self-employment. Employing this methodology reveals that accounting for tax noncompliance enhances the likelihood of opting for self-employment.
Collectively, these essays examine the influence of tax policies on economic behavior and outcomes, with a particular emphasis on wealth inequality. The findings underscore the importance of designing tax policies that enhance economic efficiency, equity, and compliance
ASSOCIATION OF TIME TO EFFECTIVE ANTIBIOTICS AND MORTALITY OUTCOMES IN PATIENTS WITH BACTEREMIA
Get PDFCurrent sepsis management guidelines recommend prompt antibiotic administration for patients
with sepsis and septic shock. The lack of solid evidence to back up the recommended time intervals of 1 hour (in patients with septic shock) and 3 hours (in patients with sepsis without
septic shock), however, weakens the strength of these recommendations. To address the current information gaps and contradictory findings in the field, this study aims to examine the
relationship between time to effective antibiotics and 28-day mortality in patients with suspected
sepsis.
This study uses logistic regression to carefully account for confounding variables such as age, gender, comorbidity score, and septic shock in a cohort of 12,395 adult patients with bacteremia from 5 hospitals, admitted during 2016-2023. Contrary to the existing belief, this study did not
find an association between time to effective antibiotic administration and 28-day mortality in patients with suspected sepsis. Furthermore, this study was not able to identify a sub-population that benefited more from the early administration of antibiotics.
To further understand the effects of antibiotic administration's timing on mortality at shorter periods, key landmark time analyses were performed. This granular analysis was not able to find a statistically significant association between time to effective antibiotics and mortality at various
time points.
The low mortality rate in the cohort as a whole and the small number of patients who had septic shock could have affected our study's results. Additionally, our results should be interpreted cautiously because some sub-populations have smaller sample sizes.
This study does not recommend or does not de-value the necessity of early administration of
effective antibiotics. However, it raises questions regarding the extent of the benefits of timing
of effective antibiotics in patients with possible sepsis
UNVEILING THE DYNAMICS OF TEACHER RETENTION IN TITLE 1 SCHOOLS: A COMPREHENSIVE EXAMINATION OF CONTEXT-SPECIFIC FACTORS
Get PDFThis dissertation delves into the complex issue of teacher retention in “high-needs” schools, with a particular emphasis on the impact of administrative support, working conditions, and teacher stress and burnout. Existing literature has extensively examined these factors, recognizing their influence on teachers' decisions to stay or leave. However, this study advances the understanding of teacher retention by employing a two-phase research approach.
The first phase of the research involved a mixed methods study conducted in a large high school situated in a major urban center. This comprehensive investigation sought to elucidate the relationships between administrative support, working conditions, teacher stress, burnout, and teacher retention. Despite the initial inconclusive results, the study highlighted the pivotal role of stress as a significant factor affecting teacher retention.
Building upon these insights, the second phase of the research focused specifically on the impact of stress. Employing a qualitative exit interview protocol, this phase aimed to uncover context-specific factors that propel teachers to exit the classroom. By delving into the narratives of departing teachers, the study aimed to provide a nuanced understanding of the challenges they face and the circumstances that contribute to their decision to leave.
The findings of this dissertation contribute valuable insights to the existing body of knowledge on teacher retention in high-needs schools. By emphasizing the centrality of stress and exploring its nuanced manifestations, this study not only enhances our understanding of the factors influencing teacher retention but also provides practical implications for educational policymakers, school administrators, and other stakeholders invested in creating supportive environments for teachers in high-needs schools. Ultimately, this research seeks to inform targeted interventions and policies that can positively impact teacher retention and, by extension, enhance the overall quality of education in high-needs school settings
We are the Intervention: Enacting new Approaches to Combat Disproportionate Discipline
Get PDFSchool segregation on the basis of race and ability seems like an issue long since overcome. While outright refusal to enter the classroom based on these characteristics is a thing of the past whether or not these students stay in the classroom is still up for debate. Students of color and students with disabilities are continually excluded from the classroom on the basis of discipline. Research demonstrates that these students experience exclusionary discipline practices–including office referrals, suspensions, and expulsions–at a disproportionately higher rate than their White and non-disabled peers. The extant literature identifies educator practices, perceptions, and sense of self-efficacy for preventing and responding to challenging student behaviors as key contributing factors. This research included a multimethod needs assessment that investigated these factors through an online survey (n = 22) and semi-structured interviews (n = 5) with recent graduates of a graduate-level certification in Applied Educational Neuroscience (AEN; Desautels, 2020) from a Midwest university. The survey included scales from the Survey of Behavior Management Practices (Reupert & Woodcock, 2010), the Classroom Management subscale of the Teacher’s Sense of Efficacy Scale (Tschanen-Moran & Woolfolk-Hoy, 2001), an experimental vignette with a racial prime (Marcucci, 2020), and a researcher created experimental vignette with a neurodivergent prime. Findings identified a shift in educator perceptions of discipline toward a new conceptualization founded in AEN, disconnects between the practices aligned with this new approach and traditional behavior management practices, and the impact of physiological state on educator self-efficacy. Perhaps the most significant finding included the consensus that educators themselves are the most powerful behavioral intervention. Based on these findings, the researcher proposed a study that departs from status quo professional development by adopting the theory of enactivism (Varela et al., 2017) as theoretical grounding for a participatory action research project (PAR; McIntyre, 2008; McTaggart, 1991; Schubotz, 2019) with educators in the field. The proposed study aims to identify enactive behavioral strategies founded in AEN principles and investigate the impact of educator physiological state when responding to challenging student behavior using small group collaborative sessions and one-on-one coaching sessions. In alignment with a PAR design, the proposed study will collect data using predetermined measures–pre and post-study interviews and session attendance–and emergent measures–tracking educator practices and physiological states–collaboratively created with participants. The researcher will analyze data using qualitative–coding, cross-analysis–and quantitative–descriptive statistics–methods. The proposed study includes formatting for small group and one-on-one sessions, sample materials for sessions, and a researcher-created coaching template grounded in Wink’s (2011) cycle of critical pedagogy