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CROSS-SECTIONAL ASSOCIATIONS BETWEEN INFLAMMATORY BIOMARKERS AND PHYSICAL HEALTH-RELATED QUALITY OF LIFE AMONG PARTICIPANTS IN THE MULTICENTER AIDS COHORT STUDY
Get PDFMaintaining high physical health-related quality of life (HRQoL) across the lifespan is a
public health priority. Inflammation and immune activation have been associated with the
incidence of various detrimental health outcomes and therefore warrant examination for their
potential impact on physical HRQoL. Our purpose was to estimate the association between
inflammation and physical HRQoL among people living with and without HIV. From 2016-2017,
1,404 participants in the Multicenter AIDS Cohort Study self-reported their physical health related quality of life using the Medical Outcomes Study’s Short Form Health Survey, while laboratory staff measured their serologic markers of inflammation. We used quantile regression to model the cross-sectional association between inflammatory biomarker quintiles and physical health-related quality of life. We found that participants in the highest quintile of interleukin-6 (β =-2.8, 95% CI: -4.0,-1.6; p < 0.001), soluble cluster of differentiation 27 (β =-2.1, 95% CI: -3.6, -0.6; p < 0.01) and B-cell activating factor (β =-2.6, 95% CI: -3.8, -1.3; p < 0.001) had lower physical HRQoL than participants in the lowest quintile of these biomarkers - we did not find significant differences in physical HRQoL by C-C chemokine ligand-2 or B-cell attracting protein 1. We found no evidence of interaction by HIV Status. This study presents novel evidence on the robust association between inflammation and physical HRQoL in a large, well-characterized sample of older men living with and without HIV
A Quantitative Synthesis of Outcomes of Educational Technology Approaches in K-12 Mathematics
Get PDFResearchers have consistently examined the effects of educational technology on K-12 students’ mathematics learning, but previous meta-analyses suffered from lax inclusion criteria, resulting in inflated effect sizes, and also treated educational technology as a method rather than a delivery mechanism. The aim of the present meta-analysis was to examine the effects of ed-tech on mathematics learning employing rigorous inclusion criteria and examining the effects of both study-related and program-related moderators. Preliminary results from a random-effects model revealed a significant, small effect for mathematics learning (g = +.12). Statistically significant moderators included study design, sample size, blended as compared to fully tech, fidelity of implementation, and personalization. The findings support the positive effects of educational technology, and also provide considerations for program evaluators in terms of study design, and for program developers in terms of intervention design.The research reported here was supported by the Institute of Education Sciences, U.S. Department of Education, though Grant R305A210186 to Johns Hopkins University. The opinions expressed are those of the authors and do not represent views of the Institute of the U.S. Department of Education
Enhancing Traumatic Brain Injury Detection through Advanced CEST-MRI Techniques: From Theory to Application
No full textTraumatic brain injury (TBI) poses a significant medical challenge, often eluding detection by conventional imaging methods. This thesis advances the application of Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI) or more specially Amide Proton Transfer weighted (APTw)-MRI to improve the sen-sitivity and specificity of TBI detection and diagnosis significantly. By incorporating advanced imaging algorithms, this research introduces novel quantification tech-niques that enhance the accuracy of detecting and assessing metabolic changes linked to TBI rat models.
The study focuses on optimizing the Region of Interest (ROI)-based analysis using automated MATLAB-based tools, which improves both the analysis process and its reproducibility. It investigates the ability of CEST-MRI to identify subtle biochemi-cal changes indicative of TBI, advocating for its integration into clinical settings. The thesis highlights the development of a MATLAB interface for streamlined ROI se-lection and APTw-MRI signal calculations, facilitating the practical use of CEST-MRI by clinicians.
A crucial part of the research involves adapting a two-pool magnetization transfer (MT) model, employing modified Bloch equations to differentiate between distinct proton pools, which are crucial for accurate TBI assessment. Parameters such as ex-change rates, relaxation times, and RF saturation dynamics are meticulously calcu-lated from CEST-MRI data using the Levenberg-Marquardt algorithm for robust da-ta fitting.
This thesis not only underscores the potential of CEST-MRI in clinical environ-ments but also its advantages over traditional MRI techniques. By offering deeper insights into the molecular pathology of TBI, CEST-MRI holds promise for marked-ly improving early diagnosis, treatment strategies, and patient outcomes, setting a new benchmark in the imaging and management of brain injuries
Effects of Mechanical Cues on Macrophage Behaviors and Their Potential Use for Adoptive Cell Therapy
No full textMacrophages are immune cells that play critical roles in various physiological activities. While soluble factors are known to regulate macrophage polarization, the effect of physical stimuli from the extracellular matrix (ECM) on macrophage behaviors remains largely unclear. Here, I investigate the effect of matrix viscoelasticity on macrophage behaviors using a 3D hydrogel system that mimics native tissue mechanics. We find that matrix viscoelasticity regulates macrophage spreading, phagocytosis capacity, and their response to inflammatory and anti-inflammatory stimuli through integrin signaling, actomyosin contractility, and cellular spatial confinement. Furthermore, I uncover a novel mechanism of macrophage mechanobiology where they develop a mechanical memory of past physical environments and response differently to subsequent polarization stimuli. Leveraging these insights, I engineered macrophages with chimeric antigen receptors (CAR) to enhance their anti-tumor functions and observed improved tumor-killing effects in vitro. Generally, our research not only advances understanding of macrophage mechanobiology but also provides a foundation for the design of new therapeutic strategies and interventions that target macrophages
REMOVAL OF BACTERIA FROM STORMWATER DURING BIOFILTRATION: THE ROLE OF ACTIVATED CARBON AND BIOFILM-FORMING STRAINS
No full textWith rapid population growth and industrial water use, the Earth is facing an unprecedented water crisis, with global freshwater demand predicted to exceed supply by more than 40% in 2030. Consequently, sustaining water resources by exploring alternative sources has become a priority in most countries. Rainwater collection represents an alternative source of water for many purposes. However, surface runoff after rainfall results in the microbial contamination of the rainwater. Therefore, calls for effective filtration of rainwater to remove microbial contaminants and safeguard human health during subsequent use are needed.
Presently, stormwater filtration is commonly carried out through sand filters, but their effectiveness on bacterial retention is low relative to other media, such as activated carbon. However, the presence of biofilms from naturally occurring bacteria in stormwater on the media can change the filter performance. This research investigated the capacities of sand filters modified with activated carbon and biofilms to remove a model bacterial species, Escherichia coli, from stormwater. We found a statistically significant improvement of E. coli retention on the columns with increasing amounts of activated carbon within the sand filter. This improvement may be due to the greater surface area and improved porosity offered by activated carbon, which gives more attachment points for the bacteria. Next, sand filters modified with 20% activated carbon were pre-inoculated with microorganisms capable of forming biofilms, which simulates the process of naturally occurring bacterial biofilm formation on the filtration media. We found that sand filters with activated carbon maintained a significant increase over sand columns in the bacterial retention capacity even in the presence of a biofilm-forming stormwater isolate. However, neither the sand nor the activated carbon breakthrough curves reached a steady-state in the presence of the biofilm-forming isolate, suggesting an extension of the experimental period is necessary to determine long term removal. These results demonstrate the potential benefit of using sand filters modified with activated carbon to further advance the treatment of stormwater for reuse, although more research is needed to determine whether it would make a sustainable long-term approach to stormwater management
Supporting the Mental Health of Intercollegiate Student-Athletes: A Qualitative Analysis
Get PDFDue to limited mental health resources, role transitions, and a lack of career exploration, student- athletes can be vulnerable to experiencing social-emotional challenges when retiring. A qualitative case study with four collegiate student-athletes from all three NCAA division levels explored the stigma associated with mental health in various student-athlete systems and any exposure to mental health education or support resources. In this needs assessment study, participants shared their lived experiences and provided suggestions for additional support and programming. The dissertation study recruited five participants to a 3-week mental health education program. This intervention program required student-athletes to participate in 2-hour weekly Zoom meetings and post-intervention interviews. In addition, participants submitted a pre-intervention survey, two journal assignments, and a post-intervention survey. Participants represented various intercollegiate competition levels, including NCAA Division I, NCAA III, and NAIA Division I. Results found that interactive learning, video-based modules, and athletic content are valuable to consider when designing future educational programs. Through an improvement science framework, this dissertation explored self-determination theory and ecological systems theory to analyze necessary changes to student-athlete mental health programming. This qualitative study can be a framework for researchers and program developers to further educate athletes on career readiness, mental health self-efficacy, and life skills to prepare for the transition from collegiate athletics into the workforce
AN EXPLORATION OF THE PERSISTENT EDUCATIONAL INEQUITIES EXPERIENCED BY BIPOC STUDENTS WITH DISABILITIES
Get PDFDespite years of progress in research, policy, and advocacy, the inequities in educational opportunities for students with learning differences resolutely persist throughout the United States. The issue of educational inequities is further compounded for Black, Indigenous, and People of Color (BIPOC) students who are disproportionately impacted by systemic inequities such as disparities in disability identification, over-placement in restrictive settings, and are significantly more likely to be subjected to exclusionary disciplinary practices. This dissertation research sought to further explore and address factors contributing to these inequities through two empirical studies. The first mixed methods needs assessment study aimed to add to the educational evidence base by exploring three contributing factors: 1) teachers of BIPOC students with disabilities’ perceptions of the Individualized Education Program (IEP) document, 2) teachers of BIPOC students with disabilities’ perceptions of BIPOC students with disabilities, and 3) parents/guardians of BIPOC students with disabilities’ perceptions of, and experiences with, the special education process. Results indicated that teachers' perceptions of BIPOC students with disabilities' abilities to meet grade-level standards and the usefulness of the IEP as an instructional tool were more positive than previous research suggested. Yet, challenges with the IEP document may hinder the ability of teachers to implement the IEP effectively. Parents/guardians of BIPOC students with disabilities reported fewer barriers to special education participation compared to previous studies but understanding and managing the IEP at home remained challenging. Given the challenges surrounding the IEP document for both families and teachers of BIPOC students with disabilities, the second empirical mixed methods study sought to improve IEP accessibility by developing a Digital IEP At-a-Glance Dashboard design that summarized the most pertinent data from the IEP vendor system in a more user-friendly and actionable way through a user-centered design process. Results included a Dashboard design that met user experience and usability standards, and a set of recommendations for further improving the design with more advanced software, recommendations for changes by IEP software vendors to make data more uniformly accessible, and recommendations for national policy changes surrounding the IEP to enable more consistent and coherent local implementation
IMPROVING MAMMALIAN CELL GROWTH MEDIA USING EQUILIBRIUM MODELING AND CAPILLARY ELECTROPHORESIS ANALYSIS
No full textChemical defined media (CDM) used for biomanufacturing requires precise monitoring and management of transition metal chemistry. Free metal ion concentrations must be might enough to ensure availability as cofactors for enzymes, but not so high as to induce toxicity or result in undesirable chemical reactions such as metal ion-catalyzed reactive oxygen species production.
In Chapter 2, the equilibrium computer program Visual MINTEQ is used to calculate how adding ten structurally related chelating agents raises FeIII solubility to targeted levels in AMBIC 1.1, a reference CDM. Additionally, pFe, equal to -log{Fe3+}, is used as a measure of bioavailability. For a given pH, equilibrium with Fe(OH)3(s) fixes pFe up to the point where all solid phase is dissolved. If additional chelating agent is added, pFe increases, indicating a decrease in bioavailability. ZnII competes with FeIII for added chelating agent, and hence the speciation of these two transition metal ions is linked. Compensating for competitive complex formation and other indirect effects using Visual MINTEQ is demonstrated.
Chapter 3 reports on the development of an analytical method for distinguishing FeII from FeIII in CDM samples. Simultaneous addition of a FeII-specific chelating agent and a FeIII-specific chelating agent followed by analytical separation and detection using capillary electrophoresis resolves issues encountered when previously reported analytical methods are used, i.e., redox reactions induced when a single chelating agent is added and possible interference from the presence of other transition metal ions.
Ascorbate has been replaced by the esters phosphoascorbate and sulfoascorbate in a wide range of biomanufacturing settings and consumer products, but little is known about their susceptibilities toward oxidation. Chapter 4 reports that rates of oxidation by hydrous manganese oxide decrease in the order ascorbate > phosphoascorbate >> sulfoascorbate. Reactant and product adsorption were quantified using comparisons of concentrations measured in filtered-only samples with those in samples where HMO had been dissolved using an ASC spike. PASC and orthophosphate concentration measurements were used to distinguish ester hydrolysis-preceding oxidation from oxidation-preceding ester hydrolysis pathways
Addressing Gifted Gatekeeping: An Investigation of Alternative Identification Approaches to Increase Racial and Economic Diversity in Advanced Academic Programs
Get PDFNon-Asian minority students and students from lower socioeconomic backgrounds are significantly less like to be identified for and reap the benefits of advanced academic programs compared to their peers. Applying critical race theory to this pervasive issue highlights flaws in the system of gifted education, firmly rooted in racism, that hinder the proper identification and support of our most vulnerable students. Inequities in identification for gifted education programs can primarily be attributed to the field’s reliance on tools that inherently advantage the White majority and are predominantly measures of privilege that facilitate gifted gatekeeping. To move identification for toward measures of academic potential instead of privilege, this study explores an alternative approach focused on assessing fundamental cognitive skills within the context of the Johns Hopkins Center for Talented Youth (CTY). The first component of this study establishes initial support for increased equity in incorporating assessments of spatial reasoning, working memory, and executive functioning into CTY’s identification approach. The second component of this study pilots the use of cognitive skills as an alternative identification tool in CTY’s identification model. The results of this analysis indicate that cognitive skills classified up to nine times many students in a group of students from historically marginalized backgrounds than CTY’s traditional math and verbal assessment. Taken together, the results of these studies provide foundational support for incorporating assessments of fundamental cognitive skills into identification models for advanced academic programs to identify students from historically underrepresented racial and economic backgrounds more proportionately and equitably
EXPLORING THE ROLE AND PARTICIPATION OF IMMUNE CELLS IN RENAL COMPENSATORY HYPERTROPHY AFTER UNILATERAL NEPHRECTOMY
No full textThe surgical removal of one kidney, also known as nephrectomy, will cause the size increase and functional compensation of the remaining kidney. Compensatory hypertrophy is considered a phenomenon with clinical importance for maintaining healthy renal function in the living kidney transplant donors after unilateral nephrectomy. However, the mechanisms behind the compensatory hypertrophy (CRH) are still largely unclear. Although previous studies about possible hemodynamic and epithelial cell mechanisms involved in hypertrophic growth in kidney have been conducted, the roles for kidney immune cells have been overlooked. This thesis provides an elaborate description on the changes in kidney immune cells after unilateral nephrectomy. Flow cytometry was used to reveal the changes of kidney immune cells while single-cell RNA sequencing was applied to elucidate the gene expression changes in different immune cells. The role of immune cell’s participation in CRH was further tested in an immune deficient mouse —the RAG1 knockout. Chapter 1 provides a comprehensive literature review of the clinical relevance of CRH and current studies exploring CRH mechanisms. Chapter 2 describes experimental designs and methods of this thesis study. Chapter 3 demonstrates the results of this study from multiple perspectives and the discussions in regarding the findings were shown