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EVALUATION OF THE CO-INFLUENCE OF HEAT INDEX, SOCIAL VULNERABILITY INDEX, AND NEIGHBORHOOD FACTORS ON CRIME RATE - A CASE STUDY OF BALTIMORE CITY
No full textThis study investigates the relationship between heat index (HI), built environment, socioeconomic status (SES), social vulnerability index (SVI), and violent crime rates in Baltimore in summer from 2016 to 2022 through a univariate analysis using zero-inflated Poisson (ZIP) regression and spatiotemporal analysis using a spatiotemporal Bayesian Hierarchical Model (BHM). First, we found in univariate ZIP analysis that a negative correlation between green space (GS) coverage and the crime rate (relative risk (RR) = 0.544, 95% confidence interval (CI ) 0.527-0.562 per 1 percentage increase) and a subtle positive correlation between HI and crime rate (RR = 1.007, 95% CI 1.004-1.008 per unit increase). SVI strongly affected crime outcomes (RR = 6.749, 95% CI 5.887-7.737 per 0.01 increase). Given HI is positively associated with crime rates in multivariate analyses, the spatiotemporal analysis also shows the same result (posterior mean = 1.006 (95% CI, 1.004-1.008) for each unit increase in 2016), its impact is largely masked by the SVI of the city (posterior mean = 6.591 (95% CI, 5.749-7.557) for each 0.01 increase in 2016). During the 2020-2022 COVID pandemic, the impact of HI, contrary to expectations, showed the opposite correlation (posterior mean = 0.995 (95% CI, 0.989-1.002) in 2020). Even so, the study assumes that, as a public health intervention, reducing HI to the lowest observed level on each day within the city, the estimated number of avoidable crime incidents in 2016-2019 (prior to the pandemic is approximately 368.48, less than 5% of the total accumulated crimes events). However, even small numbers of preventable violent crimes, especially those that result in death, highlight the significant value of such interventions
DEVELOPING THE TOOLS FOR UNDERSTANDING THE STREPTOCOCCUS THERMOPHILUS TYPE III-A CRISPR-CAS ADAPTATION SYSTEM
No full textCRISPR-Cas technique is based on bacteria's naturally occurring “adapted immunity” to bacteriophage. Among various types of CRISPR-Cas systems, the adaptation process in Type III CRISPR-Cas system is unique in its ability to recognize both DNA and RNA pre-spacers and PAM-independent mechanism. This study utilizes a selected T7 E. coli system to produce Streptococcus thermophilus Type III-A CRISPR Cas1 and Cas2 proteins, the key players of its adaptation system. Upon expression, nickel affinity purification processes for the His-SUMO Cas1 construct were refined, increasing Cas1 solubility and implementing effective tag cleavage strategies, significantly improving protein purity. Parallel efforts to express and purify Cas2 involved re-cloning to address low solubility and cleavage efficiency, with subsequent ion exchange and gel filtration chromatography producing moderately purified protein. The study also aims to propose future directions to address the Type III-A CRISPR-Cas system's ability to acquire spacers from DNA secondary structures, directing future in vitro biochemistry reactions and structural analysis and providing new avenues for genomic tool development
INVESTIGATING PRECURSOR-SUMO AND CHARACTERIZING THE ROLE OF ENDOCYTOSIS WITHIN THE D. MELANOGASTER TESTIS NICHE
Get PDFProtein interactions, stability, function, and localization are all regulated by post-translational protein modifications such as ubiquitylation and SUMOylation, which are essential for preserving ideal cell conditions. To comprehend the function of these dynamic mechanisms in maintaining an adult stem cell niche, we use the Drosophila melanogaster testis as a model system. The testis niche hosts populations of stem cells – the germline stem cells (GSCs), which eventually develop into sperm and the cyst stem cells (CySCs), which support the germline. SUMO (small ubiquitin related modifiers) is predominantly expressed within the germline progenitors in late-stage Drosophila embryo development and within the germline during spermatogenesis and oogenesis. It is synthesized as a precursor form containing a C-terminal tail which must be cleaved prior to conjugation of SUMO with substrate proteins. The function of the precursor form remains unknown, although the maturation process is evolutionarily conserved in all eukaryotes. Here we use CRISPR-Cas9 technology to target the endogenous locus of SUMO to delete the C-terminal tail for subsequent characterization of the role of precursor-SUMO in fly development and reproduction. We also explore the intercellular dynamics within the niche, focusing on potential cell communication from CySCs to the hub required to maintain optimal cell growth. ESCRTs (endosomal sorting complexes required for transport) recognize ubiquitylated receptors in endosomes and control downstream formation of multivesicular bodies (MVBs) necessary to silence receptor signaling, leading us to a model where ESCRTs mediate signaling from CySCs to their niche. Disruption of ESCRT function is seen in many diseases such as cancer and we hope to understand the etiology through pathways that lead to abnormal cellular communication
GROWING: A LEARNER, A TEACHER, AND A WRITER
No full textI liked writing but I was not sure if I was a good writer. I wanted to become a writing teacher, but I did not exactly know how to teach writing. I needed professional knowledge to write well and to teach writing well. The Johns Hopkins Teaching Writing program became the soil for my seed. I was watered and nourished with knowledge and learning experiences. And I started to grow. Slowly I started to bloom into a writer and a writing teacher. Now I would like to become a garden for my students. I want to help them to grow and to bloom beautifully as writers. “Growing: A Learner, a Teacher, and a Writer” is a collection of writings that reflect my growth as a learner, a teacher, and a writer. All of this writing was created since 2022 in the Johns Hopkins MA in Teaching Writing Program. The thesis is submitted to The Johns Hopkins University in conformance with the requirements for the degree of the MA in Teaching Writing
GOLD, COAL, AND OYSTERS: ECONOMIC BOOMS, ELITE FRACTURE, AND THE ORIGINS OF POLICE DEPARTMENTS
No full textThis dissertation asks how did the United States shift from its previous network of law enforcement to police departments. In order to answer this question, this dissertation 1) traces the development of three police departments in Maryland, arguing there is a similar process across cases where an area experiences an economic boom, then elites fracture and facilitate violence, and in response, the subnational government creates a police department; and 2) this dissertation looks at the national scope of police growth in the nineteenth century, revealing it is more contested and more widespread than previous literature suggests. Elite fracture occurs at two scales; first, economic elites fracture at the subnational level, leading to police departments, while in the second scale, elites fracture at the national level over competing ideas of policing. Maryland, the northernmost slave state in the United States, with industries representing the variety of economic activity in the country, is a useful place to see how political economy, immigration, enslavement, nativism, mining, fishing, and railways structure the ideas, interests, and institutions of police development. In Maryland, the Baltimore Police Department developed over the 1850’s as Democrats and Know-Nothing partisan gangs violently fought alongside their elected officials, meanwhile the State Oyster Police developed post-Civil War as oyster speculators and captains fought on the Chesapeake Bay. Finally, Cumberland coal companies organized themselves into an umbrella organization to prevent elite fracture, but when it collapsed in 1869, coal elites became violent and Cumberland created a police department. While violent elite fracture at the subnational level led to police departments, at the federal level, Congressmen argued over how police should be structured during the Civil War, eventually leading to the creation of the Metropolitan D.C. Police Department. The national scope of policing reveals police departments were contested, as some actors wanted to maintain the network of night-watch, constables, sheriffs, slave patrols, and private violence, while other actors wanted to create police departments. Competing visions of policing was a fundamental conflict in the nineteenth century (as it is today) and this dissertation shows the conflict through the national, and subnational development of police departments
“SAVING LIVES WITH BALDRIGE”: LEVERAGING THE MALCOLM BALDRIGE PERFORMANCE EXCELLENCE FRAMEWORK TO PROMOTE PATIENT SAFETY
Get PDFThis dissertation examines the potential association between organizational excellence and patient safety improvements in American healthcare utilizing the Malcolm Baldrige Excellence Framework.
Following a comprehensive literature review (Chapter 1), the first manuscript (Chapter 2) presents a scoping literature review. The author searched PubMed, CINAHL, SCOPUS and PsychINFO for evidence of patient safety improvement from Malcolm Baldrige National Quality Award (MBNQA) healthcare sector winners. A review of included articles found that MNBQA winners shared a strategic commitment to patient safety, financial investments in safety and approaches to communicating with team members.
In the second manuscript (Chapter 3), the MBNQA Are We Making Progress and Are We Making Progress as Leader surveys were used to assess a health system’s patient safety team’s alignment around Malcolm Baldrige Excellence Framework categories. Following administration to the entire team (n=21), paired-t tests were utilized to analyze variation in responses across employee groups of team members (i.e., staff, leaders, team leaders). These analyses revealed no statistically significant differences, suggesting that the team is aligned around Baldrige framework categories. In addition to informing the focus health system’s own Baldrige journey, the study also illustrated the survey’s utility to other patient safety practitioners seeking to promote organizational excellence.
The third manuscript (Chapter 4) utilized a case study approach to examine a health’s system’s deployment of a lean toolkit as a strategic approach to patient safety improvement. This initiative was associated with a 45% decrease in safety events and a 97% increase in voluntary reporting over a 2-year period. The case study adds to the literature base by characterizing the investment in patient safety in an integrated delivery system on the Baldrige journey.
This dissertation highlights the potential utility of the Baldrige Framework as a guide for organizations committed to eliminating patient harm and affirms the importance of senior leadership investment and organizational strategy as key facilitators to patient safety improvement. This research also demonstrates the continued variability in patient safety measurement. These findings are critical for practitioners who require a framework for aligning their organizations around zero-harm and actionable tools to translate this strategy to improvement
Biomolecular Engineering For The Discovery, Design, And Development Of Therapeutics Modulating Growth Factor Pathways
No full textGrowth factors are a diverse class of signaling molecules that mediate a wide variety of cellular processes. Here, structural biology, biophysical analysis, and molecular engineering are combined to both engineer novel proteins capable of modulating growth factor signaling and deepen understanding of how existing growth factors orchestrate cellular activity.
In one example, we describe the development of novel decoy protein traps designed to effectively and comprehensively inhibit angiogenic signaling driven by vascular endothelial growth factor (VEGF) ligands. Here, we leverage molecular engineering to develop a bispecific receptor decoy trap capable of binding both VEGF receptor 1 (VEGFR-1) and VEGFR-2 ligands including VEGF-A and VEGF-C, two of the most potent VEGF ligands. We demonstrate that our engineered VEGF antagonists are capable of binding two ligands simultaneously and show potent antagonism in functional assays for angiogenesis including proliferation, migration, and survival studies in human endothelial cells. These engineered fusion proteins present a new architecture for more complete inhibition of complex VEGF-mediated signaling networks compared to current standard-of-care therapeutics, which offers a promising treatment paradigm for highly prevalent ocular neovascularization diseases such as diabetic retinopathy and neovascular age-related macular degeneration.
In another example, we used structural biophysics and molecular engineering strategies to manipulate the interaction between the human interleukin-7 (IL-7) cytokine and the anti-human IL-7 antibody M25. Previous reports have demonstrated that the anti-IL-7 monoclonal antibody M25 neutralizes cytokine activity in vitro, but paradoxically potentiates IL-7 activity in vivo. However, the mechanism through which M25 exerts these paradoxical effects on IL-7 activity has not previously been elucidated, hindering its therapeutic advancement. Here, we present the crystallographic structure of the IL-7/M25 complex and demonstrate via biophysical, molecular, and functional characterization that M25 neutralizes IL-7 bioactivity in vitro though competition with cytokine engagement of the common gamma (γc) receptor chain. Our hypothesized exchange mechanism rationalizes sustained signaling through the IL-7 pathway in vivo through sequestration of the cytokine to prevent activation-induced downmodulation.
Overall, the work described herein demonstrates the design and characterization of growth factor-modulating proteins that harbor great promise for unraveling complex biological mechanisms and advancing therapeutic development across diverse disease landscapes
Towards Deployment of Audio-based COVID-19 Detection Tools
Get PDFThe Coronavirus disease 2019 (COVID-19) has claimed over 7 million lives globally. At the height of the COVID-19 pandemic, efforts to limit the spread of the infectious disease were hampered by diagnostic tests’ limited accessibility, high cost, and long turnaround times. With the prevalence of smart phones and the emergence of Artificial Intelligence (AI), interests in automatic detection of diseases like COVID-19 have burgeoned. Existing literature has demonstrated promising results employing voice-based detection of diseases including Parkinson’s Disease, Alzheimer’s Disease, chronic obstructive pulmonary disease (COPD), pertussis, asthma, and COVID-19. However, issues with acoustic, data, and model-specific challenges have precluded the translation of this technology for COVID-19 detection. In contrast to existing methods, which have focused on employing state-of-the-art data hungry models on limited data, the proposed body of work focuses on progressing the development of audio based COVID-19 detection (ABCD) tools towards real-world use.
First, we proposed a scalable model that accurately differentiated between COVID-19 and non-COVID-19 subjects when analyzing cough, breathing, and speech sounds. This work outperformed research teams across the globe with first place honors in The Second DiCOVA Challenge. To uncover the barriers to real-world deployment of ABCD tools, we then evaluated the performance of the presented model on noise-injected audio, spontaneous speech, repeated speech, subjects with comorbidities, confounding variables, and different recording devices. These experiments reinforced the promise of ABCD, yet also uncovered the fragility of ABCD. In efforts to bolster the reliability of ABCD tools, we explored fusion approaches, combining audio and symptom features, that demonstrated improvements in overall classification performance and robustness. Finally, we proposed a novel word-level acoustic modeling approach for speech-based detection of COVID-19. Even with the use of shallow classifiers, the proposed word-level acoustic modeling approach was shown to outperform all other approaches that have been evaluated on a specific bias-controlled audio dataset in the existing literature. The presented approaches in this body of work aimed at COVID-19 detection have the potential to be extended for audio-based detection of various diseases and progress efforts to translate this nascent technology to real-world use
The Effects of Intraoperative Methadone on Postoperative Pain Control in Pediatric Patients: A Scoping Review
Get PDFInadequate perioperative pain control has deleterious effects on children’s development and can lead to heightened pain experiences and the avoidance of future medical procedures. Reports of perioperative use of methadone in children are increasing, as it has a favorable pharmacodynamic profile; however, the effectiveness of methadone in reducing postoperative pain has not been established. We, therefore, aimed to provide a scoping review of the literature comparing the effect of intraoperative methadone versus other opioids on postoperative opioid consumption, pain scores, and adverse events in pediatric patients. We identified studies in PubMed, Scopus, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to January 2023. Postoperative opioid consumption, pain scores, and adverse events were extracted for analysis. We screened 1864 studies, of which 83 studies were selected for full-text review. Five studies were included in the final analysis. Postoperative opioid consumption was decreased overall in children who received methadone compared to those who did not. The majority of studies indicated that methadone was superior to other opioids in reported pain scores, while the frequency of adverse events was similar between the groups. Although the data reviewed highlight a potential benefit of intraoperative methadone in pediatric patients, 4 of the 5 studies had serious methodological concerns. Thus, we cannot make strong recommendations for the regular use of methadone in the perioperative setting at this time. Our results highlight the need for large, well-designed randomized trials to fully evaluate the safety and efficacy of intraoperative methadone in diverse pediatric surgical populations.</p
TruSight Oncology 500 HT HRD Demonstrated Protocol Project Paper
Get PDFIllumina is one of the world’s leading biotechnology companies that specializes in the field of NGS, delivering library prep kits, sequencing platforms, and data analysis solutions to its customers. The TSO 500 HT HRD assay is an Illumina library prep product whose use has become increasingly important in the oncology field. The assay integrates analysis of DNA and RNA tumor samples into one workflow, yielding labs with information on 500 plus cancer genes, in addition to identification of HRD in samples. Currently, TSO 500 HT HRD libraries are only validated for sequencing on the NextSeq 550 and NovaSeq 6000, meaning they are not Illumina approved to be run on newer systems that exhibit superior sequencing power, such as the NextSeq 1000/2000.
Due to the great potential of sequencing TSO 500 HT HRD samples on the NextSeq 1000/2000, it is imperative that Illumina act quickly to ensure it is validated for customers as soon as possible. To start this process, the first step involves conducting a demonstrated protocol to show sequencing TSO 500 HT HRD libraries on the NextSeq 1000/2000 produces results which meet pertinent QC metrics. To do this, DNA and RNA TSO 500 HT HRD libraries were prepared according to the TruSight Oncology 500 High-Throughput Reference Guide. The libraries were then sequenced on the NextSeq 2000 according to the NextSeq 1000/2000 System Guide in three different run configurations. Following sequencing, the runs were analyzed with DRAGEN TSO 500 v2.1 analysis software. Calculated QC metrics were then compared against TSO 500 HT HRD QC guidelines to ensure each one met specifications. After completing this, it was found that all measured metrics met or exceeded QC specifications for each run.
These results display that sequencing TSO 500 HT HRD libraries on the NextSeq 1000/2000 is a viable workflow. While this is an important step in establishing Illumina support, this demonstrated protocol did not include analytical performance testing or product validation. As a result, full Illumina support for this assay has yet to be realized. Therefore, future work should be undertaken to complete the necessary remaining steps to achieve full product validation