Environmental and Occupational Health Sciences Institute
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Epidemiological modeling of infectious diseases and coupling of viral load dynamics
No full textIn the following the impacts and importance that mathematics and epidemiological modeling plays on understanding infectious diseases is highlighted. Different methodologies which are used for computationally modeling systems of differential equations are then reviewed in context of being applied to epidemiology. Furthermore, novel methods for ODE systems are highlighted for which dynamics of a virus's variants is coupled with the model in order to investigate the effects the mutations of a virus plays on spreading throughout the population. Variants are a key aspect of viruses which play factors in how they develop and this makes it a viable component to be responsible for how they transport between individuals. Moreover, an epidemiological model for infectious diseases is introduced which has been endowed with viral load dynamics. The proposed model is of hybrid nature with deterministic and stochastic qualities. Unlike the traditional SIR models which are driven by their reproduction number from the infection and recovery rates this model is solely driven on the viral load dynamics of the agents in the population. This unique methodology helps to investigate how the viral load of individuals during the infection period will change the course a virus takes. Mathematical theory for the model and computational results are introduced as well. Overall, epidemiology and mathematics go hand in hand and the relationship they play together for understanding infectious diseases can build more profound understanding about infectious diseases and how to adapt for mitigating the negative effects they can have on a population.M.S.Includes bibliographical reference
Advanced practice nurses' knowledge, attitudes, and perceptions regarding microbiome testing, diagnosis, and evidenced-based treatment for gastrointestinal disorders
No full textThe gut microbiome also referred to as gut microbiota plays an essential role in human well-being and influences the development of related chronic conditions. We have only recently begun to acknowledge the importance of microbial organisms and the symbiotic connection that permits our health maintenance. Because of their advanced role, Advanced Practice Nurses (APNs) need to appreciate the microbiome's impact on an individual's health and the efficacy of treatments. Although the importance of genetics and genomics in nursing education has been recognized, surveys show that these subjects are not sufficiently addressed in nursing programs. This paper aims to investigate APNs’ knowledge, attitudes, and perceptions regarding the role of the microbiome in illness.
Rationale/ Significance of Study
An important role of the APN is providing primary care to patients with gastrointestinal issues that need further investigation when conventional testing doesn’t show any pathophysiology. It is unknown if APNs practicing in the outpatient setting are knowledgeable about the microbiome, related illnesses, testing, and genetics overall. Identification of knowledge deficits would identify the educational need to increase the appropriate use of related testing, diagnosis, and treatments.
Methods
This descriptive, cross-sectional study used a survey design (APNs KAP Survey) assessing sociodemographic data, knowledge level, attitudes, and perceptions of APNs providing care for patients with GI complaints. Following university IRB approval, the APNs KAP survey was administered online using Qualtrics. Statistical analysis included descriptive statistics, one-way ANOVA, and regression using SPSS for data analysis. The primary predictors were APNs’ demographic data, knowledge, attitudes, and perceptions.
Results
APNs reported a lack of knowledge with a significant difference regarding the perception of educational knowledge and the need for genetics courses in the MSN level programs. The reported lack of knowledge is important because it impacts patient quality of life if health issues are left unexplored. It can also lead to multiple visits and increased healthcare costs. This paper makes a strong case to develop, and test targeted educational curriculums.
Implications for Practice
A comprehensive understanding of the emerging microbiome field and its adverse negative effects on host health is crucial.Ph.D.Includes bibliographical reference
Love and labor: unionized teachers’ struggle for autonomy and professional respect in South Orange and Maplewood, New Jersey, 1965 to 1990
No full textThe nexus of schools as a place for childcare, teaching as a profession, and gendered norms and expectations about nuclear families have made teachers’ demands for dignity particularly charged. It has contributed to bitter public debates about a teacher’s worth and teacher strikes. The creation of a teachers’ professional organization, the legalization of public sector unionization, and development of the teachers’ union, the South Orange Maplewood Education Association, over two decades serves as a great case study of this nexus and as a way to fill of void created by the overlapping fields of history. Education history and labor history of teachers’ unions which generally fall into two camps: one in great defense of teachers and one attacking them. However, the missing link is the relationship between institutions of public education and reproductive labor. This thesis will analyze the creation of SOMEA and the 1990 strike as a struggle for professional respect and autonomy. They were criticized for using children as “bartering chips” and therefore disrupting care work. The Board of Education’s actions against the union can be interpreted as discipline for their disruption of the reproductive labor norms. This thesis is at once a labor history and a story of conservative backlash to public sector employees. This thesis will first look at the development of public education and then the development of educational professional associations. Then, it will analyze SOMEA’s transformation from a professional organization to a legalized union. SOMEA gained strength despite significant conservative backlash and then went on strike, twice. Those strikes will be compared. Finally, the thesis will end with SOMEA’s shrunken power, but its memberships’ unshaken resolve to continue to fight for their rights and the rights of their students.M.A.Includes bibliographical reference
The effects of methadone attitudes, social determinants of health, and substance use factors on intention to remain in methadone treatment
No full textBackground: Significant gaps exist in understanding the relationship between patients’ attitudes towards methadone, social determinants of health (SDOH), substance use factors as indicators of perceived behavioral control (PBC), and the intention to remain in methadone treatment. This study examined the influence of methadone attitudes and assessed the interaction effects of SDOH among people who use opioids (PWUO) in New Jersey substance use clinics. The effects of substance use factors on the intention to remain in methadone treatment among this population were also explored.
Methods: Utilizing data from the “New Jersey Opioid Overdose Study,” generalized linear regression and a series of simple moderation analyses were used to assess the main and interaction effects of methadone attitudes and SDOH on the intention to remain in methadone treatment. Multiple linear regression analyses were used to examine the predictor effects of substance use factors on intention to remain in methadone treatment.
Results: Survey responses from 290 participants were analyzed in the study. Positive methadone attitudes were significantly associated with the intention to remain in methadone treatment (p<.001). SDOH, including ethnicity, employment status, and marital status, revealed a significant interaction relationship with methadone attitudes and intention to remain in methadone treatment (p=0.013, p=0.025, and p<.001, respectively). The intention to remain in methadone treatment increased as positive attitudes toward methadone increased for non-Hispanic, full-, part-time, and unemployed participants. Marital status (married/ever married and never married) also positively enhanced the relationship between positive methadone attitudes and intention to remain in methadone treatment. Multiple linear regression indicated that prior methadone and buprenorphine treatment (p=0.004) and positive methadone attitudes (p<.001) had significant positive associations with intention to remain in methadone treatment. Negative associations existed between heavy smoking (smoking a pack of cigarettes or more per day), opioid use in the last 30 days (p=0.003 and p=0.009, respectively), and intention to remain in methadone treatment.
Conclusions: Methadone attitudes, substance use factors, and SDOH shape intention to remain in methadone treatment. Assessing factors influencing intention can aid in supporting patients' goals of remaining in methadone treatment. Healthcare providers and policymakers can use these associations to implement targeted interventions, particularly for diverse and underserved PWUO, and address issues related to methadone retention.D.N.P.Includes bibliographical reference
Strange names
No full textStrange Names is a collection of poems drawing from mythologies ancient and modern, from East and West, to speak of the limitations of familial love, English, and the American dream. It speaks of striving to understand, by way of multilingualism, and the failures of translation inherent to all language.M.F.A.Includes bibliographical reference
Birds in an obligatory body
No full textThis thesis is a poetic bildungsroman. The work explores history, violence, trauma, the body, the soul, and love. Personal experiences are investigated through the lenses of biology, painting, religion, and American history.M.F.A.Includes bibliographical reference
Resolving privacy and security challenges in collaborative genome-wide association studies
No full textGenome-wide association studies (GWAS) play a crucial role in unraveling the intricate connections between genomics and phenotypes, which have significant implications for advancing precision healthcare and personalized medicine. Collaborative GWAS, which incorporates datasets from multiple institutions, demonstrates improved power in detecting rare variations. However, privacy concerns and regulatory limitations on genetic data sharing pose significant challenges to such collaborations. This thesis develops practical, privacy-preserving techniques for collaborative GWAS, addressing kinship inference, association testing, integrity verification, and artificial genome generation. First, we introduce the Incremental Update Kinship Identification framework for accurate kinship detection in federated datasets while protecting privacy, leveraging a combination of local processing and outsourced computation. Second, leveraging the ``incremental update" principle to minimize data exchange and enhance computational efficiency without compromising privacy, we propose a novel framework for association testing that reduces data exchange and maintains privacy by eliminating non-significant loci early on, followed by iterative sharing for GWAS analysis, demonstrating robustness across different datasets and conditions. To ensure the integrity of GWAS results, we introduce a verifiable protocol that uses synthetic SNPs as a watermark to validate third-party computations, supported by a game-theoretic analysis that promotes honest participation. Lastly, we explore artificial genome generation to overcome data sharing, diversity, and privacy challenges. We evaluate generative models for their ability to produce synthetic genomic data statistically representative of real datasets without direct replication while safeguarding privacy against membership inference attacks. Taken in conjunction, this thesis improves the feasibility and integrity of collaborative GWAS, paving the way for secure and efficient genomic research.Ph.D.Includes bibliographical reference
Dynamic DNA nanomaterials to modulate ligand binding for biosensing and drug delivery
No full textDeoxyribonucleic acids (DNA) are macromolecules that code genetic information and serve as the blueprint for life. DNA molecules are also used to build various nanoobjects due to their canonical base pairs, programmable assembly addressable structures and adaptable modifications. Compared to other self-assembly molecules, DNA allows for precise control due to its programmable and predictable base pairs. In this thesis, I primarily focused on two research topics of DNA binding to ligands. The first topic is to study how DNA molecules bind to small molecule ligands. A short strand of DNAs called G-quadruplex and i-motifs are used to examine the complex formation between drug and DNA. DNA-drug complexes were characterized by dynamic light scattering and spectrometry to evaluate the drug loading efficiency. We also primarily tested DNA-drug complexes for lipid nanoparticles delivery to kill cancer cells. Another topic is to study how DNA molecules were modulated for binding to ATP. We used a special DNA structure called aptamer. Aptamers are short, single-stranded DNA or RNA molecules that selectively bind to a target molecule. Aptamer-complement duplex (ACD) is often used to design molecular switches capable of producing a detectable signal or triggering a structural change upon aptamer binding to a target. However, such aptamer switches generally face an increased dissociation constant (Kd) due to the energy barrier of the complementary duplex. We reported a competitive hybridization mechanism to modulate the binding affinity of an ACD to a target adenosine. Using the computation-guided design, we calculated the aptamer folding energy for the duplex length from 11-nt to 15-nt, and experimentally measured increased apparent Kd values resulted from these extended duplexes. Using a set of strands to compete with the ACD hybridization, it reduced the aptamer folding energy to facilitate aptamer switches with decreased apparent Kd values ranging from over 400 μM without a competing strand to ~30 μM with a competing strand. This competitive aptamer switch was also found sensitive to single-nucleotide mutations of a competing strand. Our work provides an approach to modulate the binding affinity and the sensitivity of aptamer-complement duplexes, which could be useful in the nucleic acids-based sensing and nanomedicine.M.S.Includes bibliographical reference
A systematic review of multisystemic therapy efficacy in youths 21 years and younger
No full textPurpose of Project: This review was aimed to synthesize existing evidence on the effectiveness of multisystemic therapy compared to treatment as usual in reducing disruptive behaviors in youths 21 years and younger.
Introduction: Multisystemic therapy (MST), a holistic, highly individualized, goal-oriented, evidence-based approach has been shown to effectively reduce disruptive behaviors in youths by addressing various systems influencing the youth's behavior, including the family, school, peer group, community, and individual factors. Disruptive Behavior Disorders, highly prevalent in childhood, are linked to negative outcomes, including substance abuse, psychiatric hospitalization, violent behavior, and criminal convictions. The estimated criminal justice costs for a typical offender aged 24 range between 3.7 million. It remains imperative to determine MST's efficacy to make evidence-based recommendations for clinical practice.
Inclusion Criteria: This review included full reports of randomized controlled trials (RCTs) and quasi-experimental study designs that investigated the effects of MST in children and adolescents aged 21 years and younger.
Methodology: Five databases were searched to find published and unpublished literature. Eligible articles were assessed by two independent reviewers for relevancy, duplicates were removed, and full-text articles were appraised. Studies results were synthesized narratively due to significant heterogeneity between studies.
Results: 12 RCTs and 4 Quasi-experimental studies were included. The total number of participants was 3,671. Compared to usual care, MST was more effective in reducing poor family functioning and in improving psychiatric symptomatology, externalizing and antisocial behaviors which include aggression and criminality. The impact of MST on adolescent peer relations was less consistent across different studies.
Conclusion: MST effectively reduces disruptive behaviors in youths, while improving family, parenting, psychiatric symptoms, and externalizing behaviors.
Implications for Practice: Practitioners should consider MST as a treatment option for disruptive behaviors in children and adolescents.D.N.P.Includes bibliographical reference
Tailored designs and applications of soft nanomaterials for advancing chimeric antigen receptor macrophage engineering
No full textCellular immunotherapy, a revolutionary approach in the field of cancer treatment, has garnered significant attention in recent years. This innovative strategy involves utilizing the patient's own immune system or genetically modified immune cells to identify and eliminate malignant cells, offering a promising alternative to conventional therapies. In particular, chimeric antigen receptor (CAR) T-cell therapy and adoptive transfer of stem cells have emerged as two prominent therapies, demonstrating remarkable success in the treatment of hematological malignancies and solid tumors. Despite the unparalleled potential, challenges persist, including managing adverse immune reactions and optimizing the efficacy and durability of the immune response. This dissertation details research efforts in engineering approaches for cellular immunotherapy in combination with nanotechnology. In the first chapter, we highlighted the recent breakthroughs in cellular immunotherapy, addressed the underlying mechanisms and clinical applications, and discussed ongoing research efforts aimed at expanding its scope and enhancing its safety and efficacy profile. Understanding the intricacies of cellular immunotherapy is imperative for advancing personalized medicine and paving the way for a transformative paradigm in cancer treatment. In the second and third chapters, we discussed the combinatorial approach of synthetic nanomaterials with non-viral genetic engineering to stimulate and generate CAR macrophages (CAR-Ms).
The immunosuppressive tumor microenvironment (TME) represents a major hurdle to successful chimeric antigen receptor (CAR) T-cell immunotherapy for solid tumors. As a potential strategy to mitigate the TME, we engineered macrophages with CAR-Ms using poly beta amino ester nanoparticles (PBAE NPs). PBAE NPs enabled the co-delivery of the CAR transposon and transposase for sustained expression, as well as priming of the transfected macrophages. PBAE NPs elicited a pro-inflammatory phenotype in the macrophages upon transfection, supported by the upregulated expression of pro-inflammatory cytokines and unconventional integrin receptors CD11a and CD11c. In addition, metabolic profiling showed a reprogramming of these macrophages with metabolites characteristic of pro-inflammatory macrophages. Further, we developed a nonviral approach for optimizing the co-transfection of CAR using PBAE NPs in macrophages, utilizing the combined adjuvant effect of PBAE and target specificity of CAR for enhanced phagocytosis in a pancreatic cancer model. Our results enable a better design of synthetic nanocarriers for in vivo CAR-M immunotherapy.
In the latter chapters, we explored the potential of CAR-Ms for chronic inflammatory disease application, using atherosclerosis as a proof-of-concept demonstration. Atherosclerosis is a chronic inflammatory disease defined by the continual infiltration of plasma monocytes, the release of pro-inflammatory cytokines and reactive oxygen species (ROS), and the accumulation of apoptotic cells. The removal of dying cells, which is known as efferocytosis, is an indispensable part of ending inflammation and is a crucial step in the apoptotic process. On the other hand, the inflammatory microenvironment of the atherosclerotic plaque frequently affects the biology of both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, we developed an immune-engineered scavenger platform that combines a nano-drug delivery system (NDDS) with cell therapy to improve efferocytosis. More specifically, macrophages modified with chimeric antigen receptors (CAR) could specifically target and engulf phagocytosis-resistant apoptotic cells. In both normal and inflammatory circumstances, CAR macrophages (CAR-Ms) exhibit activity equivalent to antibody blockage. The surface of CAR macrophages was modified with ROS-responsive therapeutic nanoparticles to improve their cell effector activities. Nanoparticles synthesized by nanoprecipitation can slowly disintegrate in the presence of ROS, allowing extended drug release and activation of the liver X receptor (LXR) pathway. The combination of immunoengineering and nano-drug delivery systems (NDDSs) activates lipid efflux pumps, which clear cell debris and reduce inflammation. We further demonstrated that undifferentiated CAR macrophages could travel through a micro-fabricated vessel system, suggesting the potential therapeutic utility of our platform. We believe that this cell therapy platform, combined with NDDSs, could lead to the development of next-generation cardiovascular disease therapeutics. Specifically, this innovative platform can potentially address the unmet need for more targeted and effective treatment options for patients with cardiovascular disease. In addition, by leveraging the unique properties of NDDSs, we can enhance the therapeutic potential of this cell therapy platform and improve patient outcomes. With further research and development, we are optimistic about the potential of this approach to revolutionize the treatment of cardiovascular disease and improve the lives of millions of patients worldwide.Ph.D.Includes bibliographical reference