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POLY(BETA-AMINO ESTER)-POLYETHYLENIMINE-BASED NANOPARTICLE TRANSFECTION FOR ADENO-ASSOCIATED VIRUS PRODUCTION
No full textGene therapy, which treats diseases through gene modification, is being actively researched. Among carriers for various gene therapies, adeno-associated virus (AAV) shows relatively high efficiency and safety and has become the leading gene delivery vector. Indeed, several AAV-based gene therapies are in preclinical and clinical trials and a few FDA-approved therapies are also commercially available. As interest in AAV as a promising gene therapy vector has increased, the demand for AAV has increased rapidly. In this paper, we investigated the application of a biodegradable polymer, polyethylenimine-conjugated poly(beta-amino ester) (PP), as a transfection agent for AAV production. The newly synthesized PP shows lower cytotoxicity than PEI which is the most widely used transfection agent for AAV production. The PP-based transfection shows a higher AAV production yield than PEI without any loss in purity or quality
Educational Hypogamy in Cohabitation and the Transition to Marriage
No full textThis dissertation explores how increases in women’s educational attainment are connected to changes in cohabitation and the transition to marriage through a close examination of different-sex unions in which the female partner has more education than the male partner. First, men and women in these hypogamous cohabiting unions are compared to their peers in other types of cohabiting unions in which both partners either have the same level of education or the female partner has less education than the male partner using the National Longitudinal Survey of Youth 1997 cohort. I find that women with some low status social traits such as those who have children before their first union, those in lower skilled occupations, and those whose parents have lower levels of educational attainment are more likely to enter hypogamous cohabiting unions and partner with men with low status traits. In a second analysis, men and women in hypogamous cohabiting unions are compared to men and women in hypogamous married unions using the same characteristics and data as the previous analysis. The findings from the first analysis extend to women in hypogamous married unions. Finally, the exits of men and women from hypogamous cohabiting couples are compared to their peers in other educational pairings. Trends in the transition to marriage from the National Longitudinal Survey of Youth 1997 cohort are compared to the National Longitudinal Survey of Youth 1979 cohort. Findings from these analyses show that there are no significant differences in the transition from cohabitation to marriage by relative education for either cohort. Taken together, the results of this dissertation demonstrate that the rise of women’s educational attainment and educational hypogamy have not radically altered union formation in the United States. Women from low-status backgrounds who work in low-skilled occupations and who have low-to-moderate indicators of socioeconomic status themselves, other than education, are most likely to enter hypogamous unions. They tend to partner with men with similar status characteristics, other than education, with whom they would have otherwise partnered in previous cohorts. Even when these women engage in educational hypogamy, they still maintain class homogamy
ROLE OF MICROORGANISMS IN SURFACE WATER REMEDIATION TECHNOLOGIES: EXAMPLES FROM STORMWATER BIOFILTRATION AND ARTIFICIAL AERATION IN A HYPOXIC ESTUARINE ZONE
No full textMicroorganisms affect or are affected by the function of surface water remediation technologies but are often overlooked as important components in the remediation process. Studying the interactions between microorganisms and remediation technologies can provide insight into underlying causes of the variation in remediation technology function, potentially leading to improvements in design and operation. Here, we use stormwater biofiltration as an example of how microbes can influence the function of stormwater remediation technology. We also use artificial aeration in an estuarine hypoxic zone to investigate the impact of aeration on microbial community diversity and function. Specifically, we demonstrate 1) how the surface characteristics of naturally occurring biofilm-forming strains vary and how they influence colloidal retention in porous media under stormwater biofiltration conditions; 2) how naturally occurring biofilm-forming strains influence bacteria retention individually and collectively; 3) how artificial aeration influences the diversity, composition and functional potential of microbial communities in a hypoxic estuarine system.
Overall, we found that biofilms formed by environmental strains significantly altered the retention of a model colloid in sand columns. Such variability was strongly correlated with the strain-specific colloid-biofilm adhesive energy, presumably related to the bonding between biofilm polymers and the model colloid. Furthermore, the high variability in the strain-specific biofilm surface characteristics could also strongly influence bacterial retention. By testing bacterial retention in columns modified by two-strain community biofilms, we demonstrated that bacterial retention could be influenced but not predicted by the biofilm microbial composition and the bacterial retention characteristics of the constituent strains. In addition, we found that aeration significantly impacted microbial community composition and function in a hypoxic estuarine system, likely by replenishing the dissolved oxygen in the hypolimnion and facilitating upward mixing. Similar or higher diversity was associated with microbial communities under aeration, suggesting that aeration can maintain or enhance estuarine ecosystem stability. We also observed the association between aeration and the relative abundance of a potentially harmful algal species, suggesting aeration can suppress harmful algal blooms in hypoxic estuaries. These examples demonstrate how microorganisms affect and are affected by water remediation technologies, illustrating the critical roles of microorganisms in water remediation technologies
Self-Reporting Falls is Associated with Preclinical Mobility Impairment, but Not Dismobility
No full textIntroduction: Few studies have focused on incident dismobility – a severe form of slowed walking – following falls. We aimed to characterize the degree to which self-reporting falls increases dismobility risk and preclinical mobility impairment.
Methods: We used fall history and physical performance data from the National Health and Aging Trends Study from the original 2011 cohort (n=1,761, 71.5±6.9 years old (mean ± SD), 51% women) and replenishment 2015 cohort (n=1,135, 70.4±6.2 years old, 53% women). We used Cox proportional hazard models to estimate whether reporting “at least one fall” in the past year was associated with an increased risk of dismobility (usual gait speed < 0.667 m/s) or preclinical mobility impairment (Short Physical Performance Battery < 8) compared to those reporting “no falls”. Models were adjusted for sociodemographic, baseline physical function, and medical conditions.
Results: In the 2011 sample, 28% of 1,761 participants developed dismobility and 42% developed preclinical mobility impairment. In the 2015 sample, 15% of 1,135 participants developed dismobility and 27% developed preclinical mobility impairment. Self-reported falling was associated with preclinical mobility impairment in the 2011 cohort (HR: 1.41; 95% CI: 1.13, 1.76) and the 2015 cohort (HR: 1.60; 95% CI: 1.13, 2.25). Self-reported falling was not associated with dismobility in either the 2011 sample (p=0.17) or the 2015 sample (p=0.85). The 2011 cohort results were robust to both shortening at-risk time to match the 2015 cohort and to redefining the severe physical performance outcome to SPPB<6.
Conclusions: In this nationally representative sample of US older adults, self-reported falls in the past year appeared to be more related to future functional performance than dismobility. Our results suggest that self-reporting falls is a useful tool towards identifying seemingly healthy older adults who are on a trajectory towards loss of independent living, in the form of physical performance
Oral History of Thomas H. Murray
No full textThis interview with Thomas H. Murray, PhD, was conducted by Suzanne Snider on January 20 and January 21, 2023 in Brewster, Massachusetts as part of Moral Histories: Voices and Stories from the Founding Figures of Bioethics, an oral history project of the Johns Hopkins Berman Institute of Bioethics. Prof. Murray is President and CEO Emeritus of The Hastings Center and was previously Director of the Center for Biomedical Ethics in the School of Medicine at Case Western Reserve University. His areas of expertise include ethics and performance-enhancing drugs in sports; parents, children and reproductive technologies; genetics and genomics; and organ donation and transplantation.On Day 1, Prof. Murray talks about his childhood in Philadelphia, including his Irish-Italian heritage, Catholic school, and an early love of sports. He describes his time at Temple University, where he earned his BA in Psychology in 1968. In the early 1970s, while pursuing his PhD at Princeton University, Prof. Murray assisted his advisor in a deception research study and, as a personal reaction to the nature of the study’s experiments, subsequently turned his attention to ethics. Prof. Murray also attributes his teaching and colleagues at New College in 1971 as opening his thinking to ethical questions. Prof. Murray shares memories of being a young parent during a fellowship at Yale from 1978-1979.He describes his experiences at The Hastings Center in 1979 as a Fellow and his work as a Research Associate there from 1980-1984. Memories shared include: working with Ruth Macklin, Daniel Callahan, and Willard Gaylin; group meals; and beginning his work with Carol Levine and Ronald Bayer on AIDS. Prof. Murray lists the early research focuses of the Center and defines the term “bioethics.” Prof. Murray discusses the use of drugs in sports, one of his significant research focuses: relatedly, he shares a story of bringing Philadelphia Eagles players to The Hastings Center as part of this research. He describes his experiences as the first Chair of the World Anti-Doping Agency’s Ethical Issues Review Panel, and as a member of the United States Olympics Committee for 15 years.On Day 2, Prof. Murray continues his discussion of sport, including issues of gender and his book Good Sport: Why Our Games Matter–And How Doping Undermines Them (2017). He discusses leaving The Hastings Center in 1984 and credits The Hastings Center community as inspiration for work he continued at the University of Texas Medical Branch at Galveston. He talks about spending summers in Cape Cod, Massachusetts, and moving to Cleveland, Ohio to serve as (founding) Director of the Center for Biomedical Ethics at Case Western Reserve University (CWRU) in 1986. He credits Ronald A. Carson’s work as Director of the Institute for Medical Humanities at Galveston, and The Hastings Center’s vibrant research community as significant influences for when developing the Center at CWRU and its masters program. Prof. Murray describes his return to The Hastings Center as President and CEO in 1999, including his goals and fundraising duties. He briefly explains the structure and roles for Fellows at the Center. He briefly discusses cognitive enhancement. He also speaks about the murder of his youngest daughter, Emily Murray, and notes the way this experience led to his considerations of the death penalty.Prof. Murray discusses his work on genetic testing in the workplace; potential risks involved with designer babies and genetic technologies; his experience with the Human Genome Project on the use of genetic information in insurance; and his experience delivering expert testimony in the areas of asbestos regulation and tobacco. Prof. Murray concludes the interview by mentioning areas he wishes to see emerge in the future of bioethics, including issues related to justice, gender, race, class, and international bioethics.
This interview may be of interest to those wishing to learn more about: the history of bioethics in the United States; the fields of bioethics and social psychology; regional histories of bioethics (Midwest, Northeast); single parenthood as a bioethicist; bioethics center formation and leadership; reproductive technologies; genetic technologies; and bioethics during the 1980s
Advances in the understanding of the hydrological cycle in South Asia: human intervention, meteorological forcing, and seasonal forecast
No full textSouth Asia has a wide variety of climate patterns and some of the most complex and high-elevation terrain on Earth. These conditions make the region vulnerable to natural disasters, food insecurity, and climate change, threatening the lives and well-being of over a quarter of the world’s population. Given the climate sensitivity and hydrological importance of this region, it is both challenging and crucial to establish a hydrological monitoring and forecasting system to inform disaster preparedness and resource management.
This dissertation presents research designed to better monitor and forecast hydrological anomalies and trends in South Asia, aiming to provide relevant and reliable information for disaster preparedness and resource management. I first discuss developing and establishing a South Asia hydrological monitoring and sub-seasonal to seasonal forecasting system (SAHFS-S2S), built within NASA’s Land Information System (LIS) using the Noah-MultiParameterization (NoahMP) Land Surface Model (LSM). The monitoring system is driven by meteorological forcing fields from the Global Data Assimilation System (GDAS) and Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS). The 5-km and 9-month S2S forecasting system is driven by downscaled and bias-corrected meteorological forcing fields from NASA Goddard Earth Observing System Model sub-seasonal to seasonal (GEOS-S2S) forecasts. To account for heavy irrigation and groundwater depletion in South Asia, an irrigation scheme is then added to the monitoring system. The irrigation scheme makes use of multi-source and multi-resolution irrigation parameters and is calibrated to FAO country-level irrigation water demand. The results show the necessity of including irrigation when simulating regional hydrology to capture groundwater depletion in this region. Finally, I address the challenge of reducing errors and increasing the resolution of the meteorological forcing fields used in forecast and climate projection. I present a Convolutional Neural Network (CNN) based deep learning algorithm, called an Auto-Encoder (AE), to downscale and bias correct a coarse resolution precipitation product, ERA-Interim. The result shows that adding additional meteorological forcing variables as inputs, such as sea surface temperature or surface pressure, in addition to the ERA-Interim precipitation itself, helps increase the accuracy of the downscaling and bias-correction processes
FEDERATED LEARNING BASED MEDICAL IMAGE SEGMENTATION FOR HETEROGENEOUS DATA SETS WITH PARTIAL ANNOTATIONS
No full textSegmentation is one of the primary tasks in deep learning for medical imaging, owing to its multiple downstream clinical applications in diagnosis, prognosis, and treatment planning. However, generating manual annotations for
medical images is time-consuming, requires high skill, and is an expensive
effort, especially for 3D images. In recent years, Artifcial Intelligence algorithms using deep learning have created highly accurate segmentation models
for the delineation of several organs of the body on various imaging modalities.
However, there are several limitations to training such models such as requiring a large amount of well-annotated data and high-quality images and the
need for creating a segmentation model for each use case. Federated learning
has the potential to solve both of these problems by aggregating the knowledge from several local models into a global model that can be used to segment
multiple target regions. To this end, in this thesis, I propose SegViz, a federated learning-based framework to train a segmentation model from distributed
non-i.i.d datasets with partial annotations. SegViz using FedBN as the aggregation strategy demonstrated excellent performance on the external BTCV set
with dice scores of 0.93, 0.83, 0.55, and 0.75 for segmentation of liver, spleen,
pancreas, and kidneys, respectively, significantly (p < 0.05) better (except liver
and spleen) than the dice scores of 0.88, 0.79, 0.46, and 0.64 for the baseline
models. In contrast, the central aggregation model significantly (p < 0.05) performed poorly with dice scores of 0.65, 0, 0.55, and 0.68. Furthermore, in order
to reduce the need for a large number of training samples during training, I
show that coresets using group sampling can effectively reduce the total number of training samples. The dice scores for the liver MSD dataset using coresets of sample sizes - 45,27,18 are 0.90, 0.89, and 0.87 on the external BTCV
dataset compared to the dice score of 0.89 trained on the entire training set.
Similarly, for spleen segmentation, coresets of size 20,10,6 samples yield dice
scores of 0.86,0.76,0.69 respectively compared to a dice score of 0.86 on the entire training set. In the last chapter, I conclude and discuss the future scope
and limitations of my work
GRADUATE STUDENT ENGAGEMENT: ACADEMIC ADVISING AND ADVISOR PROFESSIONAL DEVELOPMENT IN LAW SCHOOL
No full textThis study focuses on graduate student engagement and the role of academic advising. Using networked Ecological Systems Theory (EST) and social constructivist frameworks, a literature synthesis identified three factors that impact graduate student engagement: student support services; diversity and inclusion; and the academic environment. The literature review demonstrated that graduate students who are provided with opportunities for positive interactions with campus community members have higher reported rates of institutional satisfaction, academic success, and engagement outcomes. The literature review also showed that mentoring, academic advising, student organizations, social relationships, and institutional support services for specific demographics impact engagement and well-being. A mixed methods, convergent parallel needs assessment was conducted to further explore factors influencing graduate student engagement and well-being, including whether results differed by student demographic. Across demographics, academic advising emerged as a positive factor in graduate student engagement. Following the needs assessment and literature review, the research focuses on a second literature review of academic advising models in graduate, professional schools, and community colleges and a literature review of professional development practices. The research concludes with recommendations for the development of a split advising model in law schools that includes developmental and intrusive elements and for professional learning programs for academic advisors. Finally, the research includes recommendations for future research of academic advising in law schools
Patient Engagement in Diabetes Care: Missed Appointments Among Adults Living with Type Two Diabetes
No full textBackground: Missed appointments negatively impact the health outcomes of people with type 2 diabetes mellitus (T2DM), causing clinic operational disruptions, added financial cost, and longer waitlist. Yet, more than a third of the adults with T2DM missed their follow-up visits in the in-person settings. The COVID-19 pandemic has rapidly transformed healthcare delivery from in-person to telehealth settings. Although telehealth visits have reduced missed appointments by addressing some barriers of in-person visits (e.g., transportation), missed appointments still exist. Additionally, interpersonal relationships in telehealth settings have been raised as concerns by some patients.
Objectives: To understand risk factors of missed appointments in in-person and telehealth settings among adults with T2DM.
Methods: Using a sequential multi-method design guided by the modified Quality-Caring Model, the quantitative phase used electronic health records (EHR) data in Calendar Years 2019 and 2020 with 7,276 encounters made by 2,235 patients. A purposive sample of 23 adults with T2DM and 10 providers were then interviewed individually via phone or zoom.
Results: The EHR data found that having an activated patient portal account decreased the odds of missed appointments. Disparities in missed appointments were observed by age and race (older age [versus <46 years] and White [versus Black] had significantly lower odds). Telehealth was associated with 50% decreased odds of missed appointments during the COVID period (3/23/2020-12/31/2020). On the other hand, longer scheduling lag increased the odds of missed appointments. Qualitative interviews revealed that missed appointments were often related to social needs, such as lack of/limited health-related transportation and its associated financial burden. Telehealth helped break these barriers for some adults with T2DM, but technical challenges in telehealth visits persisted for those with low digital health literacy and people who did not have a digital device and/or unstable internet connection. Providers worried that these challenges might ultimately undermine the quality of diabetes care.
Conclusion: Telehealth reduced missed appointments in diabetes care with certain technical challenges. To reduce health disparities among adults living with T2DM, future studies are needed to address social needs in diabetes care, such as access to stable internet, enhancing digital health literacy, and resources navigation
