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MOLECULAR AND PHENOTYPIC CHARACTERIZATION OF ENTEROVIRUS D-68 ISOLATES FROM THE 2022 MARYLAND OUTBREAK
Get PDFEnterovirus D68 (EV-D68) is a small, non-enveloped virus known to cause respiratory symptoms such as fever, cough, and congestion. In rare cases, it has also been linked to acute flaccid myelitis (AFM), a serious neurological condition. Since its discovery in California in 1962, EV-D68 cases remained sporadic until a major outbreak occurred in 2014, which coincided with a notable increase in AFM cases. Subsequently, EV-D68 outbreaks followed a biennial pattern—except in 2020, likely due to the COVID-19 pandemic. The pattern resumed in 2022; however, unlike previous outbreaks, the increase in EV-D68 cases was not accompanied by a rise in AFM, suggesting a potential shift in the virus’s phenotype. This observation led to the hypothesis that 2022 EV-D68 isolates may contain mutations that alter or reduce viral replication and impair the virus’s ability to cause AFM, while still permitting respiratory infection.
To investigate this hypothesis, laboratory experiments were conducted to isolate and characterize clinical samples from the 2022 EV-D68 season. A total of 35 RT-qPCR-confirmed samples were initially cultured on rhabdomyosarcoma (RD) cells at both 33°C and 37°C; however, no lytic virus infection virus was detected under either condition. Due to this limitation, human nasal epithelial cells (hNECs), which more closely resemble the physiological environment of the respiratory tract, were used as an alternative. Fourteen clinical samples were directly cultured on hNECs, and five additional samples previously passaged in RD cells were also tested, with one sample overlapping both groups.
Viral replication was assessed using RT-qPCR and plaque assays across multiple passages. Although no lytic virus infection was detected in the first or second passages, RNA amplification was observed. Similar findings were obtained using a recombinant plasmid containing the 2022 EV-D68 genome, which also failed to produce lytic virus infection but showed RNA amplification in the second and third passages. These results suggest that the 2022 EV-D68 strains may exhibit altered replication dynamics or tissue tropism, potentially contributing to the low numbers of AFM cases during that outbreak season
ASSOCIATION BETWEEN METFORMIN USE AND MORTALITY AMONG INDIVIDUALS WITH NON-SMALL CELL LUNG CANCER RECEIVING IMMUNE CHECKPOINT INHIBITORS: A RETROSPECTIVE COHORT STUDY
Get PDFIntroduction. Metformin has potential to synergistically enhance the effect of immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). We evaluated the association between metformin use prior to ICI initiation and cancer-specific and all-cause mortality among NSCLC patients.
Methods. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2013 to 2019), including NSCLC patients with type 2 diabetes who newly initiated ICI therapy and had prior antidiabetic medication use. The exposure was metformin monotherapy versus sulfonylurea and/or dipeptidyl peptidase-4 (DPP-4) inhibitors. The primary outcome was cancer-specific mortality, and the secondary outcome was all-cause mortality. We used stabilized inverse probability of treatment weighting (sIPTW) to adjust for confounders. Fine-Gray competing risk model estimated cancer-specific mortality, while Cox proportional hazards model evaluated all-cause mortality.
Results. We included 1,123 metformin users and 362 sulfonylurea/DPP-4 users. Although baseline characteristics differed, groups were well balanced after weighting. The adjusted incidence rate (aIR) of cancer-specific mortality was 82 vs. 81 (aIR difference = 1, 95% CI: -13 – 16), and all-cause mortality was 71 vs. 67 (aIR difference = 4, 95% CI: -6 – 15) per 100 person-years for metformin and sulfonylurea/DPP-4 users, respectively. Metformin use was not significantly associated with cancer-specific mortality (adjusted hazard ratio (aHR) = 1.08, 95% CI: 0.88–1.33) and all-cause mortality (aHR = 1.07, 95% CI: 0.90–1.26).
Conclusions. In this large, diverse cohort of individuals with NSCLC using ICI, there was no statistically significant association between metformin use and cancer-specific or all-cause mortality
Engineering and profiling immune system components for cancer immunotherapy applications
No full textThe immune system can be a powerful force both in promoting health and in causing disease. In this work we present several strategies for leveraging components of the immune system as therapeutics and in profiling immune system components to better understand health and disease states. First, we create bispecific antibodies that can target T cells to kill cancer cells that express mutant peptides generated from somatic mutations in RAS genes. Second, we generate bispecific antibodies for treating T cell cancers based on expression of specific T cell receptor variable gene segments. Third, we engineer mammalian cells to express immunotoxin conjugates as a path towards augmenting anti-cancer cell therapies. Fourth, we develop SafeTSeqS and SafeBSeqS, methods for sequencing T cell receptors and B cell receptors respectively, and we apply these techniques for profiling immune repertoires in colorectal cancer, lymphoma, sarcoidosis, multiple sclerosis, and immune-related adverse events associated with immune checkpoint inhibition. Together, these approaches highlight the multifaceted ways in which insights into immune system mechanisms can be leveraged towards improving human health
ELABORATING STRUCTURE AND CONNECTIVITY OF AUTONOMOUS COMPUTING MATERIALS
No full textNanoparticle networks have applications in brain-like computing because of their
ability to adopt different states. In this dissertation, we reveal the dynamics of the attachment of polyelectrolytes onto gold nanoparticles (AuNPs). We first construct an all-atom model to examine that interaction and the assembly of small engineered nanoparticle networks (ENPNs). We found through our all-atom simulations that a specific polymer, poly(allylamine hydrochloride) (PAH) can bind to multiple AuNPs at the same time. It also supports the development of a bottom-up dissipative particle dynamics(DPD) model which enables the characterization of larger polymer-networked AuNP assemblies and longer times. We found that use of a single polyelectrolyte homopolymer limits the complexity of the possible small ENPNs that can be built. In surmounting this challenge, we first found the commensurability rules between the numbers of AuNPs and PAHs. This gives rise to a well-defined valency for a AuNP as the maximum number of PAHs that it can accommodate. We further
use an engineered triblock copolymer, whose conductive middle block separates the polymer ends that attach between pairs of AuNPs. By controlling the length of the conductive block connecting each of the pairs of gold nanoparticles in a given ENPN structure and the connectivity between such engineered nanoparticles (ENPs), we found that the resulting ENPNs can adopt multiple distinguishable states which persist over time. Such stable states can be used as addressable registers necessary for primitive neuromorphic computing. We also report the use of nonequilibrium simulations to characterize the molecular interactions within hydrogel systems. In particular, we found that the role of borate ions in regulating binding preferences and drug release mechanisms can be revealed using all-atom simulations. Using energy landscape and distance characterization, the hydrogen bond between a specific part of the drug molecule and borate ion has been identified to be critical to the confinement
of such ions in the hydrogel environment. In summary, this dissertation advances
the understanding of nanoparticle-based systems, laying the groundwork for future
innovations in programmable materials and nanoscale technologies
EARLY ANALYSIS OF THE BIDEN ADMINISTRATION’S INFLUENCE ON APPALACHIA’S ENERGY TRANSITION
Get PDFThe Biden Administration sought to make addressing climate change a core part of its legacy. However, it is important to consider how efforts to advance clean energy have impacted communities reliant on the fossil fuel industry, such as Appalachia. This paper investigates the early impacts of Biden Administration efforts to support the Appalachian region during the energy transition. Findings suggest that large investments in clean energy and related initiatives, primarily through the Infrastructure Investment and Jobs Act and Inflation Reduction Act, have been positive for Appalachia and incorporated elements of a just energy transition, though there is still much progress to be made. Changes under the Biden Administration compared to those under the Trump Administration show early signs that Biden-era policies supported economic development and renewable energy deployment in the region. Still, there were notable shortcomings among energy-related programs, which should serve as lessons for future policymakers
STRATEGIES FOR IMPROVEMENT OF AIR QUALITY IN PUNJAB PROVINCE OF PAKISTAN
Get PDFThis capstone explores the pressing issue of air pollution in Punjab province, Pakistan, and proposes evidence-based strategies for improving air quality by examining socio-economic, environmental and policy dimensions. Punjab, with its dense population, industrial activity, and agricultural prominence, faces severe air quality degradation primarily driven by vehicular emissions, crop residue burning, industrial pollution, and weak policy enforcement. The study employs a mixed-methods approach, combining data analysis from government reports, air quality monitoring systems, and public health databases, with case studies of successful interventions from countries such as China, India, and South Korea.
Findings reveal a strong correlation between high levels of PM2.5 and PM10 and increased incidences of acute respiratory infections, especially among children under five. The 2024–25 smog crisis highlighted this trend, with over two million respiratory patients reported during peak pollution months and a noted life expectancy reduction of up to 7.5 years in Lahore (GoP EPD, 2024). Despite certain measures and policy reforms by the Punjab government (such as the Punjab Environmental Protection Act 2023 and Punjab Clean Air Program), challenges persist. This is largely due to limited monitoring infrastructure, transboundary pollution and enforcement gaps. Also, a considerable level of criticism exists on a reactive approach being adopted by the Punjab government with implementation of low impact measures lacking any strategic vision.
This capstone is particularly important since from a neutral viewpoint, it critically analyses the key aspects influencing the air quality landscape of the province. In addition, it also presents a global perspective of good practices implemented by developed and particularly developing nations such as India in effectively managing similar air quality challenges.
The capstone concludes that integrated, year-round air quality management—featuring cleaner technologies (such as promoting solar-powered irrigation systems, electrification of public transport fleets, adoption of zigzag brick kiln technology, and installation of end-of-pipe industrial emission controls like electrostatic precipitators and wet scrubbers), stronger regulations, public transport investment, and regional cooperation—is essential.
The capstone prioritizes air quality interventions based on their expected impact and feasibility in Punjab’s socio-political context. High-priority measures include in-situ crop residue management (e.g., Happy Seeders), vehicle inspection and scrappage programs, expanded air quality monitoring, and enforcement of emission standards for brick kilns and industrial boilers. Medium-priority actions comprise public awareness campaigns, seasonal smog action plans, and promotion of electric public transport, while more complex, long-term reforms such as pollution taxes and industrial relocation are categorized as lower priority due to implementation challenges. It also provides an air quality framework for the next decade, tailored to Punjab’s context, aiming to reduce pollution, protect public health, and support sustainable development
An Interactive Educational Module for MRI Evaluation of Placenta Accreta Spectrum
Get PDFPlacenta Accreta Spectrum (PAS) is a range of conditions with high patient morbidity where the placenta is abnormally adherent to, or invades, the uterine myometrium during gestation. Patients at risk for or with suspected PAS undergo diagnostic imaging in the second trimester. While the primary modality for diagnosis of PAS is ultrasound, MRI serves as an adjunct for diagnosis and operative planning. Interpretation of placental MRI is challenging for many radiologists, as the appearance of PAS is complex, and the majority of radiologists are infrequently exposed to this type of examination. Additionally, availability of educational resources regarding MRI evaluation of PAS is limited. The project’s purpose was to develop and evaluate an interactive learning module detailing the imaging features of PAS to address the need for this educational content.
A needs assessment was conducted to evaluate radiologist confidence levels in evaluating placental MRI and preferences for educational media. This included interviews with attending radiologists with varying levels of experience reading placental MRI. Based on the results, a learning module was designed to provide a broad overview of PAS, MRI protocols for evaluation of PAS, case-based diagrammatic and interpretive illustrations of MR images detailing key features of PAS, and annotated case studies with scrollable image stacks.
A randomized controlled trial was conducted to evaluate the learning module compared to a review article from the literature, the current standard for learning MRI features of PAS. Eighteen participants including attending physicians, clinical fellows, and radiology residents at Johns Hopkins were recruited. Learning was measured with a pre- and post-test and engagement was measured using Likert-scale questions and free-response questions.
Participants who viewed the module showed an increase in post-test scores (p-value <0.001), while those that read the article did not (p-value = 0.22) on Mann–Whitney U tests. Engagement survey scores and qualitative feedback indicated that the interactive module was received positively, with all respondents preferring the interactive module over the article. The study suggests that interactive educational media for evaluating MRI images may increase both educational yield and learner engagement compared to the traditional learning method of reading relevant journal articles
Improving LNG Incident Reporting for Agencies, Industry, and the Public Interest
Get PDFIn 2023, the United States became the largest exporter of liquefied natural gas (“LNG”) (Rapier, 2024), and although as a liquid it is nontoxic and non-corrosive, LNG is certainly not free from risk (Philadelphia Gas Works, 2015). Both LNG and the facilities dedicated to storing, importing, and exporting LNG need strict regulatory oversight to reduce the risk of incidents that can have potentially devastating consequences. Fortunately, LNG has boasted a comparatively enviable safety record since the modern industry’s emergence in the 1970s, but there is still work to be done to maintain this status and continually improve the safety record of LNG facilities (Wood, Mokhatab, Mak, & Valappil, 2014, p. 5).
This paper will focus on proposing a new approach to federal reporting of incidents at LNG facilities by operators to the United States Department of Transportation (“DOT”) Pipeline and Hazardous Materials Safety Administration (“PHMSA”), the Federal Energy Regulatory Commission (“FERC”, “the Commission”), and the United States Coast Guard (“USCG”, “the Coast Guard”), which oversee and regulate the facilities with the majority of LNG through-put. The proposed approach will utilize the National Technology Transfer and Advancement Act as the vehicle to standardize what incidents should be reported, it will raise the possibility of a consolidated reporting timeline, and it will include a combined form submitted for consideration to the agencies with the goal of advancing this consolidated approach
Cultivating Cultural Connection to Food: Strengths-Based Mixed Methods Research to Inform Approaches to Eating and Nutrition Measurement in Urban American Indian/Alaska Native Communities
Get PDFIntroduction: Nutrition is a vital health concern, particularly for American Indians/Alaska Natives (AI/AN), whose food systems have been profoundly disrupted by settler colonialism, contributing to high rates of diet-related chronic diseases (e.g., Type 2 diabetes, cardiovascular disease). To effectively address AI/AN nutrition, strengths-based measures and culturally grounded approaches are essential. This dissertation aims to: 1) define nutrition through AI/AN and Native Hawaiian (NH) worldviews, 2) culturally develop strengths-based nutrition measures for AI/ANs using community-based participatory research (CBPR), and 3) assess the validity and reliability of these measures in a sample of urban AI/AN adults.
Methods: Employing an exploratory, sequential mixed-methods design with a CBPR orientation, this research involved collaboration with 2 urban AI/AN communities (Baltimore and Minneapolis) and their respective community research councils (CRCs). Aim 1 involved focus group discussions (FGDs) and in-depth interviews (IDIs) with AI/AN/NH food experts, analyzed using a grounded theory approach. In Aim 2, qualitative data from FGDs, IDIs, and cognitive interviews were used to guide measure development and revisions, analyzed iteratively using an inductive approach. Finally Aim 3 quantitative data was collected using a quantitative health survey analyzed using exploratory factor, correlation, and regression analyses.
Results: Aim 1 included FGDs and IDIs with 26 AI/AN/NH food experts, resulting in the development of the Indigenous Nourishment Model. In Aim 2, through 4 FGDs, 6 IDIs, and 10 cognitive interviews, 3 strengths-based nutrition measures were created, collectively termed the Indigenous Nourishment Scales. Aim 3 surveyed 249 urban AI/AN adults, providing evidence that the Indigenous Nourishment Scales are valid and reliable tools for assessing nutrition through AI/AN worldviews and values.
Conclusions: These findings provide new directions for addressing and measuring nutrition holistically for AI/AN communities, directly grounding health efforts in community worldviews and values
Shopping for Pearls: China's Pursuit of Foreign Military Basing
Get PDFChina’s rapid expansion as a global power has significantly increased its reliance on vulnerable maritime trade routes, exacerbating its strategic anxieties about potential containment by the U.S. and its allies and partners. To mitigate these vulnerabilities, China is pursuing an ambitious campaign to establish foreign military bases near key maritime chokepoints. This thesis analyzes China’s strategic motivations and the effectiveness of its whole-of-government approach – leveraging diplomatic, informational, military, and economic (DIME) instruments – to secure overseas basing rights. Utilizing a comparative case-study methodology, this research systematically examines China’s efforts across five distinct regions: Djibouti in East Africa, Cambodia in Southeast Asia, the United Arab Emirates (UAE) in the Middle East, Equatorial Guinea and Gabon in West Africa, and the Solomon Islands in Oceania. Each case provides insights into Beijing’s operational methods, highlighting a preference for economic and diplomatic inducements tailored to host nations' varying levels of development and susceptibility to external influence. Findings indicate that economically underdeveloped nations are particularly receptive to China’s infrastructure and financial investments, while developed nations demonstrate greater resistance due to heightened sovereignty concerns and effective counter-pressure from Western powers. PLA overseas bases currently offer limited direct offensive capabilities but serve important strategic functions, including securing maritime chokepoints, intelligence gathering, projecting soft and hard power, and enhancing China's strategic depth. The study concludes that while China's foreign basing efforts presently pose a minor immediate military threat, their likely medium- to long-term evolution into a more profound threat demands nuanced, proactive strategies from policymakers to effectively counterbalance China's incremental approach to global influence