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DEVELOPMENT OF A WHOLE GENOME SEQUENCING ASSAY FOR RESPIRATORY SYNCYTIAL VIRUS (RSV) AND ITS IMPLEMENTATION FOR GENOMIC SURVEILLANCE AND PHYLODYNAMIC INSIGHTS FROM SEVEN YEARS OF LONGITUDINAL MONITORING IN MARYLAND
Get PDFRespiratory Syncytial Virus (RSV) is a major global pathogen which can cause severe respiratory infections in infants, older adults, and immunocompromised populations. Due to its substantial healthcare burden, genomic surveillance remains critical to track viral evolution and inform public health strategies, especially with the recent introduction of vaccines and monoclonal antibodies.
We developed a two-step, long-amplicon multiplex RT-PCR assay for RSV whole-genome sequencing (WGS). Initial optimization addressed consistent dropouts at genome termini by increasing terminal primer concentrations. The assay was validated using 822 clinical RSV-positive samples, yielding 343 whole-genome and 340 partial-genome assemblies. Successful genome recovery correlated with lower cycle threshold (Ct) values: median Ct of 20.00 for RSV-A and 22.23 for RSV-B in complete genomes, compared to 30.36 in failed samples. RSV-A samples demonstrated slightly higher coverage depth than RSV-B.
The optimized assay was employed to characterize RSV strains from the 2024-2025 respiratory season in the Johns Hopkins Health System (JHHS). Among 336 RSV-positive samples, RSV-A predominated (94.9%), with clade A.D.1.6 (68.34%) accounting for most cases. Most infections occurred in children aged 1–5 years (56.2%), and comorbidities such as immunosuppression were significantly associated with severe clinical outcomes. Phylogenetic analyses revealed tight clustering and low intra-clade diversity. Multiple amino acid substitutions were detected across surface and internal proteins, with predicted gains and losses of glycosylation sites potentially affecting the effectiveness of vaccines, monoclonal antibodies, or antivirals.
Longitudinal surveillance data from 2018 to 2024 revealed distinct evolutionary dynamics between RSV-A and RSV-B. Positive selection was concentrated in the G and F glycoproteins. RSV-A evolved at a rate of 7.07 × 10⁻⁴ substitutions/site/year with a most recent common ancestor (tMRCA) around 2005, while RSV-B evolved faster (1.02 × 10⁻3 substitutions/site/year) with a tMRCA near 2013. Bayesian skyline plot analyses revealed a 2018 RSV-A bottleneck, a 2022 resurgence, and a 2023 decline. RSV-B showed a 2021-2022 bottleneck followed by recovery and stable diversity.
In conclusion, this thesis highlights the utility of long-amplicon WGS assay for RSV surveillance and the importance of ongoing genomic monitoring to guide vaccine design, therapeutic strategies, and outbreak preparedness
Testing general relativity and informing astrophysics with gravitational waves
No full textEinstein's general theory of relativity describes gravity as the curvature of spacetime. Among its elegant predictions are gravitational waves, ripples in spacetime produced by merging compact objects like black holes and neutron stars. Since 2015, we have detected hundreds of these waves, advancing our understanding of the Universe and its governing laws. In this thesis, I develop theoretical models and data analysis tools for testing general relativity and informing astrophysical theories with gravitational-wave observations.
In the first part of the thesis, I contribute to the theoretical groundwork for testing general relativity with black hole ringdown. During the final ringdown phase of a binary black hole merger, the newly formed remnant black hole emits gravitational waves as decaying quasinormal modes. I demonstrate that pseudospectral instabilities could affect the quasinormal mode spectrum of black holes, while including rapidly decaying overtone modes in ringdown models could lead to overfitting. To counter this, I develop a frequency-agnostic method for extracting these modes from numerical simulations. I confirm the existence of nonlinear modes in the ringdown and create models connecting mode amplitudes to the initial conditions of the binary black hole merger. These results are necessary for precision tests of general relativity with black hole ringdown observations.
In the second part of the thesis, I develop tools for informing astrophysical theories with gravitational-wave observations. First, I study the effects of gravitational lensing on gravitational waves. I develop software tools to model diffraction-lensing effects due to individual stars embedded in galaxies or low-mass dark matter halos, and perform Bayesian parameter inference on simulated events. These tools are useful for analyzing diffraction-lensed events potentially observed by detectors. Second, I perform a search for black hole mergers with intermediate mass ratios in the third observing run data of LIGO-Virgo-KAGRA, setting bounds on their rate density in the local Universe. This result is useful for constraining astrophysical models of binary black hole formation.
Together, these advancements help interface gravitational-wave detections with gravitational physics and astrophysics. They help prepare for the next phase of gravitational-wave astronomy, where detectors will become more sensitive and detections more frequent
THE TRANSIT AGE: OBSERVING EXOPLANET ATMOSPHERES, INTERIORS, AND PARENT STARS THROUGH TIME
No full textModern space telescopes now access the atmospheres of transiting exoplanets with an extraordinary level of precision across a diverse landscape of planet types. I present novel exoplanet transit observations collected in the first few years of operations with the revolutionary infrared space observatory, JWST. First, I characterize the pre-launch noise performance and systematic behavior of JWST's panchromatic NIRSpec PRISM mode using laboratory calibration data. I introduce the data analysis suite FIREFLy, developed for the analysis of time-series transit spectroscopy, which I apply to several JWST transit datasets. Using FIREFLy, I analyze the first NIRSpec PRISM transit, released as part of the Early Release Science program, detecting multiple molecular species such as CO2 and SO2, and revealing asymmetries between the leading and trailing limbs of the planets atmosphere. Next, I demonstrate how the extreme photometric precision of JWST enables the measurement of stellar mean densities to sub-percent precision from exoplanet transit light curves. By combining these density measurements with state-of-the-art stellar evolution models, I infer system ages with a near order-of-magnitude improvement over previous methods. Finally, I present a preliminary analysis of two PRISM transits of TRAPPIST-1 h, the coldest known transiting terrestrial exoplanet. I place constraints on the nondetection of an atmosphere, derive a precise optical-to-IR limb darkening spectrum, characterize a stellar flare and post-flare pulsation, and track the star’s changing chromospheric activity. Together, these results illustrate the unprecedented power of JWST for precision atmospheric spectroscopy, stellar characterization, and the search for atmospheres on rocky terrestrial worlds
Three Papers on Pregnancy and Motherhood
Get PDFThis dissertation explores metaphysical and ethical dimensions of pregnancy and motherhood. Chapter 1 concerns the metaphysics of pregnancy. I defend the containment view—the position that a fetus (1) is merely contained by its mother and (2) is an organism during pregnancy. I argue against the parthood view, which states that a fetus is a maternal part. I bring the personal identity literature—particularly animalism—to bear on the metaphysics of pregnancy literature. I deploy thought experiments modeled on classic remnant, fission, and transplant cases to demonstrate that the parthood view is incompatible with standard accounts of human organism persistence. By contrast, the containment view yields the right verdicts. Chapter 2 asks: What is wrong with violence? I explore an under-recognized aspect of violence: its moral significance for parents. For many parents, raising children is part of what gives meaning, structure, and shape to their lives and senses of self—it is a reproductive project. I offer an account of projects which explains their role in our moral lives, and I argue that we have an obligation not to undermine the projects of others without good reasons. Violence harms children and thereby undermines the reproductive projects which they are central to. Thus, violence fails our obligation to parents and is a pro tanto wrong in part for this reason. This is particularly salient to mothers who perform most reproductive work. Chapter 3 asks: Is it morally praiseworthy to carry out a pregnancy, rather than terminate? I argue yes. Pregnant women undertake significant costs for the benefit of their children and are thus prima facie praiseworthy. I hypothesize that this is under-recognized in part because of the dominance of maximalist liberal and conservative positions within the abortion debate. For reasons of political expediency, conservatives portray carrying 2 out a pregnancy as minimal moral decency, while liberals portray it as morally neutral. I argue that liberals face a dilemma: The maximalist position on abortion undermines the politically neutral case for expanding state support for pregnant women. I offer both utilitarian and autonomy-supporting reasons to prioritize the case for expanded state support
Fragile Foundations: Investigating the Impacts of Flame Retardants and Endocrine Disrupting Chemicals on Childhood Vitamin D and Bone Mineral Density
No full textBackground: Optimizing vitamin D and bone health during childhood and adolescence is essential for lifelong health. Mechanistic and toxicologic evidence show that flame retardants and other endocrine disrupting chemicals (EDCs) may negatively impact both the vitamin D system and bone health during this critical period of heightened susceptibility.
Objectives: In Aim 1, we examined associations of 24 EDC biomarker concentrations with three serum vitamin D biomarkers at ages 8 and 12 years. In Aims 2 and 3, we assessed associations of in utero and childhood polybrominated diphenyl ether (PBDE) concentrations in serum with bone mineral density (BMD) at age 12 years.
Methods: We used data from the Health Outcomes and Measures of the Environment Study, a prospective pregnancy and birth cohort from Cincinnati, Ohio, USA that enrolled pregnant women from 2003 to 2006. We measured 24 EDC concentrations in maternal serum samples during pregnancy and child serum samples at ages 8 and 12 years. We measured 3 vitamin D metabolites at ages 8 and 12 years. We performed dual energy x-ray absorptiometry (DXA) scans and calculated bone mineral density (BMD) Z-scores for 6 skeletal sites at age 12 years. Using linear regression models, we estimated covariate adjusted associations of repeated flame retardant and other EDC biomarker concentrations with vitamin D outcomes at ages 8 and 12 years (Aim 1) and BMD Z-scores at age 12 years (Aims 2 and 3).
Results: In Aim 1, we observed that several EDCs were associated with higher circulating total vitamin D. In Aim 2, we found that in utero exposure to PBDEs was associated with lower BMD Z-scores at age 12 years. In Aim 3, we report that PBDE exposures at ages 8 and 12 years were associated with higher BMD Z-scores at age 12 years.
Conclusion: This dissertation contributes to the growing body of evidence showing that EDC exposures may impact biomarkers of the vitamin D system and bone health during early adolescence. These findings may have implications for lifelong immune and bone health
Stratospheric Ices on Titan During South Polar Fall
Get PDFPolar hood clouds are a prominent feature of the polar fall and winter stratosphere on Titan, the largest moon of Saturn. Observations of north polar winter and south polar fall by NASA’s Cassini mission revealed clouds composed of organic ices, including hydrogen cyanide, benzene, and cyanoacetylene, as well as co-condensed mixtures of these species.
The appearance of a large hydrogen cyanide ice cloud during early southern fall (mid 2012) proved surprising because it formed at a significantly higher altitude than previously observed clouds, and in a region expected to be too warm for ice condensation. Through a series of simulations of hydrogen cyanide cloud using the TitanCARMA cloud microphysics model, I demonstrate that a pure hydrogen cyanide cloud consistent with the 2012 observations could only form at very cold temperatures, and that precipitation from the cloud could deplete much of the stratospheric hydrogen cyanide. However, while initial observations of the cloud only identified hydrogen cyanide ice, other species are expected to be present. Based on additional simulations of benzene and cyanoacetylene clouds as well as estimates derived from a toy model of mixed ices, I show that the presence of multiple ice species can significantly change the microphysical and macrophysical properties of the cloud, though estimating the precise effects requires additional experimental work. Finally, to better understand how the high-altitude cloud seen in 2012 relates to the polar hood previously observed in northern winter, I conducted a review of all of the imagery from Cassini from 2012 until the end of the mission in 2017. Using the images to measure the cloud top altitude, I demonstrate that the cloud gradually descended from an initial altitude of about 320 km in May 2012 to less than 230 km in June 2016, at which point it becomes obscured by atmospheric methane absorption. Over the same period, the cloud expands laterally, approximately following the terminator from an initial latitude of 80°S to 65°S by 2016. This suggests the necessity of radiative emission for maintaining the cold temperatures required to sustain the cloud, and provides important constraints for future models
Oral history of N.K.
No full text“NK” talks about her experiences growing up in Dallas, Texas, attending high school at a small Orthodox Jewish school, her parents (Israeli immigrants to the United States) and siblings, and choosing to attend Johns Hopkins University instead of the University of Texas, Austin. She talks about deciding to study neuroscience, being pre-med and her plans to go to medical school, her experience of Baltimore having grown up in suburban Texas, and her work as an EMT with the Hopkins Emergency Response Organization (HERO). She talks about travelling to Ethiopia and Israel during the summer, and her thoughts on the campus environment in response to the war in Gaza (which began in October 2023)
WHO GETS ACCOMMODATIONS? DECISION-MAKING PROCESSES AND DISPROPORTIONALITY IN SPECIAL EDUCATION
No full textWithin special education, Individualized Educational Programs (IEPs) facilitate the provision of special education to ensure students have equitable access to educational opportunities. One component of the IEP is the accommodations section. In the context of special education, accommodation is defined as “a change that helps a student to overcome or work around the disability” (Center for Parent Information and Resources, 2020a). This dissertation contains three studies that deeply examine accommodations to better understand how teachers select accommodations for students and to test for underlying disproportionalities and inequities.
In the first study I conducted semi-structed interviews with a sample of special education teachers and administrators from across the United States to understand how they decide which accommodations should be written in student IEPs. From these interviews I found that special educators are provided with high degrees of autonomy in making determinations about the best accommodations to support students. Additionally, they operate as street-level bureaucrats as they attempt to interpret the competing policy directives of supporting students based on their dis/ability category and creating an individually tailored IEP.
In the second study I used thematic analysis to analyze the classroom accommodations sections from a sample of IEPs in a small urban school district in the mid-Atlantic region of the United States. I found that while all IEPs in the sample included accommodations to support academics, a majority of IEPs also included accommodations focused on behavior. I also found that accommodations were more likely to have accommodations that promoted exclusionary practices over inclusionary practices and found that White students were more likely to have inclusion-oriented accommodations than their non-White peers.
For the third study I used hierarchical linear modeling to predict the likelihood of students receiving eleven different accommodations for testing based on IEP data from the same school district as the second study. I found that, when controlling for dis/ability category, multilingual learner status, gender, and school type, White students were more likely than their non-White peers to receive breaks, speech to text accommodations, and familiar test administrators in some subject area tests
UNVEILING THE HALO-GALAXY CONNECTION FROM COSMIC DAWN TO TODAY
No full textIn the next few years, observations of the 21-cm signal will open a window to the cosmic dawn epoch when the first stars formed. At the same time, ground- and space-based galaxy surveys will extend to ever higher redshifts reaching the beginning of the epoch of reionization. When combined, these measurements are poised to reveal how dark matter haloes foster the formation and evolution of their constituent galaxies across multiple epochs of cosmic time.
21-cm observations are usually interpreted with semi-numerical or hydrodynamical simulations, which are often computationally intensive and inflexible to changes in cosmological or astrophysical effects. I present a new approach to predict the 21-cm signal in the presence of Pop III stars in seconds. PopIII stars, residing in low-mass molecular-cooling halos, are highly sensitive to feedback, especially from H2-dissociating Lyman-Werner radiation and dark matter-baryon relative velocities. I will show an effective prescription of the star formation rate density in the presence of PopIII stars that recovers the full nonlinear distributions of radiative fields that determine the 21-cm signal including inhomogeneous feedback. I will show how PopIII stars impact the 21-cm global signal and power spectrum across cosmic time and at different distance scales. I show how the spatial modulation of the relative velocities induces Velocity Acoustic Oscillations in 21-cm power spectra, providing us with a new and robust cosmological standard ruler. Our public code, Zeus21, predicts 21-cm observables in seconds, presenting a meaningful first step towards rapid precision astrophysics and cosmology in the first billion years.
The nature of galaxy clustering at high redshifts will yield insight into the sources that drive reionization. I will present new clustering measurements of Lyman-Break Galaxies from the Subaru Hyper Suprime-Cam (HSC) at redshifts , deriving a more precise measurement of the halo-galaxy connection at high . We perform a joint analysis with UV luminosity functions, and show how clustering measurements can break degeneracies between mean galaxy luminosity and stochasticity to explain the enhanced abundance of UV-bright galaxies observed by JWST
Oral history of Tina Queen, LaShella Bacon, Monique Martin, and Greta Goodwin
No full textIn this interview, Dr. Warren Hayman spoke with several members of the Dunbar Hopkins program including Tina (Lockett) Queen, LaShella (Stanfield) Bacon, Monique (Walston) Martin, and Greta Goodwin. This focus group centered on individuals who ended up in professional positions focused on education.
Tina graduated from Dunbar in 1990. She was one of a few students who also played sports; she played basketball and went on to secure a 4-year scholarship for basketball at Coppin State University, also gaining acceptance into the Helene Field Nursing School. She transitioned her major into Adaptive PE. Later, she began teaching physical education and health and has been in the field for 30 years. She is currently the Athletic Administrator at Reginald F. Lewis High School. Tina reflects that the Hopkins Dunbar program structure really worked for her, and she felt the students held each other accountable. Tina shares that “Dunbar was truly a family” and helped her develop into the person she is today. She explains her professional journey and mentions financial difficulties.
LaShella graduated from Dunbar in 1990 and is currently the Principal of Cross Country Elementary Middle School. She has been in education for 25 years and held many roles including teacher, instructional support, academic liaison, and principal. She attended Frostburg University to study physical therapy but ended up switching to psychology. She was a substance abuse counselor for several years, then went back to UMBC to get her master’s degree in education. LaShella speaks to how Dunbar was a family and that peers had a competitive spirit of excellence. She shares opportunities students had as part of the program including working at the Johns Hopkins Hospital and elaborates on how the program helped her once she reached college. She reflects on shifting her career to psychology and then education. She offers advice for today’s students: “Advocate for yourself, seek opportunities, get in front of people who could help you develop who you are. Don't be afraid to ask for help.”
Greta graduated from Dunbar in 1995. She went to North Carolina Agricultural and Technical State University where she majored in engineering but changed to biology. She then went to Morgan State University and became a science teacher. Greta reflects on her recent interests in pursuing nursing. She is currently the Principal at Mary E. Rodman Elementary School and has worked for Baltimore City Schools for 25 years. She shares that the Hopkins Dunbar program impacted her life by helping her understand what a good teacher should do and how to connect with students. She mentions a couple of teachers that helped her, Ms. Nash and Ms. Robinson. She encourages today’s students to keep their goals front and center, stating “you can do anything you want to do!”
Monique graduated from Dunbar in 1990. She has worked in education for nearly 30 years. She graduated from Bowie State University after studying elementary education and went on to get her master’s degree at Johns Hopkins University. Monique currently works supporting educational equity and justice for the Delaware Department of Education. She explains the many different roles she’s held, from Ohio to Georgia, and from Virginia to Maryland. She reflects that the Hopkins Dunbar program challenged her and was made up of members of the community. It helped her understand that every possibility she wanted to manifest was within her reach, which is not something she believed in before growing up in Baltimore. She shares that learning at JHU and JHH was fundamental to her and exposed her to folks like Dr. Levi Watkins and Dr. Ben Carson. Monique indicates that going into education for her was a revolutionary act. Each interviewee reflects on their continued personal connection with Dr. Hayman and offers advice for current Dunbar students