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Characterization of Vestibular Implant Outcomes in Humans
No full textPeople with loss of vestibular sensation in both ears experience diminished reflexes that normally maintain stable vision, posture, gait, and spatial perception. Standard-of-care treatment for bilateral vestibular hypofunction involves cessation of medications that could further suppress vestibular reflexes and recruiting non-vestibular central nervous system pathways like the cervico-ocular reflex to stabilize the eyes and head during motion. However, this proves inadequate for many patients. Prosthetic vestibular stimulation is an emerging alternative.
This work investigates the use of the Multichannel Vestibular Implant in people with severe to profound, adult-onset, bilateral vestibular loss for >1 year and inadequate compensation despite standard-of-care treatment. Active since 2016, this study is an ongoing prospective, nonrandomized, single-center cohort study conducted at Johns Hopkins Hospital in which participants serve as their own controls. As of January 2025, 17 individuals have undergone unilateral vestibular implantation and have been continuously receiving motion-modulated prosthetic vestibular nerve stimulation targeting their semicircular canals.
Prosthetic stimulation of the vestibular nerve was able to elicit reflexive eye movements that targeted participants’ implanted canals with specificity. Vestibular implantation was shown to be able to drive reflexive eye movements for participants with both ototoxic and non-ototoxic loss, 1-23 years of vestibular loss before implantation, and with the return electrode placed either intra-labyrinthine or outside the temporal bone in a subperiosteal pocket. Motion-modulated vestibular stimulation during head motion increased the gain of the vestibulo-ocular reflex during head impulses and during low frequency sinusoids. Additionally, vestibular implant recipients report vestibular symptom improvements not reported by a control group. These vestibulo-ocular reflex responses and patient-reported benefits support the use of vestibular implantation as a treatment for bilateral vestibular hypofunction
Injuries to the Craniocervical Junction: A 3D Approach to Resident Education for Radiological Imaging
Get PDFInjuries to the craniocervical junction (CCJ), due to its complex anatomy, are notoriously challenging to locate in imaging and often misdiagnosed or overlooked, leading to unnecessary extension of injuries. Difficulties in reading the imaging and a lack of resources have created a need for clear and accessible educational materials for residents. This thesis investigates the use of multimedia to assist learners in visualizing CCJ structures and injury pathologies in 3D, as well as directly relate our model to medical imaging. Testing the efficacy of our materials will provide insight into the value of multimedia for enhancing radiological education and provide new resources to facilitate efficient diagnoses of injuries.
We created a series of animations highlighting CCJ injuries and still images relating them to CT/MR imaging. We tested the efficacy of the media using an online Qualtrics survey distributed to radiology-associated residencies and medical students from the Johns Hopkins School of Medicine and the University of Maryland. Our main study question was if the addition of an animation to still image explanations would help learners better understand CCJ injuries and their diagnoses. Participants were randomized into two groups– still images and still images + animation. Each participant completed a pre-test, viewed a module, then completed an engagement survey, post-test, and comparison survey.
Our survey results showed significant improvement in testing among both groups (p = 0.0045), suggesting the overall efficacy of our materials. While there was no significant difference in test scores between the still images and still images + animation groups (p = 1), there was a significant difference in total engagement survey scores (p = 0.0093) with the still images + animation group rating higher engagement. This suggests that still images only are sufficient in teaching the material, but animation can benefit a learner’s engagement and contextualization. Participants responded positively to the visuals, appreciating the dynamic animation and the imaging comparisons. Suggestions for improvement included the addition of narration and a summary slide. This study is ongoing, and we will continue distributing the survey to a larger sample audience, implementing participant feedback, and increasing content covered
The Classical Tradition in Eighteenth-Century Atlantic Women's Writing
Get PDFPhillis Wheatley, Mercy Otis Warren, and Catharine Macaulay—three eighteenth-century female writers of the Atlantic world—each employed a prose deeply rooted in the ideas and motifs of classical antiquity. All three women were published internationally, cultivated personal and intellectual relationships with prominent figures across the Atlantic, and maintained direct ties to the American Revolution. Collectively, they represent distinct and diverse positions within the dynamic and evolving landscape of the Atlantic world.
Though their engagement with antiquity differed in form and emphasis, each woman demonstrates a unique form of classical reception—one that shaped her understanding of historical time and informed her literary expression through the lens of the ancient past. Taken together, these women reveal that the classics served three key purposes in their lives and work: (1) they functioned as a means of forging transatlantic intellectual and cultural communities, (2) they offered a source of authority by aligning each writer with the prestige of classical tradition, and (3) they enabled each author to articulate ideas of patriotism and political engagement
Global Well-posedness and Scattering of the Schrödinger and Wave Equations on Hyperbolic Spaces
Get PDFThis paper studies the initial value problems of the defocusing Schrödinger and wave equations with power-type nonlinearity on the hyperbolic spaces. We aim to show that the solutions to these equations are globally well-posed and scatter under the same regularity assumption as predicted by the scaling symmetry in the Euclidean cases.
The main contribution of this paper is that we derive stronger Morawetz-type inequalities which were not avaiable on the Euclidean spaces. This allows us to establish global wellposedness and greatly simplify the proof of scattering.
The paper is divided into three parts. In the first part, we review the properties of hyperbolic spaces, as well as some useful tools for analyzing the equations.
In the second part, we study the conformal wave equation. We first establish a series of Morawetz estimates, and then prove the main result by the Fourier truncation method. The Morawetz estimates are used to control the energy growth rate of the truncated solution. We show that the solution is globally well-posed and scatters for almost sharp initial data.
In the final part, we apply the similar ideology to the Schrödinger equations. Due to the different representation of the time derivative of the energy, we were not able to obtain (almost) sharp results. Instead, we rely on a bootstrap argument to show a weaker result on 3 dimensional hyperbolic space. The same bootstrap ideology can be applied to show a decay estimate of the quintic defocusing Schrödinger equation on 3 dimensional hyperbolic space. We prove that result in the last section
CHOROIDAL NEOVASCULARIZATION IN FELLOW EYES OF PATIENTS WITH AGE-RELATED MACULAR DEGENERATION: SYSTEMATIC REVIEW AND META-ANALYSIS
Get PDFBackground: Neovascular age-related macular degeneration (nAMD), a leading cause of irreversible blindness globally, develops in one eye and frequently is followed by nAMD in the fellow eye. Knowledge on second eye involvement largely comes from clinical trials in the 1980s through 1995, prior to anti-vascular endothelial growth factor trials and imaging advances with optical coherence tomography (OCT). It remains largely unknown if rates subsequently have changed.
Methods: We conducted a systematic review and meta-analysis of CNV and associated best corrected visual acuity (BCVA) in fellow eyes of clinical trial participants with nAMD in the first eye. We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ClinicalTrials.gov from January 1, 1995 through August 8, 2024, for randomized or non-randomized trials of FDA-approved nAMD therapies. We screened, extracted data, and assessed the risk of bias using standard methods.
Main Outcomes: CNV and associated BCVA in fellow eyes of patients treated for nAMD in the study eye. We also examined risk factors associated with CNV development.
Results: We identified 26,782 records, of which 18 trials (17 randomized and 1 non-randomized) with 5,994 participants met criteria. The cumulative incidence of CNV in fellow eyes varied by type of treatment and duration of follow-up, which ranged from 0.0% to 38.0% with ranibizumab, 1.0% to 24.0% with aflibercept, and 1.0% to 5.6% with brolucizumab. PDT and laser were associated with the highest incidence beyond 24 months. Only female sex (HR 1.31, 95% CI 1.06-1.63) is associated with a higher cumulative incidence of CNV in fellow eyes, while findings for age (adjusted hazard ratio [adjHR] 1.20, 95% CI 1.05-1.36), White race (23% incidence), subretinal fluid presence on OCT (21% incidence), systemic hypertension (P = .61), baseline BCVA in study eyes (P = .07), and central retinal thickness (CRT) (HR 1.08, 95% CI 1.01-1.16) were inconsistent or not statistically significant. No study reported on visual acuity outcomes and treatments in fellow eyes.
Conclusions: As noted prior to 1995, these data confirm the continued relatively high incidence of fellow eye CNV within 2 years of initiating therapy for CNV in the first eye, even in an era of anti-VEGF therapy and OCT, with little, if any, systemic risk factors
Engineered Tumor derived Exosomes to detect and Image Pulmonary Pre-Metastatic Niches in a Lewis Lung Carcinoma Model
Get PDFThis study aims to engineer tumor-derived exosomes (TEs) that enable real-time tracking in vivo through bioluminescence and fluorescence. Using a novel mouse model that involves the centralized injection of labeled exosomes through the venous system of mice, we investigate the biodistribution and tissue-specific uptake of TE’s derived from melanoma, breast cancer, and colon cancer cell lines, each having distinct organotropism. The goal is to detect the formation of premetastatic niches (PreMNs) and to establish sensitive methods to identify and visualize the target tissues. This platform will support future evaluation of epigenetic interventions that target the development of these PreMNs
The role of telomere binding proteins in inherited telomere syndromes
No full textTelomere binding proteins play a role in telomere end protection as well as in the regulation of telomerase repeat addition. Mutations in genes encoding telomere binding proteins were recently identified in families with cancer predisposition; however, the mechanisms by which these mutations lead to cancer risk are not fully understood. In the first part of this thesis, we show that germline loss of function in POT1, the gene encoding the single stranded telomere DNA binding protein POT1, is haploinsufficient for telomere maintenance and simultaneously predisposes to long telomere length and a risk for a range of benign to malignant neoplasms and clonal hematopoiesis. A high number of clonal mutations and apparent absence of increased sensitivity to DNA damage in cells derived from these individuals suggest that cellular longevity, not a mutagenic process, underlies the neoplastic risk. In the second part of the thesis, we tested whether these findings extend to genes encoding other telomere binding proteins, including ACD and TINF2. We show that germline mutations in genes encoding telomere binding proteins are found in a small subset of familial papillary thyroid cancer (PTC). These telomere lengthening mutations cause a syndromic form of PTC that shows unique features including genetic anticipation in some cases, as is also seen in the contrasting short telomere syndrome. However, in this context, genetic anticipation was associated with inheritance of longer average telomere length and the mendelian telomere lengthening mutation. The results identify PTC as a prototypical long telomere phenotype in a least a subset of patients. Finally, in the third part of this thesis, we took a candidate gene approach to study the role of STN1, a plausible telomere length maintenance gene based on genetic evidence and corroborating molecular data. To this end, we established cell culture and mouse models to study the consequences of heterozygous and homozygous germline mutations in STN1. Collectively, our data use genetic evidence to clarify the role for telomere binding proteins in telomere length regulation and inherited telomere syndromes
THE INTERPLAY BETWEEN COASTAL TOURISM, PLASTIC POLLUTION, AND HARMFUL ALGAL BLOOMS: A CASE STUDY OF FLORIDA AND EAST CHINA SEA
Get PDFCoastal tourism provides important economic income to communities around the world, but it also generates large amounts of plastic waste, which is increasingly associated with environmental degradation. This thesis investigates the relationship between tourism-driven plastic pollution and harmful algal blooms (HABs), focusing on red tides in Florida and the East China Sea. Specifically, the study examined whether an increase in plastic waste during the peak tourist season leads to the formation or exacerbation of HABs, and whether HABs, in turn, lead to economic disruption in the tourism industry - creating a self-reinforcing feedback loop.
To assess this relationship, this study used a mixed-methods approach that included time-series analysis, tourism headcount statistics, analysis of bloom data, and policy content analysis. Key metrics analyzed included toxin concentrations, bloom surface area, plastic debris levels, tourist arrivals, and local tourism revenues from 2019 to 2024 (Florida) and from 2019 to 2023 (China).
The results of the study suggest that there is a seasonal correlation between peak tourism, increased plastic pollution and intensified HAB activity in both regions. Although the correlation does not establish causation, there is evidence that plastic waste may be a biological contributor to HAB. During periods of HAB, there is a concomitant decline in tourism, which undermines the local economy and reduces the resources available for environmental stewardship. The study concludes that current policy frameworks in Florida and China need to be supplemented with additional preventative measures and recommends an integrated coastal management approach that includes stricter pollution controls, real-time monitoring, and tourism-specific sustainability regulations
System Identification of Adaptive Control Strategies in Weakly Electric Fish
No full textHumans and other animals apply adaptive control strategies to respond to changes in control dynamics, sensory salience, and external stimuli. This dissertation employs system identification and control theory to study adaptive control strategies in weakly electric fish in three studies.
The first study investigates how nervous systems adapt to destabilizing dynamics, and how these adaptations benefit. We measured movements of the weakly glass knifefish (Eigenmannia virescens) as they tracked a moving refuge. To assess how fish adapt, we altered refuge motion through a novel augmented feedback to drive the system towards instability. We discovered that fish retuned sensorimotor controllers in a way to improve tracking performance and control-theoretic measures of robustness as the system was destabilized. The adaptation washed out over a period of minutes after the augmented feedback was removed, demonstrating the time course of the learning process.
The second study explores how active sensing and multisensory reweighting are modulated concomitantly in relation to changing sensory salience in weakly electric fish. We varied illumination levels (0.1 – 210 lx) during fish refuge tracking. Near a critical threshold, on the order of 1 to 10 lx, small increases in illumination led to steep reductions in fish active sensing movements and tracking phase lag. Outside of this range, illumination changes had a modest impact. A control-theoretic model was built to explore how animals dynamically reweight vision and electrosense under varying illumination conditions.
The final study examines how weakly electric fish adapt their tracking to simple versus complex stimuli using control-theoretic modeling approaches. We developed a nonlinear adaptive control model that incorporates an internal model for the predictable stimuli. The model captured key features of nonlinear behaviors in fish tracking: higher gain and lower phase lag during single sine tracking compared to sum-of-sines tracking and phase adaptation during transitions between stimuli.
These studies demonstrate how nervous systems adapt to changing closed-loop dynamics, manage sensory uncertainty, and form internal models for external stimuli. The findings and models provide a foundation for understanding the mechanisms underlying these adaptations in weakly electric fish and across taxa
Equipping Educators to Provide Critically Inclusive Instruction
Get PDFU.S. K–12 classrooms host expansive learner variability within them, for which specific teacher pedagogies and dispositions are needed to serve students’ ranging differences equitably and inclusively in a standardized, grade-level context. Past studies have examined how pre-service teachers are prepared for one facet of learner variability (e.g., language background), or have examined in-service teachers’ adjustments of district-provided curriculum to serve learner variability on a small-scale. This dissertation sought to understand the current landscape of how teachers are prepared for and respond to learner variability in instruction. It adopted a holistic perspective of learner variability, drawing upon Pape’s (2018) framework that outlines four pillars of variability for which teachers should serve in classrooms: content, cognition, social-emotional learning, and background. It also drew upon Cruz et al.’s (2024) InCrit framework, which posits that each child deserves access to relevant, responsive, and rigorous instruction in general education spaces, and learner variability is a strength to be leveraged in instruction. Together, these frameworks provided a lens for how to meaningfully include every child into high-quality classroom instruction.
In this dissertation, I aimed to establish baseline understandings of two important fixtures that can inform teachers’ responses to learner variability: teacher preparation policy and district-provided curriculum materials. Study 1 explored the landscape of how 15 diverse states prepare pre-service teachers for learner variability and the guidance they provide educator preparation programs to do so. In it, I used critical policy analysis and framing theory to draw eight themes about states’ requirements and framing of guidance related to learner variability. Study 2 examined nationally representative survey data of U.S. elementary educators, who indicated the priorities they hold that inform the curricular modifications they make to district-provided curriculum. Using latent class analysis, I located four sub-classes of priority patterns and compared them against the InCrit framework. I then conducted multinomial logistic regression to determine which student-, teacher-, and context-related characteristics predicted teachers’ probability of belonging to certain priority classes. Overall, this dissertation points to policy-related factors that can support equipping teachers to provide meaningful, inclusive instruction