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Personal Space Regulation in Schizophrenia
No full textRepresentation and regulation of the space surrounding the body (i.e., the buffer zone between the self and others) play a central role in one’s adaptive interactions with the external world. There are at least two distinct ways to approach the study of the personal space. Peripersonal Space (PPS) refers to the multisensory interface surrounding the body within one’s grasp (reaching space) (Rizzolatti et al., 1997; Makin et al., 2009; Serino et al., 2011). Interpersonal distance (IPD) is characterized as a safety zone or the social comfort space that individuals prefer to maintain between themselves and others (Hall, 1966; Hayduk, 1978).
The phenomenology of weakened self-boundary is a hallmark of schizophrenia but it has rarely been investigated in the context of disrupted PPS or IPD. Moreover, the role of social and emotional factors on the regulation of the personal space is poorly understood. To address this gap, novel experimental paradigms were implemented in immersive virtual reality environment to quantify PPS and IPD in individuals with schizophrenia (SZ) and control participants (CO). A multisensory integration task was used to estimate the PPS and a stop-distance task was used to measure IPD. To examine the potential impact of social and emotional factors, the stimuli were manipulated to convey appropriate contexts.
In the first study, the effect of physical (Study 1A) and social threat (Study 1B) on PPS was examined. In Study 2, various avatars with descriptions, designed to prompt positive or negative emotion, were used to examine the malleability PPS (Study 2A) and IPD (Study 2B) and its associations to symptoms and social functioning in SZ. Furthermore, since adaptive regulation of personal space has been suggested as a potential treatment target (Sambo & Iannetti, 2013; Taffou & Viaud-Delmon, 2014; Kennedy & Adolphs, 2014), the clinical significance of personal space representation was investigated. In Study 3, PPS and IPD were utilized as outcome measures for a virtual reality (VR) based social skills training study.
We found that personal space representation was altered under various social and emotional contexts in SZ compared with CO. In general, SZ showed a reduced flexibility in the regulation of personal space in response to socio-emotional changes in the environment. Personal space parameters, clinical symptoms and social functioning were closely associated, which highlights the significance of personal space regulation in schizophrenia. Importantly, we found that abnormal representation of personal space can be ameliorated through a simulation-based, social skills training program over a course of 8 sessions.
Overall, these results indicate that mechanisms underlying self-disturbances in schizophrenia involve abnormalities of personal space regulation, and that these difficulties are associated with clinical symptoms and social dysfunctions. Future studies will need to further examine and analyze more specific parameters of PPS and IPD through continued innovations in methodology
Creating a Culture of Care: A Peer-Informed Needs Assessment of Youth Protection at Duke University
No full textDuke University hosts over 60,000 minors annually through a wide range of programs, necessitating robust youth protection practices. This needs assessment, conducted utilizing inductive coding and guided by the Consolidated Framework for Implementation Research (CFIR), identified critical barriers to full policy implementation, including cultural disconnects, inconsistent training, operational inefficiencies, limited data-driven oversights, and insufficient leadership engagement. Through qualitative analysis of Duke affiliated stakeholder interviews, peer interview benchmarking, and peer document review, the study offers a five-year strategic roadmap for cultivating a university-wide Culture of Care. Strengthening youth protection at Duke not only fulfills ethical and legal obligations but also positions the institution as a national leader in higher education safety.Peabody College of Education and Human DevelopmentDepartment of Leadership Policy and Organization
Pre-matriculation Program Evaluation
No full textLeadership and Learning in Organizations capstone projectThis study evaluated the pre-matriculation program at a midwestern medical school, identified by the pseudonym St. Juan University. Medical school pre-matriculation programs are among the national strategies to address disparities in healthcare. The St. Juan University pre-matriculation program has a deficiency in program documentation that requires program administrators to rely on informal measures for decision-making. Our mixed methods research produced key findings in academic and social integration, program management, data and communications limitations, and shifts in organizational culture
Leveraging Electronic Health Record Derived Phenome to Enhance Genetic Studies of Common and Rare Disease
No full textThe integration of electronic health record (EHR) derived phenotypes with genetic data has been instrumental in enhancing our understanding of gene-phenotype associations. Vanderbilt University Medical Center has an extensive EHR system that has over 3.5 million individuals that are stored in a de-identified database, the synthetic derivative (SD) that includes ICD billing codes, medications, clinical notes, medical histories, and laboratory values. A subset of the SD, BioVU, is a de-identified EHR-linked DNA repository. Having EHR-linked genetic data has allowed for the development of scalable and accurate phenotyping methods (phecodes), the expansion of analyses beyond genome-wide association studies (GWAS) to identify associations phenome, transcriptome, and laboratory-wide (PheWAS, TWAS, LabWAS). Additionally, methods such as the development of phenotype risk scores (PheRS) have allowed us to disentangle distinct phenotypic patterns of disease and clinical presentation of the complex, multisystem Mendelian diseases as well as enhance our understanding of disease comorbidities. Leveraging these data and methods, we have been able to study common genetic disorders and provide biological context to shared genetic architecture of eye disease by implementing gene and comorbidity-based analyses. These analyses were able to identify established and novel eye disease associations. Additionally, these data and resources have allowed us to study Mendelian diseases on a large scale. We implemented an approach that leverages PheRS to ask questions about Mendelian disease gene function and explore gene-phenotype associations among genes used for clinical diagnostic testing with accurate phenotyping of craniofacial congenital anomalies. The ability to implement these methods to ask questions about both rare and common genetic diseases highlights the diversity and breadth of research questions that can be asked of EHR-linked genetic data
Implementing Short Interpulse Intervals (SIPIs) in Multi-channel Cochlear Implants
No full textCochlear implants (CIs) are the only neuroprosthetic devices that can restore hearing to people with severe‐to‐profound deafness. Yet, bilateral CI listeners still struggle to exploit interaural time difference (ITD) cues for spatial hearing because the standard continuous interleaved sampling (CIS) strategy removes temporal fine structure, leaving only envelope ITDs. Prior attempts to reintroduce ITD cues—such as mixed rate, phantom cue, and envelope sharpening methods—failed to deliver additional ITD benefits without degrading speech quality in real time. The recently proposed Short Interpulse Interval (SIPI) strategy overcomes this trade-off by embedding sparse, low-rate pulses within an high-rate train, theoretically restoring microsecond-scale ITDs while preserving sound quality. Until now, however, SIPI had been tested only in single-channel settings. This research is the first to deploy SIPI on clinical multi-channel implants and evaluate its perceptual impact. Aim 1 assessed ITD sensitivity in eight experienced bilateral CI users for three SIPI pulse rates (50, 100, 200 pps) and three insertion methods (fixed, random, local maximum). Aim 2 compared phoneme recognition for each listener’s optimal SIPI setting versus standard CIS at two signal-to-noise ratios (+10 dB, 0 dB) and two binaural configurations (N₀S₀, N₀Sπ). The SIPI rate showed a significant main effect on lateralization accuracy, peaking at 50–100 pps and declining at 200 pps, while the insertion method had no significant main effect. The best SIPI configuration improved ITD discrimination by up to 22 percentage points relative to CIS. In speech testing, SIPI preserved baseline intelligibility (N₀S₀) and delivered significant additional binaural masking release of 11.2 % at +10 dB SNR and 6.5 % at 0 dB SNR. Gains were largest for stop consonants (which have abrupt temporal characteristics) and smallest for steady-state vowels. These findings showed that multi-channel SIPI can restore meaningful ITD cues without compromising speech quality, resolving a long-standing limitation of CI processing. This research indicated that the SIPI strategy has a promising future in clinical applications, providing CI users with both high intelligibility and improved spatial hearing
Enhancing Sensitive Caregiving: Comparing Narration and Mimicking Strategies in Mother–Child Interactions
No full textCaregiver sensitivity during early interactions represents a critical factor in infant development and attachment security, yet evidence-based strategies to enhance sensitivity among parents remain limited. The present study examines whether a brief, targeted manipulation—requiring minimal effort or time investment—can meaningfully improve caregiver sensitivity. Mothers and their 6-month-old infants (N = 129; 77 male infants) from a large metropolitan city in the central southeastern part of the United States participated in a 10-minute “free play” interaction, coded in 2-minute epochs for degree of caregiver sensitivity. Prior to the final epoch, mothers were randomly assigned to "narrate" their infant's actions or "mimic" their infant's behaviors. A control group of mothers received no instructions. Consistent with our hypotheses, analyses of within-person changes in sensitivity revealed that mothers instructed to narrate their infant’s actions were significantly more sensitive after receiving these instructions than they were before receiving these instructions. Contrary to our hypotheses, mothers instructed to mimic their child’s actions were significantly less sensitive after receiving the instructions than they were before receiving the instructions. Mothers assigned to the control group did not statistically significantly change in sensitivity. Our findings suggest that narrating an infant's actions, a simple practice for parents, may enhance caregiver sensitivity, whereas imitating the actions of preverbal infants may not be beneficial for increasing sensitivity at this developmental stage. This research contributes to our understanding of how brief, evidence-based, and easily implementable caregiving strategies can promote optimal parent–child interactions from infancy
“True Beauty”: Hair, Femininity, and Self-Perception
No full textThis thesis investigates the significance of hair in women’s lives, with a focus on how hair loss and the choice to cover hair shape perceptions of femininity, beauty, and self-identity. While hair is often dismissed as superficial, it operates as a critical site of meaning. Hair is tied to cultural values, spiritual practices, racialized beauty standards, and emotional well-being. This thesis provides reasoning for why an integrated framework, The Hair-Identity Embodiment Framework, is needed to truly understand hair-related experiences. The Hair-Identity Embodiment Framework combines the biomedical, psychological, sociocultural, and economic dimensions, highlighting the complex interplay between individual experience and structural forces of hair and beauty. Beginning with a theological and historical overview, the thesis explores how hair has long symbolized. It then examines how medicalized understandings of hair loss often fail to address the emotional trauma and social stigma experienced by women. Methodologically, the thesis is based on an argumentative review. The analysis of established literature ultimately calls for a more culturally responsive and emotionally attuned approach in healthcare, public health, and media representations
Towards a Darker Sky: The Efficacy of Mitigation Strategies for Artificial Light at Night and Its Impact on Plant Phenology
No full textLight pollution, an increasingly recognized environmental hazard, disrupts urban ecosystems, including plant phenology such as leaf-out and senescence. In recent years, municipalities have enacted legislation to reduce artificial light at night (ALAN) at city levels. This study evaluates the effect of ALAN-mitigation policies on changes in intensity and spectrum composition of ALAN and consequent changes in plant phenology in U.S. cities using satellite data for 2022-2023. ALAN declined in cities with ALAN-mitigation measures the following year (New York City: -4.63%, Washington D.C.: -9.44%), with the largest decline in blue band. In contrast, ALAN increased in cities without measures (Newark: 11.78%, Philadelphia: 4.49%). Successful mitigation efforts also corresponded to reduced ALAN-induced shifts of autumn phenology of urban plants. These findings suggest that implementing ALAN-mitigation policies plays a critical role in mitigating the ecological impacts of light pollution and emphasize the need for eco-friendly lighting solutions to support ecosystem functioning
Structural and Functional Insights into Na+/I− Symporter (NIS) Transport Mechanisms and Their Implications for NIS-Mediated Internal Radiation Therapy
No full textThe Na+/I- symporter (NIS) is a plasma membrane protein crucial for human health, and a central player in both physiology and targeted internal radiation therapy. In the thyroid gland, NIS mediates the active, electrogenic transport of iodide (I⁻) with a 2 Na⁺ : 1 I⁻ stoichiometry—and this is the first, and the rate-limiting, step in the biosynthesis of the thyroid hormones (THs). These hormones, triiodothyronine (T₃) and thyroxine (T₄), are essential regulators of metabolism, influencing growth, development (especially that of the central nervous system), and energy balance. Deficiencies in I⁻ uptake or TH production can lead to severe disorders, including hypothyroidism, goiter, and developmental delays, underscoring how critical it is that the delicate homeostatic balance of circulating TH levels be maintained.
Beyond its indispensable role in physiology, NIS underpins the highly successful treatment for thyroid cancer based on radioiodide. Because many thyroid malignancies retain functional NIS expression, metastatic or residual thyroid cancer cells can be selectively targeted using radioactive 131I⁻ isotopes administered systemically post-thyroidectomy. This strategy exploits the ability of NIS-expressing cells to concentrate radioiodide, delivering cytotoxic radiation specifically to malignant tissue while largely sparing healthy organs. Because NIS is naturally expressed predominantly in thyroid tissue, radioiodide therapy remains one of the most elegantly selective anticancer therapies ever devised.
Interestingly, NIS not only transports I⁻ with a 2 Na⁺ : 1 I⁻ stoichiometry, but also transports oxyanions, such as pertechnetate (⁹⁹ᵐTcO₄⁻), perrhenate (ReO₄⁻), and the environmental pollutant perchlorate (ClO₄⁻). Strikingly, these oxyanions are transported with a different, electroneutral stoichiometry of 1 Na⁺ : 1 XO₄⁻. Chapter 2 of this dissertation investigates how the same transporter can switch between a 2 Na⁺ : 1 I⁻ (electrogenic) and a 1 Na⁺ : 1 XO₄⁻ (electroneutral) transport stoichiometry. We conducted transport assays and made electrophysiological measurements, and analyzed the data using a statistical thermodynamics-based equation. Our results show that ClO₄⁻ not only competes directly with I⁻ at the substrate binding site, but also binds at a high-affinity non-transport allosteric site. In so doing, ClO₄⁻ prevents one of the two Na⁺ ions from binding to NIS, effectively shifting I⁻ transport toward a 1 Na⁺ : 1 I⁻ stoichiometry and thus substantially diminishing the driving force for I⁻ accumulation. This finding implies that even low levels of ClO₄⁻ in drinking water may be more detrimental to thyroid physiology than previously believed, indicating that environmental safety standards for perchlorate pollution need to be reassessed.
Chapter 3 lays out how we determined the first high-resolution cryo-electron microscopy (cryo-EM) structure of a mutant NIS protein, Q72A NIS. Replacing Glu at position 72 with Ala disrupts Na⁺ binding at the Na1 and Na2 sites, and alters the conformation of transmembrane segment 2. Although this mutant does not transport I⁻, it still transports ReO₄⁻—and, crucially, it does so electrogenically, with a 2 Na⁺ : 1 ReO₄⁻ transport stoichiometry (rather than a 1 Na⁺ : 1 ReO₄⁻ stoichiometry). Detailed structural analysis reveals two newly formed Na⁺ sites (Na3 and Na4) along the translocation pathway leading to the cytoplasm, showing how even single amino acid substitutions can drastically change substrate selectivity and stoichiometry. These findings deepen our understanding of the structural plasticity of NIS and of how it coordinates ions.
Finally, chapter 4 investigates how NIS could be used to develop innovative cancer therapies, particularly ones for non-thyroidal cancers. By introducing point mutations within the π-helix of transmembrane segment 7, we engineered a variant (the L253P/V254F double mutant, dubbed PF NIS) that efficiently transports oxyanions but transports only a negligible amount of I⁻. To uncover the structural basis for this phenomenon, we determined the cryo-EM structure of PF NIS at 2.58 Å, the highest resolution achieved for any NIS structure to date. Crucially, this structure explains how NIS binds and transports 2 Na+ ions. We propose that this selectively reprogrammed PF NIS protein could be expressed in non-thyroidal cancers by gene transfer, and the malignancies then treated with radioactive 188ReO4- while protecting the thyroid by simultaneously administering non-radioactive I-. The non-radioactive I- would not prevent the cancer cells from accumulating 188ReO4-, but it would prevent healthy thyroid cells from doing so (by saturating WT NIS). As a proof of concept, we tested this hypothesis in in vitro experiments. This idea paves the way for a new approach to treating cancer that relies on the genetic transfer of engineered NIS molecules into non-thyroidal tumors, with fewer off-target side effects.
All in all, then, this work combines biochemical, functional, and structural strategies to reveal how the mechanism by which NIS couples ions changes depending on the substrates; identifies residues critical for determining substrate selectivity and transport stoichiometry; and proposes new ways to exploit NIS to treat non-thyroidal cancers in a targeted fashion. These findings not only deepen our fundamental understanding of an essential transporter involved in both normal endocrinology and cancer treatment but also have direct implications for how water pollution should be tackled and what strategies should be deployed in developing some next-generation of anticancer therapies
From Risk Genes to Functional Connectivity: Multi-Dimensional Integrative Frameworks to Unravel Genetic Mechanisms in Alzheimer’s Disease
No full textAlzheimer’s disease (AD) demands integrative approaches to resolve its genetic, molecular, and neurobiological complexity. This dissertation develops frameworks integrating multi-tissue omics and neuroimaging data to dissect AD risk mechanisms across molecular, regulatory, and clinical dimensions. Initially, we introduce Multi-tissue Splicing Gene (MTSG), a tensor decomposition and sparse canonical correlation analysis (sCCA) framework that identifies 174 splicing-mediated AD risk genes by modeling multi-tissue splicing architectures, outperforming single-tissue approaches and revealing novel pathways. Subsequently, we extend this tensor-sCCA framework to identify transcriptional gene networks, i.e., transcription factor (TF) regulons, implicating GCM2 and ZNF732 regulatory networks in AD risk and uncovering cis-/trans-eQTLs linking GWAS variants to dysregulated TF activity. Finally, we bridge genetics to neuroimaging through advanced mediation analysis, employing multi-group structural equation modeling (SEM) to reveal stage-dependent effects of the AD-risk variant rs6733839: its risk allele paradoxically reduces tau pathology in cognitively normal individuals but directly disrupts functional connectivity in subjects with mild cognitive impairment, suggesting its temporally divergent roles. Collectively, this work demonstrates how integration of splicing, regulon, and neuroimaging data can address AD’s genetic heterogeneity, offering methodological advancements in tensor decomposition, causal mediation, and genetics-neuroimaging integration