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LESIONS ASSOCIATED WITH HYPERSOMNIA MAP TO A COMMON BRAIN NETWORK
No full textAbstract.
Background: Hypersomnia is characterized by excessive daytime sleepiness, severely impairing daily functioning and often a significant source of distress for affected individuals. Brain lesions associated with new-onset hypersomnia may provide causal insights about neuroanatomy critical for sleep regulation. Moreover, mapping the whole-brain functional connectivity of these lesions may identify the brain networks that regulate sleep and wakefulness. The hypothesis that lesions causing hypersomnia map to a common brain network has not been formally tested.
Methods:
We conducted a systematic review of the literature and identified 63 hypersomnia-related lesions. Each lesion was mapped onto a common brain template, and functional networks were computed using resting-state functional connectivity data from 1,000 healthy individuals. Sensitivity analyses were performed at two thresholds (T > 4.7 and T > 7). A one-sample Welch’s t-test was performed to account for multiple comparisons. Two independent specificity analyses were conducted by comparing the hypersomnia network with lesion connectivity associated with other neuropsychiatric conditions (n = 997) and a cohort of stroke lesions (n = 135). We created a conjunction map and used it as a region of interest (ROI) to derive a hypersomnia brain network. We formally tested the hypothesis that the hypersomnia network exhibits preferential functional connectivity with the posterior hypothalamus, rather than the anterior hypothalamus, using two different ROIs from two separate atlases. The functional connectivity of the entire hypersomnia cohort to these ROIs was averaged, and a paired t-test was performed. Given the phenotypic similarities of hypersomnolence and coma, a one-sample t-test (FWE-corrected) was conducted to test the similarity of hypersomnia and coma-associated brain networks. An exploratory voxel-wise-two-sample t-test (FWE-corrected) was conducted to identify brain network patterns differentially associated with hypersomnia and coma, respectively. Lastly, we conducted an exploratory assay to compare the spatial topography of our hypersomnia network to brain networks associated with other neurological and psychiatric conditions.
Results: Hypersomnia-causing lesions are part of a common brain network (in >95% of cases) connected to relevant arousal centers, which is both specific and consistent. The posterior hypothalamus shows preferential functional connectivity to hypersomnia-associated lesions, in contrast to the anterior hypothalamus. There is a significant similarity in functional connectivity networks between hypersomnia and coma. However, exploratory analysis reveals distinguishing properties between them. Our hypersomnia network demonstrates strong, significant spatial similarity with lesion networks associated with coma.
Conclusion: Hypersomnia-associated lesions map to a common brain network, encompassing critical arousal centers and regions outside the classical ascending reticular activating system (ARAS). The functional connectivity networks are significantly similar between hypersomnia and coma. However, our exploratory analysis reveals that the functional connectivity networks of coma originate from the lower brainstem, whereas the functional connectivity networks of hypersomnia originate in the upper brainstem. These findings offer new insights into the functional networks of hypersomnia specifically and conscious arousal generally, and lays the groundwork for proposing new stimulation targets that could alleviate hypersomnia symptoms.Medical Scienc
Essays in Macroeconomics and Finance
No full textThis thesis contains three chapters in macroeconomics and finance. In the first chapter, co-authored with Pierfrancesco Mei, we propose a theory of shallow thinking to capture people’s limited understanding of the long causal chains involved in shock propagation. We cast general equilibrium as a system of causal relations in a directed cyclic graph. Estimation from our qualitative survey suggests that, on average, people understand only about 2.6 steps of propagation, overlooking much of the graph and significantly deviating from rational expectations. Our theory implies that longer causal chains have diminishing influence on beliefs. Applying shallow thinking to a New Keynesian model with active monetary policy reconciles several puzzles about long-term interest rates and inflation: (i) long-term interest rates underreact to cost-push shocks but overreact to monetary policy shocks; (ii) inflation expectations negatively predict bond excess returns; (iii) news about future cost-push shocks triggers inflation; and (iv) more persistent cost-push shocks lead to higher inflation. Notably, (iii) and (iv) contradict the predictions of rational expectations. In a real business cycle model, relative to rational expectations, shallow thinking amplifies and prolongs output fluctuations from productivity shocks and predicts negative future stock excess returns.
In the second chapter, co-authored with Xu Lu, we argue that institutional portfolio rebalancing across asset classes plays a key role in transmitting monetary shocks to equity markets. All else equal, around FOMC announcements, a stock with 10% higher ownership by institutions that routinely rebalance loses an additional 3.7 basis points following a 10-basis-point surprise rate hike. Our cross-sectional approach links this return difference to the aggregate stock market reaction through the price elasticities of both the aggregate market and individual stocks. We find that portfolio rebalancing accounts for roughly one-third to two-thirds of the aggregate stock market reaction attributed to changes in expected excess returns.
In the third chapter, I investigate the determinants of demand elasticities and distortions across industries, acknowledging that firms’ demand and pricings are interdependent in input-output networks. I propose a modeling approach of competition in markups, which micro-founds demand elasticities and markups via “network Lerner indexes” based on the network structure of the economy in general equilibrium. At the equilibrium, each firm’s markup depends on four industry-level network statistics—cycle, substitution in production, substitution in consumption, and impact on consumer price, in addition to its market share. Empirical analysis of Compustat firms from 1997 to 2019 confirms the theory predictions. Taking into account the sectoral heterogeneity explains about three times more variations in markups. Under the theory-predicted markups, the loss in total factor productivity due to misallocation is about 13% over the sample period, which is four times larger than the implied loss that ignores sectoral heterogeneity.Economic
Veteran Status and Oral Health Indicators in Older Men: An Analysis Using the 2016 and 2018 Behavioral Risk Factor Surveillance System
No full textObjectives: US veterans exhibit higher rates of oral disease than nonveterans, affecting their quality of life and systemic disease risk. Regular dental care is essential for preventing tooth loss, especially among older adults. The aim of this study was to assess the association between veteran status, dental visits, and tooth loss among older male Americans.
Methods: We analyzed data from the 2016 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) surveys in a national cross-sectional study. The study focused on males aged 65 years and older, using descriptive and multivariable logistic regression analyses to measure the association between veteran status and having a dental visit < 1 year ago, and the loss of ≥ 6 teeth due to tooth decay or gum disease. The analyses were adjusted for sociodemographic factors, including age, race/ethnicity, and education level.
Results: Veterans displayed a higher prevalence and increased odds of tooth loss compared to nonveterans after controlling for race and education. However, there was no difference in recent dental visits based on veteran status. The effect of dental visits on the odds of tooth loss indicated that veterans experienced a stronger protective effect of visits on tooth loss (OR: 0.34, 95% CI: 0.31-0.37) than nonveterans (OR: 0.41, 95% CI: 0.37-0.45).
Conclusions: Our findings indicate a potential opportunity to reduce disparities in tooth loss among older men. Promoting dental care among veterans could mitigate the risk of tooth loss and its subsequent adverse effects on overall systemic and brain health in this population.
Keywords: dental care; health inequities; longevity and healthy aging; older adults; oral health; tooth loss; veterans.Accepted Manuscrip
Tearing Down the Curtain: Heritage Management and National Identity in Lebanon
No full textHeritage site management and preservation are vital undertakings that go beyond simple conservation work since they are intricately linked to the formation and maintenance of national identity (Zeayter et al. 2017). This is never more apparent than in Lebanon, a nation with a rich cultural past that is still attempting to reconcile the intricacies of a fractured sense of national identity. It is critical to comprehend how national identity and heritage sites interact as Lebanon navigates the difficulties of historical contradictions and political unrest. In an effort to shed light on how heritage sites and their management affect Lebanon's national identity and the lack of a collective memory, this thesis proposes to unpack this complex connection. Conflict, foreign interference, and internal differences have all characterized Lebanon's historical trajectory, which has contributed to the disintegration of the country’s collective memory and national identity. Lebanon's cultural environment has been permanently shaped by the legacies of colonialism, civil wars, and geopolitical conflicts, which have shaped both past and contemporary narratives.
Using multidisciplinary viewpoints from history, anthropology, archaeology, and heritage studies, this thesis proposal seeks to offer a thorough understanding of the ways in which cultural sites shape Lebanon's sense of national identity. This research employed a case study approach, focusing on the National Museum of Beirut as a symbolic site of colonial heritage in Lebanon. I used collection of artifacts, such as pictures of major monuments and maps as well as observation logs as the major data collection techniques.
Due to the political conflict in Beirut that ensued at the time of the study, the study context was limited to the National Museum of Beirut.
The National Museum of Beirut stands as a symbol of Lebanon’s fragmented identity. Established under the French mandate, it is shaped by colonial narratives and designed to emphasize the country’s Antiquity heritage. Moreover, the Lebanese civil war transformed the museum into a battleground both literally, as it stood on the Green Line, and figuratively as the work it took to retore it post-war became part of the country’s larger fight to reconstruct its fractured identity. Despite its reopening and restoration, the museum still faces major challenges in curation such as a real inclusivity in its representation of Lebanese history, as well as a more chronological and objective historical display. The museum should rise above its storage like display in order to present a more balanced and nuanced narrative.Extension Studie
Meeting Teachers with Mindfulness: The effects of a brief online mindfulness intervention on teacher stress and burnout
No full textA teacher mental health crisis has led to high rates of teacher attrition and mass shortages in education jobs (Swider & Zimmerman, 2010). As of 2023, 90% of public- school districts in the United States report struggling to hire new teachers and nearly half of public schools report understaffing issues according to the National Center for Education Statistics survey which included more than 1,3000 public schools (2023). When asked why teachers decide to leave their jobs, high stress and burnout are among the most cited reasons (Gray et al., 2017, Kim et al., 2021). Teacher mental well-being has a direct and positive affect on school performance and student well-being (Briner & Drewberry, 2007, Swider & Zimmerman, 2010). Therefore, a viable stress and burnout intervention that is cost- and time- effective, accessible, scalable and empirically sound is imperative to solving the teacher shortage crisis and benefitting both educators and students in public-school systems.
The level of stress that teachers experience has often been compared to that of doctors and the military (Gray et al., 2017). To alleviate feelings of stress and burnout in these other demanding jobs, mindfulness-based stress reduction (MBSR) has been well- documented as a successful intervention tool (Clough et a., 2017, Roser et al., 2013, Flook et al., 2013). Additionally, limited research shows that MSBR might also have success in decreasing levels of stress and burnout in teachers. Recent studies have piloted mindfulness interventions, both online and in person, with teacher populations globally and have witnessed promising success (Roser et al., 2013, Flook et al., 2013, Janssen et al., 2022). However, research has found that teachers are not only reluctant to reach out for mental health support due to fear of judgement regarding their job competency (McCarthy, 2019), but also lack the extra time in their daily schedules to seek mental health interventions such as therapy outside of school (Flook et al., 2013). Additionally, though occupational interventions have been shown to be more beneficial for teachers than personal interventions (Routsalainen et al., 2008), teachers often hold a bias against after-school trainings and view them as wastes of time, uninteresting, and not useful (Damianidou, 2019). Providing mental health care for educators while respecting their time constraints is necessary to benefit a greater number of teachers.This study aims to explore the stress and burnout levels amongst different types of teachers across various years of experiences, subjects, and grade level. This study also asks if a brief, one-session, online MBSR intervention will have a meaningful impact on stress and burnout levels for teachers.
The study hypothesizes that the brief online intervention using mindfulness will decrease levels of teacher stress and burnout and will show success for all types of teachers. This hypothesis was tested with an online study sent out to teachers through school district email listservs and social media websites. Levels of stress and burnout prior to and following the MSBR intervention were recorded using The Perceived Stress Scale (PSS) and The Maslach Burnout Inventory - Educator
Survey (MBI-ES), as well as self-reported rating scales. Baseline and post-intervention scores were collected and compared to access intervention effect
Metamorphoses of the Past: Post-Soviet Memory in the Twenty-First Century
No full textThis dissertation examines how memories of the Soviet past are addressed and reimagined across three distinct cultural spheres: religion, literature, and film. It engages with the problem of fragmented and incomplete historical memory—a condition that many scholars identify as central to memories of the Soviet past. My dissertation explores how these three cultural domains attempt to respond to this challenge. I argue that disrupted memory demands more creative engagement in order to be shaped into a coherent narrative and to be more closely linked to the identity of its beholder. I also suggest that the creative strategies used to approach this memory must remain flexible and open-ended in order to accommodate its fragmented nature. In the discourse of the Russian Orthodox Church Outside of Russia (ROCOR), these memories take shape through the theological concept of martyrdom, adopting a highly antagonistic mode of memory. In contrast, the literary works of Maria Stepanova and Sergei Lebedev are treated as examples of cosmopolitan memory. These texts reject moral binaries and instead embrace the ethical complexity of the past. Finally, I analyze Il’ia Khrzhanovskii’s Dau project, an experimental cinematic work in which people improvised their lives within a simulated Soviet society. Dau is an example of an agonistic memory that presents the Soviet past as a multifaceted, ethically ambiguous landscape. These three examples of engagement with Soviet memory challenge simplified narratives of the past and reveal the creative potential of memory work.Slavic Languages and Literature
Taking(s) on the Mississippi: Bearing Witness for Reconciliation
No full textThe realities of retreat are destabilizing static representations of property embedded in the national identity of the United States. The Birds Point-New Madrid floodway in Missouri is a landscape formed through the survey: a technical apparatus operated to preserve the institution of private property along past American Frontiers. Landscape architecture has long utilized the survey to frame life along the Mississippi River, situating claims of ownership onto the land in service of colonial narratives.
Taking(s) on the Mississippi uses retreat as a tool to reframe the survey, addressing histories of displacement inscribed on the surface of the floodway to advocate for reparative action. Landscapes of witness are embodied through archival narratives, legal argumentation, and drawing, setting precedent for new claims of collective ownership and relationality to emerge on site. These claims lay the foundation for a future where retreat makes room for reconciliation in the contested landscapes of the Mississippi.Department of Architectur
Managed Expectations Theory: Ex Ante Likelihoods Influence Ex Post Utilities
No full textDaniel Kahneman, often in collaboration with Amos Tversky, developed foundational frameworks for understanding human decision-making. Building on that tradition, this article proposes that individuals’ ex ante assessments of the likelihood of good and bad outcomes serve as reference points that shape the ex post utility of lottery outcomes. In prospect theory, prior holdings act as reference points for evaluating outcomes—but probabilities themselves play no such role. This article introduces Managed Expectations Theory, which rests on two core hypotheses: 1. Reference Point Hypothesis: Ex ante probabilities serve as reference points for ex post utility. Specifically, more pessimistic expectations about uncertain outcomes enhance ex post utility, regardless of whether the outcome turns out to be good or bad. Four experiments, using a nationally representative adult sample of over 1,000 participants, strongly support this hypothesis. Lower [higher] ex ante likelihoods are associated with greater ex post utility for good [bad] outcomes. 2. Created Likelihoods Hypothesis: Recognizing that likelihood assessments act as reference points, individuals deliberately manage these assessments to be more pessimistic than an objective or statistical “outside view”—in order to boost their ex post utilities. Supporting this conjecture, the good outcomes participants labeled as “likely” occurred far more often than the bad outcomes they labeled as “likely.” These created likelihoods help explain a central feature of prospect theory’s probability weighting function: the underestimation of high-probability good events and the overestimation of low-probability bad events.Version of Recor
Essays on International Trade, Financial Intermediation, and Networks
No full textThis dissertation studies various aspects of how the macroeconomy is shaped by international trade and financial intermediation.
The first chapter analyzes trade in dual-use goods, items with both civilian and military applications. Xinyue Lin and I document that, historically, regulation and trade flows of critical goods have reacted to changes in the national security environment. We propose a theoretical definition of dual-use goods by integrating a military contest into a trade model.
Then we take our model to the data and deliver a ranking of dual-use goods, as well as macroeconomic magnitudes behind the consumption-security trade-off.
The second chapter, a joint work with Leonardo D’Amico, studies the dynamics of interest rate differentials for bank lending across the U.S. states between 1953 and 1983. When the national rate is high, savers invest in competitive financial instruments, and rates equalize across space. When the national rate is low, savers keep their money in checking
accounts that provide liquidity services, so demand for loans and supply of savings clear locally, resulting in a geographic dispersion of lending rates. Our model explores the spatial implications of this pattern for economic activity and considers branching counterfactuals.
The third, and final, chapter explores patterns of international currency invoicing and its implications for prices and quantities. When firms lock contracts on prices and quantities, their balance sheets become exposed to exchange rate movements. To reduce balance sheet volatility, firms match currencies of their exports to currencies of their imports. In networks, such invoicing behavior propagates beyond direct trade links, which leads to the amplification of more central currencies.Business Economic
Investigating how sequence variation in T cell receptors and human leukocyte antigens shapes T cell development
No full textT cells are critical agents of the adaptive immune system that orchestrate killing of infected and cancerous cells. Some T cells erroneously target healthy cells, leading to autoimmune disease. Whether a T cell becomes activated depends on the immunological synapse it forms with an antigen presenting cell (APC). At the core of the immunological synapse are two key proteins: (1) the T cell receptor (TCR) and (2) the major histocompatibility complex (MHC) presenting a peptide from a candidate pathogen.
This dissertation examines genetic variation on both sides of this immunological synapse. Genetic variation in the MHC confers extreme risk for autoimmune disease and largely consists of germline polymorphisms, which are consistent across an individual’s cells. In contrast, genetic variation on the T cell side of the immunological synapse is largely somatic. Each developing T cell stochastically rearranges and edits the genes encoding its TCR, creating a repertoire of TCR sequences within each individual.
Analysis of TCR sequence data traditionally proceeds by considering each TCR as a “molecular barcode” and identifying T cells that match exactly on this molecular barcode. However, the vast majority TCR sequences are observed only once, in one individual.
A major theme throughout this dissertation is an alternate approach to TCR sequence analysis: (a) decomposing each TCR amino acid sequence to a collection of physicochemical features such as hydrophobicity and electrostatic charge, and (b) testing how these sequence features relate to T cell development outcomes, such as thymic selection and transcriptional fate. This approach enables two general discoveries: (1) TCR sequence features regulate T cell transcriptional fates, and (2) MHC genetic variants which confer risk for autoimmune disease influence which TCR sequences pass thymic selection. Specifically, we find that hydrophobicity throughout the CDR3 region of the TCR sequence promotes regulatory T cell fate. Most surprisingly, we observe a constellation of TCR sequence features that are consistently enriched in memory T cells compared to naïve T cells. We develop a TCR scoring function “TCR-mem,” which quantifies the extent of these features in each TCR, and show through TCR transduction experiments that increased TCR-mem increases T cell activation even among T cells that recognize the same peptide-MHC complex. Each of these projects provide new scoring functions that allow researchers to score and rank TCR sequences for functional follow up, regardless of whether the TCR sequences have been observed previously.
Altogether, this dissertation provides new approaches to study sequence variation in MHC and TCR molecules, and sheds light on how this variation may alter critical T cell functionality.Biomedical Informatic