Our tendency to be curious about our environment and our capacity to effectively explore it are central to human intelligence. This dissertation takes a functional approach to investigating curiosity and exploration, examining the systematic, and at times approximate, manner humans seek information in service of their varied goals. In chapter one, I examine exploratory behavior in the service of a prescribed goal using a paradigm that allows for tight experimental control. Comparing participants’ choices to the optimal strategy for this task, I show that humans explore as if balancing seeking goal-relevant information with managing their limited cognitive resources. Chapters two and three focus on epistemic information-seeking driven by curiosity in more naturalistic contexts. In chapter two I chart the relationship between information seeking and motivation, asking how an acute change to motivation impacts information seeking. By measuring the profound changes to motivation affected by the onset of the COVID-19 pandemic in the United States, as well as information seeking behavior and expectations of usefulness, I show that motivation both directs information seeking to goal-relevant information, as well as energizing the seeking of information of any kind. In chapter three, I examine how fine-scale changes to motivation, brought about by previous learning experiences, influence curiosity in a continual manner. I find that learning satisfying information both enhances curiosity for similar information and decreases curiosity for dissimilar information. Combined, these three chapters demonstrate the sophistication of human information-seeking strategies, which are efficient, flexible, and adapted to the constraints of human cognition.

The problem this study addressed involves how college students since the year 2020 in the U.S. have been negotiating romance, dating, and sexual relationships in the unique historical period of the COVID-19 pandemic. Further, this study addressed the problem of needing to determine how the pandemic may have disrupted college students’ intimate sexual experiences—and impacted their mental health, physical health, and experiences of social support. The main purpose was to identify significant predictors of the study outcome variable of a higher rating of self-efficacy for engaging in safer sexual behaviors. An additional purpose of the study was to determine if there were significant differences in students’ mean ratings—when comparing mean scores for 5 time periods (i.e. 1-2018-2019/freshman year before the pandemic; 2-2019-2020/second semester of sophomore year during pandemic; 3-2020-2021/junior year during pandemic; 4-2021-2022/senior year during the pandemic; and, 5-currently, especially the past 3 months)—for physical health, mental health, social support, and level of involvement in romantic, intimate, serious dating, or sexual relationships. Overall, comparisons for time periods found deterioration during the pandemic years with some signs of improvement by the current time period of Spring 2023. Findings showed females had higher self-efficacy to perform safer sexual behaviors, but also that survey respondents who lived independently had higher self-efficacy to perform safer sexual behaviors, those who had a COVID-19 diagnosis in the past two years had higher self-efficacy to perform safer sexual behaviors, and survey respondents whose college did have a sexual assault media campaign had higher self-efficacy to perform safer sexual behaviors. The results of the backwards stepwise regression found that higher self-efficacy to perform safer sexual behaviors was significantly predicted by higher age, higher income, higher BMI, lower social support, higher current romantic involvement, higher exposure to sexual assault information on campus, lower alcohol/drug use during sex, and higher stage of change for engagement in safer sex—as a global mean score capturing four risk reduction behaviors; and, 56.4% of the variance was explained by the model. Implications and recommendations are discussed with a focus on the need for longitudinal studies with a nationally representative sample.

The study explored experiences of hate, hate crimes and microaggressions among diverse Asian adults living in the United States during the COVID-19 pandemic for a sample (N = 831) that was 26.7% Chinese, 13.6% Japanese, 13.4% Korean, 12.4% Taiwanese, 10.6 % Filipino, 10.3% Indian, 8.5% Thai, 54.9% female, and 86.8% U.S. born—with a mean age of 33. Findings showed participants had: better overall physical health before COVID-19 pandemic versus currently; mental/emotional health declined from before the pandemic to currently; moderate social support; closest to moderate past-year mental distress; closest to “more than once” for experiences of microaggressions; a high level of ability for perceiving racism and oppression; and were in the action stage for coping and responding to racism and oppression. Also, 79% (N = 831) personally experienced hate once to a great number of times, and 43.5% (N = 362) endorsed moderate to very high impact; 79.2% (N = 664) witnessed hate against someone else once to a great number of times, and, 44.5% (N = 370) endorsed moderate to very high impact. Those who received counseling in the past experienced more microaggressions than those who did not seek counseling. The higher the frequency of experiencing microaggressions then higher the age, darker the skin color, lower the self-rating of mental health pre-COVID-19, lower the self-rating of physical health pre-COVID-19, lower the self-rating of mental health during COVID-19, higher the past year depression, anxiety and trauma and overall mental distress, greater the feeling of being unable to control important things in life, higher the ability to perceive racism and oppression, higher the stage of change for coping and responding to racism and oppression, greater the impact of hate, and lower the social desirability. Backward stepwise regression showed significant predictors of a higher frequency of experiences of microaggressions were being born in the U.S, not being a student, past year counseling, older age, lower education, higher overall mental distress, and higher ability to perceive racism and oppression—with 77.4% of variance explained by the model. Implications of findings and recommendations are provided for addressing anti-Asian hate.

This study´s overarching objective analyzed the intersection of the COVID-19 pandemic, its direct impacts of disease and indirect impacts of related containment measures, and impact on the mental and psychosocial health of health workers and people from the wider population in Luzon, in the Philippines. This study focused on the Philippines, an LMIC setting in Southeast Asia, where many remained at-risk for exposure to infectious disease risks associated with COVID-19, and other conditions provoking poor mental and psychosocial health outcomes. This study included a focus on mental health, going beyond only its clinically oriented and severe health outcomes, and to also include psychosocial health to acknowledge and underscore the importance of support systems and relational, non-clinical aspects related to human well-being. This study first inquired with the emerging, peer-reviewed research literature, and then examined two sets of perspectives to meet its overarching objective: the Filipino health practitioner workforce, and the broader Filipino community in Luzon. Concretely, the first paper examined and evaluated the literature at the intersection of the COVID-19 pandemic and mental and psychosocial health in the Philippines. It used a scoping review method on peer-reviewed literature first regarding three Southeast Asian LMIC settings to identify, from a total of 405 references, 76 articles specifically about the Philippines. This review was guided by the Population(/Participants)/Concept/Context, or PCC-model, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, or PRISMA-ScR. The second paper examined health worker perspectives on mental and psychosocial health policy, services, and programming at various phases of the COVID-19 pandemic in the Philippines. This qualitative examination aimed to learn deeply about eight different health worker perspectives, using a constructivist epistemological orientation and guidance from grounded theory and thematic analysis in semi-structured, in-depth interviews with eight different health workers in the Philippines. The final and third paper examined community perspectives on mental and psychosocial health in urban and rural, provincial settings during various phases of the COVID-19 pandemic in the Philippines. This inductive qualitative work included semi-structured focus group interviews with 23 people from different urban and rural, provincial settings in the Luzon region of the Philippines, and had a constructivist epistemological orientation and leaned on guidance from grounded theory and thematic analysis to facilitate the communities´ voice and expression in this work.

Acute medical events and health-related stressors are complex life events, impacting both body and mind, challenging one’s concept of physical safety, and requiring ongoing psychological adaptation and adjustment. Anxiety sensitivity is an established transdiagnostic risk factor for mental illness; in the context of health-related stressors, physical anxiety sensitivity, or the tendency to interpret somatic sensations as catastrophic and threatening cues, may represent a meaningful mechanism informing longitudinal psychological adjustment and clinical course. This dissertation examines physical anxiety sensitivity and other key mechanisms influencing psychological adjustment following acute health-related events with three empirical studies. Study 1 sheds light on the role of perceived threat and heightened interoceptive threat bias in the development of posttraumatic stress (PTS) symptoms following a suspected acute coronary syndrome (ACS). Studies 2 and 3 share a common computational approach, latent growth mixture modeling (LGMM), allowing for the mapping of trajectory classes of psychological adjustment and highlighting distinct symptom profiles. Using LGGM, Study 2 investigates the role of peritraumatic threat and ongoing cardiac-related anxiety sensitivity on the clinical course of PTS, identifying trajectories of psychological adjustment in the 12-months following a suspected ACS. Study 3 seeks to apply these findings within the context of the COVID-19 pandemic, exploring the impact of worry and physical anxiety sensitivity on trajectories of depression and anxiety during the first 12-months of the pandemic. Together, these studies provide valuable insights into the naturalistic, heterogeneous course of psychological adjustment to health-related stressors, with particular attention to physical anxiety sensitivity as a potent mechanism driving symptom patterns over time.

Suicide is the leading cause of violent death and a major public health and clinical concern. Globally, suicide mortality has decreased over the last three decades, largely due to dramatic declines in pesticide poisonings in Asia. Recent suicide mortality trends, however, have been heterogeneous, and there have been increases in suicide in several countries and regions (e.g., the United States, Jamaica, Cameroon). Monitoring suicide rates is important for surveillance reasons as well as to generate causal hypotheses, two key components of suicide prevention efforts. Suicide increases following major societal crises, such as economic recessions, are often characterized by heterogeneity across population subgroups – with larger increases among vulnerable groups. Examining subgroups, even if evidence of an increase in suicide overall is absent, can guide identification of at-risk groups and development and implementation of targeted prevention strategies. In Spain, a country with one of the lowest suicide rates across Europe, there has been scientific debate regarding whether suicide increased following the 2008 economic recession. Most recent research suggests that suicide remained largely unchanged, but data are scarce on vulnerable groups among whom the downstream economic effects of the recession might have been more intense than in the general population. Following the initial COVID-19 pandemic outbreak, there was generalized concern that suicide rates would go up due to increases in bereavement and loss of loved ones, fear of contagion and death, increases in prevalence of mental health conditions, and negative economic effects of the pandemic and contagion control measures. Initial examinations of suicide trends, however, indicated that suicide mortality either remained unchanged or decreased in most locations across the globe during the initial months following the pandemic onset. Subsequent evidence of delayed increases in suicide in specific places (e.g., Japan), however, pointed out the importance of continued monitoring of suicide rates. In addition, there is increasing evidence that suicide rates during the COVID-19 era have changed heterogeneously across sociodemographic groups with higher vulnerability to specific pandemic-related stressors (e.g., higher suicide risk among minoritized people in the United States or women in Japan). There are no systematic reviews examining suicide during the COVID-19 era beyond the initial 6 months of the pandemic, and there has been no systematic assessment of the variation in suicide changes after the onset of the pandemic across place, over time, and across population subgroups. In Spain, there has also been substantial debate regarding the impact of the pandemic on suicide rates: two studies using a suboptimal methodological approach found somewhat contradictory results. No studies have examined suicide among population subgroups during the pandemic in Spain. The aim of this dissertation is to examine variations in suicide across population groups as defined by sociodemographic characteristics during major societal crises (i.e., the 2008 recession and the COVID-19 pandemic) in Spain, and variations across place, over time, and across sociodemographic groups globally. The first chapter uses two different approaches to age-period-cohort modelling to examine suicide between 2000 and 2019 in Spain, stratifying analyses by foreign-born status – the most salient marker of disadvantage in Spain, and further analyzing suicide among foreign-born individuals without Spanish citizenship – a proxy for lack of residency permit. I found that, while suicide following the recession remained stable among native-born men, it increased slightly among native-born women – largely due to cohort effects affecting middle-aged women, and markedly among foreign-born individuals – largely due to period effects. Suicide increased especially among foreign-born individuals without Spanish citizenship. Notably, access to specialized healthcare and welfare was interrupted for migrants without residency permit shortly following onset of the recession, in the context of austerity politics undertaken across Europe. These results highlight the moderating role of socioeconomic vulnerability on suicide risk during major economic crises. The second chapter is a systematic integrative review of the variation of population-based suicide estimates following the initial pandemic outbreak globally. In this review, I examine methodological features of all published studies examining suicide during the COVID-19 pandemic, highlighting the importance of addressing autocorrelation, non-stationarity, and seasonality in studies using an interrupted time-series analysis (ITSA) approach to test a causal question (i.e., to compare observed vs. expected or counterfactual suicide counts or rates). I also provide rationale to expect substantial heterogeneity in a so-called effect of the pandemic on suicide, given multiple versions of the exposure of interest that make it impossible to estimate a sole causal effect. I critically summarize the results overall with a focus on variation across place, over time, and across population subgroups. My findings indicate substantial geographical heterogeneity; a variable initial period of decreased suicide followed, in several locations, by delayed suicide increases – underscoring the importance of sustained monitoring of rates; and heterogeneity across population subgroups with larger suicide increases among groups at higher risk of suicide contagion and mortality (e.g., older adults, racially minoritized residents) and groups vulnerable to negative economic effects of the pandemic (e.g., groups overrepresented in hospitality and tourism jobs). The third chapter uses Seasonal Autoregressive Integrated Moving Average (SARIMA) prediction models, an approach to ITSA that can adequately deal with autoregression, non-stationarity, and seasonality, to predict monthly suicide counts between April and December 2020 in Spain had the pandemic not taken place. I do so overall and by sex- and age-group, and by foreign-born status in a set of sensitivity analyses, and I then compare observed vs. predicted suicides to determine if suicide increased. I find generalized higher-than-expected suicide rates during spring and summer of 2020, overall and across subgroups – especially among older males during the summer months. I discuss potential explanations and implications for decision-making of these findings considering the theoretical framework developed in chapters 1 and 2.

Ferroptosis, an oxidative cell death mechanism, is driven by iron-dependent lipid peroxidation. Despite being generally associated with lipid peroxidation that overwhelms endogenous repair systems, ferroptosis mechanisms and regulators in various pathological contexts remain elusive. Identifying novel modulators of the ferroptosis pathway is essential for cell-death marker development and drug discovery to target this process. Small molecule drugs and dietary intervention of metabolites and lipids can modulate ferroptosis sensitivity in diverse disease contexts. In this thesis, I investigated lipid metabolism involving ferroptosis in cancer models and an infectious lung disease model. I dissected the different roles of PUFA-containing phospholipids in dietary modulation of ferroptosis and discovered a specific phospholipid class, phosphatidylcholine with diacyl-polyunsaturated fatty acid tails (PC-PUFA2; diacyl-PUFA-PC) that promote ferroptosis. Exogenous PC-PUFA2 or free PUFA enriches PC-PUFA2 abundance in cancer cells and accounts for the ferroptosis-sensitizing effects. I also discovered the accumulation of PC-PUFA2 in the mitochondria, which disrupts mitochondrial redox homeostasis and initiates lipid peroxidation in the endoplasmic reticulum. These findings unveil the essential roles of diacyl-PUFA phospholipids during ferroptosis. Utilizing biomarkers of ferroptosis, I studied the pathogenic mechanism of COVID-19-associated pulmonary diseases. Elevated ferroptosis markers including transferrin receptor 1 and lipid peroxidation products were detected in human COVID-19 lung autopsies. Dysregulation in lipid profile, including a significant decrease in PUFA phospholipids and accumulation of lysophospholipids, further suggests dysregulation of lipid metabolism and ferroptosis that may contribute to inflammation and acute lung injury in COVID-19 lungs. Iron metabolism is affected in the COVID-19 lung and is associated with ferroptosis activation. We further discovered a strong correlation of ferroptosis markers with lung injury severity in a COVID-19 model using Syrian hamsters. These findings provide the fundament for targeting ferroptosis as a novel therapeutic and diagnostic strategy for various diseases.

Simulation is a powerful technique to study complex problems and systems. This thesis explores two different problems. Part 1 (Chapters 2 and 3) focuses on the theory and practice of the problem of simulating graphs with a prescribed degree sequence. Part 2 (Chapter 4) focuses on how simulation can be useful to assess policy changes in emergency medical services (EMS) systems. In particular, and partially motivated by the COVID-19 pandemic, we build a simulation model based on New York City’s EMS system and use it to assess a change in its hospital transport policy. In Chapter 2, we study the problem of sampling uniformly from discrete or continuous product sets subject to linear constraints. This family of problems includes sampling weighted bipartite, directed, and undirected graphs with given degree sequences. We analyze two candidate distributions for sampling from the target set. The first one maximizes entropy subject to satisfying the constraints in expectation. The second one is the distribution from an exponential family that maximizes the minimum probability over the target set. Our main result gives a condition under which the maximum entropy and the max-min distributions coincide. For the discrete case, we also develop a sequential procedure that updates the maximum entropy distribution after some components have been sampled. This procedure sacrifices the uniformity of the samples in exchange for always sampling a valid point in the target set. We show that all points in the target set are sampled with positive probability, and we find a lower bound for that probability. To address the loss of uniformity, we use importance sampling weights. The quality of these weights is affected by the order in which the components are simulated. We propose an adaptive rule for this order to reduce the skewness of the weights of the sequential algorithm. We also present a monotonicity property of the max-min probability. In Chapter 3, we leverage the general results obtained in the previous chapter and apply them to the particular case of simulating bipartite or directed graphs with given degree sequences. This problem is also equivalent to the one of sampling 0–1 matrices with fixed row and column sums. In particular, the structure of the graph problem allows for a simple iterative algorithm to find the maximum entropy distribution. The sequential algorithm described previously also simplifies in this setting, and we use it in an example of an inter-bank network. In additional numerical examples, we confirm that the adaptive rule, proposed in the previous chapter, does improve the importance sampling weights of the sequential algorithm. Finally, in Chapter 4, we build and test an emergency medical services (EMS) simulation model, tailored for New York City’s EMS system. In most EMS systems, patients are transported by ambulance to the closest most appropriate hospital. However, in extreme cases, such as the COVID-19 pandemic, this policy may lead to hospital overloading, which can have detrimental effects on patients. To address this concern, we propose an optimization-based, data-driven hospital load balancing approach. The approach finds a trade-off between short transport times for patients that are not high acuity while avoiding hospital overloading. To test the new rule, we run the simulation model and use historical EMS incident data from the worst weeks of the pandemic as a model input. Our simulation indicates that 911 patient load balancing is beneficial to hospital occupancy rates and is a reasonable rule for non-critical 911 patient transports. The load balancing rule has been recently implemented in New York City’s EMS system. This work is part of a broader collaboration between Columbia University and New York City’s Fire Department.

This dissertation is divided into two main sections describing major portions of my Ph.D. research: (1) development of two enzymatic assays for identifying inhibitors of SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and the associated proofreading exonuclease complexes, two key enzymatic activities of SARS-CoV-2, the virus responsible for the COVID-19 pandemic and (2) the design and implementation of four novel single-color fluorescent DNA sequencing by synthesis (SBS) methods, including the synthesis of many of the key nucleotide analogues required for these studies. In response to the COVID-19 pandemic, the first part of my research is focused on the discovery of potential therapeutics for combating coronavirus infections. Chapter 1 describes the identification of several polymerase and exonuclease inhibitors for SARS-CoV-2 using novel mass spectrometry-based molecular assays. SARS-CoV-2 has an exonuclease complex, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RdRp and the exonuclease could overcome this deficiency. Chapter 1 reports the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of identified exonuclease inhibitors, RNAs terminated with the active forms of the prodrugs like Sofosbuvir, Remdesivir and Favipiravir were largely protected from excision by the exonuclease, while in the absence of exonuclease inhibitors, there was rapid excision. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment. Chapters 2-6 describe the single-color DNA SBS studies. Chapter 2 provides essential background on the structure of DNA, the DNA polymerase reaction, and several key DNA sequencing technologies, with an emphasis on the design of nucleotide analogues for the DNA SBS approach. Chapter 3 delineates a one-color fluorescent DNA SBS method based on a set of nucleotide reversible terminators (NRTs) comprising two orthogonal cleavable linkers, one fluorescent dye and one anchor. Chapter 4 describes a one-color hybrid DNA sequencing approach using a set of dideoxynucleotide analogues bearing two orthogonal cleavable linkers, one fluorophore and one anchor as well as a set of unlabeled NRTs. By introducing a pH responsive fluorophore into the design of nucleotide analogues, Chapter 5 demonstrates a novel type of single-color DNA SBS method using a set of NRTs comprising one pH-responsive fluorescent dye or one non-responsive fluorescent dye tethered with one cleavable linker. Chapter 6 presents another option for the single-color DNA sequencing technique using a set of deoxynucleotide analogues comprising the above pH responsive or non-responsive dyes tethered with a cleavable linker, along with a set of unlabeled NRTs. The one-color SBS approaches have the potential for higher sensitivity, miniaturization and cost effectiveness compared with four-color SBS methods. Finally, Chapter 7 summarizes the SARS-CoV-2 antiviral drug discovery and one-color sequencing techniques and discusses potential follow-up research on these projects.

This qualitative dissertation explored the digital literacy practices of adolescent Black girls who actively engaged on social media in the midst of the 2020 COVID-19 pandemic, mandatory school shutdowns, and the aftermath of the murders of Breonna Taylor and George Floyd. I employ the Black Girls’ Literacies (BGL) framework (Haddix & Muhammad, 2016) to analyze the TikTok accounts of two adolescent Black girl influencers, as well as six qualitative interviews I conducted with adolescent Black girls who avidly used video sharing social media apps during that time. The data analysis aligned with the following components of the BGL Framework: Black girls’ literacies are multiple; Black girls’ literacies are tied to identities; and Black girls’ literacies are intellectual, political, and critical. Moreover, the data analysis also revealed that Black girls espoused three different identities while using social media to address the COVID-19 pandemic and anti-Black violence. These themes were: Crafting Digital Narratives of the Self as Educators, Crafting Digital Narratives of the Self as Nurturers, and Crafting Digital Narratives of the Self as Digital Activists. My findings suggested that for English educators, prioritizing racial literacy in the English classroom, creating learning experiences that are informed by critical media literacy, and creating a space that honors and supports Black girls’ desires to be activists within their communities are critical for their success within and outside of the English classroom.