This dissertation contains three essays studying topics in applied microeconomics. The first chapter studies the formation and the spread of crisis-driven racial animus during the coronavirus pandemic. Exploiting plausibly exogenous variation in the timing of the first COVID-19 diagnosis across US areas, we find that the first local case leads to an immediate increase in local anti-Asian animus, as measured by Google searches and Twitter posts that include a commonly used derogatory racial epithet. This rise in animus specifically targets Asians and mainly comes from users who use the epithet for the first time. These first-time ch-word users are more likely to have expressed animosity against non-Asian minorities in the past, and their interaction with other anti-Asian individuals predicts the timing of their first ch-word tweets. Moreover, online animosity and offline hate incidents against Asians both increase with the salience of the connection between China and COVID-19; while the increase in racial animus is not associated with the local economic impact of the pandemic. Finally, the pandemic-driven racial animus we documented may persist beyond the duration of the pandemic, as most racist tweets do not explicitly mention the virus.The second chapter investigate if primary care physician (physician henceforth) and patient concordance in terms of socio-economic status (SES) reduces the SES inequality in health. We exploit variations in SES concordance between physicians and patients that are induced by plausibly exogenous clinic closures. We find that SES concordance lowers low-SES patients' mortality while high-SES patients' mortality does not depend on their physicians' SES. Together, these effects translate to a 23% reduction in the SES-mortality gradient. Mortality reductions related to cardiovascular conditions are especially pronounced. We study patients' health behavior and physicians' treatment choices to explain how SES concordance reduces patient mortality. Low-SES patients with low-SES physicians receive more care at the intensive margin; making more office visits per year and receiving more services per visit. In addition, they are more likely to be prescribed Statins, adhere to diabetes check-up visits, and are less likely to have avoidable hospitalizations due to COPD, relative to comparison groups.The third chapter asks: how does employer reputation affect the online labor market? We investigate this question using a novel dataset combining reviews from Glassdoor.com and job applications data from Dice.com. Labor market institutions such as Glassdoor.com crowd-sources information about employers to alleviate information problems faced by workers when choosing an employer. Raw crowd-sourced employer ratings are rounded when displayed to job seekers. By exploiting the rounding threshold, we identify the causal impact of Glassdoor ratings using a regression discontinuity framework. We document effects from both labor demand and supply sides at equilibrium. We find that displayed employer reputation affects employer’s ability to attract workers, especially when the displayed rating is sticky. Employers respond to the rounding threshold by posting more new positions and re-activating more job postings. The effects are the strongest for firms that are private, smaller, and less established, suggesting that online reputation is a substitute for other types of reputation.
One of the factors which perpetuates gender inequality is the inequitable division of household labor, and particularly the division of child caretaking labor. Even when women are employed outside the home, many remain primarily responsible for household duties and child caretaking. This research utilizes individual interviews (N=40) with heterosexual, married or cohabitating parents of children 5 and under where fathers do the majority of child caretaking. I explore how lead-dad households are similar to and different from those with a traditional lead-mother arrangement, as well as what motivates lead-father families to choose this arrangement, and how they explain it to others. This project also considers the impact of the COVID-19 pandemic on lead-dad households and whether it has disrupted household roles in these families. This project uses atypical or negative cases to better understand the issue of gender identity of both mothers and fathers in atypical households.
Only 5% of the graduates from medical schools identify as Latinx (AAMC, 2019). While, in the state of California, the growing Latinx and bilingual community is expected to exceed 40% of the state’s population with only 5% Latinx physicians (Martinez et al., 2019). Diversity of the physician workforce is important because underrepresented students are more likely to work as a physician in underserved communities, such as urban and rural communities (Mitchell & Lassiter, 2006). The field of higher education is lacking research on Latinx student persistence in premedical studies in higher education. Moreover, the literature on underrepresented STEM students is lacking an analysis of the cultural assets that Students of Color bring with them into STEM. Through this dissertation, I advance STEM research by applying asset-based theoretical frameworks and culturally relevant methodology in order to center Latinx first-generation premedical students voices and experiences. Guided by the following theories, Community Cultural Wealth (CCW) (Yosso, 2005), Latinx STEM Student Success Model (Rendón et al., 2019) and Chicana/Latina Feminist Epistemology (Fierros & Delgado Bernal, 2016), this dissertation aims to take on an assetbased approach and use culturally-sensitive methodology to understand the persistence of Latinx students in medicine. Yosso’s CCW (2005) provides a foundation in viewing students of color entering the college environment with cultural assets and to further center Latinx premedical students, the Latinx Student STEM Success Model (Rendón et al., 2019) is applied to explore Latinx cultural assets, strengths developed from families/communities and knowledge that Latinx students have gained that are related to the Latinx asset (Rendón, Nora & Kanagala, 2014). Additionally, I employ pláticas, a culturally-sensitive methodology that draws from Chicana/Latina Feminist Epistemology (Fierros & Delgado Bernal, 2016), which acknowledges and centers Chicana/Latina scholars way of knowing and knowledge (Fierros & Delgado Bernal, 2016). This study is based on twenty four Latinx premed students from a large research university, an emerging Hispanic-Serving Institution. Each participant completed two pláticas, for a total of forty-eight pláticas, observations of the Latinx PremedInitiative sessions and website content review of activities.Findings are presented in the three articles focusing on cultural assets of Latinx students during their undergraduate years, such as navigational, resistance, giving back and a methodological article. This study presents novel findings of the use of cultural assets of Latinx students in premedical studies. Latinx premedical students use the following, navigational and resistance asset as they navigated the COVID-19 pandemic and giving back asset is related to student’s physician career aspirations to serve underserved communities and address health inequities. Additionally, pláticas methodology is introduced to call for a reframing of methodologies in STEM education research to provide a culturally relevant methodology to engage Latinx Students and advance STEM education research on Latinx students. Research on Latinx STEM students has focused on the attrition of Latinx students in STEM, however I find that Latinx students are persisting and creating meaningful pathways for themselves that is inclusive of their cultural background.This dissertation is significant because it provides an asset-based approach and culturally sensitive use of pláticas on Latinx students to identify the cultural assets Latinx students use as they persists towards medical school. I also provide recommendations for institutions of higher education to embrace and leverage cultural assets, to reimagine graduatepathways for Latinx students to persist towards their medical dreams.
IntroductionEndoscopy performance is highly variable among fellows and practicing physicians.1,2 The field lacks a standard endoscopy training curriculum. Moreover, the traditional training under the apprenticeship model has proven to be a slow and ineffective method. Trainees who underwent a simulation-based mastery learning (SBML) curriculum accelerated their acquisition of clinical competency, 2.5x faster than trainees who received traditional training under the apprenticeship model.3 During the COVID-19 pandemic, we adapted our SBML curriculum to train upper endoscopy (esophagogastroduodenoscopy [EGD]) to novice gastroenterology trainees through online virtual coaching. Herein, we performed a hypothesis-generating study to evaluate the effectiveness of SBML-based EGD training, comparing virtual to direct in-person coaching. MethodsWe conducted a 7-day virtual SBML course across 7 academic centers in the USA and Asia. A minimum passing standard was set for each topic. Theoretical material was delivered using Canvas, an online learning management system. For technical skills training, a virtual coach supervised hand-on training at scheduled intervals. At the end of training, an independent rater assessed the trainees skills using a validated scoring system. After the course, we assessed the trainees’ clinical performance for the first 30 EGDs using the Assessment of Competency of Endoscopy (ACE) form. We compared the trainees’ scores to that of our historical control cohort trained using in-person SBML training. Our primary outcomes were competence scores on the written exam, endoscope tip control, standard EGD. Our secondary outcome was clinical EGD evaluations. We used non-inferiority t-test statistics and Fisher’s exact test. ResultsThe virtual coaching group received similar scores as the direct coaching group for the written assessment (virtual coaching 81.9%+8.9% vs direct coaching 78.3%+8.2%, p=0.385). For endoscope handling analysis, the trainees reached the MPS for competency after 31.4+29.1 attempts and mastery after 51.9+36.7 attempts, similar to the control cohort that had undergone the training with direct coaching (competency: 32.5+22.8, p=0.93; mastery: 38.2+31.1, p=0.42). For Standard EGD, the mean scores for the general assessment of the UGI tract were similar between the intervention and control groups (4.6+0.6 vs 4.7+0.5, p=1.00). For clinical EGDs, there were no significant differences in scores for EGD 1-5, 11-15, 16-20, 21-25, and 26-30. For EGDs 6-10, the virtual coaching cohort performed significantly better than the direct coaching cohort (2.73+0.59 vs 1.65+0.59, p<0.001). DiscussionThe COVID-19 pandemic shifted the way we deliver endoscopy training. An SBML curriculum, delivered through virtual coaching, shows significant promise in effectively teaching novice GI trainees how to perform upper endoscopy. Moreover, SBML with virtual coaching allows trainees to learn from experts despite geographical constraints and other barriers to high-quality training. This program has the potential to improve patient safety and training efficiency compared to traditional apprentice-based training methods. We recommend a future randomized controlled trial, with a robust clinical evaluation strategy, to better understand the feasibility and effectiveness of virtual training.
SARS-CoV-2 infects multiple organs including the respiratory tract and gut. Whether regional microbiomes are disturbed significantly to affect the disease progression of COVID-19 is largely unknown. To address this question, we performed cross-sectional and longitudinal analyses of throat and anal swabs from 35 COVID-19 adults and 15 controls by 16S rRNA gene sequencing. The results allowed a partitioning of patients into 3-4 categories (I-IV) with distinct microbial community types in both sites. Lower-diversity community types often appeared in the early phase of COVID-19, and synchronous fast restoration of both the respiratory and gut microbiomes from early dysbiosis towards late near-normal was observed in 6/8 mild COVID-19 adult patients despite they had a relatively slow clinical recovery. The synchronous shift of the community types was associated with significantly positive bacterial interactions between the respiratory tract and gut, possibly along the airway-gut axis. These findings reveal previously unknown interactions between respiratory and gut microbiomes, and suggest that modulations of regional microbiota might help to improve the recovery from COVID-19 in adult patients.
Tertiary education is vital for producing the caliber and diversity of graduates needed both for the economy that exists today and for economy to which a nation aspires. It fuels competitiveness and growth by preparing professionals, like managers and engineers, medical personal and teachers. Universities are also centers of research and innovation and – working with small and medium size enterprises – support regional development. Tertiary education is both the aspiration of more and more young people around the globe and a fundamental requirement for employment in the industries that drive the global knowledge economy. As such, tertiary education provides unique opportunities for individual development and equality of opportunity as well as promoting shared prosperity. A failure to sustain effective tertiary systems can lead to perilous social upheavals, as youth fall outside the education system, unable to engage in active learning and uncertain about the future of their education and prospects. Societies are, then, confronted with a massive challenge of youth disengagement and deprived of the graduate professionals needed to keep countries on track for social cohesion and growth.
Covalent drugs incorporate a mildly electrophilic functional group that reacts with protein targets to confer additional affinity beyond the non-covalent interactions involved in drug binding. In the past, concerns about these reactive molecules’ interference with biological assays and lack of selectivity often discouraged further investigation. However, the emergence of intentionally designed covalent drugs against major disease targets over the last ten years showcases the strengths of this field. The first part of this thesis will review the historical and modern milestones in covalent drug discovery with emphasis on chemoproteomics techniques that enable success, and the remaining chapters will address my contributions to the field through the development of tool covalent compounds as novel inhibitors and new induced proximity platforms.Chemoproteomics-enabled covalent ligand screening platforms can be used to identify novel ligands against undruggable protein targets like MYC. MYC is a major oncogenic transcriptional driver of most human cancers that has remained intractable to direct targeting because much of MYC is intrinsically disordered. I performed a cysteine-reactive covalent ligand screen to identify compounds that could disrupt the binding of MYC to its DNA consensus sequence in vitro and also impair MYC transcriptional activity in situ in cells. I identified a covalent ligand EN4 that targets cysteine 171 (C171) of MYC within a predicted intrinsically disordered region of the protein. I show that EN4 directly targets MYC in cells, reduces MYC and MAX thermal stability, inhibits MYC transcriptional activity, downregulates multiple MYC transcriptional targets, and impairs tumorigenesis. I also show initial structure-activity relationships of EN4 and identify compounds that show improved potency. Overall, I identified a novel ligandable site within an intrinsically disordered region of MYC that leads to inhibition of MYC transcriptional activity. In addition to facilitating the discovery of covalent small-molecule allosteric modulators of disease relevant proteins and pathways, chemoproteomics-enabled covalent drug discovery also proves useful in identifying inhibitors of critical disease proteins that contain catalytic cysteines. Among the various genes and proteins encoded by all coronaviruses, one particularly “druggable” or relatively easy-to-drug target is the coronavirus Main Protease (3CLpro or Mpro), a cysteine-protease that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro’s catalytic cysteine with a small-molecule antiviral would effectively stop the ability of the virus to replicate, providing therapeutic benefit across coronaviruses. As part of a collaborative effort, I utilized activity-based protein profiling (ABPP)- chemoproteomic approaches to discover and further optimize cysteine-reactive pyrazoline-based covalent inhibitors for the SARS-CoV-2 Mpro. Structure-guided medicinal chemistry and modular synthesis of di- and tri-substituted pyrazolines bearing either chloroacetamide or vinyl sulfonamide cysteine-reactive warheads enabled the expedient exploration of structure-activity relationships (SAR), yielding nanomolar potency inhibitors against Mpro from not only SARS-CoV-2, but across many previous coronaviruses. Our studies highlight promising chemical scaffolds that may contribute to future pan-coronavirus inhibitors. Finally, chemoproteomics-enabled drug discovery platforms facilitate the expansion of targeted protein degradation and related fields. Many diseases are driven by proteins that are aberrantly ubiquitinated and degraded. These diseases would be therapeutically benefited by targeted protein stabilization (TPS). We designed deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small molecules consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1. We showed that a DUBTAC consisting of our EN523 OTUB1 covalent recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized ΔF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. We also demonstrated stabilization of the tumor suppressor kinase WEE1 in hepatoma cells. Our study showcases covalent chemoproteomic approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS.
The Coronavirus (COVID-19) pandemic brought forward an unprecedented economic contraction. Recessions, in turn, have typically been accompanied by an increase in the number of firms using the insolvency system. This note explores the early impact the pandemic has had on business insolvency filings, based on information from a newly created dataset. Contrary to early expectations, most economies surveyed have experienced a decline in the number of business insolvencies relative to Q2 and Q3 of 2019. shows that legal reasons may have played a key role in this decline as almost all economies covered introduced emergency measures making it more difficult to push a debtor into insolvency. Looking forward, the note explores evidence from previous crisis together with underlying factors -such as lower sales, higher unemployment, firm liquidity challenges, and heightened corporate vulnerabilities- to investigate whether the risk of a wave of insolvencies has disappeared. The analysis suggests that a rise in insolvency filings is likely to have just been postponed, renewing the calls to strengthen insolvency frameworks in EMDEs.