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Effect of Nudges to Clinicians, Patients, or Both to Increase Statin Prescribing: A Cluster Randomized Clinical Trial
Get PDFNudges — which present information or set choices to achieve desired behavior — increased guideline based statin prescribing over usual care. Clinician nudges alone had a small effect, patient nudges alone had no effect, and combined clinician and patient nudges had the greatest effect, increasing prescribing by 7.2 percentage points. The interventions employed a common electronic health record (EHR) system, making them generalizable and scalable
Same Environment, Stratified Impacts? Air Pollution, Extreme Temperatures, and Birth Weight in South China
Get PDFThis paper investigates whether associations between birth weight and prenatal ambient environmental conditions—pollution and extreme temperatures—differ by 1) maternal education; 2) children’s innate health; and 3) interactions between these two. We link birth records from Guangzhou, China, during a period of high pollution, to ambient air pollution (PM10 and a composite measure) and extreme temperature data. We first use mean regressions to test whether, overall, maternal education is an “effect modifier” in the relationships between ambient air pollution, extreme temperature, and birth weight. We then use conditional quantile regressions to test for effect heterogeneity according to the unobserved innate vulnerability of babies after conditioning on other confounders. Results show that 1) the negative association between ambient exposures and birth weight is twice as large at lower conditional quantiles of birth weights as at the median; 2) the protection associated with college-educated mothers with respect to pollution and extreme heat is heterogeneous and potentially substantial: between 0.02 and 0.34 standard deviations of birth weights, depending on the conditional quantiles; 3) this protection is amplified under more extreme ambient conditions and for infants with greater unobserved innate vulnerabilities
The Current State of U.S. Workplace Retirement Plan Coverage
Get PDFDespite widespread support for government policies aimed at improving workplace retirement plans, nearly half of wage and salary workers in the U.S. still lack coverage. The lack of employer-sponsored pensions or other workplace retirement saving plans has led to state-level government initiatives aimed at expanding coverage to workers whose employers do not offer such plans. Designing and implementing efforts to broaden workplace retirement plan coverage requires understanding what types of workers lack coverage, in terms of both demographic characteristics and across US states. However, available data on retirement plan coverage is limited, and developing an accurate picture of the current state of retirement plan coverage requires reconciling and benchmarking multiple data sources. This paper describes a method for estimating current workplace retirement plan coverage rates by age, race and ethnicity, education, gender, employer size, and earnings levels across U.S. states using data from the Current Population Survey, IRS Statistics of Income, and Survey of Consumer Finances
Penn Library\u27s LJS 312 - [ʻIr siḥon] (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1113/thumbnail.jp
Memories of Captivity in the Great East Asian War (1592-1598)
Get PDFThis thesis studies how the piroin, or enslaved Koreans, during the Great East Asian War (1592-1598) remembered and understood their experiences of captivity. It further explores how these findings help us understand Korean society during the late-16th and early 17th centuries as it underwent rapid social change in the aftermath of the devastating war. This is accomplished by exploring the various writings that emerged in the postwar period regarding experiences of the war as well as captivity, and comparing the various normative language and rhetoric within them. A close reading of the Korean royal court’s interpretation of Neo-Confucianism was compared with experiences of the piroin from both elite and popular perspectives. This thesis adds a new understanding of the Great East Asian War by bringing to light the varied social responses to it, and how these stories of captivity fit into the larger landscape of diverse opinions and perspectives within a dynamic postbellum Korea
Platform Injustice: Material Imbalances and Epistemic Injustice on Digital Discursive Platforms
Get PDFIn this paper, I argue that the existence of material power imbalances in systems of discourse represents a novel concern in the literature on epistemic injustice. This epistemic injustice, which I call Platform Injustice, arises from the undue assertion of agency over the background features of a system of discourse, in order to manipulate, diminish, or magnify the vocalization and reception of speech-acts. First, I demonstrate the unprecedented nature of platform control as an epistemic wrong. Next, I identify case studies of platform injustice in modern social media. Then, I situate platform injustice within Dotson’s typology of epistemic injustices; so, I can finally, identify paths to achieving platform justice and an epistemology of liberation
Multi-Omics Integration Through Single-Cell Copy Number Analysis in Cancer
No full textGenetic and epigenetic alterations combine to drive cancer progression. Heterogeneous cell populations within tumors are associated with poor prognosis and outcomes. Copy number aberrations (CNAs), a genetic variant commonly occurring in tumors, are used as markers to detect subclones and reconstruct tumor phylogeny. Multi-omics integration between CNAs and other modalities on tumor subclones facilitates studying the interplay between genome and epigenome, and their effects on transcriptome. So far, there is still a lack of computational methods for the multi-omics integration of different types of single-cell and ST tumor sequencing data. Therefore, the aim of this thesis is to extract (allele-specific) CNA signals in single-cell and ST tumor sequencing data, which enables the integration of multi-omics at the subclone level. We achieved this through the development of two methods — Alleloscope (Chapter 2) and Clonalscope (Chapter 3). Alleloscope is a computational method for profiling allele-specific CNAs in single-cell DNA- and/or transposase-accessible chromatin-sequencing (scDNA-seq, ATAC-seq) data, enabling integrative analysis of allele-specific copy number and chromatin accessibility. On scDNA-seq data from gastric, colorectal and breast cancer samples, with validation using matched linked-read sequencing, Alleloscope finds pervasive occurrence of highly complex, multiallelic CNAs, in which cells that carry varying allelic configurations adding to the same total copy number coevolve within a tumor. On scATAC-seq from two basal cell carcinoma samples and a gastric cancer cell line, Alleloscope detected multiallelic copy number events and copy-neutral loss-of-heterozygosity, enabling dissection of the contributions of chromosomal instability and chromatin remodeling to tumor evolution. To detect genetically different subclones based on CNAs, we also developed Clonalscope, a subclone detection method for different single-cell and ST tumor sequencing data, which leverages prior information from matched bulk DNA-seq data. Clonalscope implements a nested Chinese Restaurant Process to model the evolutionary process in tumors. On scRNA-seq and scATAC-seq data from three gastrointestinal tumor samples, Clonalscope successfully labeled malignant cells and identified genetically different subclones, which were validated in detail using matched scDNA-seq data. On ST data from a basal cell carcinoma and two invasive ductal carcinoma samples, Clonalscope was able to label malignant spots, trace subclones between related datasets, and identify spatially segregated subclones expressing genes associated with drug resistance and survival
The Innovation Ecosystem Framework: A New Strategy for Curricular Innovation
No full textThis dissertation was a qualitative study of two new higher education institutions that designed and implemented innovative curricula. The higher education sector is under increasing pressure to redesign curricula and update teaching methods to respond to needs of the knowledge economy and changing student demographics. Although there is little question that higher education must reimagine its curriculum, there is limited research on how it should be accomplished. Studies that do exist on the process of curricular design and implementation have blind spots, focusing almost exclusively on faculty and institutional culture. The process for curricular innovations needed in the 21st century may require a different approach. In business research, a construct has emerged that offers a wider lens through which to view the design and implementation process. The innovation ecosystem framework places innovation at the center of the process and maps multiple partners involved in its design and implementation. It assumes that, due to resource constraints and specialization, no one entity can create, develop, and implement an innovation alone (Adner, 2006; Talmar et al., 2020; Walrave et al., 2018). Instead, it requires a network of actors working collaboratively to achieve the identified goal. The study’s purpose was twofold: (a) to understand the process used by new institutions as they designed and implemented an innovative curriculum and (b) to determine whether the innovation ecosystem framework provides a strategic lens through which to view a new higher education institution’s process of curricular innovation. Using interviews, document review, and environmental scans, the study outlined common themes that influenced the curricular design process. Many factors that surfaced align with research on curricular reform and change management in established institutions; however, this study also introduces factors not clearly articulated in prior research. In addition, the study found the innovation ecosystem framework from business literature may provide an additional strategy for curricular innovation for new market entrants. The study provided a starting place for research on the applicability and efficacy of the innovation ecosystem framework to established higher education institutions
Identification and Characterization of RBM12 as a Novel Regulator of Fetal Hemoglobin Expression
No full textThe fetal-to-adult hemoglobin transition is clinically relevant as reactivation of fetal hemoglobin (HbF) significantly reduces morbidity and mortality associated with sickle cell disease (SCD) and β-thalassemia. Most studies on the developmental regulation of the globin genes, including genome-wide genetics screens, have focused on DNA binding proteins including BCL11A and ZBTB7A/LRF and their cofactors. Our understanding of RNA binding proteins (RBPs) in this process is much more limited. Two RBPs, LIN28B and IGF2BP1 are known post-transcriptional regulators of HbF production but a global view of RBPs is still lacking. Here, we carried out a CRISPR/Cas9-based screen targeting RBPs harboring RNA methyltransferase and/or RNA recognition motif (RRM) domains and identified RNA binding motif 12 (RBM12) as a novel HbF suppressor. Depletion of RBM12 induced HbF expression and attenuated cell sickling in erythroid cells derived from SCD patients with minimal detrimental effects on cell maturation. Transcriptome and proteome profiling revealed that RBM12 functions independently of major known HbF regulators. Enhanced crosslinking and immunoprecipitation followed by high throughput sequencing (eCLIP-Seq) revealed strong preferential binding of RBM12 to 5’UTRs of transcripts, narrowing down the mechanism of RBM12 action. Notably, we pinpointed the first of five RRM domains as essential, and, in conjunction with a linker domain, as sufficient for RBM12-mediated HbF regulation. Our characterization of RBM12 as a negative regulator of HbF points to an additional regulatory layer of the fetal-to-adult hemoglobin switch and broadens the pool of potential therapeutic targets for SCD and β-thalassemia
Cellular Plasticity in the Intestinal Epithelium Is Associated with Autophagic State
No full textThe intestinal epithelium exhibits a remarkable degree of cellular plasticity that aids in re-establishing intestinal homeostasis following acute or chronic tissue damage. Although cellular plasticity has been described in the mouse intestinal epithelium using reporter mouse models to label distinct epithelial cell types, a deeper understanding of the cellular states and signaling pathways that are required for undergoing this phenomenon has not yet been developed. Furthermore, the regulatory factors that allow rapid cellular changes that facilitate cellular plasticity are incompletely understood. Here we implement novel flow cytometry-based assays that allow the discrimination of intestinal epithelial cells with the capacity for plasticity based on the amount of autophagic vesicles present. Furthermore, we utilize novel mouse models designed for the interrogation of the role of RNA-binding proteins in regulating cellular plasticity. We show that baseline levels of autophagic vesicles positively correlate with cellular plasticity within the intestinal epithelium. Furthermore, we demonstrate that this phenomenon can be observed when sorting within the enteroendocrine and Paneth cell lineages, suggesting that cellular plasticity based on autophagic vesicle content in the intestinal epithelium is lineage agnostic. We further demonstrate that the RNA-binding protein Imp1 regulates Lrg5+ stem cell maintenance and genetic ablation of Imp1 in intestinal epithelial cells decreases stem cell frequency and enhances cellular plasticity within the epithelium. Finally, we show that Imp1 regulates intestinal regeneration following irradiation in an autophagy-dependent manner. Taken together, this dissertation sheds light on the autophagy pathway as an important determinant of cellular plasticity in the epithelium. Furthermore, we uncover the RNA-binding protein Imp1 as novel regulator of intestinal stem cell state and as potential therapeutic targets for enhancing injury resolution in the intestine