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Real-World Bleeding with Ibrutinib in B-Cell Malignancies
No full textIbrutinib is used to treat B-cell malignancies. Bleeding occurred in up to 50% of ibrutinib-treated clinical trial participants, but major bleeding was uncommon. However, trials excluded patients with certain risk factors and may underestimate major bleeding frequency in clinical practice. Furthermore, many ibrutinib-treated patients concomitantly use oral anticoagulants (OACs) to prevent thromboembolic events caused by comorbid conditions and ibrutinib-related atrial fibrillation. Thus, clinicians are confronted with the decision of concomitantly treating patients with ibrutinib and OACs without sufficient knowledge of the bleeding risk. We conducted two cohort studies in a commercially-insured population to estimate hazard ratios (HRs), using inverse probability of treatment weighting-adjusted Cox proportional hazards regression, for bleeding with ibrutinib vs. bendamustine-rituximab (BR). We also evaluated the performance of SuperLearner-high-dimensional propensity score (SL-hdPS), a novel approach that reduced propensity score overfitting and improved bias reduction vs. hdPS alone in simulation studies. In Aim 1, we assessed rates of major (resulting in hospitalization) and clinically-relevant (resulting in emergency department presentation or hospitalization) bleeding with ibrutinib versus BR in individuals not concomitantly treated with OACs. The major and clinically-relevant bleeding HRs for ibrutinib (vs. BR) were 1.61 (95% confidence interval: 0.67-3.84) and 2.66 (1.29-5.49), respectively. In Aim 2, we assessed rates of major, clinically-relevant, and provider-diagnosed (in any healthcare setting; specified post-hoc) bleeding with ibrutinib vs. BR in individuals concomitantly treated with OACs. Major and clinically-relevant bleeding HRs could not be estimated due to low event counts. The provider-diagnosed bleeding HR for ibrutinib + OAC (vs. BR + OAC) was 2.70 (1.25-5.82). In Aim 3, we evaluated the performance of SL-hdPS compared to hdPS alone using the Aim 1 and 2 cohorts. SL-hdPS resulted in better covariate balance than hdPS alone in the Aim 1 cohort but resulted in overfitting and suboptimal covariate balance in the Aim 2 cohort. This work fills an important knowledge gap in ibrutinib-related bleeding which may inform ibrutinib’s benefit-harm balance. It also provides support for the use of SL to help optimize covariate balance when using hdPS in certain small sample studies
Combining IAP Antagonists with CAR T Cell Therapy to Treat Glioblastoma: The IAP Antagonist Birinapant Enhances Chimeric Antigen Receptor T Cell Therapy for Glioblastoma by Overcoming Antigen Heterogeneity
No full textAntigen heterogeneity that results in tumor antigenic escape is one of the major obstacles to successful chimeric antigen receptor (CAR) T cell therapies in solid tumors including glioblastoma multiforme (GBM). To address this issue and improve the efficacy of CAR T cell therapy for GBM, we developed an approach that combines CAR T cells with inhibitor of apoptosis protein (IAP) antagonists, a new class of small molecules that mediate the degradation of IAPs, to treat GBM. Here, we demonstrated that the IAP antagonist birinapant could sensitize GBM cell lines and patient-derived primary GBM organoids to apoptosis induced by CAR T cell-derived cytokines, such as tumor necrosis factor. Therefore, birinapant could enhance CAR T cell-mediated bystander death of antigen-negative GBM cells, thus preventing tumor antigenic escape in antigen heterogeneous tumor models in vitro and in vivo. In addition, birinapant could promote the activation of NF-κB signaling pathways in antigen-stimulated CAR T cells, and with a birinapant-resistant tumor model, we showed that birinapant had no deleterious effect on CAR T cell functions in vitro and in vivo. Overall, we demonstrated the potential of combining the IAP antagonist birinapant with CAR T cells as a promising approach to overcoming tumor antigen heterogeneity and enhancing CAR T cell therapy for GBM
Ritualizing Al-Ibdāʿ: Language Ideology and Creative Arts in Post-2011 Morocco
No full textThe Moroccan government has promoted cultural inclusivity and linguistic pluralism as a part of its response to the country’s mass uprisings in 2011. The state has framed education as a central pillar of this national “social project”, claiming to reverse longstanding language policies that have marginalized forms of expression outside of French and Standard Arabic. However, the preeminence of Morocco’s unified national curriculum—which has historically valued scientific and technical education in French—has left little room for schooling that departs from rote exam preparation in these subjects. In this context, the Moroccan Ministry of Education has turned to extracurricular education as a site for putting into practice cultural and linguistic inclusion, particularly through programs focused on the cultivation of creativity (al-ibdāʿ). This study provides an ethnographic account of how public-school teachers implemented one such novel program in the heart of Morocco’s Arabic-Tamazight bilingual Middle Atlas region. Focusing on concrete interactions in and around the extracurricular program, I document teachers’ efforts to manage how their work is interpreted—by students, by members of the community, by their colleagues, and by their superiors. In doing so, I explore how local politics of class, ethnicity, and bureaucracy shaped the emergent program, often in ways that escaped the teachers’ control as both educational professionals and quasi-agents of the state. This study more broadly emphasizes how the ritual trappings of schooling—often theorized as mere context for teaching and learning—can function as a dynamic site for negotiating ideologies of language, personhood, and governance
Identity in the Practice and Politics of Embedded Liberalism
No full textMuch of the integration of the global economy is credited to embedded liberalism, (Ruggie 1982) which contends that states can secure support for openness by mitigating globalization-induced economic insecurity with social welfare. However, the contemporary globalization backlash has led some observers to conclude that embedded liberalism is fraying. While the micro-foundations of this theory are usually imagined as an instrumental process, a growing body of research finds that attitudes toward globalization are better explained by psychosocial factors. This dissertation adds to that literature by examining the role of group identity in the practice and politics of embedded liberalism in the United States. In the first part, I focus on workers\u27 decisions to accept government aid after a trade-related job loss using semi-structured interviews with workers in a post-industrial region of Pennsylvania. Especially for white working-class people, the loss of a job and accepting welfare can threaten group membership, and this is the context in which workers decide whether to retrain through the Trade Adjustment Assistance (TAA) program. In the second part, I consider the effect of racial in-group favoritism on attitudes toward trade and compensation. Since most people do not experience globalization-related risks to their own employment, citizens evaluate the impact of trade on others like them. White working-class people receive messages from the media and politicians that they are relatively worse off due to globalization, activating in-group favoritism. I test this theory using an experiment embedded in a survey of white Americans and original coding of anti-globalization campaign ads for the presence of white working-class identity themes. Ultimately, I do not find evidence for the role of identity in embedded liberalism. Trade-displaced workers are primarily motivated by instrumental concerns around employability and/or short-term finances in deciding whether to retrain, and white survey respondents do not condition their support for trade on other whites receiving government aid. However, Congressional candidates running in districts with a greater white share of the population are more likely to reference white identity themes in anti-trade ads
Multi-Heritagization and Its Impacts on the Conservation of Agaria Cultural Landscapes: A Case Study of Honghe Hani Rice, Terraces and Ifugao Rice Terraces
Get PDFMulti-heritagization is a product of the contemporary global heritage movement and refers to the phenomenon of different cultural heritage conservation systems overlapping in the same community. The heritagization of rice terrace communities begins with their identification as Cultural Landscapes . Heritagization is an essential concept in heritage studies, meaning the process of planning, conserving, and using cultural remains from the \u27past\u27 - a valued and selective past - through official classification as \u27heritage.\u27 The Honghe Hani Rice Terraces in Yunnan, China,（红河哈尼梯田） and the Ifugao Rice Terraces in Luzon, Philippines, have been designated as UNESCO\u27s \u27World Cultural Landscape Heritage\u27 and recognized as Globally Important Agricultural Heritage Systems (GIAHS). Their double nomination status puts them directly under the influence of multi-heritagization. This thesis explores how these terraces\u27 multiple designations affects their conservation
Penn Library\u27s LJS 342 - [Copies of documents relating to water rights in Milan] (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1115/thumbnail.jp
Substance Abuse during the Pandemic: Implications for Labor-Force Participation
Get PDFThe labor-force participation rates of prime-age U.S. workers dropped in March 2020—the start of the COVID-19 pandemic—and have still not fully recovered. At the same time, substance-abuse deaths were elevated during the pandemic relative to trend indicating an increase in the number of substance abusers, and abusers of opioids and crystal methamphetamine have lower labor-force participation rates than non-abusers. Could increased substance abuse during the pandemic be a factor contributing to the fall in labor-force participation? Estimates of the number of additional substance abusers during the pandemic presented here suggest that increased substance abuse accounts for between 9 and 26 percent of the decline in prime-age labor-force participation between February 2020 and June 2021
SOUTHERN HARM: THE UDC’S EDUCATIONAL CRUSADE PROMOTING LOST CAUSE IDEOLOGY IN THE PROGRESSIVE ERA SOUTH
Get PDFTHE PREVALENCE OF DEPRESSION IN LOW-INCOME BLACK WOMEN: A SYSTEMATIC REVIEW AND META-ANALYSIS
No full textPurpose: To conduct a systematic review and meta-analysis of studies reporting the prevalence of depression in low-income African American women. The secondary purpose of this review is to compare prevalence rates with non-low-income women and to determine whether moderators influenced the effect size.
Methods: Literature was searched for studies reporting prevalence data on women who were African American, low-income, and depressed. An academic librarian assisted with the search strategy, and the investigator conducted searches, data extraction, and methodological appraisal. Data analysis was performed using the meta and metafor packages in the statistical software environment R. The random-effects model was utilized to account for both between and within studies’ variances.
Results: The search process produced 59 included studies with a total of 57,357 participants. The primary result obtained for the point prevalence of depression across self-report studies was 36.6% (95% CI, 31.8% - 42.2%). Pooled results from studies using clinician-derived DSM diagnoses showed a point prevalence rate of 29.5% (95% CI, 25.8% - 33.4%).
Conclusions: Depression prevalence among Black women is high, afflicting over a third of women. When women have additional risk factors other than minority and low-income status, such as comorbid health problems and intimate partner violence, they are even more at risk.
Implications: Given high rates of depression, future research should focus on culturally adapted screening and interventions that best support positive outcomes. Treatment protocol must include sensitivity and understanding of the social factors that this group may face including systemic barrie
For the Economy or for Security? Using 5G to Explain Federal Intervention in US-China Technological Competition
Get PDFThe United States under the Trump administration shifted federal policy toward greater state intervention in the technology innovation economy in response to perceived advances in this space by the People’s Republic of China (PRC). This shift is noteworthy given the free-market orthodoxy that traditionally defines US politics and has persisted despite similar perceptions of competition from more state-driven economies in the past (e.g., Japan in the 1980s). This paper seeks to understand why this shift in American economic orthodoxy appears to be occurring now, in reaction to Chinese technological innovation. It does so by beginning to investigate the motivations for shifting US federal 5G policy. It evaluates two explanations for the shift: that the economic relationship with China and broader domestic backlash to globalization have initiated a genuine shift in economic thinking toward industrial policy, or that perceptions of great power competition with the PRC create a national security impetus for intervention in the technology space that supersedes economic orthodoxy. While both trends likely play a role in the shift in federal innovation strategy, I find that the national security dimension of the US-China relationship plays the most significant role in shaping this federal policy change