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"Davis, Andrew"
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Baggy pants comedy : burlesque and the oral tradition
\"Baggy Pants Comedy takes readers inside the burlesque houses of Depression-era America to explore the role of comedy in a show remembered mostly for strip-tease. It examines how burlesque comics, straightmen, and talking women approached the craft of comedy, working in a genre that relied not on scripts but on a remembered tradition of comedy bits that circulated orally. The book opens a long-neglected area of American folklore, presenting dozens of fondly-remembered routines like \"Who's On First\" and \"Niagara Falls (Slowly I Turned),\" as well as long-forgotten classics in print for the first time\"-- Provided by publisher.
Book
The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors
The development of immune checkpoint inhibitors has changed the treatment paradigm for advanced cancers across many tumor types. Despite encouraging and sometimes durable responses in a subset of patients, most patients do not respond. Tumors have adopted the PD-1/PD-L1 axis for immune escape to facilitate tumor growth, which can be leveraged as a potential target for immune checkpoint inhibitors. On this basis, PD-L1 protein expression on tumor or immune cells emerged as the first potential predictive biomarker for sensitivity to immune checkpoint blockade. The goal of our study was to evaluate PD-L1 as a predictive biomarker based on all US Food and Drug Administration (FDA) drug approvals of immune checkpoint inhibitors. We evaluated the primary studies associated with 45 FDA drug approvals from 2011 until April 2019. In total, there were approvals across 15 tumor types. Across all approvals, PD-L1 was predictive in only 28.9% of cases, and was either not predictive (53.3%) or not tested (17.8%) in the remaining cases. There were 9 FDA approvals linked to a specific PD-L1 threshold and companion diagnostic: bladder cancer (N = 3), non-small cell lung cancer (N = 3), triple-negative breast cancer (N = 1), cervical cancer (N = 1), and gastric/gastroesophageal junction cancer (N = 1) with 8 of 9 (88.9%) with immune checkpoint inhibitor monotherapy. The PD-L1 thresholds were variable both within and across tumor types using several different assays, including approvals at the following PD-L1 thresholds: 1, 5, and 50%. PD-L1 expression was also measured in a variable fashion either on tumor cells, tumor-infiltrating immune cells, or both. In conclusion, our findings indicate that PD-L1 expression as a predictive biomarker has limitations and that the decision to pursue testing must be carefully implemented for clinical decision-making.
Journal Article
Limitations of Fixed-Effects Models for Panel Data
Although fixed-effects models for panel data are now widely recognized as powerful tools for longitudinal data analysis, the limitations of these models are not well known. We provide a critical discussion of 12 limitations, including a culture of omission, low statistical power, limited external validity, restricted time periods, measurement error, time invariance, undefined variables, unobserved heterogeneity, erroneous causal inferences, imprecise interpretations of coefficients, imprudent comparisons with cross-sectional models, and questionable contributions vis-à-vis previous work. Instead of discouraging the use of fixed-effects models, we encourage more critical applications of this rigorous and promising methodology. The most important deficiencies—Type II errors, biased coefficients and imprecise standard errors, misleading p values, misguided causal claims, and various theoretical concerns—should be weighed against the likely presence of unobserved heterogeneity in other regression models. Ultimately, we must do a better job of communicating the pitfalls of fixed-effects models to our colleagues and students.
Journal Article
ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC.
Circulating tumor cell (CTC) clusters are more efficient at mediating metastasis as compared to single cells and are associated with poor prognosis in breast cancer. Here, the authors show that ICAM1 is enriched in CTC clusters and its loss suppresses cell-cell interaction and CTC cluster formation, and propose ICAM1 as a therapeutic target for treating breast cancer metastasis.
Journal Article
Impact of Ocean Warming and Ocean Acidification on Larval Development and Calcification in the Sea Urchin Tripneustes gratilla
As the oceans simultaneously warm, acidify and increase in P(CO2), prospects for marine biota are of concern. Calcifying species may find it difficult to produce their skeleton because ocean acidification decreases calcium carbonate saturation and accompanying hypercapnia suppresses metabolism. However, this may be buffered by enhanced growth and metabolism due to warming.
We examined the interactive effects of near-future ocean warming and increased acidification/P(CO2) on larval development in the tropical sea urchin Tripneustes gratilla. Larvae were reared in multifactorial experiments in flow-through conditions in all combinations of three temperature and three pH/P(CO2) treatments. Experiments were placed in the setting of projected near future conditions for SE Australia, a global change hot spot. Increased acidity/P(CO2) and decreased carbonate mineral saturation significantly reduced larval growth resulting in decreased skeletal length. Increased temperature (+3 degrees C) stimulated growth, producing significantly bigger larvae across all pH/P(CO2) treatments up to a thermal threshold (+6 degrees C). Increased acidity (-0.3-0.5 pH units) and hypercapnia significantly reduced larval calcification. A +3 degrees C warming diminished the negative effects of acidification and hypercapnia on larval growth.
This study of the effects of ocean warming and CO(2) driven acidification on development and calcification of marine invertebrate larvae reared in experimental conditions from the outset of development (fertilization) shows the positive and negative effects of these stressors. In simultaneous exposure to stressors the dwarfing effects of acidification were dominant. Reduction in size of sea urchin larvae in a high P(CO2) ocean would likely impair their performance with negative consequent effects for benthic adult populations.
Journal Article
Educational assessment on trial
\"What purpose does educational assessment serve? Are the same instruments suitable for different purposes? How much trust can we place upon the outcomes of educational assessment? The subject of educational assessment is much discussed and much misunderstood. Policymakers assert its importance to quality in education and its essential role in ensuring accountability for public education, and the results of educational assessment are thought to be of such vital interest to society that they are often made public knowledge. This approachable text explores the philosophical issues underlying these debates and how they impact on public educational policy. Two leading educators well-known for their work on educational assessment offer different perspectives on the value of exams and tests for a flourishing system of education, while the editor, Gerard Lum, comments on the strengths and weaknesses of the arguments\"-- Provided by publisher.
Book
Multidimensional Bargaining and Inventory Risk in Supply Chains: An Experimental Study
We study the impact of multidimensional bargaining and the location of inventory risk on the performance of a two-stage supply chain. We conduct a controlled human subjects experiment where a retailer and supplier either interact through ultimatum offers or dynamically bargain over contract terms, including a wholesale price and, potentially, an order quantity. We also manipulate whether the risk associated with unsold inventory lies with the retailer or the supplier or is endogenously determined in the bargaining process. One key insight is that supply chain efficiency is significantly higher when the order quantity is included in the negotiation and that, contrary to the normative theory, this leads to a Pareto improvement whereby both the supplier and retailer earn higher profits. A second important result, also counter to the normative theory, is that the party incurring the cost of unsold inventory always earns a lower profit than its counterpart, regardless of the bargaining environment or inventory risk location. To explain these data, we posit that retailers and suppliers are affected by an anchoring bias and demonstrate that it can explain many of our results.
Data and the online appendix are available at
https://doi.org/10.1287/mnsc.2017.2985
.
This paper was accepted by Gad Allon, operations management.
Journal Article