The resurrection of the author

81 leaves ; 29 cmIncludes abstract.Includes bibliographical references (leaves 76-81).In The Resurrection of the Author, Daniel Trainor-McKinnon supports a form of intentionalism by arguing that intentions and meaning are metaphysically separate from artworks. This form of intentionalism is what he calls externalist intentionalism, which is the theory of art interpretation that holds that intentions are often relevant (though not always necessary) to understanding artworks. Because it holds this, externalist intentionalism is an adequate response to both the anti-intentionalist objection that artists' intentions are inadmissible in critical examinations of artworks because they are external to those artworks, and the neo-Wittgensteinian intentionalist claim that intentions are internal properties of artworks. A consequent study of allusion shows that some features of art are dependent on intentions for their existence and correct interpretation, while a concluding section examines externalist intentionalism's compatibility with evaluative criticism

Book Reviews

Book Review

An automated and closed system for patient specific CAR-T cell therapies

Autologous cell therapies, particularly chimeric antigen receptor T-cell (CAR-T) immunotherapies, are becoming a promising treatment option for difficult diseases. Immunotherapies for blood cancers have dominated the pipeline, while treatments for solid tumors have started to become more successful. However, as the market continues to grow and more clinical trials begin globally, the challenge of manufacturing autologous cell therapies remains significant. A greater number of patients will lead to an increase in cost, labor, and the complexity of logistics for scaling out the commercial production of patient specific therapies. To enable clinical and commercial success, novel manufacturing platforms, such as closed and automated systems, will be required to produce cost effective and robust therapies. This abstract highlights a successful CAR-T process translation from a manual process to an automated patient scale system. To accomplish a CAR-T process translation, we utilized a platform that automates cell seeding, activation, transduction, real time process monitoring, feeding, washing and concentration, and harvesting. In order to mimic a therapeutic CAR-T cell process, manual research scale processes were optimized, scaled up, and then programmed to run automatically without manual intervention. In these processes, 100 million peripheral blood mononuclear cells (PBMC) were first inoculated with CD3/CD28 activation beads. The following day, cells were transduced with HER-2 lentivirus vector. Cells were then expanded with a defined feeding strategy and IL-2 supplements until harvested when target yields were reached. After harvest, cells were analyzed for cell yield, viability, transduction efficiency, and an array of cell phenotype, potency and functionality via FACS and killing assays. Specifically, CAR-T cells were analyzed for the presence of naïve T cells, T stem cell memory, T central memory, T effector memory, and T effector cells. We show here how we optimized, scaled up, and automated manual processes to reach clinical requirements. Automated runs using the above process with cells transduced by HER-2 virus yielded an average of 2 x 109 cells post harvest with a viability \u3e 90%. Automated runs and associated controls were able to support the expansion of both CD4+ and CD8+ T cells with 73% CD4+ T cells and 20% CD8+ T cells. Harvested cells yielded approximately 80% NGFR+ cells with a higher detection of NGFR in the CD4+ fraction than in the CD8+ fraction for all samples. Both CD4+ and CD8+ subsets demonstrated T cell phenotype such as naïve T cells, T stem cell memory, T central memory, T effector memory, and T effector cells. Both subsets also only expressed between 15-20% of immunosuppressive regulatory T cells. Cell health was evaluated by the levels of exhaustion marker, PD-1, which was 19% in CD4+ T cells and \u3c 1% in CD8+ T cells. Furthermore, there was a negligible amount of senescent T cells and anergic cells and \u3c 10% expression of the apoptotic marker, Caspase-3. Subsequently, cells from multiple automated runs showed the specific killing of NGFR+ tumor line were correlated with high levels of effector cytokines: TNF-alpha (~34%) and IFN-gamma (20-25%) as compared to a manual control. In summary, automated CAR-T process in the Cocoon system yields a healthy populations of T cell subsets. This system is a viable solution to translate labor-intensive CAR-T process into a fully automated system, thus allowing scalability, high yield, reduction of manufacturing cost, and better process control to yield high quality CAR-T cells

US Immigrants’ Experiences with the Covid-19 Pandemic- Findings from Online Focus Groups

Objective: Immigrants in the United States (US) are disproportionately affected by disasters. Yet the effects of one type of disaster—pandemics—have been underexplored in this regard. The purpose of this study was to better understand these effects, with specific attention to the impacts of the COVID-19 pandemic on US immigrants and their social networks. Design: Forty-five US immigrants (aged 18 and above) participated across eight online focus groups during spring 2020. Using “criterion of inclusion” sampling, participants were recruited via gatekeeper and snowball sampling methods. Anonymity was maintained throughout all online focus group sessions. Discussions were transcribed and then categorized into distinct code families for immigrants’ “experiences during pandemic” and “pandemic response activities.” The resultant human-categorized content was then qualitatively analyzed to explore the effects of COVID-19 on US immigrants. Results: COVID-19 posed unique challenges for immigrant communities in spring 2020. These challenges included added burdens of sending financial resources abroad, caring for dependent parents, and managing immigration status anxieties—alongside more commonplace challenges concerning childcare, employment, and interpersonal relationships. At the same time, US immigrants showed remarkable ability to leverage their experiences and social networks in response to COVID-19, so as to (1) provide pandemic-relevant health education within their communities, (2) provide targeted support to those in need (both in the US and in their home countries), and (3) draw upon past experiences in immigrants’ home countries when navigating the COVID-19 pandemic and the associated government lockdown in the US. Conclusions: US immigrants were significantly impacted by the COVID-19 pandemic. In addition to more broadly-imposed pandemic burdens related to concerns about childcare, employment, and interpersonal relationships, immigrant communities have faced unique challenges brought on by the pandemic. However, this study’s examination of pandemic experiences and response activities has illustrated that US immigrants’ unique backgrounds, cultures, and social networks have provided them with a number of notable resources and strategies for coping with the COVID-19 pandemic. These findings offer important insights into strategies that should be leveraged as part of planning and response to prevent the disparate impacts of current and future pandemics on immigrant populations

Dynamic modeling of public and private decision-making for hurricane risk management including insurance, acquisition, and mitigation policy

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.We develop a computational framework for the stochastic and dynamic modeling of regional natural catastrophe losses with an insurance industry to support government decision-making for hurricane risk management. The analysis captures the temporal changes in the building inventory due to the acquisition (buyouts) of high-risk properties and the vulnerability of the building stock due to retrofit mitigation decisions. The system is comprised of a set of interacting models to (1) simulate hazard events; (2) estimate regional hurricane-induced losses from each hazard event based on an evolving building inventory; (3) capture acquisition offer acceptance, retrofit implementation, and insurance purchase behaviors of homeowners; and (4) represent an insurance market sensitive to demand with strategically interrelated primary insurers. This framework is linked to a simulation-optimization model to optimize decision-making by a government entity whose objective is to minimize region-wide hurricane losses. We examine the effect of different policies on homeowner mitigation, insurance take-up rate, insurer profit, and solvency in a case study using data for eastern North Carolina. Our findings indicate that an approach that coordinates insurance, retrofits, and acquisition of high-risk properties effectively reduces total (uninsured and insured) losses.Wiley Open Access Accoun

The National Clinical Assessment Tool for Medical Students in the Emergency Department (NCAT-EM)

Introduction: Clinical assessment of medical students in emergency medicine (EM) clerkships is a highly variable process that presents unique challenges and opportunities. Currently, clerkship directors use institution-specific tools with unproven validity and reliability that may or may not address competencies valued most highly in the EM setting. Standardization of assessment practices and development of a common, valid, specialty-specific tool would benefit EM educators and students. Methods: A two-day national consensus conference was held in March 2016 in the Clerkship Directors in Emergency Medicine (CDEM) track at the Council of Residency Directors in Emergency Medicine (CORD) Academic Assembly in Nashville, TN. The goal of this conference was to standardize assessment practices and to create a national clinical assessment tool for use in EM clerkships across the country. Conference leaders synthesized the literature, articulated major themes and questions pertinent to clinical assessment of students in EM, clarified the issues, and outlined the consensus- building process prior to consensus-building activities. Results: The first day of the conference was dedicated to developing consensus on these key themes in clinical assessment. The second day of the conference was dedicated to discussing and voting on proposed domains to be included in the national clinical assessment tool. A modified Delphi process was initiated after the conference to reconcile questions and items that did not reach an a priori level of consensus. Conclusion: The final tool, the National Clinical Assessment Tool for Medical Students in Emergency Medicine (NCAT-EM) is presented here. [West J Emerg Med. 2018;19(1)66-74.

Mammalian Neurogenesis Requires Treacle-Plk1 for Precise Control of Spindle Orientation, Mitotic Progression, and Maintenance of Neural Progenitor Cells

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1+/− mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly

Longitudinal scaling property of the charge balance function in Au + Au collisions at 200 GeV

We present measurements of the charge balance function, from the charged particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au collisions at 200 GeV using the STAR detector at RHIC. We observe that the balance function is boost-invariant within the pseudorapidity coverage [-1.3, 1.3]. The balance function properly scaled by the width of the observed pseudorapidity window does not depend on the position or size of the pseudorapidity window. This scaling property also holds for particles in different transverse momentum ranges. In addition, we find that the width of the balance function decreases monotonically with increasing transverse momentum for all centrality classes.Comment: 6 pages, 3 figure

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC