182 research outputs found
Progressive multifocal leukoencephalopathy in patients treated with chimeric antigen receptor T cells
No full text: Using 2 global postmarketing surveillance databases, Goldman and colleagues report that progressive multifocal leukoencephalopathy (PML), a viral disease associated with profound immunosuppression, occurs in approximately 0.9 cases per 1000 recipients of CD19-directed CAR T-cell therapy. The risk of PML appears higher with CAR T-cell therapy than other cancer therapies, but its precise role cannot be distinguished from antecedent therapies that these patients receive
From Naturally Occurring Tumor Immunity to Supernatural T Cells: Isolation and Characterization of a Murine T Cell Receptor Specific for Human Breast and Ovarian Tumor Antigen Cdr2
No full textPatients with paraneoplastic cerebellar degeneration (PCD), a form of neuronal autoimmunity, have a co-occurring natural immune response against a protein called cdr2 in their breast and ovarian carcinomas, and thus provide an innovative starting point for understanding how to harness the immune system to fight cancer. We previously demonstrated cdr2-specific cytotoxic T lymphocytes (CTL) in the peripheral blood of HLA-A2.1+ PCD patients, suggesting that CTLs mediate tumor immunity in these patients. Cdr2 is expressed by a large proportion of breast and ovarian tumors from individuals who do not develop neurological disease, suggesting that immune responses to this antigen may develop independently of autoimmune responses. Here we explore establishing cdr2 as a target for breast and ovarian cancer immunotherapy by identifying naturally processed A2.1-restricted epitopes of cdr2. Immunization of A2.1 transgenic mice with recombinant adenovirus encoding human full length cdr2 led to the identification of two naturally processed A2.1-restricted human cdr2 peptides: cdr2(289-297) and cdr2(290-298). Mouse-derived A2.1-restricted cdr2(289-297)-specific CTLs were able to target cells expressing endogenous human cdr2, but also cross-reacted with endogenous mouse cdr2, resulting in partial tolerance to this epitope. In contrast, mouse-derived A2.1-restricted cdr2(290-298)-specific CTL were capable of recognizing tumor cells expressing endogenous human cdr2, but were unable to recognize mouse cdr2 due to nonhomology of the human and mouse cdr2(290- 298) epitopes. cdr2(290-298)-specific CTL clones were isolated, and their TCR gene cloned. Transfer of the mouse-derived TCR into human CD8+ T cells turned them into efficient cdr2-specific CTLs. We have detected CD8+ T cells specific for both cdr2(289-297) and cdr2(290-298) in peripheral blood from A2.1+ PCD patients by tetramer staining. This correlates the presence of T cells specific to these epitopes with PCD and effective anti-gynecologic tumor immunity, and suggests that these are bona fide tumor-associated CTL epitopes. We conclude swthat gene transfer of TCR specific for cdr2(290-298) could provide the basis for potent breast and ovarian cancer immunotherapies, while cdr2(289-297)-specific T cells, able to target both mouse and human cdr2, offer a platform for generating a humanized animal model to investigate the whether cdr2-TCR gene transfer is possible without inducing neuronal autoimmunity
Metrics for driving political economy of energy and growth
No full textEnergy metrics is the development of a whole new theoretical framework for the conception and measurement of energy and economic performances, energy efficiency and productivity improvements with important political economy implications consistent with the best use of all natural and economic resources. The purpose of this research is to present some vital energy indicators based on magnitude and scale of energy weakness, GDP per barrel that is an indicator of energy productivity and barrels per capita that is an indicator of energy efficiency. Energy metrics can support policy maker to monitor energy system of countries in order to design effective strategy and political economy focused to increase the competitive advantage of countries in modern economies.Energy metrics, Energy productivity, Energy efficiency, Energy systems
How I treat unique and difficult-to-manage cases of CAR T-cell therapy–associated neurotoxicity
No full textWith growing indications for chimeric antigen receptor (CAR) T-cell therapy, toxicity profiles are evolving. There is an urgent and unmet need of approaches to optimally manage emerging adverse events that extend beyond the standard paradigm of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). Although management guidelines exist for ICANS, there is little guidance on how to approach patients with neurologic comorbidities, and how to manage rare neurotoxicity presentations, such as CAR T-cell therapy-related cerebral edema, severe motor complications or late-onset neurotoxicity. In this study, we present 3 scenarios of patients treated with CAR T cells who develop unique types of neurotoxicity, and we describe an approach for the evaluation and management based on experience because objective data are limited. The goal of this study is to develop an awareness of emerging and unusual complications, discuss treatment approaches, and help institutions and health care providers establish frameworks to navigate how to best address unusual neurotoxicities to ultimately improve patient outcomes
Forecast horizon of 5th – 6th – 7th long wave and short-period of contraction in economic cycles
No full textThe purpose of this essay is to determine the forecast horizon of the fifth, sixth and seventh long wave. As the period of each long wave can change according to the data, it has been used a deterministic approach, based on historical chronologies of USA and UK economies worked out by several scholars, to determine average timing, period and forecast error of future long waves. In addition, the analysis shows that long waves have average upwave period longer than average downwave one. This result is also confirmed by US Business Cycles that have average contractions shorter than expansions phase over time.Forecast Horizon, Long Waves, Kondratieff Waves, Business Cycles, Asymmetric Path
Black Bone
No full textThe Appalachian region stretches from Mississippi to New York, encompassing rural areas as well as cities from Birmingham to Pittsburgh. Though Appalachia\u27s people are as diverse as its terrain, few other regions in America are as burdened with stereotypes. Author Frank X Walker coined the term Affrilachia to give identity and voice to people of African descent from this region and to highlight Appalachia\u27s multicultural identity. This act inspired a group of gifted artists, the Affrilachian Poets, to begin working together and using their writing to defy persistent stereotypes of Appalachia as a racially and culturally homogenized region.
After years of growth, honors, and accomplishments, the group is acknowledging its silver anniversary with Black Bone. Edited by two newer members of the Affrilachian Poets, Bianca Lynne Spriggs and Jeremy Paden, Black Bone is a beautiful collection of both new and classic work and features submissions from Frank X Walker, Nikky Finney, Gerald Coleman, Crystal Wilkinson, Kelly Norman Ellis, and many others. This illuminating and powerful collection is a testament to a groundbreaking group and its enduring legacy.
Bianca Lynne Spriggs is a writer, multidisciplinary artist, and assistant professor of English at Ohio University. She is the recipient of a Kentucky Arts Council 2013 Al Smith Individual Arts Fellowship in Poetry, as well as a recipient of multiple artist enrichment grants from the Kentucky Foundation for Women. Spriggs is the author or coeditor of a number of books, including Kaffir Lily, Call Her by Her Name, and The Galaxy Is a Dance Floor.
Jeremy Paden is an associate professor of Spanish and Latin American literature at Transylvania University. His poems have appeared in such places as the Atlanta Review, Beloit Poetry Journal, Cortland Review, Louisville Review, Naugatuck River Review, pluck! and Rattle, among others. He is the author of two collections of poems, Broken Tulips and ruina montium.https://uknowledge.uky.edu/upk_cr/1004/thumbnail.jp
Evaluating the Effect of Public Subsidies on firm R&D activity: an Application to Italy Using the Community Innovation Survey
No full textThe aim of the paper is twofold: to verify a full policy failure of public support on private R&D effort, when in presence of a potential plurality of public incentives; to compare the most recent econometric methods used for the analysis of the input additionality. Compared to previous studies our work wants to trace out an advance in two directions: adding more robustness by comparing results from various econometric techniques and providing an analysis of the R&D policy effect behind the average results. A by-product of the paper is a taxonomy of the econometric methods used in the literature, according to the structure of the models, the type of dataset and the available policy information. We exploit the third wave of the Community Innovation Survey for Italy (1998-2000) with a sample size of 1,221 supported and 1,319 non-supported firms. Given the used type of data, the article presents two main limits: first, we do not know the level of the subsidy, so that we can control only for the presence of a total crowding-out; second, we can check only the short-run effect of the supporting policy, while an increase in the private R&D effort could be more likely in the medium term. Our results suggest that: 1. the main factors influencing the probability to participate to the incentive policy are R&D experience, human skills, liquidity constraints, but also foreign capital ownership; 2. on average, the total substitution of private funding by the public one is excluded for Italy as a whole, although some cases of total crowding-out are found: low knowledge intensive services, very small firms (10-19 employees) and the auto-vehicle industry. We get, on average, 885 additional thousand Euros of R&D expenditure per firm with a ratio equal to 4.62: it means that if a generic control unit does 1 thousand Euros of R&D expenditure a matched treated does 4.62 thousand Euros. The additionality for the R&D intensity is about 0.014 with a ratio of about 2.67.Business R&D; Public Incentives; Econometric Evaluation
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