Du discours politique comme « trompe-l'oeil » chez Aristote

Prenant acte que la démocratie apparaît comme le seul régime souhaitable pour des hommes libres capables de s'autogouverner, il apparaît nécessaire pour Aristote de décrire et d'expliquer le mode de formation des discours qui s'échangent lors des procédures délibératives des assemblées de citoyens. Les conditions d'intelligibilité du discours politique conduisent Aristote à examiner le mode sur lequel le discours politique, sans renoncer à toute structure argumentative, cherche un « faire paraître » optimal dont le modèle peut être trouvé dans la représentation esthétique

Impacto de la innovación sobre el empleo en países de ingresos medios y bajos

El objetivo del trabajo es determinar si las innovaciones generan efectos positivos, negativos o neutros en el empleo a nivel empresa y agregado país, para los países con ingresos medios y bajos. El método de trabajo consiste en una revisión de la literatura que base sus estudios en el efecto de distintos tipos de innovaciones tanto en países desarrollados como en vías de desarrollo, y sobre éstos últimos que abarque varios continentes con la desagregación de los sectores empleadores industrial, agropecuario y de servicio. Se le agrega la visión de la difusión y acceso a la tecnología, y el comportamiento durante los ciclos económicos de auge y recesión. La conclusión del trabajo tiene resultados mixtos con evidencia en la creación de empleo o la destrucción del mismo, dependiendo del tipo de innovación que origina el cambio y la existencia de determinadas variables que pueden agrandar o disminuir los efectos sobre el empleo.Por motivos relacionados con los derechos de autor este documento solo puede ser consultado en la Biblioteca Di Tella. Para reservar una cita podés ponerte en contacto con [email protected]. Si sos el autor de esta tesis y querés autorizar su publicación en este repositorio, podés ponerte en contacto con [email protected]

The critical role of teaching urbanism in public university

Se pretende exponer el desafío que supone hoy la formación en Urbanismo entendiendo el contexto de la Universidad pública masiva como una oportunidad. ¿Cómo diseñar un curso de urbanismo que pueda contemplar las problemáticas urbanas, sociales y culturales con el escenario incierto del futuro cercano? Con la ambición de abarcar y considerar las problemáticas complejas que interactúan en la producción de ciudad se intenta traspolar las experiencias urbanas contemporáneas de los alumnos en experiencias proyectuales para problemáticas metropolitanas y globales. Se dicta un curso corto para estudiantes de grado de arquitectura con el desafío de producir un proyecto urbano generando crítica cultural social urbana simultáneamente. El objetivo es proveer a los estudiantes de herramientas críticas para analizar el contexto global y regional, generar una visualización proyectual de sus consecuencias y posibilidades en mediano y largo plazo en un territorio vacante del ámbito metropolitano. Buscando desarrollar una postura crítica se utilizan como herramienta diferentes esquicios que reconocen las dinámicas propias de la ciudad a través de la experiencia. Finalmente el Proyecto Urbano surge como tablero de juego para hacerse las preguntas correctas y/o aprender a identificarlas. El rol del docente es acompañar el proceso donde lo central es la dinámica de taller, el intercambio horizontal y la construcción colectiva de conocimiento, simulando una dinámica multidisciplinar. Ayudan a identificar potencialidades, divisar roles entre los grupos de trabajo, identificar puntos de conflicto y medi ar en las negociaciones.How can we design a course that addresses urban, social and cultural issues which are subject to constant change in an uncertain near future? The purpose of this article is to expose the implicit challenge in teaching urbanism, taking massivity in public university as an opportunity. Considering the complex dynamics that interact in the development of a city, the challenge is to transfer the students' urban experiences into project tools to tackle metropolitan and global problems. A short course for architecture students that aims to produce an urban project that generates critical thinking about urban social and cultural issues. The goal is to provide students with critical tools to analyze the global and regional context, generate a project visualization of its consequences and possibilities in the medium and long term in a vacant territory in the metropolitan area of Buenos Aires. Seeking to develop a critical approach, different exercises are used as a tool to recognize urban dynamics through personal experience. Ultimately, the process of creating an urban project will act as a means to introduce tools or methods that encourage students to ask the right questions. The teacher’s role is to guide the process with the focus on workshop group dynamics, horizontal exchange and the knowledge of collective construction, simulating multidisciplinary dynamics. The teacher acts as a mediator to guide potential, to recognize roles in the work group, to identify conflicts and to mediate negotiations

Treatment of chronic hepatitis C in patients unresponsive to interferon. Interest of re-treatment combining interferon induction therapy and ribavirin (a multicenter pilot study)

Aim About 45% of patients with chronic hepatitis C are unresponsive to the present reference treatment combining pegelated interferon plus ribavirin; before pegylated interferon was available the non-response rate was around 60%. This open multicenter pilot study, initiated before pegylated interferon became available, was designed to evaluate, in patients unresponsive to interferon monotherapy, the rate of biological and virological response and side-effects of the ribivirin- alpha 2b interferon combination. Methods The combination protocol was ribavirin (1 to 1.2 g/d) plus alpha 2b interferon at induction doses (9 MU/d the first week; 4.5 MU/d the eleven following weeks; 3 MU/2 days the 36 following weeks). Results Among the 27 included patients, 17 (63%) were viremia-negative (PCR) after 12 weeks of treatment, 9 (33%) were complete responders (undetectable viremia and normal transaminases) at the end of treatment (48 weeks) and of follow-up (72 weeks). Patients with non-1, non-4 genotypes who derived full benefit from this therapeutic strategy (6/7 (86%) were complete responders: 4/5 with genotype 3 and 2/2 with genotype 5). Quality-of-life was impaired during treatment, especially during the first 12 weeks of high-dose interferon therapy. Conclusion While waiting for new therapeutic possibilities, these good results suggest interferon induction at the beginning of treatment remains a valid option

TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires: Common and Specific Features

Among Immunotherapeutic approaches for cancer treatment, the adoptive transfer of antigen specific T cells is still a relevant approach, that could have higher efficacy when further combined with immune check-point blockade. A high number of adoptive transfer trials have been performed in metastatic melanoma, due to its high immunogenic potential, either with polyclonal TIL or antigen-specific polyclonal populations. In this setting, the extensive characterization of T cell functions and receptor diversity of infused polyclonal T cells is required, notably for monitoring purposes. We developed a clinical grade procedure for the selection and amplification of polyclonal CD8 T cells, specific for two shared and widely expressed melanoma antigens: Melan-A and MELOE-1. This procedure is currently used in a clinical trial for HLA-A2 metastatic melanoma patients. In this study, we characterized the T-cell diversity (T-cell repertoire) of such T cell populations using a new RNAseq strategy. We first assessed the added-value of TCR receptor sequencing, in terms of sensitivity and specificity, by direct comparison with cytometry analysis of the T cell populations labeled with anti-Vß-specific antibodies. Results from these analyzes also confirmed specific features already reported for Melan-A and MELOE-1 specific T cell repertoires in terms of V-alpha recurrence usage, on a very high number of T cell clonotypes. Furthermore, these analyses also revealed undescribed features, such as the recurrence of a specific motif in the CDR3α region for MELOE-1 specific T cell repertoire. Finally, the analysis of a large number of T cell clonotypes originating from various patients revealed the existence of public CDR3α and ß clonotypes for Melan-A and MELOE-1 specific T cells. In conclusion, this method of high throughput TCR sequencing is a reliable and powerful approach to deeply characterize polyclonal T cell repertoires, and to reveal specific features of a given TCR repertoire, that would be useful for immune follow-up of cancer patients treated by immunotherapeutic approaches

Dendritic Cells Crosspresent Antigens from Live B16 Cells More Efficiently than from Apoptotic Cells and Protect from Melanoma in a Therapeutic Model

Dendritic cells (DC) are able to elicit anti-tumoral CD8+ T cell responses by cross-presenting exogenous antigens in association with major histocompatibility complex (MHC) class I molecules. Therefore they are crucial actors in cell-based cancer immunotherapy. Although apoptotic cells are usually considered to be the best source of antigens, live cells are also able to provide antigens for cross-presentation by DC. We have recently shown that prophylactic immunotherapy by DC after capture of antigens from live B16 melanoma cells induced strong CD8+ T-cell responses and protection against a lethal tumor challenge in vivo in C57Bl/6 mice. Here, we showed that DC cross-presenting antigens from live B16 cells can also inhibit melanoma lung dissemination in a therapeutic protocol in mice. DC were first incubated with live tumor cells for antigen uptake and processing, then purified and irradiated for safety prior to injection. This treatment induced stronger tumor-specific CD8+ T-cell responses than treatment by DC cross-presenting antigens from apoptotic cells. Apoptotic B16 cells induced more IL-10 secretion by DC than live B16 cells. They underwent strong native antigen degradation and led to the expression of fewer MHC class I/epitope complexes on the surface of DC than live cells. Therefore, the possibility to use live cells as sources of tumor antigens must be taken into account to improve the efficiency of cancer immunotherapy

Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells

MAGE-A4 has been considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy. It has been well accepted that T-helper type 1 (Th1) cell-dominant immunity is critical for the successful induction of antitumour immunity in a tumour-bearing host. The adoptive Th1 cell therapy has been shown to be an attractive strategy for inducing tumour eradication in mouse systems. However, Th1-cell therapy using human tumour-specific Th1 cells, which were expanded from peripheral blood mononuclear cells (PBMCs) in a clinically useful protocol, has never been performed. Here, we first identified MAGE-A4-derived promiscuous helper epitope, peptide (MAGE-A4 280–299), bound to both HLA-DPB1*0501 and DRB1*1403. Using the peptide, we established a suitable protocol for the propagation of MAGE-A4-specific Th1 cells in vitro. Culture of CD4+ T cells with IFN-γ-treated PBMC-derived adherent cells in the presence of helper epitope peptide resulted in a great expansion of MAGE-A4-reactive Th cells producing IFN-γ , but not IL-4. Moreover, it was shown that ligation of MAGE-A4-reactive Th1 cells with the cognate peptide caused the production of IFN-γ and IL-2. Thus, our identified MAGE-A4 helper epitope peptide will become a good tool for the propagation of tumour-specific Th1 cells applicable to adoptive immunotherapy of human cancer

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes