Tensiones de la narrativa serial en el nuevo sistema mediático

El fenómeno de las narrativas transmedia, producto de la experimentación de la ficción televisiva en un marco multimedia y multiplataforma, plantea numerosos desafíos que no solo conciernen a decisiones de la industria y sus líneas de producción sino asimismo a la reflexión y el análisis que establecen como objeto de estudio estas nuevas formas. El aparato metodológico-conceptual aplicado y ensayado con medios y formas de expresión de la era predigital es puesto a prueba constantemente en la actualidad por las narrativas desplegables. En este texto, y apoyándonos en nuestra experiencia de la producción ficcional más reciente, nos referiremos a un concepto clave para el desenvolvimiento de la narración transmediática: la serialidad, muy precisamente cómo las formas de estructurar y organizar la narración son reformuladas en el nuevo y complejo contexto mediático, y en esta dirección, las tensiones generadas en torno a estas narrativas entre, por un lado, las demandas que se asocian a modalidades de consumo propias de un medio tradicional que no ha cambiado básicamente sus protocolos consolidados en la era analógica, y por el otro, las nuevas formas de acceso y uso de los contenidos propiciados por las nuevas tecnologías.El fenomen de les narratives transmedia, producte de l'experimentació de la ficció televisiva en un marc multimèdia i multiplataforma, planteja nombrosos desafiaments que no només concerneixen a decisions de la indústria i les seves línies de producció sinó també a la reflexió i anàlisi que estableixen com a objecte d'estudi aquestes noves formes. L'aparell metodològic-conceptual aplicat i assajat amb mitjans i formes d'expressió de l'era predigital és posat a prova constantment en l'actualitat per les narratives desplegables. En aquest text, i recolzant-nos en la nostra experiència sobre la producció ficcional més recent, ens referirem a un concepte clau pel desenvolupament de la narració transmediática: la serialitat, en especial com les formes d'estructurar i organitzar la narració són reformulades en el nou i complex context mediàtic, i en aquesta direcció, quines són les tensions generades entorn d'aquestes narratives entre, d'una banda, les demandes que s'associen a modalitats de consum pròpies d'un mitjà tradicional que no ha canviat bàsicament els seus protocols consolidats en l'era analògica, i de l'altre, les noves formes d'accés i ús dels continguts propiciats per les noves tecnologies.The phenomenon of the transmedia narrative, as a result of the experimentation of the fiction in television in a multiplatform and multimedia frame, arises multiple challenges which not only affect to the decisions in the industry and its production lines, but also to the reflexion and analysis, which establish new forms as an object of study. The methodological and conceptual apparatus applied and tested with the media and forms of expression in the predigital era is constantly examined nowadays by the transmedia narratives. In this text and basing our experience in the most recent fictional production, we do refer to a key concept for the transmediatic narration development: the serialized form, precisely as the way of structuring and organizing the narration are reformulated in a new complex media context, and this way, the generated tensions caused by these narratives, by both the demands associated to categories of consumption related to a traditional medium which has not changed basically its consolidated protocols in the analogical era, and by the new ways of access and usage of the contents encouraged by the new technologies

Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors

Background VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer. Methods Part I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed. Results 26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1 x10(13) viral particles (vp)/patient (Part I), and 3.3x10(12) vp/patient (Part II). Fourteen patients were included in Part Ill: there were no DLTs and the RP2D was 1 x10(13) vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1x10(13) vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1 x10(13) vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon- r,soluble lymphocyte activation ne-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration. Conclusions Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paditaxel plus gemcitabine to patients with pancreatic adenocarcinoma

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

Procedimiento para la recuperación de cobre mediante lixiviación de materiales metálicos oxidados con disoluciones de carbonato de amonio

Referencia OEPM: P9600160.-- Fecha de solicitud: 24/01/1996.-- Titulares: Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Santiago de Chile, Universidad Politécnica de Madrid.Peer reviewe

VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects

Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer. Methods VCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1x10(11) viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography. Results VCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption. Conclusions VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma

Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma

Cutaneous melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors programmed death cell protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) constituted a main breakthrough in the treatment of metastatic CM, particularly for the achievement of long-term benefits. Even though it is a very promising therapy, resistance to primary immune checkpoint blockade (ICB) arises in about 70% of CM patients treated with a CTLA-4 inhibitor, and 40–65% of CM patients administered with a PD-1-targeting treatment. Some long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are implicated in triggering pro- and anti-tumorigenic responses to various cancer treatments. The relationship between lncRNAs, circRNAs and ICB immunotherapy has not been explored in cutaneous metastatic melanoma (CMM). The aim of this pilot study is to evaluate the potential role of circRNA and lncRNA expression variability as pre-treatment predictor of the clinical response to immunotherapy in CMM patients. RNA-seq from 12 formalin-fixed paraffin-embedded (FFPE) samples from the metastatic biopsies of CMM patients treated with nivolumab was used to identify response-associated transcripts. Our findings indicate that specific lncRNAs and circRNAs, probably acting as competitive endogenous RNAs (ceRNAs), are involved in the regulatory networks of the immune response against metastatic melanoma that these patients have under treatment with nivolumab. Moreover, we established a risk score that yields predictions of the overall survival (OS) and progression-free survival (PFS) of CMM patients with high accuracy. This proof-of-principle work provides a possible insight into the function of ceRNAs, contributing to efforts to decipher the complex molecular mechanisms of ICB cancer treatment response

Anales de Edafología y Agrobiología Tomo 28 Número 3-4

Los suelos ele la parte occidental del macizo ele Gredos y el problema del Rothlehm, por T. Badorrey, J. Gallardo y W. Riedel.-- Relación entre fertilidad química del suelo y análisis de la planta (I), por L. Sánchez de la Puente, F. Lucena Conde Mª P. Lobato Berciano.-- Suelos ele la zona húmeda española (V), por F. Guitián Ojea y T. Carballas.-- Coeficientes ele actividad catiónica en suelos calizos, por O. Carpena y A. Lax.-- Contribución al estudio estructura de la grasa ele Mathiola tristis, por P. Buenadicha Núñez.-- Fundamentos ele un método para el estudio ele la micrcmorfología y micromorfometría de suelos, por J. L. Guardiola y M. Delgado.-- Capacidad de cambio catiónico y balance iónico en raíces procedentes de plantas silvestres, por A. Martín y S . Oliver.-- Relación entre fertilidad química del suelo y análisis de la planta (II), por L. Sánchez de la Puente, F. Lucena Conde y Mª P. Lobato Berciano.-- Estudio de aciclos húmicos (I), por E. Dorado Bemal.-- Efectos del tratamiento por ác1clo sobre bentonita y haloisita, por T. Fernández Alvarez.—Notas.-- Homenaje en memoria ele don José María Albarecla.-- Centro ele Edafología y Biología Aplicada del Cuarto.-- Nuevos V'Ocales ele los Consejos Técnicos-Administrativos ele los Centros.-- Nueva denominación de La Mayora.-- Peticiones al Fondo Nacional para el desarrollo de la investigación científica.-- Instituto de Alimentación y Productividad Animal.-- lII Coloquio de Investigaciones sobre el Agua. Sevilla, mayo 1969.-- BibliografíaPeer reviewe