Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas

Obtained from Haematologica/the Hematology Journal website http://www.haematologica.orgPeripheral T-cell lymphomas are very aggressive hematologic malignancies for which there is no targeted therapy. New, rational approaches are necessary to improve the very poor outcome in these patients. Phosphatidylinositol- 3-kinase is one of the most important pathways in cell survival and proliferation. We hypothesized that phosphatidylinositol- 3-kinase inhibitors could be rationally selected drugs for treating peripheral T-cell lymphomas. Several phosphatidylinositol-3-kinase isoforms were inhibited genetically (using small interfering RNA) and pharmacologically (with CAL-101 and GDC-0941 compounds) in a panel of six peripheral and cutaneous T-cell lymphoma cell lines. Cell viability was measured by intracellular ATP content; apoptosis and cell cycle changes were checked by flow cytometry. Pharmacodynamic biomarkers were assessed by western blot. The PIK3CD gene, which encodes the δ isoform of phosphatidylinositol-3-kinase, was overexpressed in cell lines and primary samples, and correlated with survival pathways. However, neither genetic nor specific pharmacological inhibition of phosphatidylinositol-3-kinase δ affected cell survival. In contrast, the pan-phosphatidylinositol-3-kinase inhibitor GDC-0941 arrested all T-cell lymphoma cell lines in the G1 phase and induced apoptosis in a subset of them. We identified phospho-GSK3b and phospho-p70S6K as potential biomarkers of phosphatidylinositol-3-kinase inhibitors. Interestingly, an increase in ERK phosphorylation was observed in some GDC-0941-treated T-cell lymphoma cell lines, suggesting the presence of a combination of phosphatidylinositol-3-kinase and MEK inhibitors. A highly synergistic effect was found between the two inhibitors, with the combination enhancing cell cycle arrest at G0/G1 in all T-cell lymphoma cell lines, and reducing cell viability in primary tumor T cells ex vivo. These results suggest that the combined treatment of pan-phosphatidylinositol-3-kinase + MEK inhibitors could be more effective than single phosphatidylinositol-3-kinase inhibitor treatment, and therefore, that this combination could be of therapeutic value for treating peripheral and cutaneous T-cell lymphomas.This work was supported by grants from the Asociación Española Contra el Cáncer, Fondo de Investigaciones Sanitarias (PI051623, PI052800 and PI080856), RTICC (RD06/0020/0107) and Ministerio de Ciencia e Innovación (SAF2008-0387-1). EMS is supported by a grant from the Department of Education, Universities and Research of the Basque Government (BFI08.207). MSB is supported by a Contract Miguel Servet from Fondo de Investigaciones Sanitarias (CP11/00018

La ganadería ante escenarios complejos.

La calidad de las contribuciones, producto de la pluma de especialistas en los temas tratados, el presente es un libro que esperamos, basándonos en la importancia de los temas tratados, sea de utilidad y abone a la reflexión de los estudiosos de la ganadería mexicana y, por supuesto, en beneficio de las familias ganaderas y de los consumidores de sus productos.este libro refleja en muchos sentidos la situación de la ganadería mexicana, a la que se le están demandando mayor producción y productividad, que los procesos productivos tengan la menor huella ecológicposible, que los alimentos sean inocuos, que se abatan costos de producción y, cada vez aumentan las presiones de diversos grupos para, que se incluyan los protocolos de bienestar animal, solamente por citar algunos de los retos que tiene. Algunas de estas demandas son complementarias, otras se contraponen, lo que hace valiosos a los estudios que desde las ciencias sociales se realizan y, desde diversas ópticas, se hagan propuestas de política pública balanceadas que consideren lo mejor de cada enfoque, pero sin desechar por completo los antagónicos.Universidad Autónoma Chaping

Совместная работа в виртуальных средах с помощью проблемно-ориентированного обучения

El objetivo es potenciar una competencia crucial como es el trabajo colaborativo y en equipo de los alumnos mediante la utilización de entornos virtuales en el aprendizaje en las enseñanzas universitarias basado en problemas Resulta innegable que el trabajo en equipo y colaborativo fomenta la motivación de los estudiantes y favorece el aprendizaje, debido al propio efecto social que genera la pertenencia a un grupo. Contribuyendo, asimismo, al desarrollo de la capacidad de debate y argumentación, el razonamiento crítico y creativo o la organización de procesos de trabajo complejos, entre otras muchas competencias esenciales. El proyecto pone el foco en el trabajo colaborativo en entornos digitales dentro del aprendizaje basado en problemas y persigue favorecer un modelo de aprendizaje más participativo, mediante el uso de los recursos que nos ofrecen las nuevas tecnologías de la comunicación, aumentando la interacción de los estudiantes, incluso en entornos digitales. El trabajo colaborativo supone la creación de grupos integrados por varios estudiantes con, a priori, el mismo nivel formativo, y con una asunción compartida del liderazgo y la responsabilidad en el proceso de aprendizaje. El trabajo colaborativo se basa, además, en la autonomía de trabajo de sus integrantes que presentan funcionalidades y competencias heterogéneas, y que tienen que desarrollar y fortalecer elementos como la confianza, la comunicación, la gestión de conflictos y solución de problemas y la adopción de decisiones.The aim is to enhance a crucial competence such as collaborative and teamwork of students through the use of virtual environments in problem-based learning in university education. It is undeniable that team and collaborative work fosters students' motivation and favours learning, due to the very social effect that belonging to a group generates. It also contributes to the development of debate and argumentation skills, critical and creative reasoning or the organisation of complex work processes, among many other essential competences. The project focuses on collaborative work in digital environments within problem-based learning and aims to promote a more participatory learning model, through the use of the resources offered by new communication technologies, increasing student interaction, even in digital environments. Collaborative work involves the creation of groups made up of several students with, a priori, the same level of training, and with a shared assumption of leadership and responsibility in the learning process. Collaborative work is also based on the working autonomy of its members, who have heterogeneous functionalities and competences, and who have to develop and strengthen elements such as trust, communication, conflict management and problem solving and decision-making.L'obiettivo è quello di migliorare una competenza cruciale come il lavoro collaborativo e di gruppo degli studenti attraverso l'uso di ambienti virtuali nell'apprendimento basato su problemi nell'istruzione universitaria. È innegabile che il lavoro di gruppo e collaborativo promuova la motivazione degli studenti e favorisca l'apprendimento, proprio per l'effetto sociale che l'appartenenza a un gruppo genera. Contribuisce inoltre allo sviluppo delle capacità di discussione e argomentazione, del ragionamento critico e creativo o dell'organizzazione di processi di lavoro complessi, oltre a molte altre competenze essenziali. Il progetto si concentra sul lavoro collaborativo in ambienti digitali nell'ambito dell'apprendimento basato su problemi e mira a promuovere un modello di apprendimento più partecipativo, attraverso l'uso delle risorse offerte dalle nuove tecnologie di comunicazione, aumentando l'interazione degli studenti, anche in ambienti digitali. Il lavoro collaborativo prevede la creazione di gruppi composti da più studenti con, a priori, lo stesso livello di formazione e con un'assunzione condivisa di leadership e responsabilità nel processo di apprendimento. Il lavoro collaborativo si basa anche sull'autonomia di lavoro dei suoi membri, che hanno funzionalità e competenze eterogenee e devono sviluppare e rafforzare elementi come la fiducia, la comunicazione, la gestione dei conflitti, la risoluzione dei problemi e il processo decisionale.L'objectif est d'améliorer une compétence cruciale telle que le travail collaboratif et d'équipe des étudiants par l'utilisation d'environnements virtuels dans l'apprentissage par problème dans l'enseignement universitaire. Il est indéniable que le travail en équipe et en collaboration stimule la motivation des élèves et favorise l'apprentissage, en raison de l'effet social même que génère l'appartenance à un groupe. Elle contribue également au développement des capacités de débat et d'argumentation, du raisonnement critique et créatif ou de l'organisation de processus de travail complexes, parmi de nombreuses autres compétences essentielles. Le projet se concentre sur le travail collaboratif dans les environnements numériques dans le cadre de l'apprentissage par problèmes et vise à promouvoir un modèle d'apprentissage plus participatif grâce à l'utilisation des ressources offertes par les nouvelles technologies de communication, en augmentant l'interaction des étudiants, même dans les environnements numériques. Le travail collaboratif implique la création de groupes composés de plusieurs étudiants ayant, a priori, le même niveau de formation, et assumant ensemble le leadership et la responsabilité du processus d'apprentissage. Le travail collaboratif repose également sur l'autonomie de travail de ses membres, qui ont des fonctionnalités et des compétences hétérogènes, et qui doivent développer et renforcer des éléments tels que la confiance, la communication, la gestion des conflits, la résolution de problèmes et la prise de décision.Ziel ist es, durch den Einsatz virtueller Umgebungen beim problembasierten Lernen in der Hochschulbildung eine entscheidende Kompetenz wie die Zusammenarbeit und die Teamarbeit von Studierenden zu fördern. Es ist unbestreitbar, dass Team- und Kooperationsarbeit die Motivation der Schüler fördert und das Lernen begünstigt, und zwar aufgrund des sozialen Effekts, den die Zugehörigkeit zu einer Gruppe bewirkt. Sie trägt auch zur Entwicklung von Diskussions- und Argumentationsfähigkeiten, kritischem und kreativem Denken oder der Organisation komplexer Arbeitsprozesse bei, neben vielen anderen wichtigen Kompetenzen. Das Projekt konzentriert sich auf die kollaborative Arbeit in digitalen Umgebungen im Rahmen des problembasierten Lernens und zielt darauf ab, ein partizipativeres Lernmodell zu fördern, indem die von den neuen Kommunikationstechnologien gebotenen Ressourcen genutzt werden und die Interaktion zwischen den Studierenden auch in digitalen Umgebungen verstärkt wird. Bei der Zusammenarbeit werden Gruppen gebildet, die sich aus mehreren Studenten zusammensetzen, die von vornherein das gleiche Ausbildungsniveau haben und die gemeinsam die Leitung und Verantwortung für den Lernprozess übernehmen. Die Zusammenarbeit beruht auch auf der Arbeitsautonomie ihrer Mitglieder, die über heterogene Funktionen und Kompetenzen verfügen und Elemente wie Vertrauen, Kommunikation, Konfliktmanagement, Problemlösung und Entscheidungsfindung entwickeln und stärken müssen.O objectivo é reforçar uma competência crucial como a colaboração e o trabalho de equipa dos estudantes através da utilização de ambientes virtuais na aprendizagem baseada em problemas no ensino universitário. É inegável que o trabalho em equipa e em colaboração promove a motivação dos estudantes e favorece a aprendizagem, devido ao próprio efeito social que a pertença a um grupo gera. Também contribui para o desenvolvimento de capacidades de debate e argumentação, de raciocínio crítico e criativo ou para a organização de processos de trabalho complexos, entre muitas outras competências essenciais. O projecto centra-se no trabalho colaborativo em ambientes digitais no âmbito da aprendizagem baseada em problemas e visa promover um modelo de aprendizagem mais participativo através da utilização dos recursos oferecidos pelas novas tecnologias de comunicação, aumentando a interacção dos estudantes, mesmo em ambientes digitais. O trabalho colaborativo envolve a criação de grupos compostos por vários estudantes com, a priori, o mesmo nível de formação, e com uma assunção partilhada de liderança e responsabilidade no processo de aprendizagem. O trabalho colaborativo baseia-se também na autonomia de trabalho dos seus membros, que têm funcionalidades e competências heterogéneas, e que têm de desenvolver e reforçar elementos tais como confiança, comunicação, gestão de conflitos e resolução de problemas e tomada de decisões.Цель - повысить такую важную компетенцию, как совместная и командная работа студентов посредством использования виртуальных сред в проблемно-ориентированном обучении в университетском образовании. Неоспоримо, что командная и совместная работа повышает мотивацию учащихся и способствует обучению, благодаря тому самому социальному эффекту, который порождает принадлежность к группе. Она также способствует развитию навыков ведения дискуссий и аргументации, критического и творческого мышления или организации сложных рабочих процессов, а также многих других важных компетенций. Проект сосредоточен на совместной работе в цифровой среде в рамках проблемно-ориентированного обучения и направлен на продвижение модели обучения с более широким участием, посредством использования ресурсов, предлагаемых новыми коммуникационными технологиями, увеличивая взаимодействие студентов даже в цифровой среде. Совместная работа предполагает создание групп, состоящих из нескольких студентов, имеющих априори одинаковый уровень подготовки, и совместно принимающих на себя руководство и ответственность в процессе обучения. Совместная работа также основана на рабочей автономии ее членов, которые обладают разнородными функциональными возможностями и компетенциями, и которые должны развивать и укреплять такие элементы, как доверие, коммуникация, управление конфликтами, решение проблем и принятие решений.Depto. de Derecho del Trabajo y Seguridad SocialFac. de DerechoFALSEUniversidad Complutense de Madridsubmitte

En marcha con las TIC : recopilación de un año de noticias TICs

Se recopilan aportaciones de docentes extremeños que han llevado a cabo iniciativas relacionadas con las nuevas tecnologías, el acceso libre a la información y el software libre. Se describen los proyectos llevados a cabo por la administración educativa extremeña para promocionar el uso de las tecnologías de la información y la comunicación, entre otras: la plataforma educativa Rayuela, el proyecto de formación a distancia Avanza, el portal del docente Profex, etc..ExtremaduraConsejería de Educación. Dirección General de Política Educativa; Calle Delgado Valencia, 6; 06800 Mérida (Badajoz); +34924006714; +34924006716; [email protected]

Effects of climate and atmospheric nitrogen deposition on early to mid-term stage litter decomposition across biomes

International audienceLitter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1– 3.5% and of the more stable substrates by 3.8–10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4–2.2% and that of low-quality litter by 0.9–1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)