Bodies in place : enactive cognition as development of ecological norms

Les partisans de l’approche énactive soutiennent que la cognition se constitue à travers l’histoire des différentes formes d'interaction (biologique, sensorimotrice, intercorporelle, linguistique, etc.) entre un vivant et son environnement. Ces interactions ne sont pas aléatoires, mais des activités obéissant à certaines normes que les énactivistes appellent sense-making. La cognition est, de ce point de vue, une forme de sense-making. Malgré les avantages indéniables que confère une telle perspective pour étudier la cognition, la présente thèse développe un point de vue critique par rapport à l’approche énactive et soutient qu'il est nécessaire d'approfondir notre compréhension de la dimension écologique du sense-making. Le but principal de la thèse est en conséquence de montrer que l'environnement joue un rôle encore plus important que l’approche énactive ne lui attribue habituellement. En m'engageant de manière critique dans le répertoire conceptuel de la cognition énactive, de la phénoménologie et des approches écologiques de la cognition, l’objectif de cette thèse consiste à poser les bases conceptuelles d'une approche énactive-écologique de la cognition. Pour ce faire, la thèse s’attèle à mettre de l’avant trois idées principales. La première consiste à redéfinir le concept du sense-making : contrairement à la conception qui s’est traditionnellement imposée dans le mouvement énactif, nous allons démontrer qu’il s’agit d’un phénomène de développement (et non de création) de normes. La rencontre du corps et du monde est toujours ancrée dans un champ normatif prédéfini, de sorte que nous devons réévaluer le rôle que joue l'environnement dans les processus de sense-making. En effet, si les agents se retrouvent toujours-déjà plongés dans un champ normatif (et non dans un environnement purement causal et physique), il faut alors reconnaître que l'environnement joue un rôle actif dans la constitution et l'auto-transformation des normes de sense-making. La deuxième idée poursuit dans cette veine et porte sur cette nouvelle conception de l'environnement, qui est ici défini comme un champ normatif actif, incarnant une tension entre le passé habituel du système agent-environnement et les contingences incessantes des événements du monde qui poussent le système vers leur auto-transformation et développement. La troisième idée principale de cette thèse consiste en une description holistique du champ d'action des agents (un lieu énactif) et des normes édictées (enacted) par des processus de sense-making sur le terrain (normes de lieu). Une esquisse générale du lieu énactif montre que les activités de sense-making sont liées à des processus écologiques qui enchevêtrent de multiples agents et localités matérielles dans un réseau écologique local. Ces réseaux écologiques forment une unité systémique et résiliente qui se déploie dans le temps avec les habitants du lieu, et fonctionne comme un champ normatif qui contraint et motive l'auto-transformation de chaque système agent-environnementSupporters of autonomist enactivism or the enactive approach claim that cognition is a phenomenon constituted by the historical development of different forms of interaction (biological, sensorimotor, intercorporeal, and linguistic) between living bodies and their environments. For autonomist enactivists, the nature of these interactions is not entirely predetermined by general laws of causation but by norms enacted in the historical path of the agent-environment system, and thanks to processes of sense-making. Cognition is, from the enactivist standpoint, a form of sense-making. While there are multiple advantages in holding such perspective to study mind and cognition, this thesis develops a critical point of view and argues that it is necessary to deepen our understanding of the ecological dimension of sense-making. Specifically, the thesis aims to show that the environment plays a more critical role than autonomist enactivism usually attributes to it. By drawing on and critically engaging with the conceptual repertoire of enactive cognition, phenomenology, and ecological approaches to cognition, my objective is to set the conceptual foundations for an enactive-ecological approach to cognition. For this task, I propose three interrelated ideas. The first redefines sense-making as a phenomenon of norm development. The most common descriptions of sense-making involve the emergence of meaning from raw physical matter thanks to the activity of living organisms. As norm development, by contrast, sense-making refers to a constant enactment and re-enactment of norms of interaction from other pregiven norms, previously enacted in the past of the agent-environment system. I argue that the encounter of the body and the world is permanently embedded in a pregiven normative field and never in an abstract void where raw physical interactions occur. From this standpoint, we need, however, to re-evaluate the role that the environment plays in sense-making processes. If agents find themselves immersed in normative fields and not in raw physical landscapes, then the environment has a more active role for the constitution and self-transformation of sense-making norms than autonomist enactivists have acknowledged. In this vein, the second main idea of this thesis concerns the environment as an active normative field that incarnates a tension between the habitual past of the agent-environment system and the ongoing contingencies of worldly events that push the system to their self-transformation and development. The third main idea of this thesis consists of a holistic description of the field of action of agents (enactive place) and the norms enacted by processes of sense-making in the field (place-norms). A general sketch of enactive place shows that sense-making is tied to processes that entangle multiple agents and material localities into a local ecological web. An enactive place constitutes a systemic and resilient unity that unfolds in time altogether with its inhabitants, working as a normative field that constrains and motivates the self-transformation of each agent-environment system. Bodies are therefore part of wider unities of historical development: places

Twenty years of ground-based NDACC FTIR spectrometry at Izaña Observatory - overview and long-term comparison to other techniques

High-resolution Fourier transform infrared (FTIR) solar observations are particularly relevant for climate studies, as they allow atmospheric gaseous composition and multiple climate processes to be monitored in detail. In this context, the present paper provides an overview of 20 years of FTIR measurements taken in the framework of the NDACC (Network for the Detection of Atmospheric Composition Change) from 1999 to 2018 at the subtropical Izaña Observatory (IZO, Spain). Firstly, long-term instrumental performance is comprehensively assessed, corroborating the temporal stability and reliable instrumental characterization of the two FTIR spectrometers installed at IZO since 1999. Then, the time series of all trace gases contributing to NDACC at IZO are presented (i.e. C2H6, CH4, ClONO2, CO, HCl, HCN, H2CO, HF, HNO3, N2O, NO2, NO, O3, carbonyl sulfide (OCS), and water vapour isotopologues H162O, H182O, and HD16O), reviewing the major accomplishments drawn from these observations. In order to examine the quality and long-term consistency of the IZO FTIR observations, a comparison of those NDACC products for which other high-quality measurement techniques are available at IZO has been performed (i.e. CH4, CO, H2O, NO2, N2O, and O3). This quality assessment was carried out on different timescales to examine what temporal signals are captured by the FTIR records, and to what extent. After 20 years of operation, the IZO NDACC FTIR observations have been found to be very consistent and reliable over time, demonstrating great potential for climate research. Long-term NDACC FTIR data sets, such as IZO, are indispensable tools for the investigation of atmospheric composition trends, multi-year phenomena, and complex climate feedback processes, as well as for the validation of past and present space-based missions and chemistry climate models.The Izaña FTIR station has been supported by the German Bundesministerium für Wirtschaft und Energie (BMWi) via DLRunder grants 50EE1711A and by the Helmholtz Society via the research program ATMO. In addition, this research was funded by the European Research Council under FP7/(2007-2013)/ERC Grant agreement nº 256961 (project MUSICA), by the Deutsche Forschungsgemeinschaft for the project MOTIV (GeschaFTIRzeichen SCHN 1126/2-1), by the Ministerio de Economía y Competitividad from Spain through the projects CGL2012-37505 (project NOVIA) and CGL2016-80688-P (project INMENSE), and by EUMETSAT under its Fellowship Programme (project VALIASI)

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere

Izaña Atmospheric Research Center. Activity Report 2019-2020

Editors: Emilio Cuevas, Celia Milford and Oksana Tarasova.[EN]The Izaña Atmospheric Research Center (IARC), which is part of the State Meteorological Agency of Spain (AEMET), is a site of excellence in atmospheric science. It manages four observatories in Tenerife including the high altitude Izaña Atmospheric Observatory. The Izaña Atmospheric Observatory was inaugurated in 1916 and since that date has carried out uninterrupted meteorological and climatological observations, contributing towards a unique 100-year record in 2016. This reports are a summary of the many activities at the Izaña Atmospheric Research Center to the broader community. The combination of operational activities, research and development in state-of-the-art measurement techniques, calibration and validation and international cooperation encompass the vision of WMO to provide world leadership in expertise and international cooperation in weather, climate, hydrology and related environmental issues.[ES]El Centro de Investigación Atmosférica de Izaña (CIAI), que forma parte de la Agencia Estatal de Meteorología de España (AEMET), representa un centro de excelencia en ciencias atmosféricas. Gestiona cuatro observatorios en Tenerife, incluido el Observatorio de Izaña de gran altitud, inaugurado en 1916 y que desde entonces ha realizado observaciones meteorológicas y climatológicas ininterrumpidas y se ha convertido en una estación centenaria de la OMM. Estos informes resumen las múltiples actividades llevadas a cabo por el Centro de Investigación Atmosférica de Izaña. El liderazgo del Centro en materia de investigación y desarrollo con respecto a las técnicas de medición, calibración y validación de última generación, así como la cooperación internacional, le han otorgado una reputación sobresaliente en lo que se refiere al tiempo, el clima, la hidrología y otros temas ambientales afines

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

Izaña Atmospheric Research Center. Activity Report 2015-2016

This report is a summary of the many activities at the Izaña Atmospheric Research Center to the broader community. The combination of operational activities, research and development in state-of-the-art measurement techniques, calibration and validation and international cooperation encompass the vision of WMO to provide world leadership in expertise and international cooperation in weather, climate, hydrology and related environmental issues

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio