Search

Background: Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after individuals reach maturity. These changes have been sometimes interpreted as a compensatory sign and others as a fingerprint of deterioration. Objective: In this context, our aim is to uncover the mechanisms that underlie and support normal cognitive functioning in the brain during the later stages of life. Methods: With this purpose, a systematic literature search was conducted using PubMed, Scopus, and Web of Science databases, which identified 781 potential articles. After applying inclusion and exclusion criteria, we selected 12 studies that examined the brain oscillations patterns in resting-state conditions associated with cognitive performance in cognitively unimpaired older adults. Results: Although cognitive healthy aging was characterized differently across studies, and various approaches to analyzing brain activity were employed, our review indicates a relationship between alpha peak frequency (APF) and improved performance in neuropsychological scores among cognitively unimpaired older adults. Conclusions: A higher APF is linked with a higher score in intelligence, executive function, and general cognitive performance, and could be considered an optimal, and easy-to-assess, electrophysiological marker of cognitive health in older adults.

Aquesta tesi realitza una recerca exhaustiva sobre els paràmetres de densitat espectral (DSA) en dispositius de monitoratge de la profunditat anestèsica (DoA), posant l’accent en la seva aplicació en el dispositiu de monitoratge CONOX® (Quantium Medical S.L.), considerant les seves pròpies particularitats. L’objectiu és desenvolupar una solució personalitzada considerant les inter-variabilitats entre pacients, per a finalment proporcionar una eina útil per a l’avaluació de la pràctica anestèsica i la pèrdua de consciència (LOC) en un entorn quirúrgic. La metodologia seguida inclou una anàlisi de les profunditats de byte (1B, 2B i 3B) i diversos valors alfa en el promitjat exponencial, per a determinar el millor ajust per a les dades de l’EEG i els interessos de l’empresa, que va donar com a resultat la selecció d’1 byte de profunditat i un promitjat amb una alfa de 0.2. A més, es proposen i analitzen 11 equacions per a millorar el reescalat de l’EEG sense processar, proporcionant una solució depenent de l’edat per a quatre rangs establerts entre 16 i 93 anys, la qual cosa facilita una visualització òptima de l’espectrograma, seleccionant tres equacions per a cada rang d’edat; una equació per defecte per a la majoria dels pacients, una equació de saturació vermella per a pacients amb baixa energia d’EEG, i una equació de saturació blava per a pacients amb alta energia d’EEG, permetent pivotar entre equacions en temps real quan sigui necessari., Esta tesis realiza una investigación exhaustiva sobre los parámetros del arreglo de densidad espectral (DSA) en dispositivos de monitorización de la profundidad anestésica (DoA), haciendo un especial énfasis en su aplicación en el dispositivo de monitorización CONOX® (Quantium Medical, S.L.), considerando sus propias particularidades. El objetivo es desarrollar una solución personalizada para la optimización de la visualización del espectrograma de la señal del electroencefalograma (EEG), considerando las inter-variabilidades del paciente, para finalmente proporcionar una herramienta útil para la evaluación de la práctica anestésica y la pérdida de consciencia (LOC) en un entorno quirúrgico. La metodología seguida incluye un análisis de las profundidades de bytes (1B, 2B, 2B) y varios valores de alfa en el promediado exponencial, para determinar el mejor ajuste para los datos del EEG y la empresa, que dio como resultado la selección de 1 profundidad de byte y un alfa de promediado de 0.2. Además, se postulan y analizan 11 ecuaciones para mejorar el re-escalado del EEG sin procesar, proporcionando una solución dependiente de la edad para cuatro rangos que abarcan desde los 16 años hasta los 93, lo que facilitaría una visualización óptima del espectrograma, seleccionando tres de las ecuaciones propuestas para cada rango de edad; una ecuación por defecto para la mayoría de casos, una ecuación de saturación roja para pacientes con baja energía de EEG, y una ecuación de saturación azul para pacientes con alta energía de EEG, permitiendo pivotar entre ecuaciones durante el tiempo real cuando sea necesario., This thesis undertakes a thorough investigation on the Density Spectral Array (DSA) parameters in Depth of Anesthesia (DoA) monitoring devices, emphasizing its application on the CONOX® (Quantium Medical S.L) monitoring device, by considering its own particularities. The aim is to develop a personalized solution for the optimization of the spectrogram visualization of the electroencephalogram (EEG) signal, considering patient inter-variabilities, to finally provide a useful tool for the assessment of the anesthesia practice and Loss of Consciousness (LOC) on a surgical environment. The followed methodology includes an analysis of 1B, 2B and 3B byte depths and several alpha values in exponential averaging, to determine the best fit for the EEG data and the company’s interests, which resulted in the selection of 1 byte depth and an averaging alpha of 0.2. Furthermore, 11 equations are postulated and analyzed to improve the rescaling of the raw EEG, providing an age-dependent solution for four age ranges covering from 16 years old to 93, which facilitates an optimal visualization of the spectrogram, by selecting three equations for each age range; a default equation for majority of cases, a red saturating equation for low EEG energy patients, and a blue saturating equation for high EEG energy patient, allowing to pivot between equations during real time when required.

The Memory stress (Mess) framework provides a unified view of the memory system benchmarking, simulation and application profiling. The Mess benchmark provides a holistic and detailed memory system characterization. It is based on hundreds of measurements that are represented as a family of bandwidth--latency curves. The benchmark increases the coverage of all the previous tools and leads to new findings in the behavior of the actual and simulated memory systems. We deploy the Mess benchmark to characterize Intel, AMD, IBM, Fujitsu, Amazon and NVIDIA servers with DDR4, DDR5, HBM2 and HBM2E memory. The Mess memory simulator uses bandwidth--latency concept for the memory performance simulation. We integrate Mess with widely-used CPUs simulators enabling modeling of all high-end memory technologies. The Mess simulator is fast, easy to integrate and it closely matches the actual system performance. By design, it enables a quick adoption of new memory technologies in hardware simulators. Finally, the Mess application profiling positions the application in the bandwidth--latency space of the target memory system. This information can be correlated with other application runtime activities and the source code, leading to a better overall understanding of the application's behavior. The current Mess benchmark release covers all major CPU and GPU ISAs, x86, ARM, Power, RISC-V, and NVIDIA's PTX. We also release as open source the ZSim, gem5 and OpenPiton Metro-MPI integrated with the Mess memory simulator for DDR4, DDR5, Optane, HBM2, HBM2E and CXL memory expanders. The Mess application profiling is already integrated into a suite of production HPC performance analysis tools., Comment: 17 pages

This thesis presents a thorough comparison between Sliding Mode Control and FieldOriented Control. The primary objective is to design, develop, and simulate both control systems to regulate the mechanical speed of a Permanent Magnet Synchronous Motor. To highlight their strengths and weaknesses, both controllers will be tested not only in a simulated environment but also during operation after their implementation. This document covers all necessary steps, from acquiring the machine?s mathematical model and designing each control technique to implementing both control systems., Esta tesis presenta una comparación exhaustiva entre el Control en Modo de Deslizamiento (Sliding Mode Control) y el Control Orientado a Campo (Field-Oriented Control). El objetivo principal es diseñar, desarrollar y simular ambos sistemas de control para regular la velocidad mecánica de un Motor Síncrono de Imán Permanente. Con el fin de resaltar sus fortalezas y debilidades, ambos controladores serán probados no solo en un entorno simulado, sino también durante su funcionamiento después de su implementación. Este documento cubre todos los pasos necesarios, desde la adquisición del modelo matemático de la máquina y el diseño de cada técnica de control hasta la implementación de ambos sistemas de control., Aquesta tesi presenta una comparació exhaustiva entre el Control en Mode de Desplaçament (Sliding Mode Control) i el Control Orientat a Camp (Field-Oriented Control). L'objectiu principal és dissenyar, desenvolupar i simular tots dos sistemes de control per regular la velocitat mecànica d'un Motor Síncron de Magnets Permanents. Per destacar els seus punts forts i febles, tots dos controladors seran provats no només en un entorn de simulació, sinó també durant el funcionament després de la seva implementació. Aquest document cobreix tots els passos necessaris, des de l'adquisició del model matemàtic de la màquina i el disseny de cada tècnica de control fins a la implementació dels dos sistemes de control.

This perspective piece on aerosol deposition to marine ecosystems and the related impacts on biogeochemical cycles forms part of a larger Surface Ocean Lower Atmosphere Study status-of-the-science special edition. A large body of recent reviews has comprehensively covered different aspects of this topic. Here, we aim to take a fresh approach by reviewing recent research to identify potential foundations for future study. We have purposefully chosen to discuss aerosol nutrient and pollutant fluxes both in terms of the journey that different aerosol particles take and that of the surrounding scientific field exploring them. To do so, we explore some of the major tools, knowledge, and partnerships we believe are required to aid advancing this highly interdisciplinary field of research. We recognize that significant gaps persist in our understanding of how far aerosol deposition modulates marine biogeochemical cycles and thus climate. This uncertainty increases as socioeconomic pressures, climate change, and technological advancements continue to change how we live and interact with the marine environment. Despite this, recent advances in modeling techniques, satellite remote sensing, and field observations have provided valuable insights into the spatial and temporal variability of aerosol deposition across the world’s ocean. With the UN Ocean Decade and sustainable development goals in sight, it becomes essential that the community prioritizes the use of a wide variety of tools, knowledge, and partnerships to advance understanding. It is through a collaborative and sustained effort that we hope the community can address the gaps in our understanding of the complex interactions between aerosol particles, marine ecosystems, and biogeochemical cycles., This publication resulted in part from support from the U.S. National Science Foundation (Grant OCE-1840868) to the Scientific Committee on Oceanic Research. DSH acknowledges that this work was supported by North Carolina State University. ARB was funded by the UK Natural Environment Research Council (grant NE/V001213/1). JL was funded by the European Space Agency—LPF (No. 4000135579/21/I-DT-lr) and the Barcelona Supercomputing Centre. SM acknowledges support by the project “PANhellenic infrastructure for Atmospheric Composition and climatE change” (MIS 5021516) implemented under the Action “Reinforcement of the Research and Innovation Infrastructure,” which is funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and cofinanced by Greece and the European Union (European Regional Development Fund) and the National Infrastructures for Research and Technology S.A. (GRNET S.A.) in the National HPC facility ARIS for computational time granted under project ID 010003 (ANION). MMGP acknowledges that this work was supported by the Interdisciplinary graduate school for the blue planet (ISBlue, ANR-17-EURE-0015) and cofunded by a grant from the French government under the program “Investissements d’Avenir” embedded in France 2030., Peer Reviewed, Postprint (published version)

At high latitudes, the biological carbon pump, which exports organic matter from the surface ocean to the interior, has been attributed to the gravitational sinking of particulate organic carbon. Conspicuous deficits in ocean carbon budgets challenge this as a sole particle export pathway. Recent model estimates revealed that particle injection pumps have a comparable downward flux of particulate organic carbon to the biological gravitational pump, but with different seasonality. To date, logistical constraints have prevented concomitant and extensive observations of these mechanisms. Here, using year-round robotic observations and recent advances in bio-optical signal analysis, we concurrently investigated the functioning of two particle injection pumps, the mixed layer and eddy subduction pumps, and the gravitational pump in Southern Ocean waters. By comparing three annual cycles in contrasting physical and biogeochemical environments, we show how physical forcing, phytoplankton phenology and particle characteristics influence the magnitude and seasonality of these export pathways, with implications for carbon sequestration efficiency over the annual cycle., L.L. was supported by a European Union’s Horizon 2020 Marie Sklodowska-Curie grant (no. 892653). Visits by L.L. to IMAS/UTas were supported by the Australian Research Council Special Research Initiative for Antarctic Gateway Partnership (Project ID SR140300001), the Australian Research Council Centre of Excellence for Climate System Science (Project ID B0018492), and the UTas visiting scholar program. J.L. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 754433. N.B. was supported by a European Research Council Consolidator Grant (GOCART, agreement number 724416). P.S. was supported by the Australian Research Council Centre of Excellence for Climate Extremes (Project ID CE170100023). P.W.B. was funded by the Australian Research Council by Laureate Fellowship FL160100131. We thank the Argo Data Management team (ADMT) and the BGC-Argo Data Management team (BGC ADMT). The specific float used in this study was funded by the ARC SRI for Antarctic Gateway Partnership (Project ID SR140300001). We thank the captain and crew of RV Investigator voyage IN2016_V03 and chief scientists Bernadette Sloyan and Susan Wijffels for deploying the float., Peer Reviewed, Postprint (published version)

El present estudi té com a objecte la creació d’una nova empresa, que estarà dedicada al sector de la restauració, concretament una pizzeria. Aquest ha estat realitzat a Itàlia, el país d’on és originari aquest producte, per a així obtenir dades i informació de font primària, concretament a la ciutat de Palermo, que és on s’ha basat tot el desenvolupament de la creació d’ambdós negocis. S’ha dut a terme la creació d’una pizzeria tradicional, la creació d’una pizzeria en model delivery, i posteriorment la comparació d’aquestes; estudiant la viabilitat econòmica, costos, ingressos, punts morts; característiques del servei i del producte; impactes socials i ambientals, i facilitat davant canvis sobtats. Aquest estudi s’ha dut a terme atès el sobtat creixement que van patir els restaurants de model delivery durant la pandèmia de COVID-19, i que ha causat un impacte en els models de negoci tradicional, motiu pel qual es fa aquesta comparació, per a finalment concloure si un dels dos models és més sostenible que l’altre o poden conviure, i que les conclusions obtingudes serveixen per a futurs empresaris que vulguin començar un negoci en aquest sector, o com a punt de partida en altres estudis més avançats.

This perspective piece on aerosol deposition to marine ecosystems and the related impacts on biogeochemical cycles forms part of a larger Surface Ocean Lower Atmosphere Study status-of-the-science special edition. A large body of recent reviews has comprehensively covered different aspects of this topic. Here, we aim to take a fresh approach by reviewing recent research to identify potential foundations for future study. We have purposefully chosen to discuss aerosol nutrient and pollutant fluxes both in terms of the journey that different aerosol particles take and that of the surrounding scientific field exploring them. To do so, we explore some of the major tools, knowledge, and partnerships we believe are required to aid advancing this highly interdisciplinary field of research. We recognize that significant gaps persist in our understanding of how far aerosol deposition modulates marine biogeochemical cycles and thus climate. This uncertainty increases as socioeconomic pressures, climate change, and technological advancements continue to change how we live and interact with the marine environment. Despite this, recent advances in modeling techniques, satellite remote sensing, and field observations have provided valuable insights into the spatial and temporal variability of aerosol deposition across the world’s ocean. With the UN Ocean Decade and sustainable development goals in sight, it becomes essential that the community prioritizes the use of a wide variety of tools, knowledge, and partnerships to advance understanding. It is through a collaborative and sustained effort that we hope the community can address the gaps in our understanding of the complex interactions between aerosol particles, marine ecosystems, and biogeochemical cycles.

The ocean plays a central role in modulating the Earth’s carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and light

At high latitudes, the biological carbon pump, which exports organic matter from the surface ocean to the interior, has been attributed to the gravitational sinking of particulate organic carbon. Conspicuous deficits in ocean carbon budgets challenge this as a sole particle export pathway. Recent model estimates revealed that particle injection pumps have a comparable downward flux of particulate organic carbon to the biological gravitational pump, but with different seasonality. To date, logistical constraints have prevented concomitant and extensive observations of these mechanisms. Here, using year-round robotic observations and recent advances in bio-optical signal analysis, we concurrently investigated the functioning of two particle injection pumps, the mixed layer and eddy subduction pumps, and the gravitational pump in Southern Ocean waters. By comparing three annual cycles in contrasting physical and biogeochemical environments, we show how physical forcing, phytoplankton phenology and particle characteristics influence the magnitude and seasonality of these export pathways, with implications for carbon sequestration efficiency over the annual cycle.

The ocean plays a central role in modulating the Earth’s carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and light, The ocean plays a central role in modulating the Earth's carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and li

The ocean plays a central role in modulating the Earth’s carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and light, The ocean plays a central role in modulating the Earth's carbon cycle. Monitoring how the ocean carbon cycle is changing is fundamental to managing climate change. Satellite remote sensing is currently our best tool for viewing the ocean surface globally and systematically, at high spatial and temporal resolutions, and the past few decades have seen an exponential growth in studies utilising satellite data for ocean carbon research. Satellite-based observations must be combined with in-situ observations and models, to obtain a comprehensive view of ocean carbon pools and fluxes. To help prioritise future research in this area, a workshop was organised that assembled leading experts working on the topic, from around the world, including remote-sensing scientists, field scientists and modellers, with the goal to articulate a collective view of the current status of ocean carbon research, identify gaps in knowledge, and formulate a scientific roadmap for the next decade, with an emphasis on evaluating where satellite remote sensing may contribute. A total of 449 scientists and stakeholders participated (with balanced gender representation), from North and South America, Europe, Asia, Africa, and Oceania. Sessions targeted both inorganic and organic pools of carbon in the ocean, in both dissolved and particulate form, as well as major fluxes of carbon between reservoirs (e.g., primary production) and at interfaces (e.g., air-sea and land–ocean). Extreme events, blue carbon and carbon budgeting were also key topics discussed. Emerging priorities identified include: expanding the networks and quality of in-situ observations; improved satellite retrievals; improved uncertainty quantification; improved understanding of vertical distributions; integration with models; improved techniques to bridge spatial and temporal scales of the different data sources; and improved fundamental understanding of the ocean carbon cycle, and of the interactions among pools of carbon and li

[EN] Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB1 receptor-mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naive rats, assessed in passive avoidance (PA) test in a non-reinforced manner. Then, we evaluated the effect of gentle handling and non-aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB1 mediated-signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories.

Altres ajuts: Acord transformatiu CRUE-CSIC, This work was supported by the Spanish Ministry of Economy and Business (BFU2014-55459 and BFU2017-87843-R)., The subgranular zone of the dentate gyrus is an adult neurogenic niche where new neurons are continuously generated. A dramatic hippocampal neurogenesis decline occurs with increasing age, contributing to cognitive deficits. The process of neurogenesis is intimately regulated by the microenvironment, with inflammation being considered a strong negative factor for this process. Thus, we hypothesize that the reduction of new neurons in the aged brain could be attributed to the age-related microenvironmental changes towards a pro-inflammatory status. In this work, we evaluated whether an anti-inflammatory microenvironment could counteract the negative effect of age on promoting new hippocampal neurons. Surprisingly, our results show that transgenic animals chronically overexpressing IL-10 by astrocytes present a decreased hippocampal neurogenesis in adulthood. This results from an impairment in the survival of neural newborn cells without differences in cell proliferation. In parallel, hippocampal-dependent spatial learning and memory processes were affected by IL-10 overproduction as assessed by the Morris water maze test. Microglial cells, which are key players in the neurogenesis process, presented a different phenotype in transgenic animals characterized by high activation together with alterations in receptors involved in neuronal communication, such as CD200R and CX3CR1. Interestingly, the changes described in adult transgenic animals were similar to those observed by the effect of normal aging. Thus, our data suggest that chronic IL-10 overproduction mimics the physiological age-related disruption of the microglia-neuron dialogue, resulting in hippocampal neurogenesis decrease and spatial memory impairment.

Subjective cognitive complaints correspond to a heterogeneous construct that frequently occurs in the early stages of older adult life. Despite being a common source of worry for middle-aged people, it can be underestimated when clinical and neuropsychological assessments discard any underlying pathological processes. Negative age stereotyping but also self-stereotyping can contribute to doing so. Although its diagnosis is a challenge, its implication as a possible predictor of mild cognitive impairment or dementia increases the interest in its early diagnosis and intervention. The present systematic review analyzes the empirical data on the relationship between these complaints and early executive dysfunction with possible predictive value for preclinical stages of dementia. The sixteen papers obtained from the PubMed and Embase databases were exploratory, cross-sectional and prospective in scope. The studies corroborated the relationship between subjective cognitive complaints and some executive processes, which is noteworthy since many people with subjective executive complaints progress to dementia. The relational studies confirmed that impaired executive performance is associated with CSF biomarkers and reduced cortical volume in specific brain regions. However, the heterogeneity of reports in these studies demands stronger efforts in future research with specific tools applied in clinical and neuropsychological assessments and analyzed under a gender perspective.

BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHOD(S): We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULT(S): Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0-17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSION(S): We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.

[EN] Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB1 receptor-mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naive rats, assessed in passive avoidance (PA) test in a non-reinforced manner. Then, we evaluated the effect of gentle handling and non-aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB1 mediated-signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories.

BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHODS: We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULTS: Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0–17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSIONS: We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.

When working with Earth system models, a considerable challenge that arises is the need to establish the set of parameter values that ensure the optimal model performance in terms of how they reflect real-world observed data. Given that each additional parameter under investigation increases the dimensional space of the problem by one, simple brute-force sensitivity tests can quickly become too computationally strenuous. In addition, the complexity of the model and interactions between parameters mean that testing them on an individual basis has the potential to miss key information. In this work, we address these challenges by developing a biased random key genetic algorithm (BRKGA) able to estimate model parameters. This method is tested using the one-dimensional configuration of PISCES-v2_RC, the biogeochemical component of NEMO4 v4.0.1 (Nucleus for European Modelling of the Ocean version 4), a global ocean model. A test case of particulate organic carbon (POC) in the North Atlantic down to 1000 m depth is examined, using observed data obtained from autonomous biogeochemical Argo floats. In this case, two sets of tests are run, namely one where each of the model outputs are compared to the model outputs with default settings and another where they are compared with three sets of observed data from their respective regions, which is followed by a cross-reference of the results. The results of these analyses provide evidence that this approach is robust and consistent and also that it provides an indication of the sensitivity of parameters on variables of interest. Given the deviation in the optimal set of parameters from the default, further analyses using observed data in other locations are recommended to establish the validity of the results obtained., This research has been supported by the Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona (grant no. LCF/BQ/PI18/11630009) and the Ministerio de Ciencia e Innovación (grant nos. PID2019-107952GA-I00 and CGL2017-84493-R)., Peer Reviewed, Postprint (published version)

[EN] Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB1 receptor-mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naive rats, assessed in passive avoidance (PA) test in a non-reinforced manner. Then, we evaluated the effect of gentle handling and non-aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB1 mediated-signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories.

When working with Earth system models, a considerable challenge that arises is the need to establish the set of parameter values that ensure the optimal model performance in terms of how they reflect real-world observed data. Given that each additional parameter under investigation increases the dimensional space of the problem by one, simple brute-force sensitivity tests can quickly become too computationally strenuous. In addition, the complexity of the model and interactions between parameters mean that testing them on an individual basis has the potential to miss key information. In this work, we address these challenges by developing a biased random key genetic algorithm (BRKGA) able to estimate model parameters. This method is tested using the one-dimensional configuration of PISCES-v2_RC, the biogeochemical component of NEMO4 v4.0.1 (Nucleus for European Modelling of the Ocean version 4), a global ocean model. A test case of particulate organic carbon (POC) in the North Atlantic down to 1000 m depth is examined, using observed data obtained from autonomous biogeochemical Argo floats. In this case, two sets of tests are run, namely one where each of the model outputs are compared to the model outputs with default settings and another where they are compared with three sets of observed data from their respective regions, which is followed by a cross-reference of the results. The results of these analyses provide evidence that this approach is robust and consistent and also that it provides an indication of the sensitivity of parameters on variables of interest. Given the deviation in the optimal set of parameters from the default, further analyses using observed data in other locations are recommended to establish the validity of the results obtained

El libro recoge de manera amplia y detallada muchas de las reflexiones necesarias sobre la compleja relación entre la utilización de medicamentos y su relación con los procesos culturales y sociales. Enfatiza desde el inicio la relación ancestral y universal de estos tres elementos y su inevitable condicionamiento con el sistema salud/enfermedad/atención-prevención (s/m/ap) que caracteriza todas las sociedades humanas y desde el cual pueden analizarse la mayoría de contradicciones y conflictos económico-políticos e ideológico-culturales. Aunque su publicación se produce en los primeros meses de la pandemia por SARS-CoV-2, en noviembre de 2020, su contenido y elaboración fueron gestados antes de la aparición de la pandemia. Este acontecimiento fortuito no quita importancia al análisis que el libro esgrime frente a las nuevas perspectivas que en salud global se nos plantean; al contrario, presenta las bases reflexivas necesarias para afrontar y analizar, ahora más que nunca, realidades como la de la COVID-19 y, quién sabe, crisis venideras: la progresiva crisis de los sistemas públicos de protección, la emergencia de discursos populistas cada vez más presentes, el desprestigio de la atención primaria frente a la idealización del sistema hospitalario y una progresiva medicalización de la sociedad o también un acuciante proceso de polarización social, que pone en evidencia las desigualdades estructurales cada vez más violentas y palpables.

The secondary impacts of the COVID-19 pandemic are distress triggers and risk factors for mental health. Conversely, self-compassion skills and compassionate thoughts/behaviors towards suffering may contribute to their alleviation. Both psychological constructs are interrelated in life-threatening diseases such as multiple sclerosis (MS). The Teruel Study retrospectively evaluated the impact of strict confinement on the 44 people with MS of this Spanish province and 24 caregivers, specifically assessing (1) fears and perceptions; (2) self-compassion (people with MS) and compassion (caregivers); (3) physical and mental health, and fatigue. Despite better housing conditions, people with MS considered confinement very difficult to handle, more than their caregivers, but they were less afraid of COVID-19 and worsening of MS. Still, they recognized worse health than before confinement. Reclusion and lack of walks were the worst of confinement. Caregivers also referred to lack of leisure and uncertainty–fear. All agreed the best was staying with the family, but some found ‘nothing’ positive. Self-compassion remained moderate–high and strongly correlated with their moderate levels of social function, vitality, physical role, and global health. Physical and cognitive fatigue scores were high, and self-compassion negatively correlated with them, explaining a 19% variance in global health. The high compassion of the caregivers did not correlate with any variable.

Funding: The work received support from Memorial Mercedes Llort Sender 2021/80/09241941/4., Ageism can be seen as systematic stereotypes, prejudice, and discrimination of people because of their age. For a long time, society has accepted negative stereotypes as a norm. When referring to older adults, the United Nations Global Report on Ageism warns about a severe impact. The Intergenerational Study for a Healthy Aging, a questionnaire about believes, stereotypes, and knowledge about older people and grandparents, was administered to 326 Spanish biology and medical students. Here we report the results of stereotype analysis through adjective qualification of the youth and older people performed before the survey. Content analysis of two open questions about metacognition at the end of the survey is also presented. The results show that: (1) The questionnaire promoted metacognition; (2) Positive metacognition toward grandparents was higher than for the general old population; (3) Most participants were not conscious about ageism; (4) Gender was a key factor-male students were more ageist than females; (5) The feeling of guilt was higher in the questionnaire about older people; (6) The metacognition exercise elicited thoughts and, in few cases, the need to take action to tackle ageism. In conclusion, both activities promoted active thoughts about older people vs. grandparents and helped participants realize unconscious ageism-specifically toward the older population-serving as an awareness activity that may help tackle ageism.

New evidence refers to a high degree of heterogeneity in normal but also Alzheimer's disease (AD) clinical and temporal patterns, increased mortality, and the need to find specific end-of-life prognosticators. This heterogeneity is scarcely explored in very old male AD mice models due to their reduced survival. In the present work, using 915 (432 APP23 and 483 C57BL/6 littermates) mice, we confirmed the better survival curves in male than female APP23 mice and respective wildtypes, providing the chance to characterize behavioral signatures in middle-aged, old, and long-lived male animals. The sensitivity of a battery of seven paradigms for comprehensive screening of motor (activity and gait analysis), neuropsychiatric and cognitive symptoms was analyzed using a cohort of 56 animals, composed of 12-, 18- and 24-month-old male APP23 mice and wildtype littermates. Most variables analyzed detected age-related differences. However, variables related to coping with stress, thigmotaxis, frailty, gait, and poor cognition better discriminated the behavioral phenotype of male APP23 mice through the three old ages compared with controls. Most importantly, non-linear age- and genotype-dependent behavioral signatures were found in long-lived animals, suggesting crosstalk between chronological and biological/behavioral ages useful to study underlying mechanisms and distinct compensations through physiological and AD-associated aging

Funding: This research was funded by the European Cooperation in Science and Technology; funding number: EU COST-Action TD1005., Facial expression is a key aspect in observational scales developed to improve pain assessment in individuals with cognitive impairments. Although these scales are used internationally in individuals with different types of cognitive impairments, it is not known whether observing facial expressions of pain might differ between regions or between different types of cognitive impairments. In a pilot study, facial responses to standardized experimental pressure pain were assessed among individuals with different types of cognitive impairments (dementia, mild cognitive impairment, Huntington's disease, and intellectual disability) from different countries (Denmark, Germany, Italy, Israel, and Spain) and were analyzed using facial descriptors from the PAIC scale (Pain Assessment in Impaired Cognition). We found high inter-rater reliability between observers from different countries. Moreover, facial responses to pain did not differ between individuals with dementia from different countries (Denmark, Germany, and Spain). However, the type of cognitive impairment had a significant impact; with individuals with intellectual disability (all being from Israel) showing the strongest facial responses. Our pilot data suggest that the country of origin does not strongly affect how pain is facially expressed or how facial responses are being scored. However, the type of cognitive impairment showed a clear effect in our pilot study, with elevated facial responses in individuals with intellectual disability.

Altres ajuts: This work was funded by UAB-GE-260408 to L.G.-L.It also received financial support from Memorial Mercedes Llort Sender 2021/80/09241941.6., The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheimer's disease and age-matched counterparts of gold-standard C57BL6 strain with normal aging unveiled sex-dependent signatures. In addition, three temporal analyses, through the (1) time course of the performance, and (2) a repeated test schedule, identified the optimal time frames and schedules to detect sex-and genotype-dependent differences. Besides, a (3) longitudinal design from 12 to 16 months of age monitored the changes in the performance with aging, worsening in AD-mice, and modulation through the repeated test. In summary, the present results allow us to conclude that (1) the marble burying test is responsive to genotype, sex, aging, and its interactions; (2) the male sex was more sensitive to showing the AD-phenotype; (3) longitudinal assessment shows a reduction in females with AD pathology; (4) burying remains stable in repeated testing; (5) the time-course of marbles burying is useful; and (6) burying behavior most likely represents perseverative and/or stereotyped-like behavior rather than anxiety-like behavior in 3xTg-AD mice.

Funding: This work was supported by grant no. 97175 from the Vice-Chancellor for Research and Technology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. It also received support from Memorial Mercè Llort Sender 2021/80/092421.1., The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people.

Altres ajuts: UAB-GE-260408, The wide heterogeneity and complexity of Alzheimer's disease (AD) patients' clinical profiles and increased mortality highlight the relevance of personalized-based interventions and the need for end-of-life/survival predictors. At the translational level, studying genetic and age interactions in a context of different levels of expression of AD-genetic-load can help to understand this heterogeneity better. In the present report, a singular cohort of long-lived (19-month-old survivors) heterozygous and homozygous male 3xTg-AD mice were studied to determine whether their AD-genotype load can modulate the brain and peripheral pathological burden, behavioral phenotypes, and neuro-immunoendocrine status, compared to age-matched non-transgenic controls. The results indicated increased amyloid precursor protein (APP) levels in a genetic-load-dependent manner but convergent synaptophysin and choline acetyltransferase brain levels. Cognitive impairment and HPA-axis hyperactivation were salient traits in both 3xTg-AD survivor groups. In contrast, genetic load elicited different anxiety-like profiles, with hypoactive homozygous, while heterozygous resembled controls in some traits and risk assessment. Complex neuro-immunoendocrine crosstalk was also observed. Bodyweight loss and splenic, renal, and hepatic histopathological injury scores provided evidence of the systemic features of AD, despite similar peripheral organs' oxidative stress. The present study provides an interesting translational scenario to study further genetic-load and age-dependent vulnerability/compensatory mechanisms in Alzheimer's disease.

According to the Research Domain Criteria (RDoC), phenotypic differences among disorders may be explained by variations in the nature and degree of neural circuitry disruptions and/or dysfunctions modulated by several biological and environmental factors. We recently demonstrated the in vivo behavioral translation of tweaking the PI3K/Akt signaling, an essential pathway for regulating cellular processes and physiology, and its modulation through aging. Here we describe, for the first time, the in vivo behavioral impact of the sex and genetic-load tweaking this pathway. The anxiety-like phenotypes of 61 mature (11-14-month-old) male and female PDK1 K465E knock-in, heterozygous, and WT mice were studied. Forced (open-field) anxiogenic environmental conditions were sensitive to detect sex and genetic-load differences at middle age. Despite similar neophobia and horizontal activity among the six groups, females exhibited faster ethograms than males, with increased thigmotaxis, increased wall and bizarre rearing. Genotype-load unveiled increased anxiety in males, resembling female performances. The performance of mutants in naturalistic conditions (marble test) was normal. Homozygotic-load was needed for reduced somatic growth only in males. Factor interactions indicated the complex interplay in the elicitation of different negative valence system's items and the fine-tuning of PI3K/Akt signaling pathway intensity by genotype-load and sex.

Altres ajuts: Memorial Mercedes Llort Sender 2021/80/09242021.2, The increase of the aging population, where quite chronic comorbid conditions are associated with pain, draws growing interest across its investigation and the underlying nociceptive mechanisms. Burn injuries associated problems might be of relevance in the older adult's daily life, but in people with dementia, exposure to high temperatures and heat sources poses a significantly increased risk of burns. In this brief report, the hind paws and tail pain withdrawal reflexes and the emotional responses to thermal nociception in 3xTg-AD mice were characterized for the first time in the plantar test and compared to their non-transgenic (NTg) counterparts. We studied a cohort of male and female 3xTg-AD mice at asymptomatic (2 months), early (6 months), middle (9 months), and advanced (12 and 15 months) stages of the disease and as compared to sex- and age-matched NTg control mice with normal aging. At 20 and 40W intensities, the sensorial-discriminative thresholds eliciting the withdrawal responses were preserved from asymptomatic to advanced stages of the disease compared to NTg counterparts. Moreover, 3xTg-AD females consistently showed a greater sensory-discriminative sensitivity already at premorbid ages, whereas increased emotionality was shown in males. False-negative results were found in "blind to sex and age" analysis, warning about the need to study sexes independently. The current results and previous report in cold thermal stimulation provide two paradigms unveiling sex-specific early AD-phenotype nociceptive biomarkers to study the mechanistic underpinnings of sex-, age- and AD-disease-dependent thermal pain sensitivity.

The secondary impacts of the COVID-19 pandemic are distress triggers and risk factors for mental health. Conversely, self-compassion skills and compassionate thoughts/behaviors towards suffering may contribute to their alleviation. Both psychological constructs are interrelated in life-threatening diseases such as multiple sclerosis (MS). The Teruel Study retrospectively evaluated the impact of strict confinement on the 44 people with MS of this Spanish province and 24 caregivers, specifically assessing (1) fears and perceptions; (2) self-compassion (people with MS) and compassion (caregivers); (3) physical and mental health, and fatigue. Despite better housing conditions, people with MS considered confinement very difficult to handle, more than their caregivers, but they were less afraid of COVID-19 and worsening of MS. Still, they recognized worse health than before confinement. Reclusion and lack of walks were the worst of confinement. Caregivers also referred to lack of leisure and uncertainty–fear. All agreed the best was staying with the family, but some found ‘nothing’ positive. Self-compassion remained moderate–high and strongly correlated with their moderate levels of social function, vitality, physical role, and global health. Physical and cognitive fatigue scores were high, and self-compassion negatively correlated with them, explaining a 19% variance in global health. The high compassion of the caregivers did not correlate with any variable.

Droughts and climate-change-driven warming are leading to more frequent and intense wildfires1,2,3, arguably contributing to the severe 2019–2020 Australian wildfires4. The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols5,6,7. Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients and bio-essential trace metals such as nitrogen and iron, respectively8,9,10. It has been suggested that the oceanic deposition of wildfire aerosols can relieve nutrient limitations and, consequently, enhance marine productivity11,12, but direct observations are lacking. Here we use satellite and autonomous biogeochemical Argo float data to evaluate the effect of 2019–2020 Australian wildfire aerosol deposition on phytoplankton productivity. We find anomalously widespread phytoplankton blooms from December 2019 to March 2020 in the Southern Ocean downwind of Australia. Aerosol samples originating from the Australian wildfires contained a high iron content and atmospheric trajectories show that these aerosols were likely to be transported to the bloom regions, suggesting that the blooms resulted from the fertilization of the iron-limited waters of the Southern Ocean. Climate models project more frequent and severe wildfires in many regions1,2,3. A greater appreciation of the links between wildfires, pyrogenic aerosols13, nutrient cycling and marine photosynthesis could improve our understanding of the contemporary and glacial–interglacial cycling of atmospheric CO2 and the global climate system.

This paper aims to provide theoretically informed practical proposals for the improvement of current drug policies, which are based on a biological model of disease and the criminalization of people who use drugs. First, we present alternatives to a biologically-oriented scientific conception centered around neuroscientific postulates, which support the idea that the etiology of addiction materializes in the brain, in favor of models based on the social sciences where context plays a relevant role in the description and management approaches regarding different uses of psychoactive substances. Second, epistemological models and proposals are offered from a practical perspective to sustain or implement policies and programs in accordance with a more sustainable approach based on the elimination of stigma and the promotion of political participation of people who use drugs. In short, drug policies based on human rights., El objetivo de este artículo es aportar ideas teóricas y prácticas para la mejora de las políticas de drogas actuales, basadas en un modelo biológico de la enfermedad y en la criminalización de las personas que consumen sustancias ilegales. Para ello, en primer lugar, se ofrecen alternativas para superar las bases científicas biologicistas centradas en los postulados neurocientíficos, que apoyan la idea de que en el cerebro se materializa la etiología de la adicción, y apoyar los modelos basados en las ciencias sociales, en los que el contexto y el aprendizaje social juegan un papel relevante para la descripción, el abordaje y la gestión de los diferentes usos de sustancias psicoactivas. En segundo término, se ofrecen modelos y propuestas epistemológicas, desde una perspectiva práctica, para sostener o implementar políticas y programas acorde con un abordaje más sostenible, basado en la eliminación del estigma y la promoción de la participación política de personas consumidoras de sustancias ilegales, es decir, unas políticas sobre drogas basadas en derechos humanos.

La Agència Catalana de l’Aigua (ACA) está promoviendo el desarrollo de una herramienta para disponer de predicciones probabilísticas de caudales, en estaciones de aforo, y de evolución de volúmenes, en embalses. Esta herramienta se plantea como un elemento adicional a ser integrado en el conjunto de recursos para la ayuda a la toma de decisiones durante el seguimiento, gestión y tareas de comunicación propias de situaciones de avenidas, tanto en cuencas reguladas por embalses como no reguladas. El conocimiento previo de la variación de niveles en embalses y caudales máximos puntuales en estaciones de aforo se pretenden conjugar para analizar la conveniencia de generar avisos y/o resguardos activos mediante unos oportunos desembalses preventivos. El objetivo principal es la gestión óptima del recurso hídrico optimizando resguardos de laminación y la mejora en la gestión de la seguridad de las presas y en la reducción de riesgos por inundación., Postprint (published version)

Droughts and climate-change-driven warming are leading to more frequent and intense wildfires1,2,3, arguably contributing to the severe 2019–2020 Australian wildfires4. The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols5,6,7. Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients and bio-essential trace metals such as nitrogen and iron, respectively8,9,10. It has been suggested that the oceanic deposition of wildfire aerosols can relieve nutrient limitations and, consequently, enhance marine productivity11,12, but direct observations are lacking. Here we use satellite and autonomous biogeochemical Argo float data to evaluate the effect of 2019–2020 Australian wildfire aerosol deposition on phytoplankton productivity. We find anomalously widespread phytoplankton blooms from December 2019 to March 2020 in the Southern Ocean downwind of Australia. Aerosol samples originating from the Australian wildfires contained a high iron content and atmospheric trajectories show that these aerosols were likely to be transported to the bloom regions, suggesting that the blooms resulted from the fertilization of the iron-limited waters of the Southern Ocean. Climate models project more frequent and severe wildfires in many regions1,2,3. A greater appreciation of the links between wildfires, pyrogenic aerosols13, nutrient cycling and marine photosynthesis could improve our understanding of the contemporary and glacial–interglacial cycling of atmospheric CO2 and the global climate system., Analyses of satellite aerosol observations used in this study were produced with the Giovanni online data system, developed and maintained by the NASA GES DISC. We thank SeaWiFS and MODIS mission scientists and associated NASA personnel for the production of the data used in this research effort. The BGC-Argo data were collected and made freely available by the International Argo Program and the national programs that contribute to it (http://www.argo.ucsd.edu, http://argo.jcommops.org). The Argo Program is part of the Global Ocean Observing System (https://doi.org/10.17882/42182). W.T. is supported by the Harry H. Hess Postdoctoral Fellowship from Princeton University. N.C. is supported by the “Laboratoire d’Excellence” LabexMER (ANR‐10‐LABX‐19) and co-funded by a grant from the French government under the program “Investissements d’Avenir”. S.B. acknowledges the AXA Research Fund for the support of the long-term research line on Sand and Dust Storms at the Barcelona Supercomputing Center (BSC) and CAMS Global Validation (CAMS-84). P.G.S., J.L., M.M.G.P. and A.R.B. are supported by the Australian Research Council Discovery Projects scheme (DP190103504). P.G.S. and J.W. are supported by the Australian Research Council Centre of Excellence for Climate Extremes (CLEX: CE170100023). J.L. is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754433. A.R.B. is supported by the Australian Research Council Future Fellowship scheme (FT130100037). R.M. is supported by the CSIRO Decadal Climate Forecasting Project. We thank M. Strzelec, M. East, T. Holmes, M. Corkill, S. Meyerink and the Wellington Park Management Trust for help with installation and sampling the Tasmanian aerosol time-series station; A. Townsend for iron aerosol analyses by ICPMS at the University of Tasmania; and A. Benedetti and S. Remy for providing insights on the validation of aerosol reanalysis., Peer Reviewed, "Article signat per 15 autors/es: Weiyi Tang, Joan Llort, Jakob Weis, Morgane M. G. Perron, Sara Basart, Zuchuan Li, Shubha Sathyendranath, Thomas Jackson, Estrella Sanz Rodriguez, Bernadette C. Proemse, Andrew R. Bowie, Christina Schallenberg, Peter G. Strutton, Richard Matear & Nicolas Cassar", Postprint (author's final draft)

Droughts and climate-change-driven warming are leading to more frequent and intense wildfires1,2,3, arguably contributing to the severe 2019–2020 Australian wildfires4. The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols5,6,7. Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients and bio-essential trace metals such as nitrogen and iron, respectively8,9,10. It has been suggested that the oceanic deposition of wildfire aerosols can relieve nutrient limitations and, consequently, enhance marine productivity11,12, but direct observations are lacking. Here we use satellite and autonomous biogeochemical Argo float data to evaluate the effect of 2019–2020 Australian wildfire aerosol deposition on phytoplankton productivity. We find anomalously widespread phytoplankton blooms from December 2019 to March 2020 in the Southern Ocean downwind of Australia. Aerosol samples originating from the Australian wildfires contained a high iron content and atmospheric trajectories show that these aerosols were likely to be transported to the bloom regions, suggesting that the blooms resulted from the fertilization of the iron-limited waters of the Southern Ocean. Climate models project more frequent and severe wildfires in many regions1,2,3. A greater appreciation of the links between wildfires, pyrogenic aerosols13, nutrient cycling and marine photosynthesis could improve our understanding of the contemporary and glacial–interglacial cycling of atmospheric CO2 and the global climate system.

The secondary impacts of the COVID-19 pandemic are distress triggers and risk factors for mental health. Conversely, self-compassion skills and compassionate thoughts/behaviors towards suffering may contribute to their alleviation. Both psychological constructs are interrelated in life-threatening diseases such as multiple sclerosis (MS). The Teruel Study retrospectively evaluated the impact of strict confinement on the 44 people with MS of this Spanish province and 24 caregivers, specifically assessing (1) fears and perceptions; (2) self-compassion (people with MS) and compassion (caregivers); (3) physical and mental health, and fatigue. Despite better housing conditions, people with MS considered confinement very difficult to handle, more than their caregivers, but they were less afraid of COVID-19 and worsening of MS. Still, they recognized worse health than before confinement. Reclusion and lack of walks were the worst of confinement. Caregivers also referred to lack of leisure and uncertainty–fear. All agreed the best was staying with the family, but some found ‘nothing’ positive. Self-compassion remained moderate–high and strongly correlated with their moderate levels of social function, vitality, physical role, and global health. Physical and cognitive fatigue scores were high, and self-compassion negatively correlated with them, explaining a 19% variance in global health. The high compassion of the caregivers did not correlate with any variable.

Si l'any 1937,fou conegut com "l Año Triunfal"; el 1938, "II Año Triunfal"; el 1939, es canvia el nom de "III Año Triunfal" per "Año de la Victoria". La Conca de Barberà va patir durant aquests tres anys situacions extremes. La història, que és un llibre obert, on hi ha hagut i haurà positures que faran reflexionar les misèries humanes, posarà en el seu lloc els fets ocorreguts, d'una forma precisa, en un context no massa llunyà. No és fàcil esbrinar els elements que varen concòrrer a l'explosió de la Guerra Civil; cada persona ho entén des d'un prisma diferent; actualment, encara subsisteixen seqüeles que conformaren aquelles situacions polítiques. Els comportaments i els hàbits imposats pel franquisme com a resultat de la interpretació partidista de la Guerra Civil ("la Cruzada frente al comunismo'') són encara latents en alguns sectors de la societat que, per motius diversos, es resisteixen a desaparèixer.

Contains fulltext : 219878.pdf (Publisher’s version ) (Closed access), BACKGROUND: Recognition of pain in people with dementia is challenging. Observational scales have been developed, but there is a need to harmonize and improve the assessment process. In EU initiative COST-Action TD1005, 36 promising items were selected from existing scales to be tested further. We aimed to study the observer agreement of each item, and to analyse the factor structure of the complete set. METHODS: One hundred and ninety older persons with dementia were recruited in four different countries (Italy, Serbia, Spain and The Netherlands) from different types of healthcare facilities. Patients represented a convenience sample, with no pre-selection on presence of (suspected) pain. The Pain Assessment in Impaired Cognition (PAIC, research version) item pool includes facial expressions of pain (15 items), body movements (10 items) and vocalizations (11 items). Participants were observed by health professionals in two situations, at rest and during movement. Intrarater and interrater reliability was analysed by percentage agreement. The factor structure was examined with principal component analysis with orthogonal rotation. RESULTS: Health professionals performed observations in 40-57 patients in each country. Intrarater and interrater agreement was generally high (>/=70%). However, for some facial expression items, agreement was sometimes below 70%. Factor analyses showed a six-component solution, which were named as follows: Vocal pain expression, Face anatomical descriptors, Protective body movements, Vocal defence, Tension and Lack of affect. CONCLUSIONS: Observation of PAIC items can be done reliably in healthcare settings. Observer agreement is quite promising already without extensive training. SIGNIFICANCE: In this international project, promising items from existing observational pain scales were identified and evaluated regarding their reliability as an alternative to pain self-report in people with dementia. Analysis on factor structure helped to u

Contains fulltext : 213543.pdf (publisher's version ) (Open Access), Background: Over the last decades, a considerable number of observational scales have been developed to assess pain in persons with dementia. The time seems ripe now to build on the knowledge and expertise implemented in these scales to form an improved, "best-of" meta-tool. The EU-COST initiative "Pain in impaired cognition, especially dementia" aimed to do this by selecting items out of existing observational scales and critically re-assessing their suitability to detect pain in dementia. This paper reports on the final phase of this collaborative task. Methods: Items from existing observational pain scales were tested for "frequency of occurrence (item difficulty)", "reliability", and "validity". This psychometric testing was carried out in eight countries, in different healthcare settings, and included clinical as well as experimental pain conditions. Results: Across all studies, 587 persons with dementia, 27 individuals with intellectual disability, 12 Huntington's disease patients, and 59 cognitively healthy controls were observed during rest and movement situations or while receiving experimental pressure pain, respectively. The psychometric outcomes for each item across the different studies were evaluated within an international and multidisciplinary team of experts and led a final selection of 15 items (5x facial expressions, 5x body movements, 5x vocalizations). Conclusions: The final list of 15 observational items have demonstrated psychometric quality and clinical usefulness both in their former scales and in the present international evaluation; accordingly, they qualified twice to form a new internationally agreed-on meta-tool for Pain Assessment in Impaired Cognition, the PAIC-15 scale.

Dysfunction and dysregulation at the genetic, neural, and behavioral levels point at the fine-tuning of broadly spread networks as critical for a wide array of behaviors and mental processes through the life span. This brain-based evidence, from basic to behavioral neuroscience levels, is leading to a new conceptualization of mental health and disease. Thus, the Research Domain Criteria considers phenotypic differences observed among disorders as explained by variations in the nature and degree of neural circuitry disruptions, under the modulation of several developmental, compensatory, environmental, and epigenetic factors. In this context, we aimed to describe for the first time the in vivo behavioral impact of tweaking the PI3K/Akt signaling pathway known to play an essential role in the regulation of cellular processes, leading to diverse physiological responses. We explored the effects in young (YA, 3-4 months of age) and mature (MA, 11-14 months of age) male and female PDK1 K465E knock-in mice in a battery of tests under different anxiogenic conditions. The results evidenced that the double mutation of the PDK1 pleckstrin homology (PH) domain resulted in an enhancement of the negative valence system shown as an increase of responses of fear- and anxiety-like behaviors in anxiogenic situations. Interestingly, this seemed to be specific of YA and found regulated at middle age. In contrast, cognitive deficits, as measured in a spatial working memory task, were found in both YA and MA mutants and independently of the level of their anxious-like profiles. These distinct age- and function-dependent impacts would be in agreement with the distinct cortical and limbic deficits in the Akt signaling in the brain we have recently described in these same animals. The elicitation of age- and neuronal-dependent specific patterns suggests that fine-tuning the intensity of the PKB/Akt signal that enables diverse physiological response has also its in vivo translation into the