First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human–environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26, 000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe. © 2021, The Author(s)

Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis

Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARSCoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+ /K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1b were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1b was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence

First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human?environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26,000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe.Tis research was carried out in the context of the ERC MULTIPALEOIBERIA project, funded by the European Research Council (ERC-2018-STG-805478), and the PALEOINTERIOR project, funded by the Spanish Ministry of Science and Innovation (HAR2017-82483-C3-3-P)

Level of discomfort in critically ill paediatric patients and its correlation with sociodemographic and clinical variables, analgosedation and withdrawal syndrome. COSAIP multicentre study (Phase 2)

Introduction: There are clinical and sociodemographic factors that have an impact on the comfort of the critically ill paediatric patient. The main aim of this study was to determine the level of discomfort of paediatric patients admitted to different national hospitals, and to analyse its correlation with sociodemographic and clinical variables, analgosedation, and withdrawal syndrome. Methods: An observational, analytical, cross-sectional, and multicentre study was conducted in five Spanish hospitals. The level of analgosedation was assessed once per shift over a 24 h period, using a BIS sensor, and pain with scales adapted to paediatric age population. The intensity of withdrawal syndrome was determined using the Withdrawal Assessment Tool (WAT-1) scale once per shift for 3 days. Discomfort level was simultaneous assessed using COMFORT Behaviour Scale-Spanish version (CBS-S). Results: A total of 261 critically ill paediatric patients with median age of 1.61 years (IQR = 0.35-6.55) were included. An overall discomfort score of 10.79 ± 3.7 was observed during morning compared to 10.31 ± 3.3 observed during the night. When comparing analgosedation and non-analgosedation groups, statistically differences were found in both shifts (χ2: 45.48; P =.001). At the same time, an association was observed (P <.001) between low discomfort scores and development of withdrawal syndrome development assessed with WAT-1. Conclusions: As there is a percentage of the studied population with discomfort, specific protocols need to be developed, guided by valuated and clinically tested tools, like the COMFORT Behaviour Scale-Spanish version.Introducción: Existen factores clínicos o sociodemográficos que pueden tener un impacto en el confort del paciente crítico pediátrico. El objetivo principal fue determinar el grado de disconfort de los pacientes pediátricos ingresados en las UCIP de diversos hospitales nacionales y analizar su relación con variables ocio demográficas y clínicas, sedoanalgesia y síndrome de abstinencia. Métodos: Estudio observacional, analítico, transversal y multicéntrico en 5 hospitalesespañoles. Se valoró el grado de analgosedación mediante el sensor BIS y las escalas de dolora daptadas a la edad pediátrica, una vez por turno durante 24 h. El grado de abstinencia se determinó con la escala Withdrawal Assessment Tool (WAT-1), una vez por turno durante 3 días consecutivos. Además, se valoró simultáneamente el grado de disconfort mediante la COMFORTBehavior Scale-versión española (CBS-ES).Resultados: Se incluyeron un total de 261 pacientes críticos pediátricos con una mediana de edad de 1,61 años (RIQ = 0,35-6,55). Se objetivaron puntuaciones globales de disconfort de10,79 ± 3,7 en el turno de mañana versus 10,31 ± 3,3 en el de noche. Se observó asociación estadística al comparar al grupo de pacientes analgosedados con el grupo de no analgosedadosen ambos turnos ( 2: 45,48; p = 0,001). A la vez, también se observó una relación estadística-mente significativa (p < 0,001) entre puntuaciones bajas de disconfort y menor desarrollo desíndrome de abstinencia

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of δCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of $\delta_{CP}$. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter.Comment: Contribution to Snowmass 202