Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19

Background. COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions. SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 – 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and fnally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la fnanciación de proyectos de investigación en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Infammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript

Mineralizaciones de magnetita asociadas a skarns y bandas de cizalla: La mina de Cala (Huelva)

The Cala iron deposit has been traditionally regarded as a classic iron skarn developed on Cambrian limestone adjacent to a Variscan monzogranitic stock. Ongoing studies show that the geologic setting is more complex and the mineralization is replacive on marble and calcsilicate and pelitic hornfels and controlled by syntectonic hydrothermal activity with a pull-apart structure. The skarn only forms a part of the hydrothermal alteration. Most of the magnetite is related to an biotite-quartz-ankerite-chlorite assemblage, while the pyrite-chalcopyrite ore seems to be slightly younger, replacing magnetite along extensional structures, sharing many features with the IOCG style of mineralization

EJERCITO MI CEREBRO DURANTE EL CONFINAMIENTO: ANÁLISIS DE UN PROYECTO DESARROLLADO DE MANERA TELEMÁTICA EN EDUCACIÓN INFANTIL

During the period of home-confinement, the education system had to adapt to unprecedented circumstances. This work shows an educational proposal that was adapted to working remotely. The “Exercising my brain” project is based on physical neuroeducation and specifically on the HERVAT neuroeducational program that was developed through 8 different sessions over two months. The families received all the instructions at the beginning of the week and the children had to do the proposed tasks for 20-25 minutes before carrying out their curricular activities. A total of 19 children participated and information was collected from 12 parents who filled out an online questionnaire in which they reflected their perceptions and evaluations about the project. The results revealed high levels of situational interest and satisfaction from the families. During the home-confinement, a significant increase in playtime with their children was also observed. In this sense, it was detected that those parents who spent more time playing with their children (before and during confinement) perceived greater enjoyment during the development of the project.Durante el periodo de confinamiento domiciliario, el sistema educativo tuvo que adaptarse a unas circunstancias sin precedentes. En este trabajo se muestra una propuesta educativa implementada de manera telemática. El proyecto “Ejercito mi cerebro” se basa en la neuroeducación física y específicamente en el programa neuroeducativo HERVAT que se desarrolló mediante 8 sesiones diferentes a lo largo de dos meses. Las familias recibían las instrucciones al principio de la semana y los niños tenían que hacer las tareas propuestas durante 20-25 minutos todos los días antes de realizar sus actividades curriculares. Participaron 19 niños y se recogió información de 12 familiares que rellenaron un cuestionario online en el que reflejaron sus percepciones y valoraciones sobre el proyecto. Los resultados revelaron altos niveles de interés situacional y de satisfacción por parte de las familias en relación a esta experiencia. También se observó que durante el confinamiento se incrementó notablemente el tiempo de juego con sus hijos. En este sentido, se detectó que los familiares que dedicaban más tiempo a jugar con sus hijos/as  (antes y durante el confinamiento) percibieron mayor disfrute durante el desarrollo del proyecto

A genetic link between albitic magmas and IOCG mineralization in the Ossa Morena Zone (SW Iberia)

A detailed geological and isotopic study of the Colmenar deposit (Ossa Morena Zone, SW Iberia) shows that the magnetite- rich mineralization formed by complex magmatic-hydrothermal processes related to the crystallization of water-rich albite- magnetite igneous rocks derived from the crystallization of unusual melts formed during anatexis in a high temperature-low pressure metamorphic regime. The most likely protolith includes a sequence of iron-rich chemical sediments, amphibolite and possible meta-evaporites of early Cambrian age. The albite-magnetite rock occurs as up to 20cm-thick dyke and breccia bodies and show complex immiscibility relationships with an albite-K-feldspar-quartz leucogranite. Iron-rich fluids exsolved during the crystallization of these melts are responsible of the formation of hydrothermal breccias and the widespread replacement of the hosting calc-silicate hornfels by a magnetite-ferroactinolite-albite assemblage along syn-mineralization shear zones. Geochronological data obtained for mineralization and related hydrothermal alteration points to a Variscan age (ca. 340Ma), interpreted also as the age of the high-grade metamorphism driving anatexis at the Valuengo Metamorphic Complex. Despite the low Cu and Au contents, this mineralization shares features with the IOCG systems, which in other districts show a spatial relationship with albite-rich rocks, evaporites and pre-existing iron mineralization. The observations presented from Colmenar support an alternative genetic model with prospective implications for the Ossa Morena Zone that can be extrapolated to other IOCG belts worldwide

A genetic link between albitic magmas and IOCG mineralization in the Ossa Morena Zone (SW Iberia)

A detailed geological and isotopic study of the Colmenar deposit (Ossa Morena Zone, SW Iberia) shows that the magnetite-rich mineralization formed by complex magmatic-hydrothermal processes related to the crystallization of water-rich albite-magnetite igneous rocks derived from the crystallization of unusual melts formed during anatexis in a high temperature-low pressure metamorphic regime. The most likely protolith includes a sequence of iron-rich chemical sediments, amphibolite and possible meta-evaporites of early Cambrian age. The albite-magnetite rock occurs as up to 20 cm-thick dyke and breccia bodies and show complex immiscibility relationships with an albite-K-feldspar-quartz leucogranite. Iron-rich fluids exsolved during the crystallization of these melts are responsible of the formation of hydrothermal breccias and the widespread replacement of the hosting calc-silicate hornfels by a magnetite-ferroactinolite-albite assemblage along syn-mineralization shear zones. Geochronological data obtained for mineralization and related hydrothermal alteration points to a Variscan age (ca. 340 Ma), interpreted also as the age of the high-grade metamorphism driving anatexis at the Valuengo Metamorphic Complex. Despite the low Cu and Au contents, this mineralization shares features with the IOCG systems, which in other districts show a spatial relationship with albite-rich rocks, evaporites and pre-existing iron mineralization. The observations presented from Colmenar support an alternative genetic model with prospective implications for the Ossa Morena Zone that can be extrapolated to other IOCG belts worldwide

The relationship between large deep mafic sills, crustal contamination and the formation of Ni-(Cu) and IOCG deposits

The Ossa Morena Zone (SW Iberia) hosts an unusual suite of ore deposits, including magmatic Ni-(Cu) and IOCG mineralization. These deposits are interpreted to have a relationship to a deep mafic sill intruded in the middle crust. Interaction of mafic magmas with crustal rocks produced immiscible sulphide-rich melts and water-rich melts. The latter exsolved large amounts of Fe- and CO2-rich brines that were responsible for widespread albite-actinolite alteration and IOCG mineralization.Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEpu

The effect of residual stress on mechanical resistance of ZrSiO4/Al2O3 laminates

Layered ceramics were obtained by sequential slip casting of suspensions containing different proportions of zircon (Z) and alumina (A) as follow; 60Z40A, 40Z60A, 50Z50A and 80Z20A. Three laminar samples were fabricated using five thick layers and four thin layers, being the composition 60Z40A used for the thick layers and 40Z60A, 50Z50A and 80Z20A for the thin layers. From those thick/thin layers configurations, the residual stresses were: −46.27 MPa/+173.53 MPa, −11.25 MPa/+42.19 MPa and +9.70 MPa/−36.38 MPa for 60Z40A/40Z60A, 60Z40A/50Z50A and 60Z40A/80Z20A, respectively. The CTE (thermal expansion coefficient) was determined using monolithic samples of each composition; all laminar components were characterized by SEM and by the determination of the modulus of rupture. The result showed that the modulus of rupture were higher than the properties obtained for a monolithic 60Z40A sample, being 218% and 182% higher for laminar components configuration of 60Z40A/50Z50Aand 60Z40A/80Z20A, respectively. Also, due to high strain mismatch the laminar component 60Z40A/40Z60A showed lower mechanical properties than the 60Z40A monolithic sample

3D reflection seismic imaging of the Zinkgruvan mineral-bearing structures in the south-eastern Bergslagen mineral district (Sweden)

Mineral exploration is facing greater challenges nowadays because of the increasing demand for raw materials and the lesser chance of finding large deposits at shallow depths. To be efficient and address new exploration challenges, high-resolution and sensitive methods that are cost-effective and environmentally friendly are required. In this work, we present the results of a sparse 3D seismic survey that was conducted in the Zinkgruvan mining area, in the Bergslagen mineral district of central Sweden. The survey covers an area of 10.5 km2 for deep targeting of massive sulphides in a polyphasic tectonic setting. A total of 1311 receivers and 950 shot points in a fixed 3D geometry setup were employed for the survey. Nine 2D profiles and a smaller 3D mesh were used. Shots were generated at every 10 m, and receivers were placed at every 10-20 m, along the 2D profiles, and 40-80 m in the mesh area. An analysis of the seismic fold coverage at depth was used to determine the potential resolving power of this sparse 3D setup. The data processing had to account for cultural noise from the operating mine and strong source-generated surface waves, which were attenuated during both pre- and post-stack processing steps. The processing workflow employed a combination of 2D and 3D refraction static corrections, and post-stack FK filters along inlines and crosslines. The resulting 3D seismic volume is correlated with downhole data (density and P-wave, acoustic impedance, reflection coefficient), synthetic seismograms, surface geology and a 3D model of mineral-bearing horizons in order to suggest new exploration targets at depth. The overall geological architecture at Zinkgruvan is interpreted as two EW overturn folds, an antiform and a synform, affected by later NS-trending folding. Two strong sets of shallow reflections, associated with the Zn-Pb mineralization, are located at the hinge of an EW-trending antiform, while a strong set of reflections, associated with the main mineralization, is located at the overturned apex of the EW synform. The NS Knalla fault that crosses the study area terminates the continuation of the mineral-bearing deposits at depth towards the west, a conclusion solely based on the reflectivity character of the seismic volume. This study illustrates that sparse 3D data acquisition, while it has its own challenges, can be a suitable replacement for 2D profiles while line cutting, and environmental footprints can totally be avoided

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates