Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Comparison of soil/solution distribution of a fresh radionuclides contamination (137Cs, 129I and 233U) added under organic or water pathways with their natural endogenous isotopes

International audienc

Hydrogen Diffusion and Shallow Acceptor Passivation in p‐Type InP

International audienceHydrogen diffusion in InP:Zn, protected by an undoped GalnAs epilayer, has been performed from a hydrogen plasma exposure. Passivation of shallow acceptors occurs in the hydrogen diffused region of InP:Zn. Secondary ion mass spectrometry, transport measurements and thermal annealing experiments indicate the existence of neutral Zn,H pairs in InP:Zn,H. We find that these pairs have a relatively higher thermal stability than in GaAs:Zn. This is interpreted with the help of the microscopic description of the Zn,H complexes

Strong chemical evidence for high Fe(II)-colloids and low As-bearing colloids (200 nm–10 kDa) contents in groundwater and flooded paddy fields in Bangladesh: A size fractionation approach

International audienceArsenic speciation in groundwater and interstitial waters from soil irrigated with As-rich groundwater in Bangladesh was investigated through a size fractionation approach performed in the field and under con-ditions that allowed the preservation of natural anoxic conditions. Based on a simple chemical character-ization, the presence of Fe(II) in the colloidal fraction (10 kDa) in anoxic groundwaters and soil waters of flooded paddy fields was assessed. Arsenic was found to be present mainly as a ''solute'' oxy-anion as indicated by the small amount of As associated with the 200 nm–10 kDa colloidal fraction (most of the time, less than 10 ± 5% of total As). When As-colloids were observed, they were linked to high Fe concentration and the As-colloid percentage was relatively well correlated with the total Fe concentra-tion in solution. This study underlined that under natural anoxic conditions, there was no impact of PO 3À 4 , SiO 4À 4 and Mn on the As-bearing colloids, which is not in agreement with results obtained under laboratory controlled conditions. Therefore, it is suspected that the impact of other naturally occurring ligands, such as organic matter, could modify Fe(II) speciation, and, in turn, As speciation. To assess the complexation of Fe(II) by organic matter, the WinHumicV model was used to calculate Fe(II) specia-tion. Using the standard parameters to describe organic matter reactivity, results showed that organi-cally-bound Fe(II) ranges from 5% to 100% and 30% to 100%, for groundwater and soil water, respectively, depending on the pH and the Fe(II) and DOC contents. Evidence for independent speciation of Fe and As under natural anoxic conditions is of great importance for predictive modelling of the mobil-ity, the availability and then the bioavailability of As in As-affected areas

Chemical element imaging for speleothem geochemistry: Application to a uranium-bearing corallite with aragonite diagenesis to opal (Eastern Siberia, Russia)

Two complementary image-based microanalysis methods, digital autoradiography of radioactive elements and X-ray fluorescence microspectroscopy (micro-XRF), were used to study the geochemistry of a speleothem from Eastern Siberia. Our objective was to show the interest of these micro-chemical methods to investigate the distribution of U and some other elements as Ca, Sr, and Si in speleothems. The sample studiedwas a corallite concretion that formed slowly by the precipitation of minerals from moisture that had condensed underground. Polished sections of the sample revealed alternating laminas of gray calcite and white aragonite. The concretion, which is older than 400 Kyr (U/Th-TIMS), showed no signs of detrital contamination 230Th/232Th>10,000). Digital autoradiography and XRF analyses indicated exceptionally high uranium contents, ranging from 3-10 to more than 1300 μg∙g−1 in different areas of the sample. Element maps for calcium(Ca), uranium(U), strontium (Sr) and silicon (Si) showed inverse correlations between Ca and U and between Ca and Si, but there is a strong correlation between Si and U. Under the optical microscope, the low Ca appears as corrosion voids, which were found to contain uranium-enriched amorphous silica replacing areas of aragonite and, in some cases, calcite. This postgenetic amorphous and uraniferous silica is composed of two kinds of opal: opal A formed by large microspheres of 30-40 μm in diameter and a gray opal CT with irregular lepispheres. This late opal, dated around 385-412 Kyr, is probably due to a special volcanic event formed by uraniferous glass ashes easily soluble bymeteoric waters, as suggested by the presence of volcanic suite in the fine fraction of the opal. Opal precipitated after speleothemcrystallization by evaporation or cryogenic supersaturation. The study of this exceptional concretion shows the value of direct chemical imaging methods, as they easily revealed the presence and distribution of U in the concretion, and allowed an unusual case of opal diagenesis in a carbonate speleothem to be described. Given the value of speleothems as geo-chronometers and recorders of environmental changes at different time scales, from season to isotopic stage, thismethodology opens newperspectives in understanding the geochemical system and consequently the validity of radiometric datings, U/Th and U/Pb, especially in speleothem samples

Sonic Hedgehog Signature in Pediatric Primary Bone Tumors: Effects of the GLI Antagonist GANT61 on Ewing’s Sarcoma Tumor Growth

International audienceOsteosarcoma (OS) and Ewing’s sarcoma (ES) are the most common malignant bone tumors in children and adolescents. In many cases, the prognosis remains very poor. The Sonic hedgehog (SHH) signaling pathway, strongly involved in the development of many cancers, regulate transcription via the transcriptional factors Gli1-3. In this context, RNAseq analysis of OS and ES cell lines reveals an increase of some major compounds of the SHH signaling cascade in ES cells, such as the transcriptional factor Gli1. This increase leads to an augmentation of the transcriptional response of Gli1 in ES cell lines, demonstrating a dysregulation of Gli1 signaling in ES cells and thus the rationale for targeting Gli1 in ES. The use of a preclinical model of ES demonstrates that GANT61, an inhibitor of the transcriptional factor Gli1, reduces ES primary tumor growth. In vitro experiments show that GANT61 decreases the viability of ES cell, mainly through its ability to induce caspase-3/7-dependent cell apoptosis. Taken together, these results demonstrates that GANT61 may be a promising therapeutic strategy for inhibiting the progression of primary ES tumors

Sonic Hedgehog Signature in Pediatric Primary Bone Tumors: Effects of the GLI Antagonist GANT61 on Ewing’s Sarcoma Tumor Growth

Osteosarcoma (OS) and Ewing&rsquo;s sarcoma (ES) are the most common malignant bone tumors in children and adolescents. In many cases, the prognosis remains very poor. The Sonic hedgehog (SHH) signaling pathway, strongly involved in the development of many cancers, regulate transcription via the transcriptional factors Gli1-3. In this context, RNAseq analysis of OS and ES cell lines reveals an increase of some major compounds of the SHH signaling cascade in ES cells, such as the transcriptional factor Gli1. This increase leads to an augmentation of the transcriptional response of Gli1 in ES cell lines, demonstrating a dysregulation of Gli1 signaling in ES cells and thus the rationale for targeting Gli1 in ES. The use of a preclinical model of ES demonstrates that GANT61, an inhibitor of the transcriptional factor Gli1, reduces ES primary tumor growth. In vitro experiments show that GANT61 decreases the viability of ES cell, mainly through its ability to induce caspase-3/7-dependent cell apoptosis. Taken together, these results demonstrates that GANT61 may be a promising therapeutic strategy for inhibiting the progression of primary ES tumors