La Possession, Saint-Paul – Rivière des Galets, paléoforêt

La paléoforêt de la Rivière des Galets est localisée dans le lit du cours d’eau du même nom, un kilomètre en amont des Deux Bras, aux portes du cirque de Mafate. Il s’agit d’un ensemble remarquable de troncs d’arbres morts, conservés dans les sédiments de la rivière à l’état de bois organique, c’est pourquoi l’on parle de « paléoforêt » et non de «forêt fossile», la matière n’étant pas minéralisée. Le site a été remis au jour par une crue exceptionnelle, à la suite d’un événement cyclonique r..

Deir el-Médina

La mission a débuté plus tard que prévu, car les autorisations de la Sécurité ont été délivrées fin janvier, deux semaines après la date du 15 janvier fixée pour l’ouverture de la mission. Faute de temps, certaines équipes n’ont pas réussi à atteindre leurs objectifs. La mission a poursuivi les travaux engagés en 2018 axés sur l’étude et la restauration des tombes de la nécropole de l’ouest et du mobilier conservé dans les magasins du site. Quatre équipes sont intervenues dans les TT 2, TT 2B..

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

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/)

Stability of frozen Amphotericin B eye drop

International audienc

MINIATURIZED EXTRACTION DEVICE COUPLED TO MASS SPECTROMETRY FOR ON-LINE PURIFICATION AND CHARACTERIZATION OF NUCLEAR SAMPLES

International audienceCharacterizing the elemental and isotopic composition of nuclear samples is of utmost importance in the case of nuclear forensics, processes for spent fuel recycling or waste treatment. Protocols already exist for extraction of radionuclides such as U and Pu using cartridges packed with commercial resins before off-line characterization by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Current methods are however time-consuming, induce exposition of operators to variable levels of radiation, and the production of large amounts of waste. In this study, we developed a miniaturized extraction device and its coupling to ICP-MS in order to reduce the scale and drawbacks of the current purification steps. Gao et al. [1] and Ouchi et al. [2] designed resin-packed microchannels and were able to carry out the off-line analysis of U or Th separated from trace elements, but the repeatability of the packing process and the performance of the separation have yet to be confirmed. Porous monoliths with larger surface area than particulate phases can be directly integrated within microdevices and represent a more convenient approach. In this sense, two routes were investigated by our group through the post-functionalization of a generic monolith in cyclic olefin copolymer (COC) microsystems, using either grafting [3] or impregnation techniques [4] but exhibit limitations. Our new integrated strategy consists in the one step synthesis of a monolith dedicated to U/Pu isolation by copolymerization of phosphorylated monomers in the channels of a COC microsystem and in its coupling to ICP-MS, that was not developed in the previous works.Optimization of monoliths compositions in relation with their permeability, morphology, extraction capacity, and selectivity properties was first realized in silica capillaries since the activation/anchoring step is well known for this material compared to COC. All monoliths were synthesized by photopolymerization. Figure 1 shows the UV collimated LED specifically set up in the laboratory to limit diffusion effects in comparison with traditional UV oven. The coupling of the functionalized capillaries to ICP-MS was performed (Figure 2) and ad-hoc quantification methods developed to determine the loading capacity of U either alone or in the presence of Th and Sm used as Pu and Am analogues (Figure 3). Several mobile phase compositions were considered for the selective retention and elution of the elements. The development of these different steps in a conventional laboratory is essential to validate the separation downscaling before performing the purification of radioactive samples, which requires the transposition of the methodology in a glove box.Once the most promising monolith was selected, we worked on the implementation of the synthesis and anchorage in the channels of COC microsystems, with particular attention paid to the repeatability of the method. One and two-steps photochemically induced activation methods were compared. Among all parameters tested, the type of photoinitiator, the time and power of irradiation had the most prominent effects on monolith anchoring. The sorbent volume in the proposed microdevice should be reduced at most by a factor of 10,000 compared to conventional methods. Word Count: 48

Development of a microfluidic device for the analysis of nuclear samples

International audienceThe miniaturization and integration of analytical tools in microfluidic devices, in the form of labs-on-chip or micro total analysis systems (µ-TAS), currently offer several advantages: the opportunity to analyze rare samples with limited quantities available, to better control parameters that influence reactions, and to develop portable systems for on-site analyses. In the nuclear field, an additional advantage consists in reducing the volume of samples to handle and the corresponding doses, the amount of reagents, as well as the amount of produced waste and the necessary costs for their specific management. Indeed, in order to characterize the elemental and isotopic composition of samples for the management of effluents from nuclear facilities, of those resulting from processing steps or of spent fuels, various purification steps by solid phase extraction are necessary, upstream of mass spectrometry measurements (ICP-MS, TIMS). While there are established protocols to perform radionuclides separation such as U and Pu from commercial resins (e.g. UTEVA™, TBP™, TRU™), those are time-consuming and require large volumes of resins and eluents. This work aims to develop a separative microsystem including a monolithic support in order to reduce the scale of nuclear samples purification protocols.First, different materials (e.g. glass, thermoplastics) for the microsystem conception were evaluated in order to find the best compromise in relation to the targeted application. These were compared in terms of resistance to concentrated acids which are associated with the sample matrices and the radiochemical separation conditions; in terms of ease and repeatability of monolith anchoring process in the microsystem channels; and of cost and ease of shaping. To date, most monoliths described in literature are synthesized and anchored in silica capillaries or glass chips, materials that are easily functionalized unlike thermoplastic polymers such as cyclic olefin copolymer (COC) or polytetrafluoroethylene (PTFE), which are known to be chemically inert but easily shaped. Organic monoliths bearing phosphate monomers with a good affinity for actinides have been synthesized by photopolymerization in commercial microsystem channels or internally fabricated by micromilling. Particular attention was paid to limit diffusion effects during monoliths synthesis.The different functionalized microsystems were characterized in terms of morphology and permeability before developing their coupling with an Inductively Coupled Plasma Mass Spectrometer (ICP-MS). Dedicated quantification methods have been developed to determine on-line their selectivity towards simulants (U, Th, and Eu as simulants for radionuclides U, Pu, and Am) in different media as well as their loading capacity. The development of these different steps in a conventional laboratory is essential to validate the downscaling of the separation protocol before applying it to the purification of radioactive samples, requiring a transposition in a glove box in a controlled area