Cytokine removal in human septic shock : where are we and where are we going?

Although improving, the mortality from septic shock still remains high despite increased international awareness. As a consequence, much effort has focused on alternative treatment strategies in an effort to improve outcomes. The application of blood purification therapies to improve immune homeostasis has been suggested as one such method, but these approaches, such as high-volume continuous haemofiltration or cytokine and/or endotoxin removal, have enjoyed little success to date. More recently, the use of sorbent technologies has attracted much attention. These adsorbers are highly effective at removing inflammatory mediators, in particular, cytokines, from the bloodstream. This narrative review is the executive summary of meetings held throughout the 6th International Fluid Academy Days in Antwerp, Belgium (Nov 23-25, 2017), focusing on the current understanding regarding the use of such adsorbers in humans with septic shock. We followed a modified Delphi approach involving a combination of evidence appraisal together with expert opinion in order to achieve recommendations for practice and, importantly, future research

Long-term magmatic evolution reveals the beginning of a new caldera cycle at Campi Flegrei

Understanding the mechanisms that control the accumulation of large silicic magma bodies in the upper crust is key to determine the potential of volcanoes to form caldera-forming eruptions. Campi Flegrei is an active and restless volcano, located in one of the most populated regions on Earth, which has produced two cataclysmic caldera-forming eruptions and numerous smaller eruptive events over the last 60,000 years. Here we combine the results of an extensive petrological survey with a thermo-mechanical model to investigate how the magmatic system shifts from frequent, small eruptions to large caldera-forming events. Our data reveal that the most recent eruption of Monte Nuovo is characterized by highly differentiated magmas akin to those that fed the pre-caldera activity and the initial phases of the caldera-forming eruptions. We suggest that this eruption is an expression of a state shift in magma storage conditions, whereby significant amounts of volatiles start to exsolve in the shallow reservoir. The presence of an exsolved gas phase has fundamental consequences for the physical properties of the reservoir and may indicate that a large magma body is currently accumulating underneath Campi Flegrei

Centimeter to decimeter hollow concretions and voids in Gale Crater sediments, Mars

Voids and hollow spheroids between ∼1 and 23 cm in diameter occur at several locations along the traverse of the Curiosity rover in Gale crater, Mars. These hollow spherical features are significantly different from anything observed in previous landed missions. The voids appear in dark-toned, rough-textured outcrops, most notably at Point Lake (sols 302-305) and Twin Cairns Island (sol 343). Point Lake displays both voids and cemented spheroids in close proximity; other locations show one or the other form. The spheroids have 1-4 mm thick walls and appear relatively dark-toned in all cases, some with a reddish hue. Only one hollow spheroid (Winnipesaukee, sol 653) was analyzed for composition, appearing mafic (Fe-rich), in contrast to the relatively felsic host rock. The interior surface of the spheroid appears to have a similar composition to the exterior with the possible exceptions of being more hydrated and slightly depleted in Fe and K. Origins of the spheroids as Martian tektites or volcanic bombs appear unlikely due to their hollow and relatively fragile nature and the absence of in-place clearly igneous rocks. A more likely explanation to both the voids and the hollow spheroids is reaction of reduced iron with oxidizing groundwater followed by some re-precipitation as cemented rind concretions at a chemical reaction front. Although some terrestrial concretion analogs are produced from a precursor siderite or pyrite, diagenetic minerals could also be direct precipitates for other terrestrial concretions. The Gale sediments differ from terrestrial sandstones in their high initial iron content, perhaps facilitating a higher occurrence of such diagenetic reactions

Comparative Long-Term Effect of Three Anti-P2Y12 Drugs after Percutaneous Angioplasty: An Observational Study Based on Electronic Drug Adherence Monitoring

Aims: Dual platelet inhibition using anti-P2Y12 drugs and aspirin is the standard of care in patients after percutaneous coronary interventions (PCI). Prasugrel and ticagrelor have been shown to be more potent than clopidogrel with less high on-treatment platelet reactivity. Whether differences in long-term adherence to these drugs can partly explain different antiplatelet efficacy has not been studied so far. The objective was to compare the long-term P2Y12 receptor inhibition and drug adherence to different anti-P2Y12 drugs, and to assess the impact of adherence on the pharmacodynamic effect.Methods: Monocentric, prospective, observational study. Stable outpatients treated with clopidogrel 75 mg once daily, prasugrel 10 mg once daily or ticagrelor 90 mg twice daily after PCI with stent implantation were included. Drug adherence was recorded during 6 months using electronic monitoring. Platelet responsiveness was assessed with the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) at inclusion, 3 and 6 months.Results: 120 patients had VASP-PRI and adherence data available. At 6-months, mean VASP-PRI (±SD) was 17.7 ± 11.0% with ticagrelor, 29.2 ± 15.5% with prasugrel and 47.2 ± 17.6% with clopidogrel (ANOVA, P < 0.0001).Median [IQR] taking adherence was 96 [82–100]% with ticagrelor, 100 [97–101]% with prasugrel and 100 [99–101]% with clopidogrel (p = 0.0001). Median [IQR] correct dosing was 88 [73–95]% with ticagrelor, 97 [92.5–98]% with prasugrel and 98 [96–99]% with clopidogrel (p = 0.0001).Anti-P2Y12 drug (p ≤ 0.001) and diabetes (p = 0.014) emerged as predictors of poor antiplatelet response after adjusting for age, BMI, sex, and CYP2C19∗2 carriers status.Conclusion: Drug adherence to anti-P2Y12 drugs assessed with electronic monitoring was very high. However, anti-P2Y12 drugs showed significant differences in antiplatelet activity, with newer anti-P2Y12 drugs ticagrelor and prasugrel exerting a stronger P2Y12 receptor inhibition.These data suggest that pharmacokinetic-pharmacodynamic differences between oral anti-P2Y12 drugs are more important than adherence in determining antiplatelet efficacy when adherence to prescription is high.The study was registered (Current Controlled Trials ISRCTN85949729)

Design, development, and scientific performance of the Raman Laser Spectrometer EQM on the 2020 ExoMars (ESA) Mission

The Raman Laser Spectrometer (RLS) is one of the three Pasteur Payload instruments located within the rover analytical laboratory drawer (ALD), for ESA’s Aurora exploration programme, ExoMars 2020 mission. The instrument will analyse the crushed surface and subsurface samples that are positioned below the Raman optical head by the ALD carousel. The RLS engineering and qualification model (EQM) was delivered to ESA at the end of 2017, after a wide technical and scientific test characterization campaign. The scientific campaign comprised instrument calibration and detailed evaluation of the scientific requirements and overall performance. For spectral calibration, continuous emission standard lamps (such as Hg-Ar, Ne, and Xe) were utilized, as well as Raman spectra of pure liquids typically used as standards (cyclohexane and carbon tetrachloride (CCl4)). In addition, Raman spectra of the RLS calibration target (CT), a small disc of polyethylene terephthalate (PET) were obtained at various temperatures. This target, placed inside the rover, will be used for both Instrument health checks and calibration activities throughout Mars operations. For the scientific requirements and performance evaluations, several liquid and solid samples were analysed under a wide range of ambient conditions. The obtained spectral band parameters (peak position, relative peak intensity, peak width, and peak profile) were evaluated. Also, the instrument response (in terms of SNR) was characterized at different integration times and detector operating temperatures. In this paper, we provide a description of the development, verification, functional test, and overall scientific performance of the RLS instrument developed for ExoMars. Particular attention is placed on the performance of the EQM, which is the most representative instrument, in terms of engineering and functionality, of the flight model (FM) and in addition is used for performing all the mechanical, thermal, and radiation tests necessary for space qualification (for planetary applications). The data presented and analysed here, comprise part of the overall dataset obtained during the full instrument characterization campaign conducted at INTA before and during delivery and integration of the EQM in the rover ALD at TAS-I facilities (Torino, Italy). The results obtained confirm that the full functionality and scientific performance of the RLS instrument was maintained after integration.Proyecto MINECO Retos de la Sociedad. Ref. ESP2017-87690-C3-1-

The SuperCam Remote Sensing Instrument Suite for Mars 2020

International audienceThe Mars 2020 rover, essentially a structural twin of MSL, is being built to a) characterize the geology and history of a new landing site on Mars, b) find and characterize ancient habitable environments, c) cache samples for eventual return to Earth, and d) demonstrate in-situ production of oxygen needed for human exploration. Remote-sensing instrumentation is needed to support the first three of these goals [1]. The SuperCam instrument meets these needs with a range of instrumentation including the highest-resolution remote imaging on the rover, two different techniques for determining mineralogy , and one technique to provide elemental compositions. All of these techniques are co-boresighted, providing rapid comprehensive characterization. In addition, for targets within 7 meters of the rover the laser shock waves brush away the dust, providing cleaner surfaces for analysis. SuperCam will use an advanced version of the AEGIS robotic target selection software

Observations of Rocks in Jezero Landing Site: SuperCam/LIBS technique overview of results from the first six months of operations.

On-board the Perseverance rover, the SuperCam instrument is being used as a remote-sensing facility to analyze rocks and soils targets. SuperCam is a suite of five coaligned techniques: just like ChemCam (onboard MSL/Curiosity rover on Mars since 2012), it uses the Laser Induced Breakdown Spectroscopy (LIBS) technique to determine the elementary composition of the targets, but it also uses Raman (for the first time in planetary science) and visible-infrared (VISIR - for the first time in situ) spectroscopic methods in order to access some mineralogical and structural information. A microphone gives access to some physical parameters of the sampled rocks (such as hardness) as well as to some atmospheric parameters (wind direction). These chemical and mineralogical analyses are contextualized thanks to a color remote micro-imager (RMI). In this study, we focus mainly on the LIBS results obtained so far

Desiccation cracks provide evidence of lake drying on Mars, Sutton Island member, Murray formation, Gale Crater

Mars Science Laboratory (MSL) Curiosity rover data are used to describe the morphology of desiccation cracks observed in ancient lacustrine strata at Gale crater, Mars, and to interpret their paleoenvironmental setting. The desiccation cracks indicate subaerial exposure of lacustrine facies in the Sutton Island member of the Murray formation. In association with ripple cross-stratification and possible eolian cross-bedding, these facies indicate a transition from longer-lived perennial lakes recorded by older strata to younger lakes characterized by intermittent exposure. The transition from perennial to episodically exposed lacustrine environments provides evidence for local to regional climate change that can help constrain Mars climate models

The Raman Laser Spectrometer for the ExoMars Rover Mission to Mars

The Raman Laser Spectrometer (RLS) on board the ESA/Roscosmos ExoMars 2020 mission will provide precise identification of the mineral phases and the possibility to detect organics on the Red Planet. The RLS will work on the powdered samples prepared inside the Pasteur analytical suite and collected on the surface and subsurface by a drill system. Raman spectroscopy is a well-known analytical technique based on the inelastic scattering by matter of incident monochromatic light (the Raman effect) that has many applications in laboratory and industry, yet to be used in space applications. Raman spectrometers will be included in two Mars rovers scheduled to be launched in 2020. The Raman instrument for ExoMars 2020 consists of three main units: (1) a transmission spectrograph coupled to a CCD detector; (2) an electronics box, including the excitation laser that controls the instrument functions; and (3) an optical head with an autofocus mechanism illuminating and collecting the scattered light from the spot under investigation. The optical head is connected to the excitation laser and the spectrometer by optical fibers. The instrument also has two targets positioned inside the rover analytical laboratory for onboard Raman spectral calibration. The aim of this article was to present a detailed description of the RLS instrument, including its operation on Mars. To verify RLS operation before launch and to prepare science scenarios for the mission, a simulator of the sample analysis chain has been developed by the team. The results obtained are also discussed. Finally, the potential of the Raman instrument for use in field conditions is addressed. By using a ruggedized prototype, also developed by our team, a wide range of terrestrial analog sites across the world have been studied. These investigations allowed preparing a large collection of real, in situ spectra of samples from different geological processes and periods of Earth evolution. On this basis, we are working to develop models for interpreting analog processes on Mars during the mission. Key Words: Raman spectroscopy—ExoMars mission—Instruments and techniques—Planetary sciences—Mars mineralogy and geochemistry—Search for life on Mars. Astrobiology 17, 627–65