Showing papers by "Pierre-and-Marie-Curie University published in 2023"

Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Abstract: Abstract Immune-checkpoint-inhibitor (ICI)–associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. Significance: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis.

Isotopic measurements in water vapor, precipitation, and seawater during EUREC⁴A

Abstract: Abstract. In early 2020, an international team set out to investigate trade-wind cumulus clouds and their coupling to the large-scale circulation through the field campaign EUREC4A: ElUcidating the RolE of Clouds-Circulation Coupling in ClimAte. Focused on the western tropical Atlantic near Barbados, EUREC4A deployed a number of innovative observational strategies, including a large network of water isotopic measurements collectively known as EUREC4A-iso, to study the tropical shallow convective environment. The goal of the isotopic measurements was to elucidate processes that regulate the hydroclimate state – for example, by identifying moisture sources, quantifying mixing between atmospheric layers, characterizing the microphysics that influence the formation and persistence of clouds and precipitation, and providing an extra constraint in the evaluation of numerical simulations. During the field experiment, researchers deployed seven water vapor isotopic analyzers on two aircraft, on three ships, and at the Barbados Cloud Observatory (BCO). Precipitation was collected for isotopic analysis at the BCO and from aboard four ships. In addition, three ships collected seawater for isotopic analysis. All told, the in situ data span the period 5 January–22 February 2020 and cover the approximate area 6 to 16∘ N and 50 to 60∘ W, with water vapor isotope ratios measured from a few meters above sea level to the mid-free troposphere and seawater samples spanning the ocean surface to several kilometers depth. This paper describes the full EUREC4A isotopic in situ data collection – providing extensive information about sampling strategies and data uncertainties – and also guides readers to complementary remotely sensed water vapor isotope ratios. All field data have been made publicly available even if they are affected by known biases, as is the case for high-altitude aircraft measurements, one of the two BCO ground-based water vapor time series, and select rain and seawater samples from the ships. Publication of these data reflects a desire to promote dialogue around improving water isotope measurement strategies for the future. The remaining, high-quality data create unprecedented opportunities to close water isotopic budgets and evaluate water fluxes and their influence on cloudiness in the trade-wind environment. The full list of dataset DOIs and notes on data quality flags are provided in Table 3 of Sect. 5 (“Data availability”).

Debate: Intermittent Hemodialysis versus Continuous Kidney Replacement Therapy in the Critically Ill Patient: The Choice Should Be Evidence Based

Abstract: Kidney replacement therapy (KRT) plays a major role in the treatment of severe AKI. Intermittent hemodialysis (HD) and continuous KRT (CKRT) are the main modalities in critically ill patients with AKI. CKRT is the preferred modality in many countries because of its alleged superiority on both hemodynamic tolerance and on kidney function recovery. In fact, randomized controlled trials (RCTs) comparing the two modalities have not shown any actual benefit of one technique over the other on mortality, hemodynamics, or kidney function recovery. Those RCTs were conducted more than 15 years ago. Major progress was eventually made leading to much lower mortality rates in recent studies than in previous studies. In addition, those RCTs included a noticeable proportion of patients who could have recovered without ever receiving KRT, as demonstrated by several recent studies. In the absence of evidence of clinical superiority of one KRT modality, the choice must be addressed not only regarding clinical outcome but also resources and logistics. Conclusions of health technology assessments and study reports were heterogeneous and conflicting concerning cost-effectiveness of intermittent HD versus CKRT. All these considerations justify a reevaluation of the issue in new RCTs that take into account recent knowledge on KRT initiation and management. Pending results of such study, the choice should be guided mainly by organizational considerations in each unit and without condemning any modality in the absence of proof.

Atmospheric nonlinearities strong contribution to the skewed ENSO amplitude and phase transition

Abstract: ENSO features prominent asymmetries, in terms of amplitude, spatial pattern and phase-transition between warm and cold events. Here we examine the contribution of atmospheric nonlinearities to ENSO asymmetries through a set of forced experiments with the CNRM-CM6 AGCM and the NEMO OGCM. Control experiments can reproduce the major atmospheric and oceanic asymmetries of ENSO, with stronger signals east of the dateline for strong El Niño events, and west of it for strong La Niñas. Ensemble atmospheric experiments forced by observed ENSO SST anomalies and their opposites allow diagnosing asymmetries in air-sea heat and momentum fluxes directly attributable to atmospheric nonlinearities. They indicate that atmospheric nonlinearities are largely attributable to nonlinearities in the rainfall-SST relation and act to enhance El Niño atmospheric signals east of the dateline and those of La Niña west of it. An ocean simulation where the non-linear signature of air-sea fluxes is removed from the forcing reveals that asymmetries in the ENSO SST pattern are primarily due to atmospheric nonlinearities, and result in a doubling of eastern Pacific warming during the peak of strong El Niño events and a 33% reduction during that of strong La Niña events. Atmospheric nonlinearities also explain most of the observed prolonged eastern Pacific warming into boreal summer after the peak of strong El Niño events. Overall, these results imply that properly simulating the nonlinear relationship between SST and rainfall in CGCMs is essential to accurately simulate asymmetries in ENSO amplitude, spatial pattern and phase transition. Finally, we discuss the inherent limitations to our two-tier forced approach.

Relative contribution of eddies ant atmospheric forcing to the Bay of Bengal non-seasonal Sea Surface Salinity Variability

Abstract: The Bay of Bengal (BoB) Sea Surface Salinity (SSS) is highly contrasted and variable, in response to the large monsoonal wind and freshwater forcing. In addition to this strong seasonal cycle, previous studies have underlined strong SSS non-seasonal variations associated with the Indian Ocean Dipole (IOD) and mesoscale eddies. In this study, we quantify the relative contributions of externally forced (wind, freshwater) and internally generated (mesoscale eddies) SSS non-seasonal variability in the BoB. To that end, we use Ocean General Circulation Model 10-member ensemble experiments from the IMHOTEP (IMpacts of freshwater discHarge interannual variability on Ocean heaT-salt contents and rEgional sea-level change over the altimetry Period) project.The model reproduces the large forced interannual SSS signals in the Northernmost part of the BoB and along the east coast of India, associated with the East Indian Coastal Current (EICC) modulation by the IOD. The internal SSS variability is largest in boreal fall in the North-Western BoB and more tightly controlled by the climatological SSS gradient distribution than by that of eddy kinetic energy. The external atmospheric forcing dominates the total variability in the regions of strongest variability, near the Ganges mouth and along the east coast of India in boreal fall and winter. Internal variability, however, contributes to 50-70% of the variability further offshore in boreal fall and winter. This confirms the strong role of eddies in controlling the freshwater extension up to ~700 km away from the coast, through stirring of the intense gradient between the coastal fresh and offshore saltier water. We finally discuss the consequences of these findings for comparing model and observations, in view of the chaotic nature of internal eddy variability.

Analysis of diffuse scattering from liquid and amorphous samples: protocols and software

Abstract: Fostered by third-generation synchrotron sources, experimental studies of physical and chemical properties of liquids at high pressure and temperatures are constantly pushed towards more and more extreme conditions, with applications ranging from Earth and planetary science, to material science, to fundamental physics.In the last 20 years, many efforts have been dedicated to the development of a method to obtain structural information from the X-ray diffuse scattering signal of a liquid [1], allowing, for instance, to improve our understanding of the structure and evolution of deep planetary interiors. However, while data collection protocols are by now quite advanced and overall comparable across beamlines worldwide, data analysis largely differs depending on user and employed codes. To answer to the need of a unified data analysis tool for liquids and amorphous systems, we developed Amorpheus [2].Amorpheus is an open-source, versatile, free and easy-to-use software for the analysis of X-ray diffuse scattering signal, allowing to perform a customizable analysis of a large amount of data and to invert for the density.  Available on GitHub [3] it is fully accessible by the community. This software has been tested on data collected with DAC and with large volume presses and it is well adapted for the analysis of liquid metals and alloys, as well as of amorphous systems. Here we will present and discuss selected examples of data analysis performed by Amorpheus in order to determine local structure and density of liquid iron binary and ternary alloys at planetary core conditions.[1] Eggert JH, Weck G, Loubeyre P, Mezouar M. Quantitative structure factor and density measurements of high-pressure fluids in diamond anvil cells by x-ray diffraction: Argon and water. Phys Rev B. 2002;65(17):174105. doi:10.1103/PhysRevB.65.174105[2] Boccato S, Garino Y, Morard G, et al. Amorpheus: a Python-based software for the treatment of X-ray scattering data of amorphous and liquid systems. High Press Res. 2022;42(1):69-93. doi:10.1080/08957959.2022.2032032[3] https://github.com/CelluleProjet/Amorpheus

The Model Intercomparison Project on the Climatic Response to Volcanic Forcing (VolMIP): Status and Future Perspectives of the Initiative

Abstract: The Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) is a protocol-driven international initiative under the umbrella of the sixth phase of the Coupled Model Intercomparison Project (CMIP6) aiming at coordinating the activities of different Research Institutes involved in numerical climate modelling focused on a multi-model assessment of climate models' performance under strong volcanic forcing conditions. The main objective of the initiative is to assess to what extent responses of the coupled ocean-atmosphere system to the same applied strong volcanic forcing are robustly simulated across state-of-the-art coupled climate models and identify the causes that limit robust simulated behavior, especially differences in their treatment of physical processes. To this purpose, four Tier-1 (mandatory) experiments branched into two main sets, named “volc-pinatubo” and “volc-long” were defined, together with eight more lower-priority experiments. Six years since the definition of the VolMIP protocol (Zanchettin et al., 2016), ensemble simulations of most of the mandatory VolMIP experiments have been completed and made publicly available through the Earth System Grid Federation open platform, with the first VolMIP results being currently published and several analyses in progress. The long turnover time between the experiment design, the integration of the simulations and the analysis of the output motivates an assessment of the overall effectiveness of the VolMIP strategy, particularly in the light of a possible second phase of the initiative.In this contribution, we will illustrate the status of the initiative, highlight its major achievements and discuss its future perspective in the light of emergent scientific questions regarding volcanically forced climate variability.Zanchettin, D., Khodri, M., Timmreck, C., Toohey, M., Schmidt, A., Gerber, E. P., Hegerl, G., Robock, A., Pausata, F. S. R., Ball, W. T., Bauer, S. E., Bekki, S., Dhomse, S. S., LeGrande, A. N., Mann, G. W., Marshall, L., Mills, M., Marchand, M., Niemeier, U., Poulain, V., Rozanov, E., Rubino, A., Stenke, A., Tsigaridis, K., and Tummon, F.: The Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP): experimental design and forcing input data for CMIP6, Geosci. Model Dev., 9, 2701–2719, https://doi.org/10.5194/gmd-9-2701-2016, 2

The Behavior of Bp He-weak Stars in the Far UV—Paper VII: HD 144334

Abstract: Abstract The analysis of 14 spectra of the B8 He-weak Si star HD 144334 recorded by the SWP camera on board the International Ultraviolet Explorer reveals variations of the far-ultraviolet spectral energy distribution shortwards of 1600 Å over a time interval of about five days in 1994 October. In contrast, the level of the mid-UV flux did not vary between phases of FUV flux maximum and minimum which suggests that changes of the silicon continuous and line opacity play an important role in the variations.

On the 2018-2020 Ice Shelf Water outflow event in the southeastern Weddell Sea

Abstract: The southern Weddell Sea features a vast perennially ice-covered continental shelf with polynyas, strong sea ice formation, first- and multi-year ice. Sea ice and the general ocean circulation maintain predominantly near-freezing waters on the shelf, which help to maintain the comparatively moderate basal melt rates of the Filchner-Ronne Ice Shelf (FRIS), Antarctica’s largest ice shelf by volume. In contrast to FRIS, other West Antarctic ice shelves show strong basal melt rates, caused by warm intruding ocean waters. In the southern Weddell Sea, however, warm water inflows occur episodically and spatially limited, when modified warm deep water enters the continental shelf through incisions in the shelf break and flows southward towards the FRIS front. Overall, the majority of the shelf is dominated by dense and cold water masses such as High Salinity Shelf Water (HSSW) and Ice Shelf Water (ISW), which are precursors of Antarctic Bottom Water and thus relevant for the global ocean circulation. In 2018, a comprehensive CTD survey found unprecedented (in the available observations) volumes of ISW in Filchner Trough. The ISW was exported from underneath the Filchner Ice Shelf (FIS) following a shift to enhanced cavity circulation due to strong sea ice formation in front of the Ronne Ice Shelf. These Filchner Trough conditions are summarized as the “Ronne-mode”, which is in contrast to the “Berkner-mode”, characterized by a greater influence of locally-formed waters. In this presentation, we introduce new multi-year time series from an international mooring network from various Southeast Weddell Sea locations (sub-FIS, Filchner Trough and Sill), to highlight the temporal and spatial extent of the recent Ronne-mode event, which lasted from 2018-2020, before shifting back into a Berkner-mode. The dominance of either circulation mode is controlled by large-scale atmospheric forcing and has implications on ice shelf basal melt and dense water export into the Weddell Sea. 

An Agent-Based Model for Land-Use Change Adaptation Strategies in the Context of Climate Change and Land Subsidence in the Mekong Delta

Abstract: The Mekong Delta region has been seriously affected by climate change, with increasing temperatures, sea-level rise, and salinization strongly impacting agricultural activities of the region. Recent studies have shown that groundwater exploitation also contributes significantly to land subsidence throughout the delta. Thus, combating climate change now makes it necessary to design strategies and policies for adapting to and mitigating climate change and subsidence, not only at the individual level (mainly farmers), but also at the institutional level (province and region). This study aims to build an integrated model for the purpose of exploring the socio-economic impact of adaptation strategies provinces choose under various climate and economic scenarios. The LUCAS–GEMMES model (an agent-based model for strategies for adapting to land-use change in the context of climate change) was developed in order to evaluate socio-economic factors, climate, and water use by farmers, as well as the subsidence dynamics and macroeconomic trends in land-use selection strategies. The simulations are carried out according to four main scenarios: (i) lack of provincial adaptation strategies and absence of subsidence dynamics, (ii) lack of adaptation strategies though subsidence and the impact of land-use production benefits, (iii) purely individual adaptation strategies combined with the impact of subsidence, and (iv) provincial and individual-scale adaptation combined with the impact of subsidence. In all the scenarios that consider subsidence, our results show that early response decisions to even low-level subsidence lead to many positive outcomes in water resource management, such as a significant reduction in water-use in the dry season and a reduction in the area vulnerable to subsidence and climate change. However, the same results also indicate a possible decrease in farmers’ income due to reduced agricultural seasons and restricted land-use transformation, which demonstrates the importance of modeling the multi-sectoral aspects of adaptation. Finally, at a more general level, in the fourth scenario, the model clearly shows the benefits when provinces located in the same agro-ecological zone harmonize strategies, thus paving the way for defining integrated land-use policies at the regional level.

Reply on RC3

Abstract: The role of surface ocean anomalies for the continental Northern Hemisphere snow cover is investigated, together with the interactions between snow cover and atmosphere. Four observational datasets and two large multi-model ensembles of atmosphere-only simulations are used, with prescribed sea surface temperature (SST) and sea ice concentration (SIC). A first ensemble uses observed interannually varying SST and SIC conditions for 1979–2014, while a second ensemble is identical except for SIC where a repeated climatological cycle is used. SST and external forcing typically explain 10 to 25 % of the snow cover variance in model simulations, with a dominant forcing from the tropical and North Pacific SST, while no robust influence of the SIC is found. In observations, the Ural blocking is the main driver of the November and April snow cover over Eastern Eurasia, while the North Atlantic Oscillation (NAO) dominates the snow cover forcing in January. In November and more robustly in January, dipolar anomalies of snow cover over Eurasia, with positive anomalies over Europe and negative anomalies over Southern Siberia, also precede the Arctic Oscillation (AO) by one month. In models, snow cover over western Eurasia in January also precedes by one or two months a negative AO phase. The detailed outputs from one of the models suggest that both the western Eurasia snow cover and polar vortex are generated by Ural blocking, and that both snow cover and polar vortex anomalies act to generate the AO one or two months later.

Entanglement and geometry from subalgebras of the Virasoro algebra

Abstract: A bstract In this work we study families of generalised coherent states constructed from SL(2,R) subalgebras of the Virasoro algebra in two-dimensional conformal field theories. We derive the energy density and entanglement entropy and discuss their equivalence with analogous quantities computed in locally excited states. Moreover, we analyze their dual, holographic geometries and reproduce entanglement entropies from the Ryu-Takayanagi prescription. Finally, we outline possible applications of this universal class of states to operator growth and inhomogeneous quenches.

Melting properties and melting phase relations of the Martian mantle from in-situ measurements on iron-rich mineralogical assemblages

Abstract: Mars’ mantle dynamical history has certainly been dominated by a stagnant-lid regime, with limited mixing and homogenization. Accordingly, the chemical and mineralogical signatures of early processes, including the crystallization of a primitive magma ocean, are overall well preserved on Mars. The major geological structures visible at its surface are the remains of an intense ancient volcanism, not so dissimilar from the large igneous provinces found on Earth at very old ages (several million/billion years).Current models used to determine the mantle thermal evolution and the crustal extraction heavily relies on melting properties of materials expected to form the Martian mantle, which, however are poorly known. In particular, the fact that the Martian mantle is probably richer in iron than the terrestrial mantle has a direct impact on the solidus and liquidus and on the chemistry of the magmas that can be produced at different pressures. Thus, the study of Martian volcanism and thermal history requires a precise understanding of the melting properties of the mantle (solidus, liquidus and extent of melting) as a function of pressure and temperature. Studies in literature are scant, mainly address the solidus, and are limited to analysis of recovered samples, missing in situ diagnostics.To address this problem, we studied the solid-liquid melting relations and, more generally, the melting diagram for a mineralogical assemblage model of mantle composition, by high-pressure and high-temperature experiments in multi anvil press performed at the PSICHE beamline of the SOLEIL synchrotron. We determined the solidus and the liquidus of the investigated rock at pressures up to 12 GPa by complementary in-situ diagnostics (X-ray diffraction and falling sphere technic). The obtained solidus and liquidus are well lower (difference >200K), especially at the highest investigated pressures, compared to previous studies, with strong implications for the origin of volcanism and notably the crystallization of the magma ocean. Furthermore, our experiments provide important data to refine the extent of melting (Φ), modal proportion and the chemistry of all the different phases present between the solidus and the liquidus at different conditions (P, T, Φ).Altogether, these new results are critical to constrain models of thermal evolution and crust extraction and formation, as well as to address the evolution of the magmatism and volcanism at the Mars surface since 3.5 Ga. Finally, depending on different parameters, such as the thickness of the crust or the concentration of radioactive elements, the estimated areotherm could cross the solidus and lead to partial melting of the mantle, especially close to the core-mantle boundary, where a high extent of melting could be reached.  

Magnetic excitations beyond the single- and double-magnons

Abstract: A photon carrying one unit of angular momentum can change the spin angular momentum of a magnetic system with one unit (ΔMs = ±1) at most. This implies that a two-photon scattering process can manipulate the spin angular momentum of the magnetic system with a maximum of two units. Herein we describe a triple-magnon excitation in α-Fe2O3, which contradicts this conventional wisdom that only 1- and 2-magnon excitations are possible in a resonant inelastic X-ray scattering experiment. We observe an excitation at exactly three times the magnon energy, along with additional excitations at four and five times the magnon energy, suggesting quadruple and quintuple-magnons as well. Guided by theoretical calculations, we reveal how a two-photon scattering process can create exotic higher-rank magnons and the relevance of these quasiparticles for magnon-based applications.

Local Structure and Density of Liquid Fe‐C‐S Alloys at Moon's Core Conditions

Abstract: The local structure and density of ternary Fe-C-S liquid alloys have been studied using a combination of in situ X-ray diffraction and absorption experiments between 1 and 5 GPa and 1600–1900 K. The addition of up to 12 at% of carbon (C) to Fe-S liquid alloys does not significantly modify the structure, which is largely controlled by the perturbation to the Fe-Fe network induced by S atoms. The liquid density determined from diffraction and/or absorption techniques allows us to build a non-ideal ternary mixing model as a function of pressure, temperature, and composition in terms of the content of alloying light elements. The composition of the Moon's core is addressed based on this thermodynamic model. Under the assumption of a homogeneous liquid core proposed by two recent Moon models, the sulfur content would be 27–36 wt% or 12–23 wt%, respectively, while the carbon content is mainly limited by the Fe-C-S miscibility gap, with an upper bound of 4.3 wt%. On the other hand, if the core is partially molten, the core temperature is necessarily lower than 1850 K estimated in the text, and the composition of both the inner and outer core would be controlled by aspects of the Fe-C-S phase diagram not yet sufficiently constrained.

Distinct and reproductible northem hemisphere winter teleconnection pattern during strong El Niño events : relative roles of Sea Surface Temperature forcing and atmospheric nonlinearities

Abstract: The strengthening and north-eastward shift of El Niño Northern hemisphere winter teleconnections relative to those of La Niña is a well-known asymmetry of ENSO (El Niño Southern Oscillation). It is generally attributed to atmospheric nonlinearities associated with the Sea Surface Temperature (SST) threshold for tropical deep convection. Here, we re-examine these teleconnection asymmetries in the context of ENSO SST pattern diversity. We find that the asymmetries are mainly attributable to strong El Niño events (eg. 1982-83, 1997-98, 2015-16), both in observations and in ensemble simulations with the atmospheric component of the CNRM-CM6 model. This strong El Niño teleconnection pattern also results in specific impacts, characterized by enhanced rainfall along the United States (US) west coast and warm anomalies over Canada and the Northern US. Our ensemble simulations further indicate that moderate “Eastern Pacific” El Niño events exhibit teleconnection patterns that are similar to those of “Central Pacific” El Niño, or to the opposite of La Niña events. We also find that the teleconnection spread between ensemble members or events is reduced for strong El Niño relative to moderate El Niño or La Niña events, with important implications for predictability. Sensitivity experiments in which the atmospheric model is forced by the opposite of observed SST anomalies are used to assess the mechanisms inducing the strong El Niño teleconnection pattern. In addition to the well-known influence of atmospheric nonlinearities, these experiments reveal an important contribution from the Eastward-shifted SST pattern during strong El Niño events.