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The Marine Ice Sheet–Ocean Model Intercomparison Project – phase 2 (MISOMIP2) is a natural progression of previous and ongoing model intercomparison exercises that have focused on the simulation of ice-sheet and ocean processes in Antarctica. The previous exercises motivate the move towards realistic configurations, as well as more diverse model parameters and resolutions. The main objective of MISOMIP2 is to investigate the performance of existing ocean and coupled ice-sheet–ocean models in a range of Antarctic environments through comparisons to observational data. We will assess the status of ice-sheet–ocean modelling as a community and identify common characteristics of models that are best able to capture observed features. As models are highly tuned based on present-day data, we will also compare their sensitivity to prescribed abrupt atmospheric perturbations leading to either very warm or slightly warmer ocean conditions compared to the present day. The approach of MISOMIP2 is to welcome contributions of models as they are, including global and regional configurations, but we request standardized variables and common grids for the outputs. We target the analysis at two specific regions, the Amundsen Sea and the Weddell Sea, since they describe two different ocean environments and have been relatively well observed compared to other areas of Antarctica. An observational “MIPkit” synthesizing existing ocean and ice-sheet observations for a common period is provided to evaluate ocean and ice-sheet models in these two regions.

Abstract The emergence of the Middle Palaeolithic, and its variability over time and space are key questions in the field of prehistoric archaeology. Many sites have been documented in the south-eastern margins of the Massif central and the middle Rhône valley, a migration path that connects Northern Europe with the Mediterranean. Well-dated, long stratigraphic sequences are essential to understand Neanderthals dynamics and demise, and potential interactions with Homo sapiens in the area, such as the one displayed at the Maras rock shelter (“Abri du Maras”). The site is characterised by exceptional preservation of archaeological remains, including bones dated using radiocarbon (14C) and teeth using electron spin resonance combined with uranium series (ESR/U-series). Optically stimulated luminescence was used to date the sedimentary deposits. By combining the new ages with previous ones using Bayesian modelling, we are able to clarify the occupation time over a period spanning 200,000 years. Between ca. 250 and 40 ka, the site has been used as a long-term residence by Neanderthals, specifically during three interglacial periods: first during marine isotopic stage (MIS) 7, between 247 ± 34 and 223 ± 33 ka, and then recurrently during MIS 5 (between 127 ± 17 and 90 ± 9 ka) and MIS 3 (up to 39,280 cal BP).

Abstract The Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) is the primary effort of CMIP6 (Coupled Model Intercomparison Project–Phase 6) focusing on ice sheets, designed to provide an ensemble of process‐based projections of the ice‐sheet contribution to sea‐level rise over the twenty‐first century. However, the behavior of the Antarctic Ice Sheet beyond 2100 remains largely unknown: several instability mechanisms can develop on longer time scales, potentially destabilizing large parts of Antarctica. Projections of Antarctic Ice Sheet evolution until 2300 are presented here, using an ensemble of 16 ice‐flow models and forcing from global climate models. Under high‐emission scenarios, the Antarctic sea‐level contribution is limited to less than 30 cm sea‐level equivalent (SLE) by 2100, but increases rapidly thereafter to reach up to 4.4 m SLE by 2300. Simulations including ice‐shelf collapse lead to an additional 1.1 m SLE on average by 2300, and can reach 6.9 m SLE. Widespread retreat is observed on that timescale in most West Antarctic basins, leading to a collapse of large sectors of West Antarctica by 2300 in 30%–40% of the ensemble. While the onset date of retreat varies among ice models, the rate of upstream propagation is highly consistent once retreat begins. Calculations of sea‐level contribution including water density corrections lead to an additional ∼10% sea level and up to 50% for contributions accounting for bedrock uplift in response to ice loading. Overall, these results highlight large sea‐level contributions from Antarctica and suggest that the choice of ice sheet model remains the leading source of uncertainty in multi‐century projections.

Patients with advanced cancer, previously treated with immune checkpoint blockade therapy, may retain residual treatment when undergoing the initial infusion of experimental monotherapy in phase 1 clinical trials. ANV419, an antibody-cytokine fusion protein, combines interleukin-2 (IL-2) with an anti-IL-2 monoclonal antibody, aiming to stimulate the expansion of CD8 T and natural killer lymphocytes while restricting regulatory T lymphocytes. In the recent publication of the phase 1 dose escalation study of ANV419, a notable gap exists in detailed information regarding patients’ prior antitumoral treatments, specifically programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) targeted monoclonal antibodies. Some patients likely retained residual anti-PD-1/PD-L1 monoclonal antibodies, potentially influencing the outcomes of ANV419. In a separate clinical cohort, we retrospectively measured the residual concentration of nivolumab and pembrolizumab, revealing persistent serum concentrations of anti-PD-1/PD-L1 antibodies even months after treatment cessation. This underscores the importance of comprehensively documenting prior immunotherapy details in clinical trials. Such information is crucial for understanding potential interactions that may impact both immunological and clinical effects.

Summary: Palaeoproteomic analysis of skeletal proteomes is used to provide taxonomic identifications for an increasing number of archaeological specimens. The success rate depends on a range of taphonomic factors and differences in the extraction protocols employed. By analyzing 12 archaeological bone specimens from two archaeological sites, we demonstrate that reducing digestion duration from 18 to 3 hours has no measurable impact on the obtained taxonomic identifications. Peptide marker recovery, COL1 sequence coverage, or proteome complexity are also not significantly impacted. Although we observe minor differences in sequence coverage and glutamine deamidation, these are not consistent across our dataset. A 6-fold reduction in digestion time reduces electricity consumption, and therefore CO2 emission intensities. We furthermore demonstrate that working in 96-well plates further reduces electricity consumption by 60%, in comparison to individual microtubes. Reducing digestion time therefore has no impact on the taxonomic identifications, while reducing the environmental impact of palaeoproteomic projects.

Abstract A generalized methodology to deploy different types of vertical coordinate system in arbitrarily defined time‐invariant local areas of quasi‐Eulerian numerical ocean models is presented. After detailing its characteristics, we show how the general localization method can be used to improve the representation of the Nordic Seas overflows in the UK Met Office NEMO‐based eddy‐permitting global ocean configuration. Three z*‐levels with partial steps configurations localizing different types of hybrid geopotential/terrain‐following vertical coordinates in the proximity of the Greenland‐Scotland ridge are implemented and compared against a control configuration. Experiments include a series of idealized and realistic numerical simulations where the skill of the models in computing pressure forces, reducing spurious diapycnal mixing and reproducing observed properties of the Nordic Seas overflows are assessed. Numerical results prove that the localization approach proposed here can be successfully used to embed terrain‐following levels in a global geopotential levels‐based configuration, provided that the localized vertical coordinate chosen is flexible enough to allow a smooth transition between the two. In addition, our experiments show that deploying localized terrain‐following levels via the multi‐envelope method allows the crucial reduction of spurious cross‐isopycnal mixing when modeling bottom intensified buoyancy driven currents, significantly improving the realism of the Nordic Seas overflows simulations in comparison to the other configurations. Important hydrographic biases are found to similarly affect all the realistic experiments and a discussion on how their interaction with the type of localized vertical coordinate affects the realism of the simulated overflows is provided.

Abstract The glaciers of North Greenland are hosting enough ice to raise sea level by 2.1 m, and have long considered to be stable. This part of Greenland is buttressed by the last remaining ice shelves of the ice sheet. Here, we show that since 1978, ice shelves in North Greenland have lost more than 35% of their total volume, three of them collapsing completely. For the floating ice shelves that remain we observe a widespread increase in ice shelf mass losses, that are dominated by enhanced basal melting rates. Between 2000 and 2020, there was a widespread increase in basal melt rates that closely follows a rise in the ocean temperature. These glaciers are showing a direct dynamical response to ice shelf changes with retreating grounding lines and increased ice discharge. These results suggest that, under future projections of ocean thermal forcing, basal melting rates will continue to rise or remain at high level, which may have dramatic consequences for the stability of Greenlandic glaciers.

How much Antarctic ice shelf basal melt rates can increase in response to global warming remains an open question. Here we describe the response of the Southern Ocean and ice shelf cavities to an abrupt change to high-end atmospheric conditions plausible by the late 23rd century under the SSP5-8.5 scenario. To achieve this objective, we first present and evaluate a new 0.25∘ global configuration of the NEMO (Nucleus for European Modelling of the Ocean NEMO System Team, 2019) ocean and sea ice model. Our present-day simulations demonstrate good agreement with observational data for key variables such as temperature, salinity, and ice shelf melt rates, despite the remaining difficulties to simulate the interannual variability in the Amundsen Sea. The ocean response to the high-end atmospheric perturbation includes a strengthening and extension of the Ross and Weddell gyres and a quasi-disappearance of sea ice, with a subsequent decrease in production of High Salinity Shelf Water and increased intrusion of warmer water onto the continental shelves favoured by changes in baroclinic currents at the shelf break. We propose to classify the perturbed continental shelf as a “warm–fresh shelf”. This induces a substantial increase in ice shelf basal melt rates, particularly in the coldest seas, with a total basal mass loss rising from 1180 to 15 700 Gt yr−1 and an Antarctica averaged melt rate increasing from 0.8 to 10.6 m yr−1. In the perturbed simulation, most ice shelves around Antarctica experience conditions that are currently found in the Amundsen Sea, while the Amundsen Sea warms by 2 ∘C. These idealised projections can be used as a base to calibrate basal melt parameterisations used in long-term ice sheet projections.

The world's largest ice shelves are found in the Antarctic Weddell Sea and Ross Sea where complex interactions between the atmosphere, sea ice, ice shelves and ocean transform shelf waters into High Salinity Shelf Water (HSSW) and Ice Shelf Water (ISW), the parent waters of Antarctic Bottom Water (AABW). This process feeds the lower limb of the global overturning circulation as AABW, the world's densest and deepest water mass, spreads outwards from Antarctica. None of the coupled climate models contributing to CMIP6 directly simulated ocean–ice shelf interactions, thereby omitting a potentially critical piece of the climate puzzle. As a first step towards better representing these processes in a global ocean model, we run a 1∘ resolution Nucleus for European Modelling of the Ocean (NEMO; eORCA1) forced configuration to explicitly simulate circulation beneath the Filchner-Ronne Ice Shelf (FRIS), Larsen C Ice Shelf (LCIS) and Ross Ice Shelf (RIS). These locations are thought to supply the majority of the source waters for AABW, and so melt in all other cavities is provisionally prescribed. Results show that the grid resolution of 1∘ is sufficient to produce melt rate patterns and total melt fluxes of FRIS (117 ± 21 Gt yr−1), LCIS (36 ± 7 Gt yr−1) and RIS (112 ± 22 Gt yr−1) that agree well with both high-resolution models and satellite measurements. Most notably, allowing sub-ice shelf circulation reduces salinity biases (0.1 psu), produces the previously unresolved water mass ISW and re-organizes the shelf circulation to bring the regional model hydrography closer to observations. A change in AABW within the Weddell Sea and the Ross Sea towards colder, fresher values is identified, but the magnitude is limited by the absence of a realistic overflow. This study presents a NEMO configuration that can be used for climate applications with improved realism of the Antarctic continental shelf circulation and a better representation of the precursors of AABW.

Abstract Melt rates at the base of Antarctic ice shelves are needed to drive projections of the Antarctic ice sheet mass loss. Current basal melt parameterizations struggle to link open ocean properties to ice‐shelf basal melt rates for the range of current sub‐shelf cavity geometries around Antarctica. We present a proof of concept exploring the potential of simple deep learning techniques to parameterize basal melt. We train a simple feedforward neural network, or multilayer perceptron, acting on each grid cell separately, to emulate the behavior of circum‐Antarctic cavity‐resolving ocean simulations. We find that this kind of emulator produces reasonable basal melt rates for our training ensemble, at least as close as or closer to the reference than traditional parameterizations. On an independent ensemble of simulations that was produced with the same ocean model but with different model parameters, cavity geometries and forcing, the neural network yields similar results to traditional parameterizations on present conditions. In much warmer conditions, both traditional parameterizations and neural network struggle, but the neural network tends to produce basal melt rates closer to the reference than a majority of traditional parameterizations. While this shows that such a neural network is at least as suitable for century‐scale Antarctic ice‐sheet projections as traditional parameterizations, it also highlights that tuning any parameterization on present‐like conditions can introduce biases and should be used with care. Nevertheless, this proof of concept is promising and provides a basis for further development of a deep learning basal melt parameterization.

In response to an increasing demand for bespoke or tailored regional ocean modelling configurations, we outline fundamental principles and practices that can expedite the process to generate new configurations. The paper develops the principle of reproducibility and advocates adherence by presenting benefits to the community and user. The elements of this principle are reproducible workflows and standardised assessment, with additional effort over existing working practices being balanced against the added value generated. The paper then decomposes the complex build process, for a new regional ocean configuration, into stages and presents guidance, advice and insight for each component. This advice is compiled from across the NEMO (Nucleus for European Modelling of the Ocean) user community and sets out principles and practises that encompass regional ocean modelling with any model. With detailed and region-specific worked examples in Sects. 3 and 4, the linked companion repositories and DOIs all target NEMOv4. The aim of this review and perspective paper is to broaden the user community skill base and to accelerate development of new configurations in order to increase the time available for exploiting the configurations.

Five nearly identical fragments of specialized bone tools, interpreted as lissoirs (French for "smoothers"), have been found at two Middle Paleolithic sites in southwest France. The finds span three separate archaeological deposits, suggesting continuity in the behavior of late Neandertals. Using standard morphological assessments, we determined that the lissoirs were produced on ribs of medium-sized ungulates. However, since these bones are highly fragmented and anthropogenically modified, species determinations were challenging. Also, conservative curation policy recommends minimizing destructive sampling of rare, fragile, or small artifacts for molecular identification methods. To better understand raw material selection for these five lissoirs, we reassess their taxonomy using a non-destructive ZooMS methodology based on triboelectric capture of collagen. We sampled four storage containers and obtained identifiable MALDI-TOF MS collagen fingerprints, all indicative of the same taxonomic clade, which includes aurochs and bison (Bos sp. and Bison sp.). The fifth specimen, which was stored in a plastic bag, provided no useful MALDI-TOF MS spectra. We show that the choice of large bovid ribs in an archaeological layer dominated by reindeer (Rangifer tarandus) demonstrates strategic selection by these Neandertals. Furthermore, our results highlight the value of a promising technique for the non-destructive analysis of bone artifacts.

Ocean-induced ice-shelf melt is one of the largest uncertainty factors in the Antarctic contribution to future sea-level rise. Several parameterisations exist, linking oceanic properties in front of the ice shelf to melt at the base of the ice shelf, to force ice-sheet models. Here, we assess the potential of a range of these existing basal melt parameterisations to emulate basal melt rates simulated by a cavity-resolving ocean model on the circum-Antarctic scale. To do so, we perform two cross-validations, over time and over ice shelves respectively, and re-tune the parameterisations in a perfect-model approach, to compare the melt rates produced by the newly tuned parameterisations to the melt rates simulated by the ocean model. We find that the quadratic dependence of melt to thermal forcing without dependency on the individual ice-shelf slope and the plume parameterisation yield the best compromise, in terms of integrated shelf melt and spatial patterns. The box parameterisation, which separates the sub-shelf circulation into boxes, the PICOP parameterisation, which combines the box and plume parameterisation, and quadratic parameterisations with dependency on the ice slope yield basal melt rates further from the model reference. The linear parameterisation cannot be recommended as the resulting integrated ice-shelf melt is comparably furthest from the reference. When using offshore hydrographic input fields in comparison to properties on the continental shelf, all parameterisations perform worse; however, the box and the slope-dependent quadratic parameterisations yield the comparably best results. In addition to the new tuning, we provide uncertainty estimates for the tuned parameters.

The Antarctic Ice Sheet will play a crucial role in the evolution of global mean sea level as the climate warms. An interactively coupled climate and ice sheet model is needed to understand the impacts of ice–climate feedbacks during this evolution. Here we use a two-way coupling between the UK Earth System Model and the BISICLES (Berkeley Ice Sheet Initiative for Climate at Extreme Scales) dynamic ice sheet model to investigate Antarctic ice–climate interactions under two climate change scenarios. We perform ensembles of SSP1–1.9 and SSP5–8.5 (Shared Socioeconomic Pathway) scenario simulations to 2100, which we believe are the first such simulations with a climate model that include two-way coupling of atmosphere and ocean models to dynamic models of the Greenland and Antarctic ice sheets. We focus our analysis on the latter. In SSP1–1.9 simulations, ice shelf basal melting and grounded ice mass loss from the Antarctic Ice Sheet are generally lower than present rates during the entire simulation period. In contrast, the responses to SSP5–8.5 forcing are strong. By the end of the 21st century, these simulations feature order-of-magnitude increases in basal melting of the Ross and Filchner–Ronne ice shelves, caused by intrusions of masses of warm ocean water. Due to the slow response of ice sheet drawdown, this strong melting does not cause a substantial increase in ice discharge during the simulations. The surface mass balance in SSP5–8.5 simulations shows a pattern of strong decrease on ice shelves, caused by increased melting, and strong increase on grounded ice, caused by increased snowfall. Despite strong surface and basal melting of the ice shelves, increased snowfall dominates the mass budget of the grounded ice, leading to an ensemble mean Antarctic contribution to global mean sea level of a fall of 22 mm by 2100 in the SSP5–8.5 scenario. We hypothesise that this signal would revert to sea-level rise on longer timescales, caused by the ice sheet dynamic response to ice shelf thinning. These results demonstrate the need for fully coupled ice–climate models in reducing the substantial uncertainty in sea-level rise from the Antarctic Ice Sheet.

Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2–0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies. Methods: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify HRAS molecular alterations in NSCLC patients. We identified and described four HRAS p.GlnQ61Leu mutated patients. Literature of previously HRAS-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented. Results: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had HRAS p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis. Conclusions: The clinical course of patients with HRAS-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target HRAS-mutant tumours and should be explored in NSCLC patients.

Global mean sea level has been rising at a rate of 3.25 ± 0.4 mm yr−1 over 1993–2018. Yet several regions are increasing at a much faster rate, such as the Beaufort Gyre in the Arctic Ocean at a rate of 9.3 ± 7.0 mm yr−1 over 2003–2014. At interannual to decadal time scales, the Beaufort Gyre sea level is controlled by salinity changes due to sea ice melt and wind‐driven lateral Ekman convergence–divergence of freshwater. This study uses recent Greenland discharge and river runoff estimates to isolate and quantify the sea level response to freshwater fluxes variability over the period 1980–2018. It relies on sensitivity experiments based on a global ocean model including sea‐ice and icebergs. These sensitivity experiments only differ by the freshwater fluxes temporal variability of Greenland and global rivers which are either seasonal climatologies or fully time varying, revealing the individual and combined impact of these freshwater sources fluctuations. Fully varying Greenland discharge and river runoff produce an opposite impact on sea level trends over 2005–2018 in the Beaufort Gyre region, the former driving an increase, while the latter, a decrease. Their combined impact leads to a fairly weak sea level trend. The sea level response is primarily driven by salinity variations in the upper 300 m, which are mainly caused by salinity advection involving complex compensations between passive, active, and nonlinear advection. This study shows that including the temporal variability of freshwater fluxes in forced global ocean models results in a better representation of regional sea level change. Plain Language Summary: Sea level is rising globally but not at the same rate everywhere. In the Arctic Ocean, the Beaufort Gyre sea level has been increasing at a fast rate of 9.3 ± 7.0 mm yr−1 over 2003–2014. At long time scales, the Beaufort Gyre sea level change is controlled by salinity, which depends mainly on continental freshwater runoff—particularly high in this region—and sea ice melt. This study uses recent estimates of Greenland discharge and river runoff in a global ocean model. The aim is to isolate and quantify the sea level response of the Beaufort Gyre to freshwater fluxes variability. We compare numerical simulations where Greenland discharge and river runoff are fully varying or set to a repeated seasonal cycle to reveal the individual and combined impacts of the variability of these freshwater sources on regional sea level. Both Greenland discharge and global river runoff impact remotely the Beaufort Gyre sea level. They induce salinity variations in the upper 300 m of the gyre through salinity advection. This study highlights the importance of the variability of continental freshwater fluxes in models in order to better represent regional sea level variability. Key Points: Greenland discharge and river runoff variability contribute to sea level rise and fall in the Beaufort GyreThe positive impact of Greenland is greater than the negative impact of rivers in the 0–78‐m range, and vice versa in the 78–300‐m rangeSea level change in the sensitivity experiments is mostly halosteric with salinity changes mainly controlled by advection [ABSTRACT FROM AUTHOR]

We introduce PARASO, a novel five-component fully coupled regional climate model over an Antarctic circumpolar domain covering the full Southern Ocean. The state-of-the-art models used are the fast Elementary Thermomechanical Ice Sheet model (f.ETISh) v1.7 (ice sheet), the Nucleus for European Modelling of the Ocean (NEMO) v3.6 (ocean), the Louvain-la-Neuve sea-ice model (LIM) v3.6 (sea ice), the COnsortium for Small-scale MOdeling (COSMO) model v5.0 (atmosphere) and its CLimate Mode (CLM) v4.5 (land), which are here run at a horizontal resolution close to 1/4∘. One key feature of this tool resides in a novel two-way coupling interface for representing ocean–ice-sheet interactions, through explicitly resolved ice-shelf cavities. The impact of atmospheric processes on the Antarctic ice sheet is also conveyed through computed COSMO-CLM–f.ETISh surface mass exchange. In this technical paper, we briefly introduce each model's configuration and document the developments that were carried out in order to establish PARASO. The new offline-based NEMO–f.ETISh coupling interface is thoroughly described. Our developments also include a new surface tiling approach to combine open-ocean and sea-ice-covered cells within COSMO, which was required to make this model relevant in the context of coupled simulations in polar regions. We present results from a 2000–2001 coupled 2-year experiment. PARASO is numerically stable and fully operational. The 2-year simulation conducted without fine tuning of the model reproduced the main expected features, although remaining systematic biases provide perspectives for further adjustment and development.

Background: Teachers report higher levels of stress than most occupational groups. Burnout is a specific psychological condition that results from chronic job stress characterized by emotional exhaustion, low personal accomplishment, and depersonalization. This study considers associations between aspects of the school environment and teacher burnout. Methods: Exploratory analysis of baseline data from a cluster randomized controlled trial of 40 schools and 2278 teachers in the United Kingdom. Multilevel methods were used to consider the associations between different compositional and contextual aspects of the school environment and teacher burnout. Results: There was evidence for school effects on teacher burnout, evidenced by ICCs and likelihood ratio tests, supporting the association between school environment and teacher burnout. The factors most consistently associated with teacher burnout in our study were teachers' perceptions of the school's safety and support and student attitudes to learning. Conclusions: The school environment does influence teacher burnout. More research is needed to develop and test causal pathways between the school environment and teacher burnout, and to understand ecological and individual predictors of teacher burnout and the interaction between the two.

Abstract Bone surface modifications are crucial for understanding human subsistence and dietary behaviour, and can inform about the techniques employed in the production and use of bone tools. Permission to destructively sample such unique artefacts is not always granted. The recent development of non-destructive proteomic extraction techniques has provided some alternatives for the analysis of rare and culturally significant artefacts, including bone tools and personal ornaments. The Eraser Extraction Method (EEM), first developed for ZooMS analysis of parchment, has recently been applied to bone and ivory specimens. To test the potential impact of the EEM on ancient bone surfaces, we analyse six anthropogenically modified Palaeolithic bone specimens from Bacho Kiro Cave (Bulgaria) through a controlled sampling experiment using qualitative and 3D quantitative microscopy. Although the overall bone topography is generally preserved, our findings demonstrate a slight flattening of the microtopography alongside the formation of micro-striations associated with the use of the eraser for all bone specimens. Such modifications are similar to ancient use-wear traces. We therefore consider the EEM a destructive sampling approach for Palaeolithic bone surfaces. Together with low ZooMS success rates in some of the reported studies, the EEM might not be a suitable approach to taxonomically identify Pleistocene bone specimens.

Abstract We develop a site-bond percolation model, called PERCOVID, in order to describe the time evolution of all epidemics propagating through respiratory tract or by skin contacts in human populations. This model is based on a network of social relationships representing interconnected households experiencing governmental non-pharmaceutical interventions. As a very first testing ground, we apply our model to the understanding of the dynamics of the COVID-19 pandemic in France from December 2019 up to December 2021. Our model shows the impact of lockdowns and curfews, as well as the influence of the progressive vaccination campaign in order to keep COVID-19 pandemic under the percolation threshold. We illustrate the role played by social interactions by comparing two typical scenarios with low or high strengths of social relationships as compared to France during the first wave in March 2020. We investigate finally the role played by the α and δ variants in the evolution of the epidemic in France till autumn 2021, paying particular attention to the essential role played by the vaccination. Our model predicts that the rise of the epidemic observed in July and August 2021 would not result in a new major epidemic wave in France.

Abstract Evidence of mobiliary art and body augmentation are associated with the cultural innovations introduced by Homo sapiens at the beginning of the Upper Paleolithic. Here, we report the discovery of the oldest known human-modified punctate ornament, a decorated ivory pendant from the Paleolithic layers at Stajnia Cave in Poland. We describe the features of this unique piece, as well as the stratigraphic context and the details of its chronometric dating. The Stajnia Cave plate is a personal 'jewellery' object that was created 41,500 calendar years ago (directly radiocarbon dated). It is the oldest known of its kind in Eurasia and it establishes a new starting date for a tradition directly connected to the spread of modern Homo sapiens in Europe.

Neuropilin 1 (NRP1), a cell-surface co-receptor of a number of growth factors and other signaling molecules, has long been the focus of attention due to its association with the development and the progression of several types of cancer. For example, the KDKPPR peptide has recently been combined with a photosensitizer and a contrast agent to bind NRP1 for the detection and treatment by photodynamic therapy of glioblastoma, an aggressive brain cancer. The main therapeutic target is a pocket of the fragment b1 of NRP1 (NRP1-b1), in which vascular endothelial growth factors (VEGFs) bind. In the crystal packing of native human NRP1-b1, the VEGF-binding site is obstructed by a crystallographic symmetry neighbor protein, which prevents the binding of ligands. Six charged amino acids located at the protein surface were mutated to allow the protein to form a new crystal packing. The structure of the mutated fragment b1 complexed with the KDKPPR peptide was determined by X-ray crystallography. The variant crystallized in a new crystal form with the VEGF-binding cleft exposed to the solvent and, as expected, filled by the C-terminal moiety of the peptide. The atomic interactions were analyzed using new approaches based on a multipolar electron density model. Among other things, these methods indicated the role played by Asp320 and Glu348 in the electrostatic steering of the ligand in its binding site. Molecular dynamics simulations were carried out to further analyze the peptide binding and motion of the wild-type and mutant proteins. The simulations revealed that specific loops interacting with the peptide exhibited mobility in both the unbound and bound forms.

Glutathione transferases (GSTs) constitute a widespread superfamily of enzymes notably involved in xenobiotic detoxification and/or in specialized metabolism. Populus trichocarpa genome (V4.1 assembly, Phytozome 13) consists of 74 genes coding for full-length GSTs and ten likely pseudogenes. These GSTs are divided into 11 classes, in which the tau class (GSTU) is the most abundant with 54 isoforms. PtGSTU19 and 20, two paralogs sharing more than 91% sequence identity (95% of sequence similarity), would have diverged from a common ancestor of P. trichocarpa and P. yatungensis species. These enzymes display the distinctive glutathione (GSH)-conjugation and peroxidase activities against model substrates. The resolution of the crystal structures of these proteins revealed significant structural differences despite their high sequence identity. PtGSTU20 has a well-defined deep pocket in the active site whereas the bottom of this pocket is disordered in PtGSTU19. In a screen of potential ligands, we were able to identify an interaction with flavonoids. Some of them, previously identified in poplar (chrysin, galangin, and pinocembrin), inhibited GSH-conjugation activity of both enzymes with a more pronounced effect on PtGSTU20. The crystal structures of PtGSTU20 complexed with these molecules provide evidence for their potential involvement in flavonoid transport in P. trichocarpa.

Abstract Background Little is known about volunteers from Northern research settings who participate in vaccine trials of highly infectious diseases with no approved treatments. This article explores the motivations of HIV immunocompromised study participants in Canada who volunteered in a Phase II clinical trial that evaluated the safety and immunogenicity of an Ebola vaccine candidate. Methods Observation at the clinical study site and semi-structured interviews employing situational and discursive analysis were conducted with clinical trial participants and staff over one year. Interviews were recorded, transcribed and analysed using critical qualitative interpretivist thematic analytical techniques. Patterns were identified, clustered and sorted to generate distinct and comprehensive themes. We then reassembled events and contexts from the study participants’ stories to develop two ideal portraits based on "composite characters" based on study participants features. These provide ethnographically rich details of participants’ meaningful social worlds while protecting individual identities. Results Ten of the 14 clinical trial participants, and 3 study staff were interviewed. Participant demographics and socio-economic profiles expressed limited contextual diversity. Half were men who have sex with men, half were former injection drug users experiencing homelessness, one was female, none were racialized minorities and there were no people from HIV endemic countries. Fully 90% had previous involvement in other clinical studies. Their stories point to particular socio-economic situations that motivated their participation as clinical labor through trial participation. Conclusions Our findings support Fisher’s argument of “structural coercion” in clinical trial recruitment of vulnerable individuals experiencing precarious living conditions. Clinical trials should provide more detail of the structural socio-economic conditions and healthcare needs which lie “under consent” of study participants. Going well beyond an overly convenient narrative of altruism, ethical deliberation frameworks need to sufficiently address the structural conditions of clinical trials. We offer concrete possibilities for this and acknowledge that further research and clinical data should be made available underlying study participant contexts with regards to recruitment and participation in resource poor settings, in both the South and the North.

Education policy increasingly promotes action groups as a key strategy for student and/or staff participation in school improvement and whole-school health promotion. Such groups can coordinate multi-component interventions, increase participation and engagement, and enable local adaptations, but few process evaluations have assessed this. We evaluated fidelity, feasibility and acceptability of action groups as part of a trial of a whole-school intervention to reduce bullying and aggression and promote health in English secondary schools, which reported multiple health and educational impacts. Action groups involved students and staff, supported by external facilitators, and drew on data on student needs. They aimed to: coordinate implementation of restorative practices and a social and emotional competencies curriculum; review policies and rules; and enact local decisions to modify school environments. Our process evaluation used interviews, focus groups, observations and questionnaires to assess action groups' fidelity, role in coordination, role in local adaptation, support from external facilitators and data on student needs, and acceptability in engaging members. Fidelity was high in the first two years but lower in the third year when external facilitators withdrew. Student needs data were perceived as useful, but views on external facilitators were mixed. Groups successfully reviewed policies and rules, planned activities and coordinated restorative practices, but were less successful in implementing the curriculum. Success was facilitated by the involvement of school leaders. Members reported high satisfaction and empowerment. Action groups are a promising strategy for leading whole-school health promotion. Implementation is supported by external facilitation, local data and involvement of senior managers.

Coupled ice sheet-ocean models capable of simulating moving grounding lines are just becoming available. Such models have a broad range of potential applications in studying the dynamics of marine ice sheets and tidewater glaciers, from process studies to future projections of ice mass loss and sea level rise. The Marine Ice Sheet-Ocean Model Intercomparison Project (MISOMIP) is a community effort aimed at designing and coordinating a series of model intercomparison projects (MIPs) for model evaluation in idealized setups, model verification based on observations, and future projections for key regions of the West Antarctic Ice Sheet (WAIS). Here we describe computational experiments constituting three interrelated MIPs for marine ice sheet models and regional ocean circulation models incorporating ice shelf cavities. These consist of ice sheet experiments under the Marine Ice Sheet MIP third phase (MISMIP+), ocean experiments under the Ice Shelf-Ocean MIP second phase (ISOMIP+) and coupled ice sheet-ocean experiments under the MISOMIP first phase (MISOMIP1). All three MIPs use a shared domain with idealized bedrock topography and forcing, allowing the coupled simulations (MISOMIP1) to be compared directly to the individual component simulations (MISMIP+ and ISOMIP+). The experiments, which have qualitative similarities to Pine Island Glacier Ice Shelf and the adjacent region of the Amundsen Sea, are designed to explore the effects of changes in ocean conditions, specifically the temperature at depth, on basal melting and ice dynamics. In future work, differences between model results will form the basis for the evaluation of the participating models.

Coupled ice sheet-ocean models capable of simulating moving grounding lines are just becoming available. Such models have a broad range of potential applications in studying the dynamics of marine ice sheets and tidewater glaciers, from process studies to future projections of ice mass loss and sea level rise. The Marine Ice Sheet-Ocean Model Intercomparison Project (MISOMIP) is a community effort aimed at designing and coordinating a series of model intercomparison projects (MIPs) for model evaluation in idealized setups, model verification based on observations, and future projections for key regions of the West Antarctic Ice Sheet (WAIS). Here we describe computational experiments constituting three interrelated MIPs for marine ice sheet models and regional ocean circulation models incorporating ice shelf cavities. These consist of ice sheet experiments under the Marine Ice Sheet MIP third phase (MISMIP+), ocean experiments under the Ice Shelf-Ocean MIP second phase (ISOMIP+) and coupled ice sheet-ocean experiments under the MISOMIP first phase (MISOMIP1). All three MIPs use a shared domain with idealized bedrock topography and forcing, allowing the coupled simulations (MISOMIP1) to be compared directly to the individual component simulations (MISMIP+ and ISOMIP+). The experiments, which have qualitative similarities to Pine Island Glacier Ice Shelf and the adjacent region of the Amundsen Sea, are designed to explore the effects of changes in ocean conditions, specifically the temperature at depth, on basal melting and ice dynamics. In future work, differences between model results will form the basis for the evaluation of the participating models.