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Observations of glacier mass changes are key to understanding the response of glaciers to climate change and related impacts, such as regional runoff, ecosystem changes, and global sea level rise. Spaceborne optical and radar sensors make it possible to quantify glacier elevation changes, and thus multi-annual mass changes, on a regional and global scale. However, estimates from a growing number of studies show a wide range of results with differences often beyond uncertainty bounds. Here, we present the outcome of a community-based inter-comparison experiment using spaceborne optical stereo (ASTER) and synthetic aperture radar interferometry (TanDEM-X) data to estimate elevation changes for defined glaciers and target periods that pose different assessment challenges. Using provided or self-processed digital elevation models (DEMs) for five test sites, 12 research groups provided a total of 97 spaceborne elevation-change datasets using various processing approaches. Validation with airborne data showed that using an ensemble estimate is promising to reduce random errors from different instruments and processing methods but still requires a more comprehensive investigation and correction of systematic errors. We found that scene selection, DEM processing, and co-registration have the biggest impact on the results. Other processing steps, such as treating spatial data voids, differences in survey periods, or radar penetration, can still be important for individual cases. Future research should focus on testing different implementations of individual processing steps (e.g. co-registration) and addressing issues related to temporal corrections, radar penetration, glacier area changes, and density conversion. Finally, there is a clear need for our community to develop best practices, use open, reproducible software, and assess overall uncertainty to enhance inter-comparison and empower physical process insights across glacier elevation-change studies.

Avalanches are important contributors to the mass balance of glaciers located in mountain ranges with steep topographies. Avalanches result in localized over-accumulation that is seldom accounted for in glacier models due to the difficulty of quantifying this contribution, let alone the occurrence of avalanches in these remote regions. Here, we developed an approach to semi-automatically map avalanche deposits over long time periods and at scales of multiple glaciers, utilizing imagery from Sentinel-1 synthetic aperture radar (SAR). This approach performs particularly well for scenes acquired in winter and in the morning but can also be used to identify avalanche events throughout the year. We applied this method to map 16 302 avalanche deposits over a period of 5 years at a 6 to 12 d interval over the Mt Blanc massif (European Alps), the Everest (central Himalaya) region, and the Hispar (Karakoram) region. These three survey areas are all characterized by steep mountain slopes but also present contrasting climatic characteristics. Our results enable the identification of avalanche hotspots on these glaciers and allow us to quantify the avalanche activity and its spatio-temporal variability across the three regions. The avalanche deposits are preferentially located at lower elevations relative to the hypsometry of the glacierized catchments and are also constrained to a smaller elevation range at the Asian sites, where they have a limited influence on their extensive debris-covered tongues. Avalanche events coincide with solid precipitation events, which explains the high avalanche activity in winter in the Mt Blanc massif and during the monsoon in the Everest region. However, there is also a time lag of 1–2 months, visible especially in the Everest region, between the precipitation and avalanche events, indicative of some snow retention on the mountain headwalls. This study therefore provides critical insights into these mass redistribution processes and tools to account for their influence on glacier mass balance.

The surface energy budget drives the melt of the snow cover and glacier ice and its computation is thus of crucial importance in numerical models. This surface energy budget is the result of various surface energy fluxes, which depend on the input meteorological variables and surface temperature; of heat conduction towards the interior of the snow/ice; and potentially of surface melting if the melt temperature is reached. The surface temperature and melt rate of a snowpack or ice are thus driven by coupled processes. In addition, these energy fluxes are non-linear with respect to the surface temperature, making their numerical treatment challenging. To handle this complexity, some of the current numerical models tend to rely on a sequential treatment of the involved physical processes, in which surface fluxes, heat conduction, and melting are treated with some degree of decoupling. Similarly, some models do not explicitly define a surface temperature and rather use the temperature of the internal point closest to the surface instead. While these kinds of approaches simplify the implementation and increase the modularity of models, they can also introduce several problems, such as instabilities and mesh sensitivity. Here, we present a numerical methodology to treat the surface and internal energy budgets of snowpacks and glaciers in a tightly coupled manner, including potential surface melting when the melt temperature is reached. Specific care is provided to ensure that the proposed numerical scheme is as fast and robust as classical numerical treatment of the surface energy budget. Comparisons based on simple test cases show that the proposed methodology yields smaller errors for almost all time steps and mesh sizes considered and does not suffer from numerical instabilities, contrary to some classical treatments.

Climate change modifies the water and energy fluxes between the atmosphere and the surface in mountainous regions such as the Qinghai–Tibet Plateau (QTP), which has shown substantial hydrological changes over the last decades, including rapid lake level variations. The ground across the QTP hosts either permafrost or is seasonally frozen, and, in this environment, the ground thermal regime influences liquid water availability, evaporation and runoff. Consequently, climate-induced changes in the ground thermal regime may contribute to variations in lake levels, but the validity of this hypothesis has yet to be established. This study focuses on the cryo-hydrology of the catchment of Lake Paiku (southern Tibet) for the 1980–2019 period. We process ERA5 data with downscaling and clustering tools (TopoSCALE, TopoSUB) to account for the spatial variability of the climate in our forcing data (Fiddes and Gruber, 2012, 2014). We use a distributed setup of the CryoGrid community model (version 1.0) to quantify thermo-hydrological changes in the ground during this period. Forcing data and simulation outputs are validated with data from a weather station, surface temperature loggers and observations of lake level variations. Our lake budget reconstruction shows that the main water input to the lake is direct precipitation (310 mm yr−1), followed by glacier runoff (280 mm yr−1) and land runoff (180 mm yr−1). However, altogether these components do not offset evaporation (860 mm yr−1). Our results show that both seasonal frozen ground and permafrost have warmed (0.17 ∘C per decade 2 m deep), increasing the availability of liquid water in the ground and the duration of seasonal thaw. Correlations with annual values suggest that both phenomena promote evaporation and runoff. Yet, ground warming drives a strong increase in subsurface runoff so that the runoff/(evaporation + runoff) ratio increases over time. This increase likely contributed to stabilizing the lake level decrease after 2010. Summer evaporation is an important energy sink, and we find active-layer deepening only where evaporation is limited. The presence of permafrost is found to promote evaporation at the expense of runoff, consistently with recent studies suggesting that a shallow active layer maintains higher water contents close to the surface. However, this relationship seems to be climate dependent, and we show that a colder and wetter climate produces the opposite effect. Although the present study was performed at the catchment scale, we suggest that this ambivalent influence of permafrost may help to understand the contrasting lake level variations observed between the south and north of the QTP, opening new perspectives for future investigations.

The Tarantula Nebula in the Large Magellanic Cloud is known for its high star formation activity. At its center lies the young massive star cluster R136, providing a significant amount of the energy that makes the nebula shine so brightly at many wavelengths. Recently, young massive star clusters have been suggested to also efficiently produce very high-energy cosmic rays, potentially beyond PeV energies. Here, we report the detection of very-high-energy γ -ray emission from the direction of R136 with the High Energy Stereoscopic System, achieved through a multicomponent, likelihood-based modeling of the data. This supports the hypothesis that R136 is indeed a very powerful cosmic-ray accelerator. Moreover, from the same analysis, we provide an updated measurement of the γ -ray emission from 30 Dor C, the only superbubble detected at TeV energies presently. The γ -ray luminosity above 0.5 TeV of both sources is (2–3) × 10 ^35 erg s ^−1 . This exceeds by more than a factor of 2 the luminosity of HESS J1646−458, which is associated with the most massive young star cluster in the Milky Way, Westerlund 1. Furthermore, the γ -ray emission from each source is extended with a significance of >3 σ and a Gaussian width of about 30 pc. For 30 Dor C, a connection between the γ -ray emission and the nonthermal X-ray emission appears likely. Different interpretations of the γ -ray signal from R136 are discussed.

The South Col Glacier is a small body of ice and snow (approx. 0.2 km2) located at the very high elevation of 8000 m a.s.l. (above sea level) on the southern ridge of Mt. Everest. A recent study by Potocki et al. (2022) proposed that South Col Glacier is rapidly losing mass. This is in contradiction to our comparison of two digital elevation models derived from aerial photographs taken in December 1984 and a stereo Pléiades satellite acquisition from March 2017, from which we estimate a mean elevation change of 0.01 ± 0.05 m a−1. To reconcile these results, we investigate some aspects of the surface energy and mass balance of South Col Glacier. From satellite images and a simple model of snow compaction and erosion, we show that wind erosion has a major impact on the surface mass balance due to the strong seasonality in precipitation and wind and that it cannot be neglected. Additionally, we show that the melt amount predicted by a surface energy and mass balance model is very sensitive to the model structure and implementation. Contrary to previous findings, melt is likely not a dominant ablation process on this glacier, which remains mostly snow-covered during the monsoon.

In 2021 July, PKS 1510−089 exhibited a significant flux drop in the high-energy γ -ray (by a factor 10) and optical (by a factor 5) bands and remained in this low state throughout 2022. Similarly, the optical polarization in the source vanished, resulting in the optical spectrum being fully explained through the steady flux of the accretion disk and the broad-line region. Unlike the aforementioned bands, the very-high-energy γ -ray and X-ray fluxes did not exhibit a significant flux drop from year to year. This suggests that the steady-state very-high-energy γ -ray and X-ray fluxes originate from a different emission region than the vanished parts of the high-energy γ -ray and optical jet fluxes. The latter component has disappeared through either a swing of the jet away from the line of sight or a significant drop in the photon production efficiency of the jet close to the black hole. Either change could become visible in high-resolution radio images.

Magnetic fields in galaxies and galaxy clusters are believed to be the result of the amplification of intergalactic seed fields during the formation of large-scale structures in the universe. However, the origin, strength, and morphology of this intergalactic magnetic field (IGMF) remain unknown. Lower limits on (or indirect detection of) the IGMF can be obtained from observations of high-energy gamma rays from distant blazars. Gamma rays interact with the extragalactic background light to produce electron−positron pairs, which can subsequently initiate electromagnetic cascades. The gamma-ray signature of the cascade depends on the IGMF since it deflects the pairs. Here we report on a new search for this cascade emission using a combined data set from the Fermi Large Area Telescope and the High Energy Stereoscopic System. Using state-of-the-art Monte Carlo predictions for the cascade signal, our results place a lower limit on the IGMF of B > 7.1 × 10 ^−16 G for a coherence length of 1 Mpc even when blazar duty cycles as short as 10 yr are assumed. This improves on previous lower limits by a factor of 2. For longer duty cycles of 10 ^4 (10 ^7 ) yr, IGMF strengths below 1.8 × 10 ^−14 G (3.9 × 10 ^−14 G) are excluded, which rules out specific models for IGMF generation in the early universe.

GRB 221009A is the brightest gamma-ray burst (GRB) ever detected. To probe the very-high-energy (VHE; >100 GeV) emission, the High Energy Stereoscopic System (H.E.S.S.) began observations 53 hr after the triggering event, when the brightness of the moonlight no longer precluded observations. We derive differential and integral upper limits using H.E.S.S. data from the third, fourth, and ninth nights after the initial GRB detection, after applying atmospheric corrections. The combined observations yield an integral energy flux upper limit of ${{\rm{\Phi }}}_{\mathrm{UL}}^{95 \% }=9.7\times {10}^{-12}\,\mathrm{erg}\,{\mathrm{cm}}^{-2}\,{{\rm{s}}}^{-1}$ above E _thr = 650 GeV. The constraints derived from the H.E.S.S. observations complement the available multiwavelength data. The radio to X-ray data are consistent with synchrotron emission from a single electron population, with the peak in the spectral energy distribution occurring above the X-ray band. Compared to the VHE-bright GRB 190829A, the upper limits for GRB 221009A imply a smaller gamma-ray to X-ray flux ratio in the afterglow. Even in the absence of a detection, the H.E.S.S. upper limits thus contribute to the multiwavelength picture of GRB 221009A, effectively ruling out an IC-dominated scenario.

Mass balance observations are very useful to assess climate change in different regions of the world. As opposed to glacier-wide mass balances which are influenced by the dynamic response of each glacier, point mass balances provide a direct climatic signal that depends on surface accumulation and ablation only. Unfortunately, major efforts are required to conduct in situ measurements on glaciers. Here, we propose a new approach that determines point surface mass balances from remote sensing observations. We call this balance the geodetic point surface mass balance. From observations and modelling performed on the Argentière and Mer de Glace glaciers over the last decade, we show that the vertical ice flow velocity changes are small in areas of low bedrock slope. Therefore, assuming constant vertical velocities in time for such areas and provided that the vertical velocities have been measured for at least 1 year in the past, our method can be used to reconstruct annual point surface mass balances from surface elevations and horizontal velocities alone. We demonstrate that the annual point surface mass balances can be reconstructed with an accuracy of about 0.3 m of water equivalent per year (m w.e. a−1) using the vertical velocities observed over the previous years and data from unmanned aerial vehicle images. Given the recent improvements of satellite sensors, it should be possible to apply this method to high-spatial-resolution satellite images as well.

The lower parts of two glaciers in the Aru range on the western Tibetan Plateau (TP) collapsed on 17 July and 21 September 2016, respectively, causing fatal damage to local people and their livestock. The giant ice avalanches, with a total volume of 150 × 106 m3, had almost melted by September 2019 (about 30 % of the second ice avalanche remained). The impact of these extreme disasters on downstream lakes has not been investigated yet. Based on in situ observation, bathymetry survey and satellite data, we explore the impact of the ice avalanches on the two downstream lakes (i.e., Aru Co and Memar Co) in terms of lake morphology, water level and water temperature in the subsequent 4 years (2016–2019). After the first glacier collapse, the ice avalanche slid into Aru Co along with a large amount of debris, which generated great impact waves in Aru Co and significantly modified the lake's shoreline and underwater topography. An ice volume of at least 7.1 × 106 m3 was discharged into Aru Co, spread over the lake surface and considerably lowered its surface temperature by 2–4 ∘C in the first 2 weeks after the first glacier collapse. Due to the large amount of meltwater input, Memar Co exhibited more rapid expansion after the glacier collapses (2016–2019) than before (2003–2014), in particular during the warm season. The melting of ice avalanches was found to contribute to about 23 % of the increase in lake storage between 2016 and 2019. Our results indicate that the Aru glacier collapses had both short-term and long-term impacts on the downstream lakes and provide a baseline in understanding the future lake response to glacier melting on the TP under a warming climate.

We report on multiwavelength target-of-opportunity observations of the blazar PKS 0735+178, located 2.°2 away from the best-fit position of the IceCube neutrino event IceCube-211208A detected on 2021 December 8. The source was in a high-flux state in the optical, ultraviolet, X-ray, and GeV γ -ray bands around the time of the neutrino event, exhibiting daily variability in the soft X-ray flux. The X-ray data from Swift-XRT and NuSTAR characterize the transition between the low-energy and high-energy components of the broadband spectral energy distribution (SED), and the γ -ray data from Fermi-LAT, VERITAS, and H.E.S.S. require a spectral cutoff near 100 GeV. Both the X-ray and γ -ray measurements provide strong constraints on the leptonic and hadronic models. We analytically explore a synchrotron self-Compton model, an external Compton model, and a lepto-hadronic model. Models that are entirely based on internal photon fields face serious difficulties in matching the observed SED. The existence of an external photon field in the source would instead explain the observed γ -ray spectral cutoff in both the leptonic and lepto-hadronic models and allow a proton jet power that marginally agrees with the Eddington limit in the lepto-hadronic model. We show a numerical lepto-hadronic model with external target photons that reproduces the observed SED and is reasonably consistent with the neutrino event despite requiring a high jet power.

In a context of climate change and water demand growth, understanding the origin of water flows in the Himalayas is a key issue for assessing the current and future water resource availability and planning the future uses of water in downstream regions. Two of the main issues in the hydrology of high-altitude glacierized catchments are (i) the limited representation of cryospheric processes controlling the evolution of ice and snow in distributed hydrological models and (ii) the difficulty in defining and quantifying the hydrological contributions to the river outflow. This study estimates the relative contribution of rainfall, glaciers, and snowmelt to the Khumbu River streamflow (Upper Dudh Koshi, Nepal, 146 km2, 43 % glacierized, elevation range from 4260 to 8848 m a.s.l.) as well as the seasonal, daily, and sub-daily variability during the period 2012–2015 by using the DHSVM-GDM (Distributed Hydrological Soil Vegetation Model – Glaciers Dynamics Model) physically based glacio-hydrological model. The impact of different snow and glacier parameterizations was tested by modifying the snow albedo parameterization, adding an avalanche module, adding a reduction factor for the melt of debris-covered glaciers, and adding a conceptual englacial storage. The representation of snow, glacier, and hydrological processes was evaluated using three types of data (MODIS satellite images, glacier mass balances, and in situ discharge measurements). The relative flow components were estimated using two different definitions based on the water inputs and contributing areas. The simulated hydrological contributions differ not only depending on the used models and implemented processes, but also on different definitions of the estimated flow components. In the presented case study, ice melt and snowmelt contribute each more than 40 % to the annual water inputs and 69 % of the annual stream flow originates from glacierized areas. The analysis of the seasonal contributions highlights that ice melt and snowmelt as well as rain contribute to monsoon flows in similar proportions and that winter outflow is mainly controlled by the release from the englacial water storage. The choice of a given parametrization for snow and glacier processes, as well as their relative parameter values, has a significant impact on the simulated water balance: for instance, the different tested parameterizations led to ice melt contributions ranging from 42 % to 54 %. The sensitivity of the model to the glacier inventory was also tested, demonstrating that the uncertainty related to the glacierized surface leads to an uncertainty of 20 % for the simulated ice melt component.

A set of supraglacial ponds filled rapidly between April and July 2017 on Changri Shar Glacier in the Everest region of Nepal, coalescing into a ∼180 000 m2 lake before sudden and complete drainage through Changri Shar and Khumbu glaciers (15–17 July). We use PlanetScope and Pléiades satellite orthoimagery to document the system's evolution over its very short filling period and to assess the glacial and proglacial effects of the outburst flood. We also use high-resolution stereo digital elevation models (DEMs) to complete a detailed analysis of the event's glacial and geomorphic effects. Finally, we use discharge records at a stream gauge 4 km downstream to refine our interpretation of the chronology and magnitude of the outburst. We infer largely subsurface drainage through both of the glaciers located on its flow path, and efficient drainage through the lower portion of Khumbu Glacier. The drainage and subsequent outburst of 1.36±0.19×106 m3 of impounded water had a clear geomorphic impact on glacial and proglacial topography, including deep incision and landsliding along the Changri Nup proglacial stream, the collapse of shallow englacial conduits near the Khumbu terminus and extensive, enhanced bank erosion at least as far as 11 km downstream below Khumbu Glacier. These sudden changes destroyed major trails in three locations, demonstrating the potential hazard that short-lived, relatively small glacial lakes pose.

Ice cliff backwasting on debris-covered glaciers is recognized as an important mass-loss process that is potentially responsible for the debris-cover anomaly, i.e. the fact that debris-covered and debris-free glacier tongues appear to have similar thinning rates in the Himalaya. In this study, we quantify the total contribution of ice cliff backwasting to the net ablation of the tongue of Changri Nup Glacier, Nepal, between 2015 and 2017. Detailed backwasting and surface thinning rates were obtained from terrestrial photogrammetry collected in November 2015 and 2016, unmanned air vehicle (UAV) surveys conducted in November 2015, 2016 and 2017, and Pléiades tri-stereo imagery obtained in November 2015, 2016 and 2017. UAV- and Pléiades-derived ice cliff volume loss estimates were 3 % and 7 % less than the value calculated from the reference terrestrial photogrammetry. Ice cliffs cover between 7 % and 8 % of the total map view area of the Changri Nup tongue. Yet from November 2015 to November 2016 (November 2016 to November 2017), ice cliffs contributed to 23±5 % (24±5 %) of the total ablation observed on the tongue. Ice cliffs therefore have a net ablation rate 3.1±0.6 (3.0±0.6) times higher than the average glacier tongue surface. However, on Changri Nup Glacier, ice cliffs still cannot compensate for the reduction in ablation due to debris-cover. In addition to cliff enhancement, a combination of reduced ablation and lower emergence velocities could be responsible for the debris-cover anomaly on debris-covered tongues.

Band ogives are a striking and enigmatic feature of Mer de Glace glacier flow. The surface mass balances (SMBs) of these ogives have been thoroughly investigated over a period of 12 years. We find similar cumulative SMBs over this period, ranging between −64.1 and −66.2 m w.e., on the dark and light ogives even though the dark ogive albedo is ~40% lower than that of the light ogives. We, therefore, looked for another process that could compensate for the large difference of absorbed short-wave radiation between dark and light ogives. Based on in situ roughness measurements, our numerical modeling experiments demonstrate that a significant difference in turbulent flux over the dark and light ogives due to different surface roughnesses could compensate for the difference in radiative forcing. Our results discard theories for the genesis of band ogives that are based on the assumption of a strong ice ablation contrast between dark and light ogives. More generally, our study demonstrates that future roughness changes are as important to analyze as the radiative impacts of a potential increase of aerosols or debris at the surface of glaciers.

Abstract The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

Abstract Correlative approaches are a powerful tool in the investigation of biological samples, but require specific preparation procedures to maintain the strength of the employed methods. Here we report the optimization of the embedding protocol of nervous system samples for a correlative synchrotron X-ray computed microtomography (micro-CT) and transmission electron microscopy (TEM) approach. We demonstrate that it is possible to locate, with the micrometric resolution of micro-CT, specific volumes of interest for a further ultrastructural characterization to be performed with TEM. This approach can be applied to samples of different size and morphology up to several cm. Our optimized method represents an invaluable tool for investigating those pathologies in which microscopic alterations are localized in few confined regions, rather than diffused in entire tissues, organs or systems. We present a proof of concept of our method in a mouse model of Globoid Cells Leukodistrophy.

Approximately 25 % of the glacierized area in the Everest region is covered by debris, yet the surface mass balance of debris-covered portions of these glaciers has not been measured directly. In this study, ground-based measurements of surface elevation and ice depth are combined with terrestrial photogrammetry, unmanned aerial vehicle (UAV) and satellite elevation models to derive the surface mass balance of the debris-covered tongue of Changri Nup Glacier, located in the Everest region. Over the debris-covered tongue, the mean elevation change between 2011 and 2015 is −0.93 m year−1 or −0.84 m water equivalent per year (w.e. a−1). The mean emergence velocity over this region, estimated from the total ice flux through a cross section immediately above the debris-covered zone, is +0.37 m w.e. a−1. The debris-covered portion of the glacier thus has an area-averaged mass balance of −1.21 ± 0.2 m w.e. a−1 between 5240 and 5525 m above sea level (m a.s.l.). Surface mass balances observed on nearby debris-free glaciers suggest that the ablation is strongly reduced (by ca. 1.8 m w.e. a−1) by the debris cover. The insulating effect of the debris cover has a larger effect on total mass loss than the enhanced ice ablation due to supraglacial ponds and exposed ice cliffs. This finding contradicts earlier geodetic studies and should be considered for modelling the future evolution of debris-covered glaciers.

Few glaciological field data are available on glaciers in the Hindu Kush–Karakoram–Himalayan (HKH) region, and remote sensing data are thus critical for glacier studies in this region. The main objectives of this study are to document, using satellite images, the seasonal changes of surface albedo for two Himalayan glaciers, Chhota Shigri Glacier (Himachal Pradesh, India) and Mera Glacier (Everest region, Nepal), and to reconstruct the annual mass balance of these glaciers based on the albedo data. Albedo is retrieved from Moderate Resolution Imaging Spectroradiometer (MODIS) images, and evaluated using ground based measurements. At both sites, we find high coefficients of determination between annual minimum albedo averaged over the glacier (AMAAG) and glacier-wide annual mass balance (Ba) measured with the glaciological method (R2 = 0.75). At Chhota Shigri Glacier, the relation between AMAAG found at the end of the ablation season and Ba suggests that AMAAG can be used as a proxy for the maximum snow line altitude or equilibrium line altitude (ELA) on winter-accumulation-type glaciers in the Himalayas. However, for the summer-accumulation-type Mera Glacier, our approach relied on the hypothesis that ELA information is preserved during the monsoon. At Mera Glacier, cloud obscuration and snow accumulation limits the detection of albedo during the monsoon, but snow redistribution and sublimation in the post-monsoon period allows for the calculation of AMAAG. Reconstructed Ba at Chhota Shigri Glacier agrees with mass balances previously reconstructed using a positive degree-day method. Reconstructed Ba at Mera Glacier is affected by heavy cloud cover during the monsoon, which systematically limited our ability to observe AMAAG at the end of the melting period. In addition, the relation between AMAAG and Ba is constrained over a shorter time period for Mera Glacier (6 years) than for Chhota Shigri Glacier (11 years). Thus the mass balance reconstruction is less robust for Mera Glacier than for Chhota Shigri Glacier. However our method shows promising results and may be used to reconstruct the annual mass balance of glaciers with contrasted seasonal cycles in the western part of the HKH mountain range since the early 2000s when MODIS images became available.

Abstract The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin® and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin® similarly secreted IL-6, TNF-α, IL-1β, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals.

The ambient-temperature compressibility and room-pressure thermal expansion of two Mg3(PO4)2 polymorphs (farringtonite = Mg3(PO4)2-I, with 5- and 6-fold coordinated Mg, and chopinite = “Mg-sarcopside” = [6]Mg3(PO4)2-II), three Mg2PO4OH polymorphs (althausite, hydroxylwagnerite and ε-Mg2PO4OH, all with [5]Mg and [6]Mg) and phosphoellenbergerite ([6]Mg) were measured on synthetic powders using a synchrotron-based multi-anvil apparatus to 5.5 GPa and a laboratory high-temperature diffractometer, with whole-pattern fitting procedures. Bulk moduli range from 64.5 GPa for althausite to 88.4 GPa for hydroxylwagnerite, the high-pressure Mg2PO4OH polymorph. Chopinite, based on an olivine structure with ordered octahedral vacancies (K0 = 81.6 GPa), and phosphoellenbergerite, composed of chains of face-sharing octahedra (K0 = 86.4 GPa), are distinctly more compressible than their homeotypical silicate (127 and 133 GPa, respectively). The compressibility anisotropy is the highest for chopinite and the lowest for phosphoellenbergerite. First-order parameters of quadratic thermal expansions range from v1 = 2.19×10-5 K−1 for ε-Mg2PO4OH to v1 = 3.58×10-5 K−1 for althausite. Phosphates have higher thermal-expansion coefficients than the homeotypical silicates. Thermal anisotropy is the highest for farringtonite and the lowest for hydroxylwagnerite and chopinite. These results set the stage for a thermodynamic handling of phase-equilibrium data obtained up to 3 GPa and 1000 °C in the MgO–P2O5–H2O and MgO–Al2O3–P2O5–H2O systems.

ABSTRACT Leishmania (L.) infantum is one of the main causative agents of animal and human leishmaniasis across many endemic areas in South America, Europe, North Africa, and Asia. Despite its clinical significance, little is known about the genetic diversity of L. infantum circulating in a given endemic area. Here, we investigate this important open question by applying a comparative genomics approach to seven L. infantum isolates from different hosts and Italian regions, including the northern part of the country (Emilia-Romagna, RER), Sicily, and Sardinia, as an initial attempt to explore the breadth of parasite genetic heterogeneity in Italy. Additionally, microsatellite analysis was carried out to compare the isolates from RER with other 70 L. infantum strains from the same region as well as 65 strains belonging to the L. donovani complex from other countries. We revealed important karyotypic instability and identified strain-specific changes in gene dosage, which affected important virulence factors such as amastins and surface antigen-like proteins. Single nucleotide polymorphism-based clustering analysis of these genomes together with over 80 publicly available L. infantum and L. donovani genomes placed the Italian isolates into three geographically distinct clusters within the Mediterranean basin and uncovered three isolates clustering with putative L. infantum/L. donovani hybrids isolated in Cyprus. As judged by microsatellite profiling, these hybrid isolates are representative of a sub-population of parasites circulating in northern Italy that preferentially infect humans but not dogs. Our results place Italy at the crossroads of L. infantum infection in the Mediterranean and call attention to the public health risk represented by the introduction of non-European Leishmania species.IMPORTANCEThis study closes important knowledge gaps with respect to Leishmania (L.) infantum genetic heterogeneity in a given endemic country, as exemplified here for Italy, and reveals genetic hybridization as a main cause for re-emerging human leishmaniasis in northern Italy. The observed high diversity of Leishmania parasites on the Italian peninsula suggests different geographical origins, with genomic adaptation to various ecologies affecting both pathogenicity and transmission potential. This is documented by the discovery of a putative L. infantum/L. donovani hybrid strain, which has been shown to preferentially infect humans but not dogs. Our results provide important information to health authorities, which need to consider the public health risk represented by the introduction of new Leishmania species into EU countries due to population displacement or travel from countries where exotic/allochthonous parasite species are endemic.

The coralligenous build-ups located on the Mediterranean shelf in front of Marzamemi (SE Sicily, Italy) represent useful natural examples to use in studying the relationship between skeletal organisms and non-skeletal components in marine bioconstructions. Coralligenous build-ups are formed in open marine systems, and their comparison with coeval bioconstructions (biostalactites) of confined environments, like submarine caves, allows depicting the complex interactions between metazoans and microbial communities in the formations of recent bioconstructions in different Mediterranean settings. In this study, two coralligenous build-ups were characterized in terms of organisms and sediments involved in their formation. The framework mainly consists of coralline algae and subordinate bryozoans and serpulids. Sponges affect the general morphology of the bioconstructions both interacting with skeletonized organisms and through bioerosion activity. The micrite or microcrystalline calcite is present in minor amounts compared to other components that form the build-ups and consists of two types: autochthonous (in situ) and allochthonous (detrital). Fine autochthonous micrite mineralized directly inside the framework cavities and shows aphanitic or peloidal fabric, produced by organomineralization processes of soft sponge tissues and microbial metabolic activity, respectively. The detrital micrite occurring inside cavities derives from external sources or erosion processes of the bioconstructions themselves. This component has been classified as organic or inorganic based on the organic matter contents deduced by UV epifluorescence. A great quantity of sponges live in cavities of the coralligenous build-ups and compete with carbonatogenic bacteria for the same cryptic spaces, limiting the production of microbialites. The sharing of a similar relationship between sponges and microbial communities by coralligenous concretion and biotic crusts of particular submarine caves suggests that this competition is not habitat-specific. On the contrary, it may develop in a range of environmental settings, from open to cryptic systems, and could be used to clarify the role of metazoans vs. microbialites in palaeoecological reconstructions.

Urban and peri-urban lands can be an important source of food production for localised and sustainable food systems, however, their soils can be of poor quality, degraded or damaged by anthropic activities, and little is known about their suitability or safety. This paper aims to contribute to this knowledge gap by assessing the soil remediation capacity and qualities of different types of compost made from urban and peri-urban organic wastes for agroecological food production. Prepared over the course of 2021, and used in 2022 for food growing, five different composts were observed and analysed, in two different farms in the city of Rosario, Argentina. Four raw materials generated largely by local industries were used to make the composts: chicken manure, rumen (cow’s stomachs), brewer’s bagasse (byproducts of the beer industry) and urban leaves collected from the municipality waste collection. These were mixed in different proportions (all reaching the 20–30 C/N ratio, typical of quality compost) to produce viable growing substrates where radishes and lettuces were grown. The aim of the study was to assess the possibility, quality and limitations to use locally available organic inputs for soil fertility management in agroecological farming, in the context of urbanisation and to assess pathways to develop closed-cycle agroecological agriculture at metropolitan level. Natural manure substrates (raw and composted) were analysed, as well as crops grown and fertilised with each of the substrates. The attributes and limiting factors of each substrate and their response to local soil conditions were compared and physicochemical, biochemical, and microbiological analyses were performed, including among others, the study of microbial biomass, biological activity, biophytotoxicity, pH, aerobic heterotrophs, nitrogen fixation, and the presence of antibiotics, agrochemicals and heavy metals. The results of the analyses show that all the composted materials improved the physical, chemical and biological properties. However, in some cases, pollutants were present even after composting. Analysis carried out on the vegetables generally indicate undetectable levels or levels below the admissible limits, demonstrating the filtering capacity of the different composts and the soil.

Exercise is recognized as a part of the management of obesity and diabetes. Various protocols of exercise are proposed for the management of obesity, diabetes, and other metabolic diseases. One of the strategies proposed by several authors is low intensity endurance training targeted at the level of maximal oxidation. Large series using this technique are lacking. Addressing this issue, we performed a meta-analysis of the studies on anthropometric measurements. From a database of 433 articles, 15 were selected, including 279 subjects with 6 different populations. Studies duration ranged from 2 months to 12 months. Concerning weight loss, in the intervention versus control analysis, five studies with 185 participants were included with a significant effect size favors exercise (P=0.02) without significant heterogeneity (I2=0.0%, P=0.83). Further randomized controlled trials for comparing it with other exercise protocols and defining its dose effectiveness on large samples are needed.

Objectives: Modic type 1 changes (MC1) are vertebral endplate bone marrow (BM) lesions observed on magnetic resonance images in sub-populations of chronic low back pain (CLBP) patients. The etiopathogenesis remains unknown and treatments that modify the underlying pathomechanisms do not exist. We hypothesized that two biological MC1 subtypes exist: a bacterial and a non-bacterial. This would have important implications for developing treatments targeting the underlying pathomechanisms. Methods: Intervertebral disc (IVD) samples adjacent to MC1 (n ​= ​34) and control (n ​= ​11) vertebrae were collected from patients undergoing spinal fusion. Cutibacterium acnes (C.acnes) genome copy numbers (GCNs) were quantified in IVD tissues with 16S qPCR, transcriptomic signatures and cytokine profiles were determined in MC1 and control BM by RNA sequencing and immunoassay. Finally, we assessed if C.acnes GCNs are associated with blood plasma cytokines. Results: IVD tissues from control levels had 870) C.acnes GCNs. MC1 patients with “high” C.acnes GCNs had upregulated innate immune cell signatures (neutrophil, macrophage/monocyte) and pro-inflammatory cytokines related to neutrophil and macrophage/monocyte function in the BM, consistent with a host defense against bacterium. MC1 patients with “low” C.acnes GCNs had increased adaptive immune cell signatures (T-and B-cell) in the BM and elevated IL-13 blood plasma levels. Conclusion: Our study provides the first evidence for the existence of bacterial (C.acnes “high”) and non-bacterial (C.acnes “low”) subtypes in MC1 patients with CLBP. This supports the need for different treatment strategies.