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Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies., Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

Urinary tract infections (UTIs) are one of the most common bacterial infections in women, often as a recurrent disease. Uropathogenic Escherichia coli (UPEC) is the most common pathotype of extraintestinal pathogenic E. coli (ExPEC) found among patients with UTI. The human intestinal can act as a reservoir of UPEC, with the female urethra being infected by fecal material containing UPEC. Adhesion of bacteria to the epithelial cells of urogenital mucosa is an important mechanism in the pathogenesis of UTI. Alternative nonantibiotic based approaches, such as mechanical barrier protection of the intestinal mucosa have been proposed to reduce bacterial adherence to intestinal epithelium, bacteria proliferation and decrease of the load of UPEC in the intestinal lumen and in the fecal material.

Summary Although the mammalian microbiota is well contained within the intestine, it profoundly shapes development and metabolism of almost every host organ. We questioned the range and depth of microbial metabolite penetration into the host, and how this is modulated by intestinal immunity. Chemically identical microbial and host metabolites were distinguished by stable isotope tracing from 13C-labeled live non-replicating Escherichia coli, differentiating 12C host isotopes with high-resolution mass spectrometry. Hundreds of endogenous microbial compounds penetrated 23 host tissues and fluids after intestinal exposure: subsequent 12C host metabolome signatures included lipidemia, reduced glycolysis, and inflammation. Penetrant bacterial metabolites from the small intestine were rapidly cleared into the urine, whereas induced antibodies curtailed microbial metabolite exposure by accelerating intestinal bacterial transit into the colon where metabolite transport mechanisms are limiting. Pervasive penetration of microbial molecules can cause extensive host tissue responses: these are limited by immune and non-immune intestinal mucosal adaptations to the microbiota., Graphical Abstract, Highlights • Metabolites from mutualistic bacteria broadly penetrate host tissues and organs • Bacterial metabolites induce widespread host metabolic and immunological responses • The small intestine is highly susceptible to host-microbial metabolomic exchange • Secretory immunoglobulins accelerate microbial clearance from the small intestine, Bacteria-derived metabolites pervade the mammalian host, shaping immunity and metabolism. Using stable isotope tracing, Uchimura and colleagues profile the scope and depth of host tissue penetration by bacterial metabolites. Extensive host immune and metabolic responses to microbial metabolite penetration are constrained by secretory antibodies that limit microbial small-intestinal dwell time.

In the version of this article initially published, Figs. 5a,c and 6a were incorrect because of an error in a metadata spreadsheet that led to the healthy donor patient 2 (HD2) samples being used twice in the analysis of baseline samples and in the analysis at 12 weeks of anti-PD-1 therapy, while HD3 samples had not been used.

Cancer-associated thrombocytosis and high concentrations of circulating transforming growth factor-β1 (TGF-β1) are frequently observed in patients with progressive cancers. Using genetic and pharmacological approaches, we show a direct link between thrombin catalytic activity and release of mature TGF-β1 from platelets. We found that thrombin cleaves glycoprotein A repetitions predominant (GARP), a cell surface docking receptor for latent TGF-β1 (LTGF-β1) on platelets, resulting in liberation of active TGF-β1 from the GARP-LTGF-β1 complex. Furthermore, systemic inhibition of thrombin obliterates TGF-β1 maturation in platelet releasate and rewires the tumor microenvironment toward favorable antitumor immunity, which translates into efficient cancer control either alone or in combination with programmed cell death 1-based immune checkpoint blockade therapy. Last, we demonstrate that soluble GARP and GARP-LTGF-β1 complex are present in the circulation of patients with cancer. Together, our data reveal a mechanism of cancer immune evasion that involves thrombin-mediated GARP cleavage and the subsequent TGF-β1 release from platelets. We propose that blockade of GARP cleavage is a valuable therapeutic strategy to overcome cancer's resistance to immunotherapy.

ObjectiveTo investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.MethodsA phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.ResultsOf the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.ConclusionsEfgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.Classification of evidenceThis study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

The outdoor gamma background of the historic center of Rome was studied by in situ measurements and average values of the outcropping geological formations. The survey resulted in two maps of dose equivalent rate, related to pre-anthropic and present conditions. Presently, the average of the dose equivalent rate from outdoor gamma-ray field is equal to 0.31 μSv h−1, corresponding to an outdoor annual effective dose equivalent of 0.548 mSv a−1 and to an outdoor excess lifetime cancer risk [International Commission on Radiological Protection (ICRP). Recommendations of the ICRP, 21, 1/3, Publication 60, 1990] of 2.56 × 10−3. The originary radioactivity was enhanced by anthropic action up to a level of health risk comparable to that one deriving by fine particulate matter. The assessment of the evolution and dispersion of the outdoor gamma background offers a new perspective to study the urban architectural evolution. Such a mapping allows us to individuate mitigation actions and neighborhoods in which the monitoring of illicit trafficking of radioactive material can be efficiently tested.

Activated regulatory T (Treg) cells express the surface receptor glycoprotein-A repetitions predominant (GARP), which binds and activates latent TGFβ. How GARP modulates Treg function in inflammation and cancer remains unclear. Here we demonstrate that loss of GARP in Treg cells leads to spontaneous inflammation with highly activated CD4+ and CD8+ T cells and development of enteritis. Treg cells lacking GARP were unable to suppress pathogenic T-cell responses in multiple models of inflammation, including T-cell transfer colitis. GARP−/− Treg cells were significantly reduced in the gut and exhibited a reduction in CD103 expression, a colon-specific migratory marker. In the colitis-associated colon cancer model, GARP on Treg cells dampened immune surveillance, and mice with GARP−/− Treg cells exhibited improved antitumor immunity. Thus, GARP empowers the functionality of Treg cells and their tissue-specific accumulation, highlighting the importance of cell surface TGFβ in Treg function and GARP as a potential therapeutic target for colorectal cancer therapy. Significance: These findings uncover functions of membrane-bound TGFβ and GARP that tune the activity of Treg cells, highlighting a potential treatment strategy in autoimmune diseases and cancer.

High-dimensional mass and flow cytometry (HDCyto) experiments have become a method of choice for high-throughput interrogation and characterization of cell populations. Here, we present an updated R-based pipeline for differential analyses of HDCyto data, largely based on Bioconductor packages. We computationally define cell populations using FlowSOM clustering, and facilitate an optional but reproducible strategy for manual merging of algorithm-generated clusters. Our workflow offers different analysis paths, including association of cell type abundance with a phenotype or changes in signalling markers within specific subpopulations, or differential analyses of aggregated signals. Importantly, the differential analyses we show are based on regression frameworks where the HDCyto data is the response; thus, we are able to model arbitrary experimental designs, such as those with batch effects, paired designs and so on. In particular, we apply generalized linear mixed models or linear mixed models to analyses of cell population abundance or cell-population-specific analyses of signaling markers, allowing overdispersion in cell count or aggregated signals across samples to be appropriately modeled. To support the formal statistical analyses, we encourage exploratory data analysis at every step, including quality control (e.g., multi-dimensional scaling plots), reporting of clustering results (dimensionality reduction, heatmaps with dendrograms) and differential analyses (e.g., plots of aggregated signals).

This paper presents an overview of the various innovative methodologies used in the recovery of valuable metals and critical raw materials (CRMs) from secondary sources. Valuable metals are interesting due to their vast industrial applications, high market prices and extensively used precious metal. The sanctuary value attributed to valuable metals such as gold during international political and economical crises and the limited resource of this metal, may explain the recent increasing gold share value. This article provides an overview of past achievements and presents scenario of studies carried out on the use of some promising methods which could serve as an economical means for recovering valuable metals and CRMs. The review also highlights the used varieties of application on large scale in real situations and hopes to provide insights into valorization of spent sources.

Mining and mineral-processing wastes represent one of the world's largest chronic waste concerns. A number of environmental problems are associated with the disposal of these wastes, including ecological losses, downstream contamination and pronounced landscape transformation. In recent years, difficulties to access raw materials (RMs) lead to progressive resource depletion, increase in metals price and environmental pressures. The recovery of critical raw materials (CRMs) from low-grade ore, steel works by-products and industrial wastes has become an important issue and a global challenge for present and future economy. Due to the continuous need for mining activities to collect RMs to sustain our economy, the recycling and reuse of mining and mineral-processing wastes should be pursued through appropriate innovative management strategies aimed at minimizing the environmental impacts and preserving human health. Furthermore, it is generally difficult to assign a universal method to reuse all kinds of mining and mineral-processing wastes; hence, the choice of possible recycling, reprocessing and reuse strategies should be case-specific. Aim of this paper is to evaluate integrated multidisciplinary strategy for the characterization and analysis of mining waste, their possible recycling and re-use and strategies for CRMs recovery. Proposed strategies have been applied to wastes produced in the Fe-Mn mine in Bichakundi (near Joda West, Odisha-India). In the first phase, in situ sampling campaigns have been carried out; mining wastes have been thoroughly characterized by X-Ray Powder Diffraction (XRPD), X-Ray Fluorescence (XRF) and spectral signatures analysis and the acquired mineralogical, chemical and spectral information have been used to create a map of mining waste deposits by means of the new multispectral satellite Sentinel-2A classification. The use of Fe-Mn rich wastes in arsenic removal and phosphorus recovery from water will be discussed. Furthermore, the potential metals uptake from contaminated soils and their possible recovery from incinerated/lyophilized biomass by hydrometallurgical methods is evaluated also according to preliminary phyto-myco-remediation tests carried out using Helianthus annuus (i.e., sunflower) and Rhizophagus intraradices.

The availability of raw materials (RMs) from marginal resources as industrial wastes is fundamental for the European and non-European countries for economic and environmental reasons, and of strategic importance for industrial production, due to their high concentration on valuable metals. It is therefore important the development of innovative environmentally friendly processes, to achieve RMs and critical raw materials (CRMs) of economic interest, by exploitation of the secondary RMs. Hydrometallurgical gold extraction by thiosulphate leaching represents an example of the application of these new processes: Au extraction of 85% was experimentally obtained after leaching; moreover, the overall process achieved about 80% Au recovery, this being in line with the conventional cyanidation process. These results are very encouraging, considering that this is a commercially innovative process. The optimization of process parameters and operating conditions should permit the best results in terms of process yields to be achieved.

The worldwide mining industry produces millions of tons of rock wastes, raising a considerable burden for managing both economic and environmental issues. The possible reuse of Fe/Mn-rich materials for arsenic removal in water filtration units, along with rock properties, was evaluated. By characterizing and testing 47 samples collected from the Joda West Iron and Manganese Mine in India, we found As removal up to 50.1% at 1 mg/L initial As concentration, with a corresponding adsorption capacity of 0.01&ndash, 0.46 mgAs/g mining waste. The As removal potential was strictly related to spectral, mineralogical, and elemental composition of rock wastes. Unlike rock crystallinity due to quartz and muscovite, the presence of hematite, goethite, and kaolinite, in association with the amorphous fractions of Fe and Al, enhanced the As adsorption. The natural content of arsenic indicated itself the presence of active sorptive sites. The co-occurrence of site-specific competitors (i.e., phosphate) represented a consequent limitation, whereas the content of Ce, Cu, La, and Pb contributed positively to the As adsorption. Finally, we proposed a simplified multiple linear model as predictive tool to select promising rock wastes suitable for As removal by water filtration in similar mining environments: As predicted = 0.241 + 0.00929[As] + 0.000424[La] + 0.000139[Pb] &minus, 0.00022[P].

Recent advances in fire management led landscape managers to adopt an integrated fire fighting strategy in which fire suppression is supported by prevention actions and by knowledge of local fire history and ecology. In this framework, an accurate evaluation of fire ignition risk and its environmental drivers constitutes a basic step toward the optimization of fire management measures. In this paper, we propose a multivariate method for identifying and spatially portraying fire ignition risk across a complex and heterogeneous landscape such as the National Park of Cilento, Vallo di Diano, and Alburni (southern Italy). The proposed approach consists first in calculating the fire selectivity of several landscape features that are usually related to fire ignition, such as land cover or topography. Next, the fire selectivity values of single landscape features are combined with multivariate segmentation tools. The resulting fire risk map may constitute a valuable tool for optimizing fire prevention strategies and for efficiently allocating fire fighting resources.

Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases. Copyright © 2021 Elsevier Inc. All rights reserved.

Several lines of evidence suggest that inflammation plays a pivotal role in the development and progression of colorectal cancer (CRC) and can be unleashed by the loss of innate immunosurveillance. The complement system is a well characterized first line of defense against pathogens and a central component of the immune response. Emerging evidence suggests that complement anaphylatoxin C3a produced upon complement activation and acting via its receptor (C3aR) may play a role in intestinal homeostasis. However, to date, it is unknown whether and how the C3a/C3aR axis can affect CRC. By mining publicly available datasets, we found that CpG island methylation of c3ar1 occurs in CRC patients and is associated with significant downregulation of C3aR. By reverse-translating this finding we were able to shift in APCMin/+ mice the tumorigenesis from the small intestine to the colon therefore generating a novel mouse model, which more closely mirrors the CRC in humans. Transcriptomic analysis on colorectal polyps from our newly developed genetic mouse model revealed a significant increase in innate and adaptive immune signatures in absence of C3aR. Furthermore, loss of C3aR significantly impacted the fecal and tumor-associated microbiota and supported the blooming of pro-inflammatory bacterial species as confirmed by experiments of fecal microbiota transplantation. Future studies will elucidate whether loss of C3aR can be exploited as a biomarker for sub-groups of CRC and whether the C3a/C3aR axis may be exploited for the generation of more effective therapeutic interventions.

Hypercoagulation is a common feature of several tumors to the extent that individuals with coagulation defects often present with occult visceral cancers. Recent evidence has shown that hypercoagulation is not just a mere secondary effect due to the presence of the tumor, rather it actively contributes to tumor development and dissemination. Among the numerous mechanisms that can contribute to cancer-associated hypercoagulation, the ones involving immune-mediated processes are gaining increasing attention. In particular, complement cascade and hypercoagulation are one inducing the other in a vicious circle that involves neutrophil extracellular traps (NETs) formation. Together, in this feedback loop, they can promote the protumorigenic phenotype of immune cells and the protection of tumor cells from immune attack, ultimately favouring tumor development, progression and metastases formation. In this review, we summarize the role of these processes in cancer development and highlight new possible intervention strategies based on anticoagulants that can arrest this vicious circle.

The extremely thin absorber (ETA) solar cell architecture can enable higher efficiencies than planar cells for absorbers that have low carrier lifetimes or mobilities. Efficient charge separation requires that interfacial electron and hole transfer proceed much faster than the recombination lifetime of photoexcited carriers. In this work, transient absorption spectroscopy was employed to measure these ultrafast photophysical processes in CdSe-coated ZnO nanowire ETA cells and model planar films. At low pump fluences, carrier lifetime was controlled by Shockley–Read–Hall and surface recombination. Annealing the electrodeposited CdSe films increased the lifetime 50-fold, to >1 ns as measured by transient absorption spectroscopy, which correlated to improved ETA cell performance. Interfacial electron transfer from the CdSe coating into the ZnO nanowires occurred 3 orders of magnitude faster, within 1 ps, independent of the presence or absence of an interfacial CdS buffer layer. Interfacial hole transfer to t...

A 9-year-old girl with chronic constipation was seen in the gastroenterology clinic because of increasingly frequent episodes of abdominal pain with associated nonbilious vomiting. A diagnosis was made.

Synaptic plasticity is an essential mechanism for both the creation of memories and the formation of associations between those memories. A crucial component of learning and memory is the hippocampus. The works included in this thesis probe the cellular basis of learning and memory in the hippocampus through two primary means. The first builds upon existing information highlighting the stark difference in plasticity between the dorsal and ventral poles of the hippocampus along with the preferential influence of neuromodulators on ventral plasticity. The second examines the importance of phosphorylation-based regulation of the AMPA receptor subunit, GluA1, and how this mediates hippocampal plasticity. Despite similar basal excitatory and inhibitory synaptic transmission between the two poles, the ventral hippocampus exhibits much weaker long term potentiation (LTP) and complex spiking compared to the dorsal. This deficit was due to a down regulation of the NMDA receptors in the ventral region, which resulted in weaker E-S coupling and EPSP amplification. LTP induction and complex spiking, however, could be rescued with the addition of a [beta]-adrenergic agonist. Additionally, [beta]-adrenergic activation inhibited the small conductance calcium-activated potassium channel, SK, which serves to hyperpolarize the cell and resist NMDA receptor activation. Indeed, pharmacological inhibition of the SK channel enhanced LTP induction, complex spiking, E-S coupling, and EPSP amplification in the ventral hippocampus. The second part of this thesis examined the role of two particular GluA1 phosphorylation sites, S845 and T840, and how their phosphorylation states affect hippocampal plasticity. We found that S845 and T840 are regulated by distinct calcium sources and phosphatases and also track synaptic strength in different ways. S845 is persistently dephosphorylated following either depolarization or LTD induction, whereas T840 only remains dephosphorylated after LTD induction. Furthermore, we found inhibitory phospho-site interactions between the two sites, due to their close proximity to one another. We then determined the basal phosphorylation levels of both sites and discovered that S845 phosphorylation levels were so low we could not adequately quantify them while T840 residues were phosphorylated in approximately ~50% of GluA1 subunits. This thesis has served two important roles in the elucidation of plasticity in the hippocampus, as it has i) identified a potent role of noradrenergic signaling in facilitating LTP induction in the ventral hippocampus and ii) detailed the regulation and prevalence of T840 and S845 in the hippocampus, along with their involvement in plasticity.

The emergence of immuno-oncology (IO) agents has led to unprecedented successes in the treatment of deadly cancers and sometimes even cures. These agents act by “releasing the brakes” and thereby unleashing the full potential of cells that fight tumors. Sadly, not every patient benefits from these new treatments. We need to know who will benefit and who may not. Here we approached the problem by designing a customized workflow by using high-dimensional single-cell mass cytometry (CyTOF) combined with machine-learning bioinformatics for the in-depth characterization of single immune cells in predicting and monitoring immune responses. The analysis is data driven, can be adapted to high-throughput approaches, and can model arbitrary trial designs such as batch effects and paired designs. We tested our workflow on two studies: a) Predict response to anti-PD-1 immunotherapy in melanoma. In our discovery cohort peripheral blood mononuclear cells (PBMCs) from 20 patients with stage IV melanoma before and after 12 weeks of anti-PD-1 therapy were analyzed. We observed a clear T-cell response on therapy. The most evident difference in responders before therapy was an enhanced frequency of CD14+ CD16+HLA-DRhi classical monocytes. We validated our results using conventional flow cytometry in an independent exploratory cohort of 31 patients before therapy. Finally, we correlated enhanced monocyte frequencies before therapy initiation with clinical response and could show association with lower hazard, extended progression-free and overall survival. b) Monitoring the immune response in anti-PD-1 immunotherapy-refractory non-small cell lung cancer to a novel combination immunotherapy of anti-PD-1 and an IL-15 superagonist. Twenty-one patients with non-small cell lung cancer who mostly were refractory to previous anti-PD-1 treatment received a novel combination therapy of IL-15 superagonist plus anti-PD-1. A response in the CD8+ T cell compartment was observed. Unexpectedly, our high-dimensional approach was able to detect and characterize a strong expansion of innate tumor-reactive effector NK cells starting around day 4 of therapy. Taken together, our unbiased artificial intelligence-driven immune workflow might support patient selection prior to therapy, select the right drug combination, and identify new druggable cell populations. Citation Format: Luis Cardenas, Silvia Guglietta, John Wrangle, Mark Rubinstein, Mark Robinson, Carsten Krieg. Using high-dimensional machine-assisted analysis for biomarkers detection and guidance of immunotherapy to cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr IA09.

The astrophysics community prefers to use the FITS format for storage of data of interest. This article compares this classic approach and one related to the use of non-relational databases high- lighting their many similarities. Among the main advantages of using non-relational database stands out the possibility of moving and replicate automatically your data minimizing the risks related to their loss or corruption. Once you realize that a header FITS is nothing more than a sequence of key-value pairs, the jump to the NoSQL world becomes almost natural.

A smart economy minimizes the production of waste and reuses waste as a potential resource, moving towards a near-zero waste society. Mining waste not of interest for steel industry due to their low iron content and need of prior ore dressing, are dumped in overburden dumps as waste and can find a valuable use in applications other than mining industry. The wastes having higher percentage of Fe, Mn and Al oxy-hydroxides, are materials widely used as adsorption filters for metals and metalloids, especially arsenic (As), in drinking water treatments. In addition, due to chemical similarity between arsenate and phosphate, their application in P-recovery, from treated wastewater, where phosphate is present at high concentration, has recently gained attention since P is a critical raw material and an essential and limited resource. Aim of our research is to individuate suitable waste mining materials of iron ore for the efficient reuse in water treatment, in particular for the removal of As and extraction of P.

Preliminary absorption tests were conducted to evaluate the efficiency in As(V) removal of selected waste materials (Fe 10-60%) of different mineralogical compositions. Arsenic removal kinetic was not so fast compared to Granular Ferrous Oxides (GFH, common As commercial removal adsorption media, amorphous and Fe>70%), but As removal reached in some case 30-50% removal. The prevalence of goethite, identified among the several FeOOH minerals by XRD spectra, seems to enhance As adsorption capacity. Further studies are needed to elucidate As and P adsorption driving process in order to give more hints on the characteristics of waste material to select by support of remote sensing images and ground-based mineralogical and spectroscopic evidences.

Immune-checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) has been found to be effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable responses. Therefore, predictive biomarkers of a clinical response are urgently needed. Here we used high-dimensional single-cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of patients with stage IV melanoma before and after 12 weeks of anti-PD-1 immunotherapy. During therapy, we observed a clear response to immunotherapy in the T cell compartment. However, before commencing therapy, a strong predictor of progression-free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16-HLA-DRhi monocytes. We confirmed this by conventional flow cytometry in an independent, blinded validation cohort, and we propose that the frequency of monocytes in PBMCs may serve in clinical decision support.

In human-affected fire environments, assessing the influence of human activities on the spatial distribution of wildfire ignitions is of paramount importance for fire management planning. Previous studies have shown that roads have significant effects on fire ignition. However, since different land cover classes are subject to different levels of ignition risk, roads in different land cover classes may differently affect fire ignition. The aim of this paper is thus to assess the influence of roads on fire ignition in selected land cover classes subjected to different levels of anthropogenic pressure in Sardinia (Italy). Our results show that fires are preferentially ignited close to roads in all land cover classes. However, the influence of roads is much stronger in less impacted land uses, where the availability of human-induced ignitions highly depends on the accessibility networks. Our approach represents a first step towards the systematic integration of interacting fire ignition drivers such as roads and land cover into fire risk analysis.

Europe is confronted with an increasing supply risk of critical raw materials (CRMs). CRMs can be defined as materials of which the risks of supply shortage and their impacts on the economy are higher compared to most of other raw materials. The European Commission has created the three lists of critical raw materials for the EU (in 2011, 2014 and 2017). To tackle the supply risk challenge, innovation is required with respect to sustainable primary mining, substitution of critical metals, and urban mining. In these three categories, bio-hydrometallurgy can play a crucial role. The natural biogeochemical cycles of elements under the microorganisms influence are the base of the bio-hydrometallurgical methods. Indeed, microbe-metal interactions have been successfully applied on full scale to win materials from primary sources, but are not sufficiently explored for metal recovery or recycling. Bio-hydrometallurgy is the advanced technology of the mineral raw recovery and processing as well as the environmental protection. This paper focuses on one of the basic processes of bio-hydrometallurgy - the extracellular precipitation of metals with biogenic compounds.

Purpose: the metals and industrial minerals contained in the tailings produced by mining and quarrying activities, are cause of environmental damage. The objective of this experimental work is the application of innovative technologies for the treatment and exploitation of mining tailings in Romania, in order to recover materials high grade raw to be placed on the market, reducing the volume of the wastes. Further objective, is to optimize some parameters relating to the dissolution of gold and the subsequent recovery from purified solutions, determining beforehand the technical feasibility of the scheme of process developed on a laboratory scale. Methods: the study is focused on hydrometallurgical process for the recovery of gold. The innovative treatment chosen is the thiosulphate process that, compared to conventional cyanide, has several advantages, first of all the most eco-friendly and non- toxic to humans. The conventional process shows operating limits in the case of auriferous minerals refractory materials, such as Romanian wastes object of the study. Another fundamental characteristic of the ammoniacal thiosulphate solutions, is the best selectivity towards gold, not attacking the majority of the gangue mineral constituents. Results: the dissolution rates of gold reached a final value of 70% Au - working at room temperature - with recoveries of the global process of about 65%, in line with the conventional process. Main conclusions: these results are very encouraging, considering that this is an innovative process, applied to a low content gold ore. The optimization of parameters and operating conditions, and the industrial treatment, continuous and scale greater would certainly permit to reach the best results in terms of process yields and energetic and reagents consumption.