In the state-of-the-art of structural engineering the actions for design or assessment of bridges should derive from a probabilistic (i.e., frequentist) characterization of the loads. Data from ...weigh-in-motion (WIM) systems can inform stochastic models for traffic loads. However, WIM is not widespread, and data of this kind are scarce in the literature and often not recent. Due to structural safety reasons, the 52 km long A3 highway in Italy, connecting the cities of Naples and Salerno, has been equipped with a WIM system which has been operational since the beginning of 2021. The system's measurements of each vehicle transiting over the WIM devices, impede overloads on the many bridges featured in the transportation infrastructure. By the time of this writing the WIM system has seen one year of uninterrupted operation, collecting more than thirty-six million datapoints in the meantime. This short paper presents and discusses these WIM measurements, deriving the empirical distributions of traffic loads and making the original data available for further research and applications.
Cannabidiol (CBD) is a non-psychotropic phytocannabinoid which represents one of the constituents of the "phytocomplex" of Cannabis sativa. This natural compound is attracting growing interest since ...when CBD-based remedies and commercial products were marketed. This review aims to exhaustively address the extractive and analytical approaches that have been developed for the isolation and quantification of CBD. Recent updates on cutting-edge technologies were critically examined in terms of yield, sensitivity, flexibility and performances in general, and are reviewed alongside original representative results. As an add-on to currently available contributions in the literature, the evolution of the novel, efficient synthetic approaches for the preparation of CBD, a procedure which is appealing for the pharmaceutical industry, is also discussed. Moreover, with the increasing interest on the therapeutic potential of CBD and the limited understanding of the undergoing biochemical pathways, the reader will be updated about recent in silico studies on the molecular interactions of CBD towards several different targets attempting to fill this gap. Computational data retrieved from the literature have been integrated with novel in silico experiments, critically discussed to provide a comprehensive and updated overview on the undebatable potential of CBD and its therapeutic profile.
Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, ...post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple costimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells. Likewise, we documented the frequent loss of surface expression of HLA-DR, -DQ and -DP on leukemia cells, due to downregulation of the HLA class II regulator CIITA. We show that loss of HLA class II expression and upregulation of inhibitory checkpoint molecules represent alternative modalities to abolish AML recognition from donor-derived T cells, and can be counteracted by interferon-γ or checkpoint blockade, respectively. Our results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies.
Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to ...achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence‐based recommendations for the use of house dust mites (HDM) AIT as add‐on treatment for HDM‐driven allergic asthma. This guideline was developed by a multi‐disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT‐tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add‐on to regular asthma therapy for adults with controlled or partially controlled HDM‐driven allergic asthma (conditional recommendation, moderate‐quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM‐driven allergic asthma as the add‐on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low‐quality evidence).
Describing the slip behavior of an active fault system is central to understanding the seismic potential of seismogenic areas. Different elements control the nature and the extent of the coseismic ...and post-seismic ruptures, including the geometry of faults, the nature of faulted rocks, and the stress changes caused by the mainshocks. In May–June 2012 a severe seismic sequence struck a portion of the Po Plain (Northern Italy), where a thick blanket of Plio-Quaternary sediments hides a number of seismogenic sources corresponding to the external thrust systems of the Northern Apennines. We used deep seismic reflection data to reconstruct the geometry of the faults responsible for the sequence. These faults exhibit significant non-planarity due to tectono-stratigraphic heterogeneities inherited from a complex pre-thrusting extensional tectonic phase. A comparison of the fault parameters derived from our geological analysis and the evidence supplied by seismological (aftershock distributions) and geodetic data (InSAR) allowed to identify the causative fault segments of the two mainshocks. We then modeled the Coulomb stress changes produced by two mainshocks to analyze on- and off-fault seismicity. Discrepancies between the magnitude of the earthquakes and the extent of active faults suggest that the mainshocks did not rupture the entire thrust planes. We contend that seismogenic ruptures were confined in the Mesozoic carbonates and were stopped by lithological changes and/or mechanical complexities of the fault planes, both along dip and along strike. Our findings highlight that along the active structures of the Po Plain slip tends to be seismogenic where faults are located in Mesozoic carbonate rocks.
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•Seismic reflection data allow us to image the active faults in the Emilia area.•Seismological, geodetic and geological data are used to analyze the 2012 sequence.•Active faults in Emilia show different rupture behavior and downdip segmentation.
The development of new reverse faults and related folds is strongly controlled by the mechanical characteristics of the host rocks. In this study we analyze the impact of a specific kind of ...anisotropy, i.e. thin mechanical and frictional discontinuities, in affecting the development of reverse faults and of the associated folds using physical scaled models. We perform analog modeling introducing one or two initially horizontal, thin discontinuities above an initially blind fault dipping at 30° in one case, and 45° in another, and then compare the results with those obtained from a fully isotropic model. The experimental results show that the occurrence of thin discontinuities affects both the development and the propagation of new faults and the shape of the associated folds. New faults 1) accelerate or decelerate their propagation depending on the location of the tips with respect to the discontinuities, 2) cross the discontinuities at a characteristic angle (∼90°), and 3) produce folds with different shapes, resulting not only from the dip of the new faults but also from their non-linear propagation history. Our results may have direct impact on future kinematic models, especially those aimed to reconstruct the tectonic history of faults that developed in layered rocks or in regions affected by pre-existing faults.
•We focus on the role of thin frictional discontinuities in affecting the development of reverse faults.•Our method is based on wet clay analog models.•Our study show the impact of discontinuities on both propagation rate of faults and on development of the associated folds.
The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led ...pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive. In fact, the mechanisms of action of psychedelics are not yet fully understood and some molecular aspects have yet to be well defined. Thus, this review aims to summarize the ethnobotanical uses of the best-known psychedelic plants and the pharmacological mechanisms of the main active ingredients they contain. Furthermore, an up-to-date overview of structural and computational studies performed to evaluate the affinity and binding modes to biologically relevant receptors of ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide is presented. Finally, the most recent clinical studies evaluating the efficacy of psychedelic molecules in some psychiatric disorders are discussed and compared with drugs already used in therapy.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide since December 2019, causing the COVID-19 pandemic. Several measures have taken place in many countries to avoid further ...spread of the virus and to manage infected people according to disease severity. Notably, telemedicine (TM) was successfully used to manage less severe patients. Our aim was to assess the impact and the edges of using TM in home-isolated or hospitalized patients affected by SARS-CoV-2 infection and its further application.
We performed a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, focusing on randomized controlled trials (RCTs) published in English and available on PubMed database. Full texts were blindly reviewed and then assessed according to PICO model.
Our research identified a total of 1,959 records, of which 24 were potentially eligible through the articles full-text review. Six papers were included for data extraction and 18 articles were excluded: 10 articles were not RCTs and 8 articles did not involve SARS-CoV-2 patients. The TM application showed an improvement in psychological stress, mental disorders, and a significant reduction of general stress in patients affected by SARS-CoV-2 infection. The effectiveness of using TM in rehabilitative respiratory programs has been also reported. Furthermore, the benefits of TM application in tailored monitoring of vital parameters in home-isolated patients helped clinicians to early identify a deterioration of clinical conditions.
The use of TM during COVID-19 pandemic represented a novel, intriguing, versatile, and useful tool to support clinical practice. This evidence suggests considering TM in a wider range of clinical applications.
We use wet-clay analog models to investigate how pre-existing discontinuities (i.e. structures inherited from previous tectonic phases) affect the evolution of a normal fault at the Earth's surface. ...To this end we first perform a series of three reference experiments driven by a 45° dipping master fault unaffected by pre-existing discontinuities to generate a mechanically isotropic learning set of models. We then replicate the experiment six times introducing a 60°-dipping precut in the clay cake, each time with a different attitude and orientation with respect to an initially-blind, 45°-dipping, master normal fault. In all experiments the precut intersects the vertical projection of the master fault halfway between the center and the right-hand lateral tip. All other conditions are identical for all seven models. By comparing the results obtained from the mechanically isotropic experiments with results from experiments with precuts we find that the surface evolution of the normal fault varies depending on the precut orientation. In most cases the parameters of newly-forming faults are strongly influenced. The largest influence is exerted by synthetic and antithetic discontinuities trending respectively at 30° and 45° from the strike of the master fault, whereas a synthetic discontinuity at 60° and an antithetic discontinuity at 30° show moderate influence. Little influence is exerted by a synthetic discontinuity at 45° and an antithetic discontinuity at 60° from the strike of the master fault. We provide a ranking chart to assess fault-to-discontinuity interactions with respect to essential surface fault descriptors, such as segmentation, vertical-displacement profile, maximum displacement, and length, often used as proxies to infer fault properties at depth. Considering a single descriptor, the amount of deviation induced by different precuts varies from case to case in a rather unpredictable fashion. Multiple observables should be taken into consideration when analyzing normal faults evolving next to pre-existing discontinuities.
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•We use wet-clay analog models to simulate isolated initially-blind normal faults.•We analyze the interaction of surface normal faults with inherited discontinuities.•Inherited discontinuities strongly affect fault development at the Earth's surface.•The influence of a discontinuity strongly depends on its orientation relative to the fault.•We provide a ranking chart to assess fault-to-discontinuity interactions.
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