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Earthen river embankments are typically in unsaturated conditions during their lifetime and the degree of saturation within their bodies may vary significantly throughout the year, due to seasonalfluctuations of the river stage, as well as infiltrations of meteoric precipitation and evapotranspiration phenomena. Given the significant effects of partial saturation on the hydro-mechanical behaviour of soils, realistic assumptions on the actual water content distribution inside the embankments are essential forproperly modelling their response to hydraulic loadings. In this framework, centrifuge modelling is a useful tool to get insights into the evolution of saturation conditions of a water retaining structure during flood events. It allows for the direct observation of the groundwater flow process, which is hardly detectable at the prototype scale, enabling, at the same time, the validation and calibration of predictive numerical tools.In this paper, the results of a centrifuge test carried out on small-scale physical model of a compacted silty clayey sand embankment subjected to a simulated high-water event, at the enhanced gravity of 50-g, are presented and discussed. The physical model was carefully instrumented with potentiometers, miniaturized pore pressure transducers and tensiometers. Pore pressures and suctions measured during the experiment showed that the stationary flow conditions were reached only after an unrealistic hydrometric peak persistence. It therefore emerges that, for the design and/or the assessment of the safety conditions of a river embankment similar to the one tested, the simplified hypothesis of a steady-state seepage, in equilibrium with the maximum river stage expected could result, in many cases, an excessively conservative assumption.

The paper presents the results of an experimental campaign aimed at characterizing the hydro-mechanical behaviour of a sandy silt from a river embankment. Due to continuous river level fluctuations and changing climatic and environmental conditions, flood embankment materials experience frequent variations in degree of saturation and suction values. Such variations strongly impact the earthwork performance both in terms of seepage and stability conditions. For these reasons, a detailed characterization of the material behaviour in unsaturated conditions was carried out. Experiments were designed in order to highlight the response of the involved soil in terms of changes in matric suction and confining stress. All tests were performed on undisturbed samples from the embankment. To cover the suction range, which is expected to be significant for the material and assessed through field monitoring, a combination of several suction-control and suction-measurement techniques was used (e.g. negative water column, axial translation, tensiometers). Obtained results enabled (i) to quantify the evolution of the yield stress with suction, (ii) to assess the collapse upon wetting behaviour, (iii) to get detailed information on the water retention behaviour and (iv) to define the relative permeability of the soil. This extensive characterization work serves as a basis for the analysis of the embankment response following river level variations, the final purpose of the research being to establish a reliable methodology and a feasible procedure for the realistic assessment of the safety margins under transient seepage.

Soil mechanical behaviour is strictly related to its natural water content, which is primarily dependent on hydraulic boundary conditions. When soils are partially saturated, as frequently occur in river embankments, soil suction also turns into a fundamental variable worth of investigation and monitoring, both in laboratory and in the field, for a reliable interpretation of the related soil response to external actions. The case of earthen water retaining structures and their safety condition assessment towards local or global collapse mechanisms requires special attention for soil characterization and site measurement of unsaturated soil states. Moreover, strength and hydraulic models used for relevant stability analyses should be adequate for representing the site-specific behaviour of soil in terms of water content, pore water pressure and suction values, relying on the effective possibility to properly calibrate all required parameters. Nevertheless, these aspects typically receive only limited attention, especially in standard practice, leading to inaccurate estimates of flood hazard and related risk management. In this context, with the aim of comprehensively studying the strength and retention properties of a riverbank silty soil, a series of laboratory investigations – including oedometric and direct shear tests under suction-controlled conditions – have been performed. Laboratory tests are here used as the main direct source of information to model unsaturated soil behaviour, monitoring different state variables under suction-controlled conditions. The results have been then interpreted using both literature and soil-specific mechanical and hydraulic models, to be possibly implemented in integrated methodologies for the stability assessment of river embankments.

River flood risk is considered being one of the most costly hazards in Europe and under a further major potential impact of climate change, in combination with land-use changes and water management practices, flood risk is expected to increase for many river basins. In engineering practice, the design of river embankments is usually performed using simplified approaches, considering steady-state flow conditions induced by the retained water and almost neglecting issues related to partially saturated soils, thus leading to potentially heavily over conservative results of stability analyses. To provide a realistic assessment of river bank stability conditions and to get a more accurate prediction of flood risk it is necessary to consider river bank soil behaviour at different saturation degrees in connection with transient seepage flow. A numerical study on stability conditions of a specific river embankment focusing on the partially saturated soil strength contribution is presented herein. Seepage and stability analyses have been carried out using the information collected on river Secchia flooding case study, occurred north of the city of Modena (Italy) in January 2014. Limit equilibrium method has been adopted for assessing the overall stability in steady-state and transient flow conditions. Useful indications for accounting unsaturated soil strength in similar circumstances are finally provided in the paper.

Aims: To date, precision medicine has played a pivotal role in the clinical administration of solid-tumor patients. In this scenario, a rapidly increasing number of predictive biomarkers have been approved in diagnostic practice or are currently being investigated in clinical trials. A pitfall in molecular testing is the diagnostic routine sample available to analyze predictive biomarkers; a scant tissue sample often represents the only diagnostical source of nucleic acids with which to conduct molecular analysis. At the sight of these critical issues, next-generation sequencing (NGS) platforms emerged as referral testing strategies for the molecular analysis of predictive biomarkers in routine practice, but the need for highly skilled personnel and extensive working time drastically impacts the widespread diffusion of this technology in diagnostic settings. Here, we technically validate a fully integrated NGS platform on diagnostic routine tissue samples previously tested with an NGS-based diagnostic workflow by a referral institution. Methods: A retrospective series of n = 64 samples (n = 32 DNA, n = 32 RNA samples), previously tested using a customized NGS assay (SiRe™ and SiRe fusion), was retrieved from the internal archive of the University of Naples Federico II. Each sample was tested by adopting an Oncomine Precision Assay (OPA), which is able to detect 2769 molecular actionable alterations [hotspot mutations, copy number variations (CNV) and gene fusions] on fully integrated NGS platforms (Genexus, Thermo Fisher Scientific (Waltham, MA, USA). The concordance rate between these technical approaches was determined. Results: The Genexus system successfully carried out molecular analysis in all instances. A concordance rate of 96.9% (31 out of 32) was observed between the OPA and SiRe™ panels both for DNA- and RNA-based analysis. A negative predictive value of 100% and a positive predictive value of 96.9% (62 out of 64) were assessed. Conclusions: A fully automatized Genexus system combined with OPA (Thermo Fisher Scientific) may be considered a technically valuable, time-saving sequencing platform to test predictive biomarkers in diagnostic routine practice.

Background: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an alternative treatment for stroke prevention in patients with atrial fibrillation (AF) at high risk of thromboembolism, who cannot tolerate long-term oral anticoagulation (OAC). Questions persist regarding effectiveness and safety of this treatment and the optimal post-interventional antithrombotic regimen after LAAO. Methods: We retrospectively gathered data from 428 patients who underwent percutaneous LAAO in 6 Italian high-volume centres, aimed at describing the real-world utilization, safety, and effectiveness of LAAO procedures, also assessing the clinical outcomes associated with different antithrombotic strategies. Results: Among the entire population, 20 (4.7 %) patients experienced a combination of pericardial effusion and periprocedural major bleeding: 8 (1.9 %) pericardial effusion, 1 (0.3 %) fatal bleeding, and 3 (0.7 %) non-fatal procedural major bleeding. Patients were discharged with different antithrombotic regimens: dual (DAPT) (27 %) or single (SAPT) (26 %) antiplatelet therapy, OAC (27 %), other antithrombotic regimens (14 %). Very few patients were not prescribed with antithrombotic drugs (6 %). At a medium 523 ± 58 days follow-up, 14 patients (3.3 %) experienced all-cause death, 6 patients (1.4 %) cardiovascular death, 3 patients (0.7 %) major bleeding, 10 patients (2.6 %) clinically relevant non-major bleeding, and 3 patients (0.7 %) ischemic stroke. At survival analysis, with DAPT as the reference group, OAC therapy was associated with better outcomes. Conclusions: Our findings confirm that LAAO is a safe procedure. Different individualized post-discharge antithrombotic regimens are now adopted, likely driven by the perceived thrombotic and hemorrhagic risk. The incidence of both ischemic and bleeding events tends to be low.

Abstract Dicksonia sellowiana (Dicksoniaceae) is a tree fern characteristic of the mixed ombrophilous forests of southern Brazil in the Atlantic Forest. Due to its extensive use in the past for making garden pots, this species is at risk of extinction. The objective of this study was to evaluate the phytochemical composition of D. sellowiana leaves and their structures and correlate it with their antioxidant potential. Measurements of moisture content, extraction yield, preliminary phytochemical analysis, chemometric analysis by 1H NMR PCA, UPLC-PDA-MS analysis, total polyphenol content, and antioxidant activity were conducted on the leaves and their structures. The phytochemical composition confirmed the presence of polyphenols, including tannins and flavonoids (derived from kaempferol), with higher concentrations in the pinna and lower in the rachis. The pinnule exhibits high diversity and concentration of phytochemical compounds, which justify its antioxidant activity due to the presence of polyphenols. In conclusion, this study highlights that the pinnae and leaves of D. sellowiana exhibit a similar and more diverse phytochemical composition compared to the other evaluated structures, showing higher concentrations of polyphenols and antioxidant activity. The results reinforce the preservation of the endangered species and its potential as a resource for pharmacological and nutritional phytochemical compounds.

Immune checkpoint inhibitors (ICIs) are specific monoclonal antibodies directed against inhibitory targets of the immune system, mainly represented by programmed death-1 (PD1) ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), thus enabling an amplified T-cell–mediated immune response against cancer cells. These drugs have significantly improved prognosis in patients with advanced metastatic cancer (e.g., melanoma, non-small cell lung cancer, renal cell carcinoma). However, uncontrolled activation of anti-tumor T-cells could trigger an excessive immune response, possibly responsible for multi-organ damage, including, among others, lymphocytic myocarditis. The incidence of ICIs-induced myocarditis is underestimated and the patients affected are poorly characterized. The diagnosis and management of this condition are mainly based on expert opinion and case reports. EKG and ultrasound are tests that can help identify patients at risk of myocarditis during treatment by red flags, such as QRS complex enlargement and narrowing of global longitudinal strain (GLS). Therapy of ICI-related myocarditis is based on immunosuppressors, monoclonal antibodies and fusion proteins. A future strategy could involve the use of microRNAs. This review considers the current state of the art of immune-related adverse cardiovascular events, focusing on histological and clinical features, diagnosis and management, including current treatments and future pharmacological targets. [ABSTRACT FROM AUTHOR]

Primary percutaneous coronary intervention (PCI) is the current class I therapeutic approach to treat acute ST-elevation myocardial infarction (STEMI). While primary PCI can restore adequate flow in the infarcted artery in the majority of cases, some patients experience the ‘no-reflow’ phenomenon, i.e., an abnormal myocardial reperfusion occurring even after the occluded coronary artery has been opened. No-reflow occurs when microvascular obstruction arises from embolization of thrombus or components of the atheromatous plaques. These embolic materials travel downstream within the infarct-related artery at time of primary PCI, leading to compromised blood flow. Currently, no expert consensus documents exist to outline an optimal strategy to prevent or treat no-reflow. Interventional cardiologists frequently employ intracoronary adenosine, calcium channel blockers, nicorandil, nitroprusside or glycoprotein IIb/IIIa inhibitors. However, evidence suggests that these interventions consistently enhance myocardial blood flow in only a specific subset of patients experiencing no-reflow. A recent and innovative therapeutic approach gaining attention is low-dose fibrinolysis during primary PCI, which offers the potential to augment coronary flow post-myocardial revascularization.