The mesoscale variability in the Mediterranean Sea is investigated through eddy detection techniques. The analysis is performed over 24 years (1993–2016) considering the three-dimensional (3D) fields ...from an ocean re-analysis of the Mediterranean Sea (MED-REA). The objective is to achieve a fit-for-purpose assessment of the 3D mesoscale eddy field. In particular, we focus on the contribution of eddy-driven anomalies to ocean dynamics and thermodynamics. The accuracy of the method used to disclose the 3D eddy contributions is assessed against pointwise
in-situ
measurements and observation-based data sets. Eddy lifetimes ≥ 2 weeks are representative of the 3D mesoscale field in the basin, showing a high probability (> 60
%
) of occurrence in the areas of the main quasi-stationary mesoscale features. The results show a dependence of the eddy size and thickness on polarity and lifetime: anticyclonic eddies (ACE) are significantly deeper than cyclonic eddies (CE), and their size tends to increase in long-lived structures which also show a seasonal variability. Mesoscale eddies result to be a significant contribution to the ocean dynamics in the Mediterranean Sea, as they account for a large portion of the sea-surface height variability at temporal scales longer than 1 month and for the kinetic energy (50–60
%
) both at the surface and at depth. Looking at the contributions to ocean thermodynamics, the results exhibit the existence of typical warm (cold) cores associated with ACEs (CEs) with exceptions in the Levantine basin (e.g., Shikmona gyre) where a structure close to a mode-water ACE eddy persists with a positive salinity anomaly. In this area, eddy-induced temperature anomalies can be affected by a strong summer stratification in the surface water, displaying an opposite sign of the anomaly whether looking at the surface or at depth. The results show also that temperature anomalies driven by long-lived eddies (≥ 4 weeks) can affect up to 15–25
%
of the monthly variability of the upper ocean heat content in the Mediterranean basin.
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 ...(IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9–10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vβ chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.)
The need to contain the spread of the SARS-CoV-2 pandemic has forced national and local organizations to define and implement targeted emergency response and management measures. As the knowledge ...about the infection grew, a wider range of organizational measures were deployed.
This study involves the SARS-CoV-2 infected people managed by the Local Health Authority of Rieti (Italy). Diagnostic test waiting times and hospital admission rates in the Province of Rieti are investigated as the pandemic evolved. Trends were analyzed in relation to the tempora spreading of SARS-CoV-2, to the organizational actions taken by the Local Health Authority of Rieti, and to the deployment of actions across the territory. A municipalities classification of the province of Rieti was conducted after a cluster analysis based on the diagnostic test waiting times and the hospital admission rates.
Our findings show a declining trend, thus indicating a possible positive effect of the measures taken to contain the pandemic. The cluster analysis of the municipalities of the Province of Rieti makes evident an inhomogeneous geographical distribution of examined parameters (diagnostic test waiting times and the hospital admission rates), demonstrating the capability of Local Health Authority of Rieti to reach even the most disadvantaged areas and implying that the differences are due to the demographical variabilities.
Despite some limitations, this study outlines the importance of management measures in response of the pandemic. These measures should adapt to social, cultural and geographical nature of the territory involved. The findings of the present study will contribute to the update of further pandemic preparedness plans of the Local Health Authorities.
•An integrated approach is proposed to characterize tunnel ventilation systems.•The approach combines an innovative experimental setup and numerical algorithms.•A traveling survey rake for continuous ...airflow measurement has been constructed.•Results of the first test campaign at the Mont Blanc Tunnel are presented.
The knowledge of the flow field inside road tunnels under normal operation, let alone fire conditions, is only approximate and partial. The reason is that while the full three-dimensional, unsteady problem is out of reach of numerical methods, on the other hand accurate measurement of the airflow in road and railway tunnels constitutes an extremely demanding task. The present work, structured as a twofold study, takes up the challenge and proposes an original integrated experimental and numerical approach for the analysis and modeling of flow inside a road tunnel and its ventilation systems, aiming at defining a methodology for the creation of “digital twins” of the system itself, on which advanced ventilation and smoke control strategies can be tested and fine-tuned. In this first part, an innovative experimental facility for the continuous acquisition of the longitudinal velocity profile along the whole length of a road tunnel has been designed and built. The facility consists of a survey rake with five bidirectional vane anemometers, which is mounted on a small electric vehicle that can travel through the tunnel at constant speed. This paper reports the design procedure of the measurement facility, with particular focus on the conception and realization of the vehicle carrying the survey rake. Results of the first experimental campaign carried out under the 11611 meters long Mont Blanc road tunnel are presented to corroborate the validity of the approach adopted and the accuracy of the measurement chain.
•An integrated approach is proposed to characterize tunnel ventilation systems.•The approach combines an innovative experimental setup and numerical simulation.•The 1D code is calibrated against ...experimental data using a genetic algorithm.•Further validation is performed against data from the Mont Blanc Tunnel.
The present work represents the second and final part of a twofold study aiming at the definition and validation of an integrated methodology for the analysis and modeling of road tunnel ventilation systems. A numerical approach is presented, based on the Finite Volume integration of the 1D mechanical and thermal energy conservation equations on a network of ducts, representing the ventilation system of the 11.6 km long Mont Blanc Tunnel. The set of distributed and concentrated loss coefficients, representing dissipation of mechanical energy by friction in each part of the ventilation system, is calibrated against a rich experimental dataset, collected throughout a dedicated set of in situ tests and presented in the first part of the work. The calibration of the model is carried out by means of genetic optimization algorithms. Predictions of the flow field using the calibrated parameters are in remarkable agreement with the experimental data, with an overall RMS error of ± 0.27 m/s, i.e. of the same order of the accuracy of the measurement probes. Further validation against a selection of field data recorded by the tunnel monitoring and control system is brought forward, highlighting the robustness and potential general applicability of the proposed approach.
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•An experimental and theoretical approach is applied to analyse the Mont Blanc Tunnel.•In situ velocity measurements are carried out with a specifically built survey rake.•A ...simplified time-dependent analytical model of tunnel flow is developed.•Experimental data and additional CFD are used for the model fine-tuning.•Estimates of the friction factor and jet fan efficiency coefficients are proposed.
Long road and railway tunnels necessitate of a fine-tuned control of the ventilation system to be activated, for both safety and air quality maintenance reasons. This, in turn, requires that the main fluid-dynamic parameters of the tunnel are known with sufficient accuracy, so that the system behaviour can be predicted with reasonable confidence under standard and emergency operative conditions. As a first step in the modelling of the complex system embodying the 11,611m long Mont Blanc road tunnel, and its ventilation facilities, a movable 5-point survey rake was designed and built-up, for detecting the distribution of the axial velocity on the tunnel cross-section. Two extensive experimental campaigns were carried out, where the airflow-rates were either measured at different stations along the tunnel length (C1), or at a fixed location, under purely axial main-flow conditions and varying the number of the activated axial fan pairs (C2). A simplified dynamic model of the tunnel was developed, and the airflow data from the experiments were used for the model fine-tuning, additional CFD analyses having provided extra information on concentrated pressure losses connected with air inlet and discharge through the tunnel ends. The Mont Blanc tunnel was finally characterised in terms of friction factors and jet-fans installation efficiency.
Unstable angina is associated with enhanced lipid peroxidation and reduced antioxidant defenses. We have previously reported aspirin failure in the suppression of enhanced thromboxane (TX) ...biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane 8-iso-prostaglandin (PG)F(2alpha), a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis.
Urine samples were obtained from patients with unstable angina (n=32), stable angina (n=32), or variant angina (n=4) and from 40 healthy subjects for the measurement of immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2). 8-Iso-PGF(2alpha) excretion was significantly higher in patients with unstable angina (339+/-122 pg/mg creatinine) than in matched patients with stable angina (236+/-83 pg/mg creatinine, P:=0.001) and control subjects (192+/-71 pg/mg creatinine, P:<0.0001). In patients with unstable angina, 8-iso-PGF(2alpha) was linearly correlated with 11-dehydro-TXB(2) excretion (rho=0.721, P:<0.0001) and inversely correlated with plasma vitamin E (rho=-0.710, P:=0. 004). Spontaneous myocardial ischemia in patients with variant angina or ischemia elicited by a stress test in patients with stable angina was not accompanied by any change in 8-iso-PGF(2alpha) excretion, thus excluding a role of ischemia per se in the induction of increased F(2)-isoprostane production.
These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.
Abstract Introduction Pulmonary hypertension (PH) is a disease with an unfavorable prognosis, characterized by increasing in pulmonary resistence and right heart failure. One of the most important ...prognostic factors is the adaptation of the right ventricle to increased pressure overload, witch can be evaluated through tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PAPs), a prognostic echocardiographic index of right ventricle–pulmonary artery coupling. In this setting, NT–proBNP, until now, is the only biomarker that, reflecting right ventricular function, gives prognostic information. However, NT–proBNP levels are influenced by age, body mass index, sex and comorbidities, such as anemia and renal failure. In previous studies soluble– Suppression of Tumorigenicity (s–ST2), a marker of myocardial stress, resulted a strong predictor of death in heart failure, acute coronary syndromes and pulmonary hypertension. Aim Our purpose is to study the possible correlation between sST2 and different echocardiographic parameters, in particular TAPSE/PAPs. Methods This is a prospective study conducted on 45 PH patients (75% affected by pulmonary arterial hypertension), which were followed for survival. They underwent echocardiography, right heart catheterization and venous sampling to measure s–ST2 levels. Results During an average 18–month follow–up, 17 patients died, 76% of whom had pulmonary arterial hypertension (PAH). sST2>78 ng/ml represents a numerical value with the highest association with mortality in our study population: at 6–12 months the patients with sST2>78 ng/ml showed statistically significant early higher mortality in comparison with sST2 <78 ng/ml patients. Patients with sST2>78ng/ml had statistically significantly higher right ventricular inflow diameter, reduced tricuspid annular planer systolic excursion, greater right atrial area, lower pulmonary artery acceleration time and lower TAPSE/PAPs, compared with patients with sST2<78 ng/ml values. We showed a statistically significant inverse correlation between sST2 and TAPSE/PAPs. Conclusions s–ST2, predicting right ventricular/pulmonary artery coupling through TAPSE/PAPs, represents an usefull and promising marker in noninvasive hemodynamic assessment and risk stratification of PH patients.
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