A djuvant treatment in patients at high risk of recurrence of thymoma: Efficacy and safety of a three-dimensional conformal radiation therapy regimen

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. METHODS: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. RESULTS: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. CONCLUSION: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma

THE QUALITY PROBLEM IN WATER DISTRIBUTION SYSTEM

In the last decades attention towards human health and the rise of life quality standards have lead to a higher interest in the quality of water flowing within pressurized flow systems, such as Water Supply Systems (WSSs) and urban Water Distribution Systems (WDSs). Indeed, it is even more necessary to guarantee high quality levels for drinkable water during the ordinary operation of the system, trying to avoid, for example, the formation of harmful elements such as disinfection by-products (DBPs). Another important issue is the intentional contamination, through the introduction of biological, chemical or radio-active contaminants, whose effects could have a strong repercussion on both public health and safety feeling. As a consequence, to adequately simulate contamination phenomena and individuate alternative intervention policies, such as optimum sites for chlorination booster stations (very important, in ordinary conditions, to decrease DBPs) and monitoring early warning stations (very important to deal with emergency conditions rising from intentional contamination), it is necessary to use appropriate analysis tools and therefore produce specific mathematical models in order to analyze space and time variability of the parameters that characterize the quality of water flowing within both WDSs and WSSs. One of the most complete models quoted in literature for the analysis of changes of water quality characteristics along WDSs, is undeniably the one proposed by Rossman et al. [10], which allows to evaluate the variability of chlorine concentration in the water distribution systems. The model uses a Lagrangian approach and is based on the subdivision of the water volume contained in each pipe into a given number of segments (elementary cells), which have the same velocity inside the pipe as that of the flow and behave like completely stirred tanks. Because of its characteristics, last version of this model, denominated EPANET 2 [10], is considered, at present, the world standard, even though it presents some problems, hereafter described. Starting from these considerations, the aim of this paper is to propose a new mathematical problem, denominated QualSim_PFN (Quality Simulation in Pressurized Flow Networks), which is able to overcome EPANET's lacks. As a consequence, in this paper it will first described the EPANET model, then the approach used in the QualSim_PFN model and, finally, it will be synthesized the results of a few runs carried out in order to compare their features and performances. In particular, the contaminants moving within WDSs are usually characterized by very low concentrations and small particle size. As a consequence, they can be considered completely dissolved in the water and, thus, unable to change the flow characteristics (such as velocity and pressure fields). For these reasons, the analysis of time and space changes of quality parameters of water flowing within WDSs is usually carried out in two steps. In the first step, using appropriate hydraulic simulator (hydraulic module), the main characteristics of flow (flow velocities in the pipes, pressure heads at nodes, water levels at reservoirs, etc.) are determined (eventually, for each operating conditions if a period of time characterized by different users’ demands and/or different working conditions of pumps, valves, pipes, etc., have to be considered). In the second step, starting from the knowledge of hydraulic variables (in particular: i) the mean flow velocities along the WDSs’ sides; ii) the water volume in the reservoirs; and iii) the discharge delivered at nodes or in-flowing/out-flowing in/ from the reservoirs), assigned the boundary conditions concerning the contaminants input at nodes and/or reservoirs and, eventually, the coefficients of reaction kinetics, using appropriate quality changes simulator (quality module), the changes in time and space of contaminant(s) concentration(s) are evaluated, together with the mass of contaminant(s) delivered at each node in each time interval and the time spent from a given contaminant input to arrive at various WDSs’ nodes (Early Warning Time). As a consequence, the changes of water quality characteristics within a WDS are strictly linked to the functioning of the distribution system itself. For this reason, before deepen into the ‘quality’ issue, it is important to focus on the WDS ‘hydraulic’. Generally speaking, the module directed to the analysis of the hydraulic behaviour of the water system should be able to simulate different operating conditions that can occur in the system, such as steady and unsteady flows. In order to determine the flow parameters, assuming as certain the geometrical and hydraulic characteristics of the system, initial water levels in the tanks and reservoirs, and the users’ water demand in each time interval in which it is possible to subdivide the whole operation period to examine, it is necessary to solve a set of non linear equations formed by the continuity equations at nodes, the loop equations for each closed circuit existing in the system and roughness formulas for each side. In its turn, the analysis of contaminants propagation should be based on a module directed to the resolutions of a set of continuity equations for contaminant(s), written as for the WDSs’ nodes, as for each of the cells in which every side will be subdivided, as for each tank and reservoirs. These conservation mass equations have to consider different aspects: the mass already present and/or introduced into the tanks and reservoirs, the mass of the substances out-flowing at the water consumption nodes, the mass of the substances that are present and pass in the each side of the WDS as well the kinetic reactions of chemical components, the decay, volatilization phenomena in the tanks/ reservoirs, etc

One-dimensional Simulation of Debris-flow Inception and Propagation

The paper describes the development and the assessment of a numerical model for the simulation of debris flow phenomena. Aiming at this, after having considered the causes of triggering, this work focuses on the simulation of propagation characteristics of the masses mobilized, taking into account both the actual internal dissipative processes characterizing the sediment-water mixture and the effects induced by the modification of the boundaries where the flow takes place. The propagation model implemented is based on the one-dimensional hyper-concentrated shallow flows equations, suitable to take into account also the solid and fluid mass exchanges with the bottom. This system of non-linear partial differential equations is integrated by means of a one-dimensional finite volume scheme, second-order accurate in space and time. In order to show the performance and capabilities of the model, the results of its application to a laboratory dam-break experiment are analysed, and finally the application to a real-world test-case is discussed

Liquid Biopsy in <i>EGFR</i>-Mutated Advanced NSCLC from T790M to <i>MET</i> Amplification: Clinical Implications and Possibilities in the Resistance Setting

According to the ESMO and ASCO clinical guidelines, the main role of liquid biopsy in EGFR+ advanced NSCLC patients is represented by T790M detection after erlotinib/gefitinib/afatinib progression. However, the general international expert consensus regards osimertinib as the preferred upfront treatment in this setting; therefore, this role has been scaled back in recent years. As of today, liquid biopsy has no ASCO or ESMO recommendation following first-line osimertinib; in the same vein, no targeted therapy has received ASCO or ESMO recommendation following post upfront Osimertinib progression. However, this standard could change in the near future. Therefore, adopting a clinical point of view, this paper aims to provide a comprehensive review on the previous, the current and the possible future role of liquid biopsy in the framework of the diagnostic–therapeutic algorithm of EGFR+ advanced NSCLC

One-dimensional Mathematical Modelling of Debris Flow Impact on Open-check Dams

The impact of debris flows on open-check dams is modeled as a Riemann problem in a rectangular cross-section channel with downstream dry state. Under the assumption that the energy is conserved through the structure, this special Riemann problem exhibits four different solution configurations. It is shown that the solution always exists, but there are ranges of the initial conditions and of the geometric characteristics for which the solution is not unique. Two different criteria for the disambiguation of the solution are proposed, and it is shown that these criteria are in agreement. The exact solutions presented can be used as internal boundary conditions in one-dimensional numerical models for the propagation of the debris-flow in river channels and narrow valleys, or as a numeric benchmark

Epithelial-mesenchymal transition in prostate cancer: an overview

Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance.In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance