Production and Characterization of Glass Microspheres for Hepatic Cancer Treatment

A simple theoretical mathematical model was developed to assess the process of glass particles spheroidization in a propane-butane-oxygen flame. The model has been designed to gain a better understanding of the dependency amongst the variables that come into play during glass spheroidization. Using the model and theoretical values of: glass viscosity, density, shear modulus, thermal conductivity as well as measured values of the temperature of the flame at different positions, particle size and the vitreous transition temperature, the particle«s time-temperature history was calculated inside the flame for different particle sizes and trajectories. For yttrium aluminosilicate (YAS) glass microspheres, of diameter size: 20-50 microns, it was found that the spheroidization process is completed within the flame in short time intervals in the order of 4 x 10-3 to 9 x 10-3 seconds, depending on its thermal trajectory and size of the particle. In this paper the trajectories, degree of spheroidization, temperature variations and velocities of different particle sizes are shown. Using the results obtained from the model, YAS glass microspheres were produced and characterized. Density measurements were done using Helium Pycnometry, chemical composition was studied by Energy Dispersive Spectroscopy. The microsphere surface was characterized using Scanning Electron Microscopy and the glass was thermally characterized by means of Differential Thermal Analysis.Fil: Bortot, M. B.. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Prastalo, S.. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Gerencia de Investigacion Aplicada. Grupo de Materiales Nucleares; ArgentinaFil: Prado, Miguel Oscar. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Gerencia de Investigacion Aplicada. Grupo de Materiales Nucleares; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; Argentina. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Solid state microdosimetry of a 148 MeV proton spread-out Bragg peak with a pixelated silicon telescope

A constant value of the Relative Biological Effectiveness (RBE), equal to 1.1, to weight the physical dose of proton therapy treatment planning collides with the experimental evidence of an increase of effectiveness along the depth dose profile, especially at the end of the particle range. In this context, it is desirable to develop new optimized treatment planning systems that account for a variable RBE when weighting the physical dose. In particular, due to the increasing interest on microdosimetry as a possible methodology for measuring physical quantities correlated with the biological effectiveness of the therapeutic beam, the development of new Tissue-Equivalent Proportional Counters (TEPCs) specifically designed for the clinical environment are in progress. In this framework, the silicon technology allows to produce solid state detectors of real micrometric dimensions. This is a valid alternative to the TEPC from a practical point of view, being simple, easy-of-use and more versatile. The feasibility of a solid state microdosimeter based on a monolithic double stage silicon telescope has been previously proposed and deeply investigated by comparing its response to the one obtained by reference TEPCs in various radiation fields. The device is constituted by a matrix of cylindrical elements, 2 μm in thickness and 9 μm in diameter, coupled to a single E stage, 500 μm in thickness. Each segmented ΔE stage acts as a solid state microdosimeter, while the E stage gives information on the energy of the impinging proton up to about 8 MeV. This work is dedicated to the description of the microdosimetric characterization of the 148 MeV energy-modulated proton beam at the radiobiological research line of the Trento Proton Therapy Centre by means of a pixelated silicon microdosimeter. All measurements were carried out at different positions across the spread-out Bragg peak (SOBP) and the corresponding microdosimetric distributions were derived by applying a novel extrapolation algorithm. Finally, microdosimetric assessment of Relative Biological Effectiveness was carried out by weighting the dose distribution of the lineal energy with the Loncol's biological weighting function. Benefits and possible limitations of this approach are discussed

Characterization of a Be(p,xn) neutron source for fission yields measurements

We report on measurements performed at The Svedberg Laboratory (TSL) to characterize a proton-neutron converter for independent fission yield studies at the IGISOL-JYFLTRAP facility (Jyv\"askyl\"a, Finland). A 30 MeV proton beam impinged on a 5 mm water-cooled Beryllium target. Two independent experimental techniques have been used to measure the neutron spectrum: a Time of Flight (TOF) system used to estimate the high-energy contribution, and a Bonner Sphere Spectrometer able to provide precise results from thermal energies up to 20 MeV. An overlap between the energy regions covered by the two systems will permit a cross-check of the results from the different techniques. In this paper, the measurement and analysis techniques will be presented together with some preliminary results.Comment: 3 pages, 3 figures, also submitted as proceedings of the International Conference on Nuclear Data for Science and Technology 201

Platelet Activation in Ovarian Cancer Ascites: Assessment of GPIIb/IIIa and PF4 in Small Extracellular Vesicles by Nano-Flow Cytometry Analysis

In ovarian cancer, ascites represent the microenvironment in which the platelets extravasate to play their role in the disease progression. We aimed to develop an assay to measure ascites’ platelet activation. We enriched small extracellular vesicles (EVs) (40–200 nm) from ascites of high-grade epithelial ovarian cancer patients (n = 12) using precipitation with polyethylene glycol, and we conducted single-particle phenotyping analysis by nano-flow cytometry after labelling and ultra-centrifugation. Atomic force microscopy single-particle nanomechanical analysis showed heterogeneous distributions in the size of the precipitated particles and their mechanical stiffness. Samples were fluorescently labelled with antibodies specific to the platelet markers GPIIb/IIIa and PF4, showing 2.6 to 18.16% of all particles stained positive for the biomarkers and, simultaneously, the EV membrane labelling. Single-particle phenotyping analysis allowed us to quantify the total number of non-EV particles, the number of small-EVs and the number of platelet-derived small-EVs, providing a platelet activation assessment independent of the ascites volume. The percentage of platelet-derived small-EVs was positively correlated with platelet distribution width to platelet count in sera (PDW/PLT). Overall, we presented a high-throughput method that can be helpful in future studies to determine the correlation between the extent of platelet activation in ascites and disease status

Cooperation, collective action, and the archeology of large-scale societies

Archeologists investigating the emergence of large-scale societies in the past have renewed interest in examining the dynamics of cooperation as a means of understanding societal change and organizational variability within human groups over time. Unlike earlier approaches to these issues, which used models designated voluntaristic or managerial, contemporary research articulates more explicitly with frameworks for cooperation and collective action used in other fields, thereby facilitating empirical testing through better definition of the costs, benefits, and social mechanisms associated with success or failure in coordinated group action. Current scholarship is nevertheless bifurcated along lines of epistemology and scale, which is understandable but problematic for forging a broader, more transdisciplinary field of cooperation studies. Here, we point to some areas of potential overlap by reviewing archeological research that places the dynamics of social cooperation and competition in the foreground of the emergence of large-scale societies, which we define as those having larger populations, greater concentrations of political power, and higher degrees of social inequality. We focus on key issues involving the communal-resource management of subsistence and other economic goods, as well as the revenue flows that undergird political institutions. Drawing on archeological cases from across the globe, with greater detail from our area of expertise in Mesoamerica, we offer suggestions for strengthening analytical methods and generating more transdisciplinary research programs that address human societies across scalar and temporal spectra

Microdosimetry on nanometric scale with a new low-pressure avalanche-confinement TEPC

The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of common TEPCs is about 0.3 μm. On the other hand, the pattern of particle interactions is measured by track-nanodosimetry, which derives the single-event distribution of ionization cluster size at the nanometric scale. Anyway, only three nanodosimeters are available worldwide. A feasibility study for extending the performances of TEPC down to the nanometric region was performed and a novel avalanche-confinement TEPC was designed and constructed. This detector is constituted by a cylindrical chamber, based on a three-electrode structure, connected to a vacuum and gas flow system to ensure a continuous replacement of the tissue equivalent gas, thus allowing to simulate different biological site sizes in the range 300-25 nm. This TEPC can be calibrated by exploiting a built-in alpha source and a miniaturized solid-state detector as a trigger. Irradiations with photons, fast neutrons and two hadron beams demonstrated the good performances of the device. A satisfactory agreement with FLUKA simulations was obtained

Plasma-Based Longitudinal Evaluation of ESR1 Epigenetic Status in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer

Background: Endocrine therapy (ET) is the mainstay of treatment for hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer; however, adaptive mechanisms emerge in about 25\u201330% of cases through alterations in the estrogen receptor ligand-binding domain, with a consequent ligand-independent estrogen receptor activity. Epigenetic-mediated events are less known and potentially involved in alternative mechanisms of resistance. The aim of this study was to test the feasibility of estrogen receptor 1 (ESR1) epigenetic characterization through liquid biopsy and to show its potential longitudinal application for an early ET sensitivity assessment. Methods: A cohort of 49 women with hormone receptor-positive HER2-negative MBC was prospectively enrolled and characterized through circulating tumor DNA using methylation-specific droplet digital PCR (MS-ddPCR) before treatment start (BL) and after 3 months concomitantly with computed tomography (CT) scan restaging (EV1). ESR1 epigenetic status was defined by assessing the methylation of its main promoters (promA and promB). The most established cell-free tumor DNA (ctDNA) factors associated with ET resistance [ESR1 and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations] were assessed through next-generation sequencing. Associations were tested through Mann\u2013Whitney U test, matched pairs variations through Wilcoxon signed rank test, and survival was analyzed by log-rank test. Results: The ET backbone was mainly based on aromatase inhibitors (AIs) (70.83%) in association with CDK4/6 inhibitors (93.75%). Significantly lower promA levels at baseline were observed in patients with liver metastases (P = 0.0212) and in patients with ESR1 mutations (P = 0.0091). No significant impact on PFS was observed for promA (P = 0.3777) and promB (P = 0.7455) dichotomized at the median while a 652-fold increase in promB or in either promA or promB at EV1 resulted in a significantly worse prognosis (respectively P = 0.0189, P = 0.0294). A significant increase at EV1 was observed for promB among patients with PIK3CA mutation (P = 0.0173). A trend was observed for promB in ESR1 wild-type patients and for promA in the ESR1 mutant subgroup. Conclusion: The study proofed the concept of an epigenetic characterization strategy based on ctDNA and is capable of being integrated in the current clinical workflow to give useful insights on treatment sensitivity

Non-linear regression models for Approximate Bayesian Computation

Approximate Bayesian inference on the basis of summary statistics is well-suited to complex problems for which the likelihood is either mathematically or computationally intractable. However the methods that use rejection suffer from the curse of dimensionality when the number of summary statistics is increased. Here we propose a machine-learning approach to the estimation of the posterior density by introducing two innovations. The new method fits a nonlinear conditional heteroscedastic regression of the parameter on the summary statistics, and then adaptively improves estimation using importance sampling. The new algorithm is compared to the state-of-the-art approximate Bayesian methods, and achieves considerable reduction of the computational burden in two examples of inference in statistical genetics and in a queueing model.Comment: 4 figures; version 3 minor changes; to appear in Statistics and Computin

INTENSE THERMAL NEUTRON FIELDS FROM A MEDICAL-TYPE LINAC: THE E_LIBANS PROJECT

The e_LiBANS project aims at producing intense thermal neutron fields for diverse interdisciplinary irradiation purposes. It makes use of a reconditioned medical electron LINAC, recently installed at the Physics Department and INFN in Torino, coupled to a dedicated photo-converter, developed within this collaboration, that uses (\u3b3,n) reaction within high Z targets. Produced neutrons are then moderated to thermal energies and concentrated in an irradiation volume. To measure and to characterize in real time the intense field inside the cavity new thermal neutron detectors were designed with high radiation resistance, low noise and very high neutron-to-photon discrimination capability. This article offers an overview of the e_LiBANS project and describes the results of the benchmark experiment