Characterisation of the secondary-neutron production in particle therapy treatments with the MONDO tracking detector

Particle Therapy (PT) is a non-invasive technique that exploits charged light ions for the irradiation of tumours that cannot be effectively treated with surgery or conventional radiotherapy. While the largest dose fraction is released to the tumour volume by the primary beam, a non-negligible amount of additional dose is due to the beam fragmentation that occurs along the path towards the target volume. In particular, the produced neutrons are particularly dangerous as they can release their energy far away from the treated area, increasing the risk of developing a radiogenic secondary malignant neoplasm after undergoing a treatment. A precise measurement of the neutron flux, energy spectrum and angular distributions is eagerly needed in order to improve the treatment planning system software, so as to predict the normal tissue toxicity in the target region and the risk of late complications in the whole body. The MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is dedicated to the characterisation of the secondary ultra-fast neutrons ([20-400] MeV energy range) produced in PT. The neutron tracking system exploits the reconstruction of the recoil protons produced in two consecutive (n, p) elastic scattering interactions to measure simultaneously the neutron incoming direction and energy. The tracker active media is a matrix of thin squared scintillating fibers arranged in orthogonally oriented layers that are read out by a sensor (SBAM) based on SPAD (Single-Photon Avalanche Diode) detectors developed in collaboration with the Fondazione Bruno Kessler (FBK)

Design, fabrication, and characterization of a multimodal reconfigurable bioreactor for bone tissue engineering

In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio-physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many stimulation systems into a single bioreactor led to the generation of several unimodal bioreactors, investigating one or at mostly two of the required biophysical stimuli. These systems miss the physiological mimicry of bone cells environment, and often produced contrasting results, thus making the knowledge of bone mechanotransduction fragmented and often inconsistent. To overcome this issue, in this study we developed a perfusion and electroactive-vibrational reconfigurable stimulation bioreactor to investigate the differentiation of SaOS-2 bone-derived cells, hosting a piezoelectric nanocomposite membrane as cell culture substrate. This multimodal perfusion bioreactor is designed based on a numerical (finite element) model aimed at assessing the possibility to induce membrane nano-scaled vibrations (with ~12 nm amplitude at a frequency of 939 kHz) during perfusion (featuring 1.46 dyn cm−2 wall shear stress), large enough for inducing a physiologically-relevant electric output (in the order of 10 mV on average) on the membrane surface. This study explored the effects of different stimuli individually, enabling to switch on one stimulation at a time, and then to combine them to induce a faster bone matrix deposition rate. Biological results demonstrate that the multimodal configuration is the most effective in inducing SaOS-2 cell differentiation, leading to 20-fold higher collagen deposition compared to static cultures, and to 1.6- and 1.2-fold higher deposition than the perfused- or vibrated-only cultures. These promising results can provide tissue engineering scientists with a comprehensive and biomimetic stimulation platform for a better understanding of mechanotransduction phenomena beyond cells differentiation

Scintillating fiber devices for particle therapy applications

Particle Therapy (PT) is a radiation therapy technique in which solid tumors are treated with charged ions and exploits the achievable highly localized dose delivery, allowing to spare healthy tissues and organs at risk. The development of a range monitoring technique to be used on-line, during the treatment, capable to reach millimetric precision is considered one of the important steps towards an optimization of the PT efficacy and of the treatment quality. To this aim, charged secondary particles produced in the nuclear interactions between the beam particles and the patient tissues can be exploited. Besides charged secondaries, also neutrons are produced in nuclear interactions. The secondary neutron component might cause an undesired and not negligible dose deposition far away from the tumor region, enhancing the risk of secondary malignant neoplasms that can develop even years after the treatment. An accurate neutron characterization (flux, energy and emission profile) is hence needed for a better evaluation of long-term complications. In this contribution two tracker detectors, both based on scintillating fibers, are presented. The first one, named Dose Profiler (DP), is planned to be used as a beam range monitor in PT treatments with heavy ion beams, exploiting the charged secondary fragments production. The DP is currently under development within the INSIDE (Innovative Solutions for In-beam DosimEtry in hadrontherapy) project. The second one is dedicated to the measurement of the fast and ultrafast neutron component produced in PT treatments, in the framework of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project. Results of the first calibration tests performed at the Trento Protontherapy center and at CNAO (Italy) are reported, as well as simulation studies

Faf1 is expressed during neurodevelopment and is involved in Apaf1-dependent caspase-3 activation in proneural cell

Fas-associated factor 1 (Faf1) has been described as a Fas-binding pro-apoptotic protein and as a component of the death-inducing signaling complex (DISC) in Fas-mediated apoptosis. Faf1 is able to potentiate Fas-induced apoptosis in several cell lines, although its specific functions are still not clear. Here we show that Faf1 is highly expressed in several areas of the developing telencephalon. Its expression pattern appears to be dynamic at different embryonic stages and to be progressively confined within limited territories. To decipher the specific role of Faf1 in developing brain, we used cDNA over-expression and mRNA down-regulation experiments to modulate Faf1 expression in telencephalic neural precursor cells, and we showed that in neural cell death Faf1 acts as a Fas-independent apoptotic enhancer. Moreover, we found that Faf1 protein level is down-regulated during apoptosis in a caspase- and Apaf1-dependent manner

In-room test results at CNAO of an innovative PT treatments online monitor (Dose Profiler)

The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological effectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved efficacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high efficiency in a nearly background-free environment. The Dose Profiler (DP) detector, developed within the INSIDE project, is a scintillating fibre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed

Tracing the sound horizon scale with photometric redshift surveys

We propose a new method for the extraction cosmological parameters using the baryon acoustic oscillation (BAO) scale as a standard ruler in deep galaxy surveys with photometric determination of redshifts. The method consists in a simple empirical parametric fit to the angular two-point correlation function ω(θ). It is parametrized as a power law to describe the continuum and as a Gaussian to describe the BAO bump. The location of the Gaussian is used as the basis for the measurement of the sound horizon scale. This method, although simple, actually provides a robust estimation, since the inclusion of the power law and the use of the Gaussian remove the shifts which affect the local maximum. We discuss the effects of projection bias, non-linearities, redshift space distortions and photo-z precision and apply our method to a mock catalogue of the Dark Energy Survey, built upon a large N-body simulation provided by the MICE collaboration. We discuss the main systematic errors associated with our method and show that they are dominated by the photo-z uncertaint