The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

The Status of Multi-Dimensional Core-Collapse Supernova Models

Models of neutrino-driven core-collapse supernova explosions have matured considerably in recent years. Explosions of low-mass progenitors can routinely be simulated in 1D, 2D, and 3D. Nucleosynthesis calculations indicate that these supernovae could be contributors of some lighter neutron-rich elements beyond iron. The explosion mechanism of more massive stars remains under investigation, although first 3D models of neutrino-driven explosions employing multi-group neutrino transport have become available. Together with earlier 2D models and more simplified 3D simulations, these have elucidated the interplay between neutrino heating and hydrodynamic instabilities in the post-shock region that is essential for shock revival. However, some physical ingredients may still need to be added/improved before simulations can robustly explain supernova explosions over a wide range of progenitors. Solutions recently suggested in the literature include uncertainties in the neutrino rates, rotation, and seed perturbations from convective shell burning. We review the implications of 3D simulations of shell burning in supernova progenitors for the ‘perturbations-aided neutrino-driven mechanism,’ whose efficacy is illustrated by the first successful multi-group neutrino hydrodynamics simulation of an 18 solar mass progenitor with 3D initial conditions. We conclude with speculations about the impact of 3D effects on the structure of massive stars through convective boundary mixing.

Detector for imaging and dosimetry of laser-driven epithermal neutrons by alpha conversion

An epithermal neutron imager based on detecting alpha particles created via boron neutron capture mechanism is discussed. The diagnostic mainly consists of a mm thick Boron Nitride (BN) sheet (as an alpha converter) in contact with a non-borated cellulose nitride film (LR115 type-II) detector. While the BN absorbs the neutrons in the thermal and epithermal ranges, the fast neutrons register insignificantly on the detector due to their low neutron capture and recoil cross-sections. The use of solid-state nuclear track detectors (SSNTD), unlike image plates, micro-channel plates and scintillators, provide safeguard from the x-rays, gamma-rays and electrons. The diagnostic was tested on a proof-of-principle basis, in front of a laser driven source of moderated neutrons, which suggests the potential of using this diagnostic (BN+SSNTD) for dosimetry and imaging applications.

Improving composite damage modelling through automatic placement of cohesive elements

Numerous experimental studies of damage in composite laminates have shown that intralaminar (in-plane) matrix cracks lead to interlaminar delamination (out-of-plane) at ply interfaces. The smearing of in-plane cracks over a volume, as a consequence of the use of continuum damage mechanics, does not always effectively capture the full extent of the interaction between the two failure mechanisms. A more accurate representation is obtained by adopting a discrete crack approach via the use of cohesive elements, for both in-plane and out-of-plane damage. The difficulty with cohesive elements is that their location must be determined a priori in order to generate the model; while ideally the position of the crack migration, and more generally the propagation path, should be obtained as part of the problem’s solution. With the aim of enhancing current modelling capabilities with truly predictive capabilities, a concept of automatic insertion of interface elements is utilized. The consideration of a simple traction criterion in relation to material strength, evaluated at each node of the model (or of the regions of the model where it is estimated cracks might form), allows for the determination of initial crack location and subsequent propagation by the insertion of cohesive elements during the course of the analysis. Several experimental results are modelled using the commercial package ABAQUS/Standard with an automatic insertion subroutine developed in this work, and the results are presented to demonstrate the capabilities of this technique.