Demonstration of the FLASH Effect Within the Spread-out Bragg Peak After Abdominal Irradiation of Mice.

Purpose: The effects of FLASH-level dose rates delivered at the spread-out Bragg peak (SOBP) on normal tissue damage in mice were investigated. Materials and Methods: Fifty nontumor-bearing mice received abdominal irradiation, 30 at FLASH dose rates (100 Gy/s) and 20 at conventional dose rates (0.1 Gy/s). Total dose values ranged from 10 to 19 Gy, delivered in a single spot by a synchrocyclotron proton therapy system. Centered on the abdomen, the collimated field delivered was an 11-mm diameter circle with a water-equivalent depth of 2.4 cm from entrance to distal 80% dose. A ridge filter was used to provide dose uniformity over the full 2.4-cm range. The spatial distribution was identical for both the FLASH and conventional deliveries. Results: Overall survival and individual mouse weights were tracked for 21 days after the exposure date, and LD50 values were compared for the FLASH and conventional dose rate groups. Mice exposed to FLASH dose rates had a higher LD50 value as compared with mice exposed to conventional dose rates, with a dose-dependent improvement in survivability of 10% to 20%. The FLASH cohort also showed greater or equal percent population survival for each day of the study. Conclusion: These results are preliminary confirmation of the potential for the combination of the advantages of the Bragg peak with the normal tissue sparing benefits of FLASH treatments. This experiment also confirms that pulsed synchrocyclotrons can be used for the purpose of FLASH research and treatment.

Spread-out Bragg peak proton FLASH irradiation using a clinical synchrocyclotron: Proof of concept and ion chamber characterization.

PURPOSE: The purpose of this work is to (a) demonstrate the feasibility of delivering a spread-out Bragg peak (SOBP) proton beam in ultra-high dose rate (FLASH) using a proton therapy synchrocyclotron as a major step toward realizing an experimental platform for preclinical studies, and (b) evaluate the response of four models of ionization chambers in such a radiation field. METHODS: A clinical Mevion HYPERSCAN® synchrocyclotron was adjusted for ultra-high dose rate proton delivery. Protons with nominal energy of 230 MeV were delivered in pulses with temporal width ranging from 12.5 µs to 24 µs spanning from conventional to FLASH dose rates. A boron carbide absorber and a range modulator block were placed in the beam path for range modulation and creating an SOBP dose profile. The radiation field was defined by a brass aperture with 11 mm diameter. Two Faraday cups were used to determine the number of protons per pulse at various dose rates. The dosimetric response of two cylindrical (IBA CC04 and CC13) and two plane-parallel (IBA PPC05 and PTW Advanced Markus® ) ionization chambers were evaluated. The dose rate was measured using the plane-parallel ionization chambers. The integral depth dose (IDD) was measured with a PTW Bragg Peak® ionization chamber. The lateral beam profile was measured with EBT-XD radiochromic film. Monte Carlo simulation was performed in TOPAS as the secondary check for the measurements and as a tool for further optimization of the range modulators' design. RESULTS: Faraday cups measurement showed that the maximum protons per pulse is 39.9 pC at 24 µs pulse width. A good agreement between the measured and simulated IDD and lateral beam profiles was observed. The cylindrical ionization chambers showed very high ion recombination and deemed not suitable for absolute dosimetry at ultra-high dose rates. The average dose rate measured using the PPC05 ionization chamber was 163 Gy/s at the pristine Bragg peak and 126 Gy/s at 1 cm depth for the SOBP beam. The SOBP beam range and modulation were measured 24.4 mm and 19 mm, respectively. The pristine Bragg peak beam had 25.6 mm range. Simulation results showed that the IDD and profile flatness can be improved by the cavity diameter of the range modulator and the number of scanned spots, respectively. CONCLUSIONS: Feasibility of delivering protons in an SOBP pattern with >100 Gy/s average dose rate using a clinical synchrocyclotron was demonstrated. The dose heterogeneity can be improved through optimization of the range modulator and number of delivered spots. Plane-parallel chambers with smaller gap between electrodes are more suitable for FLASH dosimetry compared to the other ion chambers used in this work.

Opinion formation on dynamic networks: identifying conditions for the emergence of partisan echo chambers.

Modern political interaction is characterized by strong partisanship and a lack of interest in information sharing and agreement across party lines. It remains largely unclear how such partisan echo chambers arise and how they coevolve with opinion formation. Here, we explore the emergence of these structures through the lens of coevolutionary games. In our model, the payoff of an individual is determined jointly by the magnitude of their opinion, their degree of conformity with their social neighbours and the benefit of having social connections. Each individual can simultaneously adjust their opinion and the weights of their social connections. We present and validate the conditions for the emergence of partisan echo chambers, characterizing the transition from cohesive communities with a consensus to divisive networks with splitting opinions. Moreover, we apply our model to voting records of the US House of Representatives over a timespan of decades to understand the influence of underlying psychological and social factors on increasing partisanship in recent years. Our work helps elucidate how the division of today has come to be and how cohesion and unity could otherwise be attained on a variety of political and social issues.