Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak

Purpose: To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited.

Methods and Materials: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism.

Results: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens.

Conclusions: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.

Multilinear and Integer Programming for Markov Decision Processes with Imprecise Probabilities

Markov Decision Processes (MDPs) are extensively used to encode sequences of decisions with probabilistic effects. Markov Decision Processes with Imprecise Probabilities (MDPIPs) encode sequences of decisions whose effects are modeled using sets of probability distributions. In this paper we examine the computation of Γ-maximin policies for MDPIPs using multilinear and integer programming. We discuss the application of our algorithms to “factored” models and to a recent proposal, Markov Decision Processes with Set-valued Transitions (MDPSTs), that unifies the fields of probabilistic and “nondeterministic” planning in artificial intelligence research. 

PageRank in Malware Categorization

In this paper, we propose a malware categorization method that models malware behavior in terms of instructions using PageRank. PageRank computes ranks of web pages based on structural information and can also compute ranks of instructions that represent the structural information of the instructions in malware analysis methods. Our malware categorization method uses the computed ranks as features in machine learning algorithms. In the evaluation, we compare the effectiveness of different PageRank algorithms and also investigate bagging and boosting algorithms to improve the categorization accuracy.

Who needs evidence? Radical Feminism, the Christian Right and sex work research in Northern Ireland

This chapter describes my experiences of conducting research on commercial sex in Belfast, Northern Ireland which was conducted as part of a larger British Academy – Leverhulme Trust funded study that examined the policing and legal regulation of commercial sex in Belfast (Northern Ireland) along with three other cities: Manchester (England), Berlin (Germany) and Prague (Czech Republic). This study provided the first empirical analysis of commercial sex in the jurisdiction and was instrumental in shedding light on prevalence rates for those involved in the industry as well as providing demographic information on the age, nationality and sexual orientation of sex workers along with the sector worked in, whether on-street or off-street. In the chapter I consider my role as a researcher and highlight some of the difficulties that I experienced conducting what was seen as controversial research in the politically, socially and culturally conservative context of Northern Ireland.

A transport beamline solution to control optically accelerated proton beams

Laser-target interaction represents a very promising field for several potential applications,
from the nuclear physics to the radiobiology. However optically accelerated particle beams are
characterized by some extreme features, not suitable for many applications. Therefore, beyond
the improvements at the laser-target interaction level, many researchers are spending their efforts
for the development of specific beam transport devices in order to obtain controlled and
reproducible output beams.In this background, the ELIMED (ELI-Beamlines MEDical applications)
project was born. Within 2017, a dedicated transport beam-line coupled with dosimetric
systems, named ELIMED, will be installed at the Extreme Light Infrastructure Beamlines
(ELI-Beamlines) facility in Prague (CZ),as a part of the ELIMAIA (ELI Multidisciplinary Applications
of laserâA ¸SIon Acceleration) beamline