TOPAS-nBio validation for simulating water radiolysis and DNA damage under low-LET irradiation.

The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.

LET-Dependent Intertrack Yields in Proton Irradiation at Ultra-High Dose Rates Relevant for FLASH Therapy.

FLASH radiotherapy delivers a high dose (≥10 Gy) at a high rate (≥40 Gy/s). In this way, particles are delivered in pulses as short as a few nanoseconds. At that rate, intertrack reactions between chemical species produced within the same pulse may affect the heterogeneous chemistry stage of water radiolysis. This stochastic process suits the capabilities of the Monte Carlo method, which can model intertrack effects to aid in radiobiology research, including the design and interpretation of experiments. In this work, the TOPAS-nBio Monte Carlo track-structure code was expanded to allow simulations of intertrack effects in the chemical stage of water radiolysis. Simulation of the behavior of radiolytic yields over a long period of time (up to 50 s) was verified by simulating radiolysis in a Fricke dosimeter irradiated by 60Co γ rays. In addition, LET-dependent G values of protons delivered in single squared pulses of widths, 1 ns, 1 µs and 10 µs, were obtained and compared to simulations using no intertrack considerations. The Fricke simulation for the calculated G value of Fe3+ ion at 50 s was within 0.4% of the accepted value from ICRU Report 34. For LET-dependent G values at the end of the chemical stage, intertrack effects were significant at LET values below 2 keV/µm. Above 2 keV/µm the reaction kinetics remained limited locally within each track and thus, effects of intertrack reactions remained low. Therefore, when track structure simulations are used to investigate the biological damage of FLASH irradiation, these intertrack reactions should be considered. The TOPAS-nBio framework with the expansion to intertrack chemistry simulation provides a useful tool to assist in this task.

TOPAS-nBio: An Extension to the TOPAS Simulation Toolkit for Cellular and Sub-cellular Radiobiology.

The TOPAS Monte Carlo (MC) system is used in radiation therapy and medical imaging research, having played a significant role in making Monte Carlo simulations widely available for proton therapy related research. While TOPAS provides detailed simulations of patient scale properties, the fundamental unit of the biological response to radiation is a cell. Thus, our goal was to develop TOPAS-nBio, an extension of TOPAS dedicated to advance understanding of radiobiological effects at the (sub-)cellular, (i.e., the cellular and sub-cellular) scale. TOPAS-nBio was designed as a set of open source classes that extends TOPAS to model radiobiological experiments. TOPAS-nBio is based on and extends Geant4-DNA, which extends the Geant4 toolkit, the basis of TOPAS, to include very low-energy interactions of particles down to vibrational energies, explicitly simulates every particle interaction (i.e., without using condensed histories) and propagates radiolysis products. To further facilitate the use of TOPAS-nBio, a graphical user interface was developed. TOPAS-nBio offers full track-structure Monte Carlo simulations, integration of chemical reactions within the first millisecond, an extensive catalogue of specialized cell geometries as well as sub-cellular structures such as DNA and mitochondria, and interfaces to mechanistic models of DNA repair kinetics. We compared TOPAS-nBio simulations to measured and published data of energy deposition patterns and chemical reaction rates (G values). Our simulations agreed well within the experimental uncertainties. Additionally, we expanded the chemical reactions and species provided in Geant4-DNA and developed a new method based on independent reaction times (IRT), including a total of 72 reactions classified into 6 types between neutral and charged species. Chemical stage simulations using IRT were a factor of 145 faster than with step-by-step tracking. Finally, we applied the geometric/chemical modeling to obtain initial yields of double-strand breaks (DSBs) in DNA fibers for proton irradiations of 3 and 50 MeV and compared the effect of including chemical reactions on the number and complexity of DSB induction. Over half of the DSBs were found to include chemical reactions with approximately 5% of DSBs caused only by chemical reactions. In conclusion, the TOPAS-nBio extension to the TOPAS MC application offers access to accurate and detailed multiscale simulations, from a macroscopic description of the radiation field to microscopic description of biological outcome for selected cells. TOPAS-nBio offers detailed physics and chemistry simulations of radiobiological experiments on cells simulating the initially induced damage and links to models of DNA repair kinetics.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Human Papilloma Virus- Associated Head and Neck Cancer: A 21st Century Pandemic; Assessing Student Awareness and Knowledge

Background The Human Papillomavirus (HPV) is a causal agent in a subset of Head and Neck Cancers (HNC) being diagnosed in younger patients without significant tobacco and alcohol use. This survey assessed the awareness level of HNC and HPV vaccinations in university students. Methods An anonymous, questionnaire-based survey of registered students of the National University of Ireland, Galway (NUIG) was carried out. Results 1,550 responded, 1,494 completed the survey; 1,018 female (68.1%), 476 male (31.9%). 63% had never heard the term HNC. 45% had never heard the term HPV. 69% were unaware of how one would be exposed to HPV. 84% were unaware of the association between HNC and HPV. Conclusions There are poor levels of awareness of HNC, HPV and HPV vaccination. HPV vaccination needs to be appreciated as a major cancer breakthrough. However the public health benefits of increased awareness of HPV, HNC and HPV vaccination have yet to be realised.

Monte Carlo simulation of chemistry following radiolysis with TOPAS-nBio.

Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advanced computational skills, extending the pool of users. Thus, a new extension to TOPAS, TOPAS-nBio, is under development to facilitate the configuration of track-structure simulations as well as water radiolysis simulations with Geant4-DNA for radiobiological studies. In this work, radiolysis simulations were implemented in TOPAS-nBio. Users may now easily add chemical species and their reactions, and set parameters including branching ratios, dissociation schemes, diffusion coefficients, and reaction rates. In addition, parameters for the chemical stage were re-evaluated and updated from those used by default in Geant4-DNA to improve the accuracy of chemical yields. Simulation results of time-dependent and LET-dependent primary yields Gx (chemical species per 100 eV deposited) produced at neutral pH and 25 °C by short track-segments of charged particles were compared to published measurements. The LET range was 0.05-230 keV µm-1. The calculated Gx values for electrons satisfied the material balance equation within 0.3%, similar for protons albeit with long calculation time. A smaller geometry was used to speed up proton and alpha simulations, with an acceptable difference in the balance equation of 1.3%. Available experimental data of time-dependent G-values for [Formula: see text] agreed with simulated results within 7% ± 8% over the entire time range; for [Formula: see text] over the full time range within 3% ± 4%; for H2O2 from 49% ± 7% at earliest stages and 3% ± 12% at saturation. For the LET-dependent Gx, the mean ratios to the experimental data were 1.11 ± 0.98, 1.21 ± 1.11, 1.05 ± 0.52, 1.23 ± 0.59 and 1.49 ± 0.63 (1 standard deviation) for [Formula: see text], [Formula: see text], H2, H2O2 and [Formula: see text], respectively. In conclusion, radiolysis and subsequent chemistry with Geant4-DNA has been successfully incorporated in TOPAS-nBio. Results are in reasonable agreement with published measured and simulated data.

Yield of Image-Guided Needle Biopsy for Infectious Discitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Image-guided biopsy is routinely conducted in patients with suspected discitis, though the sensitivity reported in the literature ranges widely. PURPOSE: We applied a systematic review and meta-analysis to estimate the yield of image-guided biopsy for infectious discitis. DATA SOURCES: We performed a literature search of 4 data bases: PubMed, Cochrane CENTRAL Register of Controlled Trials, Embase.com, and Scopus from data base inception to March 2016. STUDY SELECTION: A screen of 1814 articles identified 88 potentially relevant articles. Data were extracted for 33 articles, which were eligible if they were peer-reviewed publications of patients with clinical suspicion of discitis who underwent image-guided biopsy. DATA ANALYSIS: Patients with positive cultures out of total image-guided biopsy procedures were pooled to estimate yield with 95% confidence intervals. Hypothesis testing was performed with an inverse variance method after logit transformation. DATA SYNTHESIS: Image-guided biopsy has a yield of approximately 48% (793/1763), which is significantly lower than the open surgical biopsy yield of 76% (152/201; P < .01). Biopsy in patients with prior antibiotic exposure had a yield of 32% (106/346), which was not significantly different from the yield of 43% (336/813; P = .08) in patients without prior antibiotic exposure. LIMITATIONS: The conclusions of this meta-analysis are primarily limited by the heterogeneity of the included studies. CONCLUSIONS: Image-guided biopsy has a moderate yield for the diagnosis of infectious discitis, which is significantly lower than the yield of open surgical biopsy. This yield is not significantly affected by prior antibiotic use.

Comparing stochastic proton interactions simulated using TOPAS-nBio to experimental data from fluorescent nuclear track detectors.

Whilst Monte Carlo (MC) simulations of proton energy deposition have been well-validated at the macroscopic level, their microscopic validation remains lacking. Equally, no gold-standard yet exists for experimental metrology of individual proton tracks. In this work we compare the distributions of stochastic proton interactions simulated using the TOPAS-nBio MC platform against confocal microscope data for Al2O3:C,Mg fluorescent nuclear track detectors (FNTDs). We irradiated [Formula: see text] mm3 FNTD chips inside a water phantom, positioned at seven positions along a pristine proton Bragg peak with a range in water of 12 cm. MC simulations were implemented in two stages: (1) using TOPAS to model the beam properties within a water phantom and (2) using TOPAS-nBio with Geant4-DNA physics to score particle interactions through a water surrogate of Al2O3:C,Mg. The measured median track integrated brightness (IB) was observed to be strongly correlated to both (i) voxelized track-averaged linear energy transfer (LET) and (ii) frequency mean microdosimetric lineal energy, [Formula: see text], both simulated in pure water. Histograms of FNTD track IB were compared against TOPAS-nBio histograms of the number of terminal electrons per proton, scored in water with mass-density scaled to mimic Al2O3:C,Mg. Trends between exposure depths observed in TOPAS-nBio simulations were experimentally replicated in the study of FNTD track IB. Our results represent an important first step towards the experimental validation of MC simulations on the sub-cellular scale and suggest that FNTDs can enable experimental study of the microdosimetric properties of individual proton tracks.

Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol.

Gold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies ∼70 eV, substantially lower than that of liquid water ∼78 eV. Monte Carlo simulations for 10-50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of ∼1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol.

Polarisation-based coincidence event discrimination: an in silico study towards a feasible scheme for Compton-PET.

Current positron emission tomography (PET) systems use temporally localised coincidence events discriminated by energy and time-of-flight information. The two annihilation photons are in an entangled polarisation state and, in principle, additional information from the polarisation correlation of photon pairs could be used to improve the accuracy of coincidence classification. In a previous study, we demonstrated that in principle, the polarisation correlation information could be transferred to an angular correlation in the distribution of scattered photon pairs in a planar Compton camera system. In the present study, we model a source-phantom-detector system using Geant4 and we develop a coincidence classification scheme that exploits the angular correlation of scattered annihilation quanta to improve the accuracy of coincidence detection. We find a [Formula: see text] image quality improvement in terms of the peak signal-to-noise ratio when scattered coincidence events are discriminated solely by their angular correlation, thus demonstrating the feasibility of this novel classification scheme. By integrating scatter events (both single-single and single-only) with unscattered coincidence events discriminated using conventional methods, our results suggest that Compton-PET may be a promising candidate for optimal emission tomographic imaging.

The cytoplasm as a radiation target: an in silico study of microbeam cell irradiation.

We performed in silico microbeam cell irradiation modelling to quantitatively investigate ionisations resulting from soft x-ray and alpha particle microbeams targeting the cytoplasm of a realistic cell model. Our results on the spatial distribution of ionisations show that as x-rays are susceptible to scatter within a cell that can lead to ionisations in the nucleus, soft x-ray microbeams may not be suitable for investigating the DNA damage response to radiation targeting the cytoplasm alone. In contrast, ionisations from an ideal alpha microbeam are tightly confined to the cytoplasm, but a realistic alpha microbeam degrades upon interaction with components upstream of the cellular target. Thus it is difficult to completely rule out a contribution from alpha particle hits to the nucleus when investigating DNA damage response to cytoplasmic irradiation. We find that although the cytoplasm targeting efficiency of an alpha microbeam is better than that of a soft x-ray microbeam (the probability of stray alphas hitting the nucleus is 0.2% compared to 3.6% for x-rays), stray alphas produce more ionisations in the nucleus and thus have greater potential for initiating damage responses therein. Our results suggest that observed biological responses to cytoplasmic irradiation include a small component that can be attributed to stray ionisations in the nucleus resulting from the stochastic nature of particle interactions that cause out-of-beam scatter. This contribution is difficult to isolate experimentally, thus demonstrating the value of the in silico approach.

Towards optimal imaging with PET: an in silico feasibility study.

The efficacy of Positron Emission Tomography (PET) imaging relies fundamentally on the ability of the system to accurately identify true coincidence events. With existing systems, this is currently accomplished with an energy acceptance criterion followed by correction techniques to remove suspected false coincidence events. These corrections generally result in signal and contrast loss and thus limit the PET system's ability to achieve optimum image quality. A key property of annihilation radiation is that the photons are polarised with respect to each other. This polarisation correlation offers a potentially powerful discriminator, independent of energy, to accurately identify true events. In this proof of concept study, we investigate how photon polarisation information can be exploited in PET imaging by developing a method to discriminate true coincidences using the polarisation correlation of annihilation pairs. We implement this method using a Geant4 PET simulation of a GE Advance/Discovery LS system and demonstrate the potential advantages of the polarisation coincidence selection method over a standard energy criterion method. Current PET ring detectors are not capable of exploiting the polarisation correlation of the photon pairs. Compton PET systems, however are promising candidates for this application. We demonstrate the feasibility of a two-component Compton camera system in identifying true coincidences with Monte Carlo simulations. Our study demonstrates the potential of improving signal gain using polarisation, particularly for high photon emission rates. We also demonstrate the ability of the Compton camera at exploiting this polarisation correlation in PET.

Optimisation of the imaging and dosimetric characteristics of an electronic portal imaging device employing plastic scintillating fibres using Monte Carlo simulations.

A Monte Carlo model of a novel electronic portal imaging device (EPID) has been developed using Geant4 and its performance for imaging and dosimetry applications in radiotherapy has been characterised. The EPID geometry is based on a physical prototype under ongoing investigation and comprises an array of plastic scintillating fibres in place of the metal plate/phosphor screen in standard EPIDs. Geometrical and optical transport parameters were varied to investigate their impact on imaging and dosimetry performance. Detection efficiency was most sensitive to variations in fibre length, achieving a peak value of 36% at 50 mm using 400 keV x-rays for the lengths considered. Increases in efficiency for longer fibres were partially offset by reductions in sensitivity. Removing the extra-mural absorber surrounding individual fibres severely decreased the modulation transfer function (MTF), highlighting its importance in maximising spatial resolution. Field size response and relative dose profile simulations demonstrated a water-equivalent dose response and thus the prototype's suitability for dosimetry applications. Element-to-element mismatch between scintillating fibres and underlying photodiode pixels resulted in a reduced MTF for high spatial frequencies and quasi-periodic variations in dose profile response. This effect is eliminated when fibres are precisely matched to underlying pixels. Simulations strongly suggest that with further optimisation, this prototype EPID may be capable of simultaneous imaging and dosimetry in radiotherapy.

Influenza in hospitalized children in Ireland in the pandemic period and the 2010/2011 season: risk factors for paediatric intensive-care-unit admission.

Influenza causes significant morbidity and mortality in children. This study's objectives were to describe influenza A(H1N1)pdm09 during the pandemic, to compare it with circulating influenza in 2010/2011, and to identify risk factors for severe influenza defined as requiring admission to a paediatric intensive care unit (PICU). Children hospitalized with influenza during the pandemic were older, and more likely to have received antiviral therapy than children hospitalized during the 2010/2011 season. In 2010/2011, only one child admitted to a PICU with underlying medical conditions had been vaccinated. The risk of severe illness in the pandemic was higher in females and those with underlying conditions. In 2010/2011, infection with influenza A(H1N1)pdm09 compared to other influenza viruses was a significant risk factor for severe disease. An incremental relationship was found between the number of underlying conditions and PICU admission. These findings highlight the importance of improving low vaccination uptake and increasing the use of antivirals in vulnerable children.

In vivo pharmacological characterization of TD-4208, a novel lung-selective inhaled muscarinic antagonist with sustained bronchoprotective effect in experimental animal models.

Tiotropium is currently the only once-daily, long-acting muscarinic antagonist (LAMA) approved in the United States and other countries for the treatment of chronic obstructive pulmonary disease (COPD). Glycopyrronium has shown promise as a LAMA and was recently approved for once-daily maintenance treatment of COPD in the European Union. Here, we describe the in vivo preclinical efficacy and lung selectivity of a novel inhaled muscarinic antagonist, TD-4208 (biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester) and compare its profile to tiotropium and glycopyrronium. In anesthetized dogs, TD-4208, along with tiotropium and glycopyrronium, produced sustained inhibition of acetylcholine-induced bronchoconstriction for up to 24 hours. In anesthetized rats, inhaled TD-4208 exhibited dose-dependent 24-hour bronchoprotection against methacholine-induced bronchoconstriction. The estimated 24-hour potency (expressed as concentration of dosing solution) was 45.0 µg/ml. The bronchoprotective potencies of TD-4208 and tiotropium were maintained after 7 days of once-daily dosing, whereas glycopyrronium showed a 6-fold loss in potency after repeat dosing. To assess systemic functional activity using a clinically relevant readout, the antisialagogue effect of compounds was also evaluated. The calculated lung selectivity index (i.e., ratio of antisialagogue and bronchoprotective potency) of TD-4208 was superior to glycopyrronium after both single and repeat dosing regimens and was superior to tiotropium after repeat dosing. In conclusion, the in vivo preclinical profile suggests that TD-4208 has the potential to be a long-acting bronchodilator for once-daily treatment of respiratory diseases. Its greater functional selectivity for the lung in preclinical models may translate to an improved tolerability profile compared with marketed muscarinic receptor antagonists.

Investigation and management of an outbreak of Salmonella Typhimurium DT8 associated with duck eggs, Ireland 2009 to 2011.

Salmonella Typhimurium DT8 was a very rare cause of human illness in Ireland between 2000 and 2008, with only four human isolates from three patients being identified. Over a 19-month period between August 2009 and February 2011, 34 confirmed cases and one probable case of Salmonella Typhimurium DT8 were detected, all of which had an MLVA pattern 2-10-NA-12-212 or a closely related pattern. The epidemiological investigations strongly supported a linkbetween illness and exposure to duck eggs. Moreover, S. Typhimurium with an MLVA pattern indistinguishable (or closely related) to the isolates from human cases, was identified in 22 commercial and backyard duck flocks, twelve of which were linked with known human cases. A range of control measures were taken at farm level, and advice was provided to consumers on the hygienic handling and cooking of duck eggs. Although no definitive link was established with a concurrent duck egg-related outbreak of S. Typhimurium DT8 in the United Kingdom, it seems likely that the two events were related. It may be appropriate for other countries with a tradition of consuming duck eggs to consider the need for measures to reduce the risk of similar outbreaks.

Radiation damage on sub-cellular scales: beyond DNA.

This study investigates a model cell as a target for low-dose radiation using Monte Carlo simulations. Mono-energetic electrons and photons are used with initial energies between 10 and 50 keV, relevant to out-of-field radiotherapy scenarios where modern treatment modalities expose relatively large amounts of healthy tissue to low-dose radiation, and also to microbeam cell irradiation studies which show the importance of the cytoplasm as a radiation target. The relative proportions of number of ionizations and total energy deposit in the nucleus and cytoplasm are calculated. We show that for a macroscopic dose of no more than 1 Gy only a few hundred ionizations occur in the nucleus volume whereas the number of ionizations in the cytoplasm is over a magnitude larger. We find that the cell geometry can have an appreciable effect on the energy deposit in the cell and can cause a nonlinear increase in energy deposit with cytoplasm density. We also show that changing the nucleus volume has negligible effect on the total energy deposit but alters the relative proportion deposited in the nucleus and cytoplasm; the nucleus volume must increase to approximately the same volume as the cytoplasm before the energy deposit in the nucleus matches that in the cytoplasm. Additionally we find that energy deposited by electrons is generally insensitive to spatial variations in chemical composition, which can be attributed to negligible differences in electron stopping power for cytoplasm and nucleus materials. On the other hand, we find that chemical composition can affect energy deposited by photons due to non-negligible differences in attenuation coefficients. These results are of relevance in considering radiation effects in healthy cells, which tend to have smaller nuclei. Our results further show that the cytoplasm and organelles residing therein can be important targets for low-dose radiation damage in healthy cells and warrant investigation as much as the conventional focus of a high-dose radiation DNA target in tumour cells.

The determination of the efficiency of a Compton suppressed HPGe detector using Monte Carlo simulations.

A Compton suppressed high-purity germanium (HPGe) detector is well suited to the analysis of low levels of radioactivity in environmental samples. The difference in geometry, density and composition of environmental calibration standards (e.g. soil) can contribute to excessive experimental uncertainty to the measured efficiency curve. Furthermore multiple detectors, like those used in a Compton suppressed system, can add complexities to the calibration process. Monte Carlo simulations can be a powerful complement in calibrating these types of detector systems, provided enough physical information on the system is known. A full detector model using the Geant4 simulation toolkit is presented and the system is modelled in both the suppressed and unsuppressed mode of operation. The full energy peak efficiencies of radionuclides from a standard source sample is calculated and compared to experimental measurements. The experimental results agree relatively well with the simulated values (within ∼5 - 20%). The simulations show that coincidence losses in the Compton suppression system can cause radionuclide specific effects on the detector efficiency, especially in the Compton suppressed mode of the detector. Additionally since low energy photons are more sensitive to small inaccuracies in the computational detector model than high energy photons, large discrepancies may occur at energies lower than ∼100 keV.

The influence of participation in Better Bones and Balance™ on skeletal health: evaluation of a community-based exercise program to reduce fall and fracture risk.

UNLABELLED: Older women participating in Better Bones and Balance™ (BBB) had similar bone mass at the hip compared to a sample of low active/sedentary controls. However, both groups had higher than expected hip BMD, despite higher risk for osteoporosis among BBB participants. INTRODUCTION: BBB is a community-based fall and fracture risk reduction program shown to reduce bone loss at the hip in older women under controlled laboratory conditions. Whether bone benefits are derived from BBB as delivered in the community setting is unknown. The purpose of this study is to evaluate the relationship between community-based BBB participation and parameters of skeletal health in postmenopausal women. METHODS: Women were recruited from BBB classes (n=69) and compared to low active/sedentary controls (n=46); total sample aged 69 + 7.7 years. Bone mineral density (BMD) of the hip and spine was measured using DXA; hip bone structure [cross-sectional area, cross-sectional moment of inertia] at the narrow neck and intertrochanter were derived using hip structural analysis software. Diet, physical activity, and health history were assessed by questionnaires. Group differences in bone outcomes were determined using ANCOVA controlling for age and body mass. RESULTS: While controls were heavier and exhibited greater total body BMD compared to BBB participants (p<0.05), there were no differences between groups in hip or spine BMD or bone structural outcomes (p>0.05) despite BBB participants reporting more frequent prior diagnoses of or risk factors for osteoporosis compared to controls. Both controls and BBB participants had higher than average T-scores at the hip (p<0.05) when compared to an age-matched cohort from NHANES. CONCLUSIONS: These data suggest that participation in BBB may not result in direct benefits to bone. However long-term participation may be associated with other positive outcomes.

SU-E-I-109: Sensitivity Analysis of an Electronic Portal Imaging Device Monte Carlo Model to Variations in Optical Transport Parameters.

PURPOSE: To investigate the sensitivity of a Monte Carlo (MC) model of a standard clinical amorphous silicon (a-Si) electron portal imaging device (EPID) to variations in optical photon transport parameters. METHODS: The Geant4 MC toolkit was used to develop a comprehensive model of an indirect-detection a-Si EPID incorporating x-ray and optical photon transport. The EPID was modeled as a series of uniform layers with properties specified by the manufacturer (PerkinElmer, Santa Clara, CA) of a research EPID at our centre. Optical processes that were modeled include bulk absorption, Rayleigh scattering, and boundary processes (reflection and refraction). Model performance was evaluated by scoring optical photons absorbed by the a-Si photodiode as a function of radial distance from a point source of x-rays on an event-by-event basis (0.025 mm resolution). Primary x-ray energies were sampled from a clinical 6 MV photon spectrum. Simulations were performed by varying optical transport parameters and the resulting point spread functions (PSFs) were compared. The optical parameters investigated include: x-ray transport cutoff thresholds; absorption path length; optical energy spectrum; refractive indices; and the 'roughness' of boundaries within phosphor screen layers. RESULTS: The transport cutoffs and refractive indices studied were found to minimally affect resulting PSFs. A monoenergetic optical spectrum slightly broadened the PSF in comparison with the use of a polyenergetic spectrum. The absorption path length only significantly altered the PSF when decreased drastically. Variations in the treatment of boundaries noticeably broadened resulting PSFs. CONCLUSIONS: Variation in optical transport parameters was found to affect resulting PSF calculations. Current work is focusing on repeating this analysis with a coarser resolution more typical of a commercial a-Si EPID to observe if these effects continue to alter the EPID PSF. Experimental measurement of the EPID line spread function to validate these results is also underway. Cancer Institute NSW Research Equipment Grants 10/REG/1-20 and 10/REG/1-10 Cancer Council NSW Grant, ID RG 11-06 NHMRC Project Grant, ID569211 The University of Sydney Postgraduate Research Scholarship in Medical Physics SWSCS Radiation Oncology Student Scholarship, 2012.