Studies involving Monte Carlo simulations are common in both diagnostic and therapy medical physics research, as well as other fields of basic and applied science. As with all experimental studies, the conditions and parameters used for Monte Carlo simulations impact their scope, validity, limitations, and generalizability. Unfortunately, many published peer-reviewed articles involving Monte Carlo simulations do not provide the level of detail needed for the reader to be able to properly assess the quality of the simulations. The American Association of Physicists in Medicine Task Group #268 developed guidelines to improve reporting of Monte Carlo studies in medical physics research. By following these guidelines, manuscripts submitted for peer-review will include a level of relevant detail that will increase the transparency, the ability to reproduce results, and the overall scientific value of these studies. The guidelines include a checklist of the items that should be included in the Methods, Results, and Discussion sections of manuscripts submitted for peer-review. These guidelines do not attempt to replace the journal reviewer, but rather to be a tool during the writing and review process. Given the varied nature of Monte Carlo studies, it is up to the authors and the reviewers to use this checklist appropriately, being conscious of how the different items apply to each particular scenario. It is envisioned that this list will be useful both for authors and for reviewers, to help ensure the adequate description of Monte Carlo studies in the medical physics literature.

Motion of thoracic tumors with respiration presents a challenge for three-dimensional (3D) conformal radiation therapy treatment. Validation of techniques aimed at measuring and minimizing the effects of respiratory motion requires a realistic deformable phantom for use as a gold standard. The purpose of this study was to develop and study the characteristics of a reproducible, tissue equivalent, deformable lung phantom. The phantom consists of a Lucite cylinder filled with water containing a latex balloon stuffed with dampened natural sponges. The balloon is attached to a piston that mimics the human diaphragm. Nylon wires and Lucite beads, emulating vascular and bronchial bifurcations, were uniformly glued at various locations throughout the sponges. The phantom is capable of simulating programmed irregular breathing patterns with varying periods and amplitudes. A tissue equivalent tumor, suitable for holding radiochromic film for dose measurements was embedded in the sponge. To assess phantom motion, eight 3D computed tomography data sets of the static phantom were acquired for eight equally spaced positions of the piston. The 3D trajectories of 12 manually chosen point landmarks and the tumor center-of-mass were studied. Motion reproducibility tests of the deformed phantom were established on seven repeat scans of three different states of compression. Deformable image registration (DIR) of the extreme breathing phases was performed. The accuracy of the DIR was evaluated by visual inspection of image overlays and quantified by the distance-to-agreement (DTA) of manually chosen point landmarks and triangulated surfaces obtained from 3D contoured structures. In initial tests of the phantom, a 20-mm excursion of the piston resulted in deformations of the balloon of 20 mm superior-inferior, 4 mm anterior-posterior, and 5 mm left-right. The change in the phantom mean lung density ranged from 0.24 (0.12 SD) g/cm3 at peak exhale to 0.19 (0.12 SD) g/cm3 at peak inhale. The SI displacement of the landmarks varied between 94% and 3% of the piston excursion for positions closer and farther away from the piston, respectively. The reproducibility of the phantom deformation was within the image resolution (0.7 x 0.7 x 1.25 mm3). Vector average registration accuracy based on point landmarks was found to be 0.5 (0.4 SD) mm. The tumor and lung mean 3D DTA obtained from triangulated surfaces were 0.4 (0.1 SD) mm and 1.0 (0.8 SD) mm, respectively. This phantom is capable of reproducibly emulating the physically realistic lung features and deformations and has a wide range of potential applications, including four-dimensional (4D) imaging, evaluation of deformable registration accuracy, 4D planning and dose delivery.

A method for simulating spot-scanned delivery to a moving tumour was developed which uses patient-specific image and plan data. The magnitude of interplay effects was investigated for two patient cases under different fractionation and respiratory motion variation scenarios. The use of volumetric rescanning for motion mitigation was also investigated. For different beam arrangements, interplay effects lead to severely distorted dose distributions for a single fraction delivery. Baseline shift variations for single fraction delivery reduced the dose to the clinical target volume (CTV) by up to 14.1 Gy. Fractionated delivery significantly reduced interplay effects; however, local overdosage of 12.3% compared to the statically delivered dose remained for breathing period variations. Variations of the tumour baseline position and respiratory period were found to have the largest influence on target inhomogeneity; these effects were reduced with fractionation. Volumetric rescanning improved the dose homogeneity. For the CTV, underdosage was improved by up to 34% in the CTV and overdosage to the lung was reduced by 6%. Our results confirm that rescanning potentially increases the dose homogeneity; however, it might not sufficiently compensate motion-induced dose distortions. Other motion mitigation techniques may be required to additionally treat lung tumours with scanned proton beams.

Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall. Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogenactivated protein kinase (MAPK) activation, although the molecular mechanisms of this process are poorly understood. Here we report that tribbles-1, a recently described modulator of MAPK activation, controls vascular smooth muscle cell proliferation and chemotaxis via the Jun kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whereas the activation and the expression of MKK4/SEK1 are not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries when compared with non-atherosclerotic controls, suggesting that this protein may play a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology.

A new component module (CM), designated DYNVMLC, was developed to fully model the geometry of the Varian Millennium 120 leaf collimator using the BEAMnrc Monte Carlo code. The model includes details such as the leaf driving screw hole, support railing groove and leaf tips. Further modifications also allow sampling of leaf sequence files to simulate the movement of the multileaf collimator (MLC) leaves during an intensity modulated radiation therapy (IMRT) delivery. As an initial validation of the code, the individual leaf geometries were visualized by tracing particles through the component module and recording their position each time a leaf boundary was crossed. A model of the Varian CL21EX linear accelerator 6 MV photon beam incorporating the new CM was built with the BEAMnrc user code. The leaf material density and abutting leaf air gap were chosen to match simulated leaf leakage profiles with film measurements in a solid water phantom. Simulated depth dose and off-axis profiles for a variety of MLC defined static fields agreed to within 2% with ion chamber and diode measurements in a water phantom. Simulated dose distributions for IMRT intensity patterns delivered using both static and dynamic techniques were found to agree with film measurements to within 4%. A comparison of interleaf leakage profiles for the new CM and an equivalent leaf model using the existing VARMLC CM demonstrated that the simplified geometry of VARMLC is not able to accurately predict the details of the MLC leakage for the 120 leaf collimator.