Source description and sampling techniques in PEREGRINE Monte Carlo calculations of dose distributions for radiation oncology

We outline the techniques used within PEREGRINE, a 3D Monte Carlo code calculation system, to model the photon output from medical accelerators. We discuss the methods used to reduce the phase-space data to a form that is accurately and efficiently sampled

Treatment of patient-dependent beam modifiers in photon treatments by the Monte Carlo dose calculation code PEREGRINE

The goal of the PEREGRINE Monte Carlo Dose Calculation Project is to deliver a Monte Carlo package that is both accurate and sufficiently fast for routine clinical use. One of the operational requirements for photon-treatment plans is a fast, accurate method of describing the photon phase-space distribution at the surface of the patient. The open-field case is computationally the most tractable; we know, a priori, for a given machine and energy, the locations and compositions of the relevant accelerator components (i.e., target, primary collimator, flattening filter, and monitor chamber). Therefore, we can precalculate and store the expected photon distributions. For any open-field treatment plan, we then evaluate these existing photon phase-space distributions at the patient`s surface, and pass the obtained photons to the dose calculation routines within PEREGRINE. We neglect any effect of the intervening air column, including attenuation of the photons and production of contaminant electrons. In principle, for treatment plans requiring jaws, blocks, and wedges, we could precalculate and store photon phase-space distributions for various combinations of field sizes and wedges. This has the disadvantage that we would have to anticipate those combinations and that subsequently PEREGRINE would not be able to treat other plans. Therefore, PEREGRINE tracks photons through the patient-dependent beam modifiers. The geometric and physics methods used to do this are described here. 4 refs., 8 figs

A Computational Study on the Role of Gap Junctions and Rod Ih Conductance in the Enhancement of the Dynamic Range of the Retina

Recent works suggest that one of the roles of gap junctions in sensory systems is to enhance their dynamic range by avoiding early saturation in the first processing stages. In this work, we use a minimal conductance-based model of the ON rod pathways in the vertebrate retina to study the effects of electrical synaptic coupling via gap junctions among rods and among AII amacrine cells on the dynamic range of the retina. The model is also used to study the effects of the maximum conductance of rod hyperpolarization activated current Ih on the dynamic range of the retina, allowing a study of the interrelations between this intrinsic membrane parameter with those two retina connectivity characteristics. Our results show that for realistic values of Ih conductance the dynamic range is enhanced by rod-rod coupling, and that AII-AII coupling is less relevant to dynamic range amplification in comparison with receptor coupling. Furthermore, a plot of the retina output response versus input intensity for the optimal parameter configuration is well fitted by a power law with exponent . The results are consistent with predictions of more theoretical works and suggest that the earliest expression of gap junctions along the rod pathways, together with appropriate values of rod Ih conductance, has the highest impact on vertebrate retina dynamic range enhancement

MAPK pathway activation in pilocytic astrocytoma

Pilocytic astrocytoma (PA) is the most common tumor of the pediatric central nervous system (CNS). A body of research over recent years has demonstrated a key role for mitogen-activated protein kinase (MAPK) pathway signaling in the development and behavior of PAs. Several mechanisms lead to activation of this pathway in PA, mostly in a mutually exclusive manner, with constitutive BRAF kinase activation subsequent to gene fusion being the most frequent. The high specificity of this fusion to PA when compared with other CNS tumors has diagnostic utility. In addition, the frequency of alteration of this key pathway provides an opportunity for molecularly targeted therapy in this tumor. Here, we review the current knowledge on mechanisms of MAPK activation in PA and some of the downstream consequences of this activation, which are now starting to be elucidated both in vitro and in vivo, as well as clinical considerations and possible future directions

High-sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina.

Small bistratified cells (SBCs) in the primate retina carry a major blue-yellow opponent signal to the brain. We found that SBCs also carry signals from rod photoreceptors, with the same sign as S cone input. SBCs exhibited robust responses under low scotopic conditions. Physiological and anatomical experiments indicated that this rod input arose from the AII amacrine cell-mediated rod pathway. Rod and cone signals were both present in SBCs at mesopic light levels. These findings have three implications. First, more retinal circuits may multiplex rod and cone signals than were previously thought to, efficiently exploiting the limited number of optic nerve fibers. Second, signals from AII amacrine cells may diverge to most or all of the approximately 20 retinal ganglion cell types in the peripheral primate retina. Third, rod input to SBCs may be the substrate for behavioral biases toward perception of blue at mesopic light levels