No abstract

Challenging issues in treatment planning for scanned carbon-ion (C-ion) therapy are (i) accurate calculation of dose distribution, including the contribution of large angle-scattered fragments, (ii) reduction in the memory space required to store the dose kernel of individual pencil beams and (iii) shortening of computation time for dose optimization and calculation. To calculate the dose contribution from fragments, we modeled the transverse dose profile of the scanned C-ion beam with the superposition of three Gaussian distributions. The development of pencil beams belonging to the first Gaussian component was calculated analytically based on the Fermi-Eyges theory, while those belonging to the second and third components were transported empirically using the measured beam widths in a water phantom. To reduce the memory space for the kernels, we stored doses only in the regions of interest considered in the dose optimization. For the final dose calculation within the patient's whole body, we applied a pencil beam redefinition algorithm. With these techniques, the triple Gaussian beam model can be applied not only to final dose calculation but also to dose optimization in treatment planning for scanned C-ion therapy. To verify the model, we made treatment plans for a homogeneous water phantom and a heterogeneous head phantom. The planned doses agreed with the measurements within ±2% of the target dose in both phantoms, except for the doses at the periphery of the target with a high dose gradient. To estimate the memory space and computation time reduction with these techniques, we made a treatment plan for a bone sarcoma case with a target volume of 1.94 l. The memory space for the kernel and the computation time for final dose calculation were reduced to 1/22 and 1/100 of those without the techniques, respectively. Computation with the triple Gaussian beam model using the proposed techniques is rapid, accurate and applicable to dose optimization and calculation in treatment planning for scanned C-ion therapy.

In the conventional procedure for accurate Monte Carlo simulation of radiotherapy, a CT number given to each pixel of a patient image is directly converted to mass density and elemental composition using their respective functions that have been calibrated specifically for the relevant x-ray CT system. We propose an alternative approach that is a conversion in two steps: the first from CT number to density and the second from density to composition. Based on the latest compilation of standard tissues for reference adult male and female phantoms, we sorted the standard tissues into groups by mass density and defined the representative tissues by averaging the material properties per group. With these representative tissues, we formulated polyline relations between mass density and each of the following; electron density, stopping-power ratio and elemental densities. We also revised a procedure of stoichiometric calibration for CT-number conversion and demonstrated the two-step conversion method for a theoretically emulated CT system with hypothetical 80 keV photons. For the standard tissues, high correlation was generally observed between mass density and the other densities excluding those of C and O for the light spongiosa tissues between 1.0 g cm(-3) and 1.1 g cm(-3) occupying 1% of the human body mass. The polylines fitted to the dominant tissues were generally consistent with similar formulations in the literature. The two-step conversion procedure was demonstrated to be practical and will potentially facilitate Monte Carlo simulation for treatment planning and for retrospective analysis of treatment plans with little impact on the management of planning CT systems.

PCRL requires a longer treatment time than PCRV for high numbers of rescannings in the NIRS scanning system but is more robust. Although four or more rescans provided good dose homogeneity and conformity, the authors prefer to use more rescannings for clinical cases to further minimize dose degradation effects due to organ motion.

The accuracy of computed tomography number to electron density (CT‐ED) calibration is a key component for dose calculations in an inhomogeneous medium. In a previous work, it was shown that the tolerance levels of CT‐ED calibration became stricter with an increase in tissue thickness and decrease in the effective energy of a photon beam. For the last decade, a low effective energy photon beam (e.g., flattening‐filter‐free (FFF)) has been used in clinical sites. However, its tolerance level has not been established yet. We established a relative electron density (ED) tolerance level for each tissue type with an FFF beam. The tolerance levels were calculated using the tissue maximum ratio (TMR) and each corresponding maximum tissue thickness. To determine the relative ED tolerance level, TMR data from a Varian accelerator and the adult reference computational phantom data in the International Commission on Radiological Protection publication 110 (ICRP‐110 phantom) were used in this study. The 52 tissue components of the ICRP‐110 phantom were classified by mass density as five tissues groups including lung, adipose/muscle, cartilage/spongy‐bone, cortical bone, and tooth tissue. In addition, the relative ED tolerance level of each tissue group was calculated when the relative dose error to local dose reached 2%. The relative ED tolerances of a 6 MVFFF beam for lung, adipose/muscle, and cartilage/spongy‐bone were ±0.044, ±0.022, and ±0.044, respectively. The thicknesses of the cortical bone and tooth groups were too small to define the tolerance levels. Because the tolerance levels of CT‐ED calibration are stricter with a decrease in the effective energy of the photon beam, the tolerance levels are determined by the lowest effective energy in useable beams for radiotherapy treatment planning systems.

Nonphotic entrainment of an overt sleep-wake rhythm and a circadian pacemaker-driving temperature/melatonin rhythm suggests existence of feedback mechanisms in the human circadian system. In this study, the authors constructed a phase dynamics model that consisted of two oscillators driving temperature/melatonin and sleep-wake rhythms, and an additional oscillator generating an overt sleep-wake rhythm. The feedback mechanism was implemented by modifying couplings between the constituent oscillators according to the history of correlations between them. The model successfully simulated the behavior of human circadian rhythms in response to forced rest-activity schedules under free-run situations: the sleep-wake rhythm is reentrained with the circadian pacemaker after release from the schedule, there is a critical period for the schedule to fully entrain the sleep-wake rhythm, and the forced rest-activity schedule can entrain the circadian pacemaker with the aid of exercise. The behavior of human circadian rhythms was reproduced with variations in only a few model parameters. Because conventional models are unable to reproduce the experimental results concerned here, it was suggested that the feedback mechanisms included in this model underlie nonphotic entrainment of human circadian rhythms.

The recent widespread consumption of Western diets and food additives worldwide is associated with excessive inorganic phosphate intake. However, researchers have known little about the impact of dietary phosphate intake on the development of inflammatory bowel disease to date. In this study, we investigated the effects of dietary phosphate on intestinal inflammation in experimental colitis. Sprague-Dawley rats were fed different phosphate diets (0.5%, 1.0% and 1.5% phosphate) with or without dextran sulfate sodium. For in vitro study, the effects of phosphate on proinflammatory cytokine induction and reactive oxygen species production in RAW264.7 macrophage were examined. Dietary phosphate exacerbated intestinal inflammation in experimental colitis in a dose-dependent manner, as assessed by the clinical disease activity score, colon length, and histology. Furthermore, the high phosphate diet increased myeloperoxidase activity and proinflammatory cytokine mRNA expression through the activation of nuclear factor κB in the inflamed colon. In addition, high phosphate loading in RAW264.7 cells directly enhanced reactive oxygen species production and proinflammatory cytokine gene expression. Our results demonstrated that the high phosphate diet exacerbated intestinal inflammation in experimental colitis. These findings have important therapeutic implications for inflammatory bowel disease patients.

The type IIa sodium-dependent phosphate cotransporter (Npt2a) plays a critical role in reabsorption of inorganic phosphate (Pi) by renal proximal tubular cells. Pi abnormalities during early stages of sepsis have been reported, but the mechanisms regulating Pi homeostasis during acute inflammation are poorly understood. We examined the regulation of Pi metabolism and renal Npt2a expression during lipopolysaccharide (LPS)-induced inflammation in mice. Dose-response and time-course studies with LPS showed significant increases of plasma Pi and intact parathyroid hormone (iPTH) levels and renal Pi excretion, while renal calcium excretion was significantly decreased. There was no difference in plasma 1,25-dihydroxyvitamin D levels, but the induction of plasma intact fibroblast growth factor 23 levels peaked 3 h after LPS treatment. Western blotting, immunostaining, and quantitative real-time PCR showed that LPS administration significantly decreased Npt2a protein expression in the brush border membrane (BBM) 3 h after injection, but there was no change in renal Npt2a mRNA levels. Moreover, tumor necrosis factor-␣ injection also increased plasma iPTH and decreased renal BBM Npt2a expression. Importantly, we revealed that parathyroidectomized rats had impaired renal Pi excretion and BBM Npt2a expression in response to LPS. These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation.LPS; phosphate; kidney; Npt2a; PTH ELECTROLYTE DISORDERS IN CRITICALLY ill patients during a stay in the intensive care unit (ICU) are a significant concern. Hypocalcemia and hyperparathyroidism are common findings in critically ill patients. These disorder alterations are related to the severity of disease and poor prognoses (8,24,49). Abnormal serum inorganic phosphate (P i ) levels have also been reported in critically ill patients such as sepsis and are associated with illness severity or higher mortality (3, 41). P i plays a critical role in mineral metabolism and diverse cellular functions involving intermediary metabolism and energy transfer mechanisms. Serum P i levels are normally maintained within a narrow range through a complex interplay among intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. Renal proximal tubular reabsorption is thought to be the primary mechanism for regulating P i metabolism and mainly mediated by type II sodium-dependent phosphate (NaP i ) cotransporters (Npt2a and Npt2c) in the brush border membrane (BBM) (6, 26, 42). The importance of Npt2a and Npt2c has been demonstrated in gene-deficient mice (5, 36, 38). Type III sodiumdependent phosphate cotransporters (PiT1 and PiT2) are known to be P i housekeeping transporters. However, it has been reported that PiT2 is a novel mediator of P i reabsorption in the BBM (6, 44). Intact parathyroid hormone (iPTH) and intact fibroblast growth factor 23 (iFGF23) have been known as P i -regulating ho...