Development of a dual phantom technique for measuring the fast neutron component of dose in boron neutron capture therapy.

[Purpose]: Research and development of various accelerator-based irradiation systems for boron neutroncapture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiationconditions in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fastneutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a “dual phantom technique” for measuring the fast neutron component of dose is reported. [Methods]: One phantom was filled with pure water. The other phantom was filled with a water solution of lithiumhydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons.Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution.Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % [6]LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % [6]LiOH solution based on the simulation results. Experimental characterization of the depth dose distributions of the neutron andgamma-ray components along the central axis was performed at Heavy Water Neutron IrradiationFacility installed at Kyoto University Reactor using activation foils and thermoluminescent dosimeters, respectively. [Results]: Simulation results demonstrated that the absorbing effect for thermal neutrons occurred when the LiOH concentration was over 1%. The most effective Li-6 concentration was determined to be enriched [6]LiOH with a solubility approaching its upper limit. Experiments confirmed that the thermalneutron flux and secondary gamma-ray dose rate decreased substantially; however, the fastneutron flux and primary gamma-ray dose rate were hardly affected in the 10%-[6]LiOH phantom. It was confirmed that the dose contribution of fast neutrons is improved from approximately 10% in the pure water phantom to approximately 50% in the 10%-[6]LiOH phantom. [Conclusions]: The dual phantom technique using the combination of a pure water phantom and a 10%-[6]LiOH phantom developed in this work provides an effective method for dose estimation of the fast neutroncomponent in BNCT. Improvement in the accuracy achieved with the proposed technique results in improved RBE estimation for biological experiments and clinical practice

Blood Pressure and Arterial Stiffness

Background—The difference in the predictive ability of the brachial-ankle pulse wave velocity (baPWV) and its stiffness index β-transformed value (β-baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results—In study 1, a 7-year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for β-baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P<0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P<0.01) by the end of the study period. During study 2, a 3-year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions—Stiffness index β transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects

sdLDL-C and Cardiovascular Events

Aim: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. Methods: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. Results: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. Conclusions: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL

Diagnostic Criteria of FMD and NID

Background - Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results - We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions - We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects

Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell

More than 10 years have passed since the naming of periostin derived from its expression sites in the periosteum and periodontal ligament. Following this finding, we have accumulated more data on the expression patterns of periostin, and, finally, with the generation of periostin-deficient mice, have revealed functions of periostin in the regeneration of tissues in bone, tooth, heart, and skin, and its action in cancer invasion. Since periostin is a matricellular protein, the first investigation of periostin function showed its enhancement of cell migration by acting outside the cell. On the other hand, recent observations have demonstrated that periostin functions in fibrillogenesis in association with extracellular matrix molecules inside the cell