Bayesian inference for multivariate meta‐analysis Box–Cox transformation models for individual patient data with applications to evaluation of cholesterol‐lowering drugs

In this paper, we propose a class of Box–Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data in meta‐analysis. Our modeling formulation uses a multivariate normal response meta‐analysis model with multivariate random effects, in which each response is allowed to have its own Box–Cox transformation. Prior distributions are specified for the Box–Cox transformation parameters as well as the regression coefficients in this complex model, and the deviance information criterion is used to select the best transformation model. Because the model is quite complex, we develop a novel Monte Carlo Markov chain sampling scheme to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol‐lowering drugs where the goal is to jointly model the three‐dimensional response consisting of low density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C), and triglycerides (TG) (LDL‐C, HDL‐C, TG). Because the joint distribution of (LDL‐C, HDL‐C, TG) is not multivariate normal and in fact quite skewed, a Box–Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately; however, a multivariate approach would be more appropriate because these variables are correlated with each other. We carry out a detailed analysis of these data by using the proposed methodology. Copyright © 2013 John Wiley & Sons, Ltd.     

丹皮多糖对正常及高血糖小鼠的降血糖作用

观察了丹皮多糖对正常小鼠血糖及葡萄糖致小鼠血糖的影响。结果表明,丹皮多糖粗品１００ｍｇ／ｋｇ,２００ｍｇ／ｋｇ灌胃给药可使正常小鼠血糖显著降低,２００ｍｇ／ｋｇ,４００ｍｇ／ｋ灌胃给药对葡萄糖诱发的小鼠高血糖有显著降低作用。     

Cellular- and micro-dosimetry of heterogeneously distributed tritium

Abstract

Purpose: The assessment of radiotoxicity for heterogeneously distributed tritium should be based on the subcellular dose and relative biological effectiveness (RBE) for cell nucleus. In the present work, geometry-dependent absorbed dose and RBE were calculated using Monte Carlo codes for tritium in the cell, cell surface, cytoplasm, or cell nucleus.

Materials and methods: Penelope (PENetration and Energy LOss of Positrins and Electrons) code was used to calculate the geometry-dependent absorbed dose, lineal energy, and electron fluence spectrum. RBE for the intestinal crypt regeneration was calculated using a lineal energy-dependent biological weighting function. RBE for the induction of DNA double strand breaks was estimated using a nucleotide-level map for clustered DNA lesions of the Monte Carlo damage simulation (MCDS) code.

Results: For a typical cell of 10 μm radius and 5 μm nuclear radius, tritium in the cell nucleus resulted in much higher RBE-weighted absorbed dose than tritium distributed uniformly. Conversely, tritium distributed on the cell surface led to trivial RBE-weighted absorbed dose due to irradiation geometry and great attenuation of beta particles in the cytoplasm. For tritium uniformly distributed in the cell, the RBE-weighted absorbed dose was larger compared to tritium uniformly distributed in the tissue.

Conclusions: Cellular- and micro-dosimetry models were developed for the assessment of heterogeneously distributed tritium.     

Monte Carlo single-cell dosimetry of I-131, I-125 and I-123 for targeted radioimmunotherapy of B-cell lymphoma

Abstract

Purpose: To study the dosimetric characteristics of a non-internalizing and an internalizing monoclonal antibody (MAb) labeled with ¹³¹I, ¹²⁵I or ¹²³I, which targets a typical lymphoma B-cell. Materials and methods: Using our hybrid Monte Carlo (MC) code which combines detailed- and condensed-history electron track simulation we carry out transport calculations of Auger and beta electrons for different intracellular distributions of radioactivity. Results: Assuming permanent retention of the MAb in cells, ¹²⁵I gave the highest absorbed dose and ¹²³I the highest absorbed dose rate. Under the more realistic scenario of biologic excretion from the cells, ¹²³I resulted in the highest absorbed dose and absorbed dose rate. Conclusion: The present dosimetric analysis shows that biological half-life, subcellular localization, and the proper account of low-energy electrons is critical in assessing the energy deposition inside the targeted cells from the three iodide radioisotopes examined. From a dosimetric point of view and under the present approximations ¹²³I might be superior to the other two radioiodides in the treatment of microscopic disease in B-cell lymphoma patients.     

Geometrical optimization of an annulus Compton suppression system using Monte Carlo simulation

We are planning to construct a Compton-suppression system permitting accurate and precise determinations of radioactivity of low-level environmental samples. An annulus guard detector (NaI) and a plug-in detector (NaI) are being used as suppression detectors with an HPGe primary detector. The geometry of the Compton suppression spectrometer was optimized by simulation with PENELOPE for obtaining the highest suppression factor (SF) for a point source. The results of the simulations show that the ultimate value of the suppression factor is 7.87±0.18, obtained when the source is located at 57% of an annuls guard detector.