No abstract

Background/Aims: In genetic studies of complex disease a consideration for the investigator is detection of joint effects. The Multifactor Dimensionality Reduction (MDR) algorithm searches for these effects with an exhaustive approach. Previously unknown aspects of MDR performance were the power to detect interactive effects given large numbers of non-model loci or varying degrees of heterogeneity among multiple epistatic disease models. Methods: To address the performance with many non-model loci, datasets of 500 cases and 500 controls with 100 to 10,000 SNPs were simulated for two-locus models, and one hundred 500-case/500-control datasets with 100 and 500 SNPs were simulated for three-locus models. Multiple levels of locus heterogeneity were simulated in several sample sizes. Results: These results show MDR is robust to locus heterogeneity when the definition of power is not as conservative as in previous simulation studies where all model loci were required to be found by the method. The results also indicate that MDR performance is related more strongly to broad-sense heritability than sample size and is not greatly affected by non-model loci. Conclusions: A study in which a population with high heritability estimates is sampled predisposes the MDR study to success more than a larger ascertainment in a population with smaller estimates.

The purpose of this study was to demonstrate that a commercially available cabinet x-ray system is capable of phase-contrast radiography (PC-R) and to evaluate the effect of different system parameters on the degree of edge enhancement. An acrylic plastic edge phantom was imaged at different tube potentials (25-60 kV) and in different geometries (variable object-to-detector distances, R(2), at a constant source-to-detector distance, R(1) + R(2)). In addition, the effect of noise on the perceived edge enhancement was studied as a function of exposure time. Our results show that a modest degree of phase contrast can be achieved in an unmodified cabinet x-ray system. In addition, the particular system evaluated allowed low-noise PC-R images to be obtained with short (6 s or less) exposures. These results suggest that with appropriate geometric choices PC-R is already available to a wide range of research scientists for use in both small-animal and human-specimen experiments.

Radiopharmaceuticals targeting cell surface expression of somatostatin receptors (SSTRs) are particularly useful in the evaluation of neuroendocrine tumors. Gallium-68 DOTA-Tyr3-octreotatate (68Ga-DOTATATE) primarily binds to SSTR type 2 receptors. 68Ga DOTATATE PET/CT is proven to have high impact on the management of neuroendocrine patients compared to traditional anatomical imaging as well as provides additional information over that of conventional nuclear medicine studies (indium-III DTPA-octreotide). It can result in change in management of approximately 75% of patients with neuroendocrine tumors. 68Ga DOTATATE and 18F FDG PET/CT imaging are complementary, with the degree of uptake varying depending on the degree of differentiation of the tumor. Well-differentiated tumors maintain their SSTRs and are positive on 68Ga DOTATATE PET/CT scan, while dedifferentiated tumors are less likely to demonstrate uptake of 68Ga DOTATATE but will demonstrate uptake with 18F FDG PET/CT. In addition, 68Ga DOTATATE PET/CT identifies patients with SSTR expression in their tumors, who have progressed on somatostatin analog therapy, for treatment with 177Lu DOTATATE.

We have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate our simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air, a standard 16-cm acrylic head phantom, and a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of our Monte Carlo simulations. We found that simulated and measured CTDI values were within an overall average of 6% of each other.