Clinical application of high throughput molecular screening techniques for pharmacogenomics.

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing

Testing Models of the Individual and Cosmological Evolutions of Powerful Radio Galaxies

We seek to develop an essentially analytical model for the evolution of Fanaroff-Riley Class II radio galaxies as they age individually and as their numbers vary with cosmological epoch. Such modeling is required in order to probe in more detail the impact of radio galaxies on the growth of structures in the universe, which appears likely to have been quite significant at z > 1. In this first paper of a series we compare three rather sophisticated analytical models for the evolution of linear size and lobe power of FR II radio galaxies, those of Kaiser, Dennett-Thorpe & Alexander (1997), Blundell, Rawlings & Willott (1999), and Manolakou & Kirk (2002). We perform multi-dimensional Monte Carlo simulations in order to compare the predictions of each model for radio powers, sizes, redshifts and spectral indices with data. The observational samples used here are the low frequency radio surveys, 3CRR, 6CE and 7CRS, which are flux-limited and complete. We search for and describe the best parameters for each model, after doing statistical tests on them. We find that no existing model can give acceptable fits to all the properties of the surveys considered, although the Kaiser, Dennett-Thorpe & Alexander (1997) model gives better overall results than do the Manolakou & Kirk (2002) or Blundell, Rawlings & Willott (1999) models for most of the tests we performed. We suggest ways in which these models may be improved.Comment: 26 pages, 5 figures; substantially improved version, with additional statistical tests; to appear in MNRA

Jet propagation and the asymmetries of CSS radio sources

As Compact Steep Spectrum radio sources have been shown to be more asymmetrical than larger sources of similar powers, there is a high probability that they interact with an asymmetric medium in the central regions of the host elliptical galaxy. We consider a simple analytical model of the propagation of radio jets through a reasonable asymmetric environment and show that they can yield the range of arm-length and luminosity asymmetries that have been observed. We then generalize this to allow for the effects of orientation, and quantify the substantial enhancements of the asymmetries that can be produced in this fashion. We present two-dimensional and three-dimensional simulations of jets propagating through multi-phase media and note that the results from the simulations are also broadly consistent with the observations.Comment: 11 pages, 6 figures, 1 table, accepted for publication in A&