The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer

Thirty-four post-menopausal women with early breast cancer who had received 20 mg tamoxifen once daily as adjuvant therapy for at least 10 weeks participated in a randomized, double-blind, parallel-group, multicentre trial. The primary aim of the trial was to determine the effect of anastrozole upon tamoxifen pharmacokinetics, with secondary aims of assessing the tolerability of the two drugs in combination and whether or not tamoxifen had any effect upon the oestradiol suppression seen with anastrozole. Patients were randomized to receive either 1 mg anastrozole (16 patients) or matching placebo (18 patients) once daily on a double-blind basis for 28 days. No significant difference (P = 0.919) was observed in serum tamoxifen concentrations between the anastrozole and placebo groups during the trial. The serum concentration of oestradiol was significantly suppressed (P < 0.0001) in patients co-administered anastrozole compared with placebo in the presence of tamoxifen, confirming that anastrozole remained an effective suppressant of oestradiol in the presence of tamoxifen. The combination of tamoxifen and anastrozole was well tolerated, with very little difference in side-effects reported between anastrozole and placebo. In conclusion, the results of this study confirm that anastrozole does not affect the pharmacokinetics of tamoxifen when the two drugs are given in combination to post-menopausal women with early breast cancer. In addition, the oestradiol suppressant effects of anastrozole appear unaffected by tamoxifen. © 1999 Cancer Research Campaig

A Comparison of the Effects of Random and Selective Mass Extinctions on Erosion of Evolutionary History in Communities of Digital Organisms

The effect of mass extinctions on phylogenetic diversity and branching history of clades remains poorly understood in paleobiology. We examined the phylogenies of communities of digital organisms undergoing open-ended evolution as we subjected them to instantaneous “pulse” extinctions, choosing survivors at random, and to prolonged “press” extinctions involving a period of low resource availability. We measured age of the phylogenetic root and tree stemminess, and evaluated how branching history of the phylogenetic trees was affected by the extinction treatments. We found that strong random (pulse) and strong selective extinction (press) both left clear long-term signatures in root age distribution and tree stemminess, and eroded deep branching history to a greater degree than did weak extinction and control treatments. The widely-used Pybus-Harvey gamma statistic showed a clear short-term response to extinction and recovery, but differences between treatments diminished over time and did not show a long-term signature. The characteristics of post-extinction phylogenies were often affected as much by the recovery interval as by the extinction episode itself

An overview of tissue engineering approaches for management of spinal cord injuries

Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed

IceCube-Gen2: A Vision for the Future of Neutrino Astronomy in Antarctica

20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)The recent observation by the IceCube neutrino observatory of an astrophysical flux of neutrinos represents the "first light" in the nascent field of neutrino astronomy. The observed diffuse neutrino flux seems to suggest a much larger level of hadronic activity in the non-thermal universe than previously thought and suggests a rich discovery potential for a larger neutrino observatory. This document presents a vision for an substantial expansion of the current IceCube detector, IceCube-Gen2, including the aim of instrumenting a $10\,\mathrm{km}^3$ volume of clear glacial ice at the South Pole to deliver substantial increases in the astrophysical neutrino sample for all flavors. A detector of this size would have a rich physics program with the goal to resolve the sources of these astrophysical neutrinos, discover GZK neutrinos, and be a leading observatory in future multi-messenger astronomy programs

The IceCube Neutrino Observatory Part III: Cosmic Rays

Papers on cosmic rays submitted to the 33nd International Cosmic Ray Conference (Rio de Janeiro 2013) by the IceCube Collaboration