Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Reliability and scale effect in toughness of concrete structures

In the present work, the distribution of the random toughness characteristics (i.e. critical energy release rate, G_1c) has been evaluated on the basis of experimental observations. Fracture test results from three groups of geometrically similar concrete specimens of size (width×total depth×thickness), 420×420×50–1680×1680×200 mm³, made with different maximum aggregate size of 9.5, 19, 38, and 76 mm were analyzed using a recently proposed distribution of extremes. In applications of probability, it is important to use an appropriate distribution type and adequate techniques for estimating the parameters of distribution. In this study, a new type distribution of minima is employed for probability computations. It was noticed that the entropy of distribution increases with the crack length, i.e. the uncertainty of toughness, G_1c, value increases with crack length. A non-linear reduction of the maximum allowable splitting force with the defect size, a, was noticed. For large specimens, the maximum allowable splitting load is more sensitive to the required reliability level than that for small specimens. Reliability increases with aggregate size when all other conditions were constant.     

Evolving artificial neural network ensembles

Using a coordinated group of simple solvers to tackle a complex problem is not an entirely new idea. Its root could be traced back hundreds of years ago when ancient Chinese suggested a team approach to problem solving. For a long time, engineers have used the divide-and-conquer strategy to decompose a complex problem into simpler sub-problems and then solve them by a group of solvers. However, knowing the best way to divide a complex problem into simpler ones relies heavily on the available domain knowledge. It is often a manual process by an experienced engineer. There have been few automatic divide-and-conquer methods reported in the literature. Fortunately, evolutionary computation provides some of the interesting avenues to automatic divide-and-conquer methods. An in-depth study of such methods reveals that there is a deep underlying connection between evolutionary computation and ANN ensembles. Ideas in one area can be usefully transferred into another in producing effective algorithms. For example, using speciation to create and maintain diversity had inspired the development of negative correlation learning for ANN ensembles, and an in-depth study of diversity in ensembles. This paper will review some of the recent work in evolutionary approaches to designing ANN ensembles.     

Algorithms in the W-Hierarchy

We show new upper bounds for problems in the W-hierarchy of fixed-parameter complexity. A crucial ingredient of our proofs is an extension to the W-RAM model, which permits more-powerful operations but remains equivalent to the original. We use the extended model to give new upper bounds for Subsetsum, Maximum Irredundant Set, and various problems concerning intersection of finite-state machines.     

Quality of data regarding diagnoses of spinal disorders in administrative databases. A multicenter study

The purpose of the present study was to evaluate the accuracy of data regarding diagnoses of spinal disorders in administrative databases at eight different institutions. The records of 189 patients who had been managed for a disorder of the lumbar spine were independently reviewed by a physician who assigned the appropriate diagnostic codes according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The age range of the 189 patients was seventeen to eighty-four years. The six major diagnostic categories studied were herniation of a lumbar disc, a previous operation on the lumbar spine, spinal stenosis, cauda equina syndrome, acquired spondylolisthesis, and congenital spondylolisthesis. The diagnostic codes assigned by the physician were compared with the codes that had been assigned during the ordinary course of events by personnel in the medical records department of each of the eight hospitals. The accuracy of coding was also compared among the eight hospitals, and it was found to vary depending on the diagnosis. Although there were both false-negative and false-positive codes at each institution, most errors were related to the low sensitivity of coding for previous spinal operations: only seventeen (28 per cent) of sixty-one such diagnoses were coded correctly. Other errors in coding were less frequent, but their implications for conclusions drawn from the information in administrative databases depend on the frequency of a diagnosis and its importance in an analysis. This study demonstrated that the accuracy of a diagnosis of a spinal disorder recorded in an administrative database varies according to the specific condition being evaluated. It is necessary to document the relative accuracy of specific ICD-9-CM diagnostic codes in order to improve the ability to validate the conclusions derived from investigations based on administrative databases.     

Lowered antioxidant status of red blood cells in post-parturient haemoglobinuria of buffaloes

Vaccination against tick-borne encephalitis with FSME-Immun vaccine was started in the Department of Infectious Diseases, University Medical School of Bia?ystok, Poland, in 1992. No serious adverse reactions after vaccine administration were observed. Post-vaccine side effects were reported in 242 (11.3%) persons after the first dose (n = 2,135) and only in 14 patients (1.2%) after the second one (n = 1,183). These effects were mild and transitory. No relationship was observed between the frequency of adverse reactions, general or local, and the initial anti-TBE virus antibody titres or the age of the immunized individuals. Post-vaccine side effects were reported significantly more frequently among people not bitten by ticks.     

Family practice physicians' firearm safety counseling beliefs and behaviors

The purpose of this study was to identify family physicians' firearm safety counseling beliefs and behaviors. A survey was mailed to a random sample of 600 members of the American Academy of Family Physicians. A three wave mailing technique was used to maximize the response rate and yielded 271 usable surveys (55% response rate). Outcome measures included training experience in firearm safety counseling, the prevalence of firearm safety counseling by family physicians, and their perceptions regarding such counseling. The majority (78%) of family physicians lacked formal training on how to counsel patients about firearm safety and 49% believed more time should be spent in residency programs on firearm safety counseling. The majority (84%) of respondents never or rarely counseled patients on firearm safety and 50% believed firearm safety counseling should be a low priority in their delivery of primary care. The majority of respondents did not regularly counsel patients about firearm safety, did not believe firearm safety counseling should be a priority, and did not believe firearm safety counseling would be effective in reducing firearm-related trauma.     

Familial jejunal atresia with renal dysplasia

Although jejunal atresia occasionally may occur with a familial pattern, an association with renal disease has not been described. The authors report on three family members treated over two generations, all of whom had both proximal jejunal atresia and renal dysplasia. This association was most likely inherited as an autosomal dominant trait.