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.     

Water-Quality Monitoring in Anguilla

Anguilla is a UK overseas (non-independent) territory in the Caribbean. It is a small middle-income island with a population of 13 000, and recent statistics indicate that it is more dependent on tourism than any other country or territory in the world. Rapid population growth and development have placed more emphasis on the need for human health and environmental protection. For the first time, a systematic water-quality monitoring programme has been developed, based on the realities of the local situation, e.g. low resource base, limited capabilities, dependence on household rainwater catchment, storage cisterns, and a poor water-supply network. Development of the programme incorporated the key themes of pragmatic, realistic, incremental, responsive, and consultative approaches.     

Analysis of a stiffener intersection eccentricity in a steel containment

Containment structures have several regions in which the continuity of the cylindrical pressure boundary is interrupted, e.g., shell penetrations, discontinuous stiffeners, and changes in the shell thickness. Significant strain concentrations can occur in these areas of discontinuity. The Sandia National Laboratories 1:8-scale steel containment equipment hatch was analyzed as an example of an eccentricity at a stiffener intersection.A portion of the as-built 1:8-scale model was modeled with the ANSYS general purpose finite element program using triangular, thin shell finite elements. The overall size of the model was determined from Saint-Venant type considerations of the stress field around the hatch. Shell elements were used to model the ring and formed stiffeners. Geometric and material nonlinear behavior were included. The model was loaded using discrete load steps up to a pressure of 165 psig. At this pressure, the maximum strain was 19.7 percent in the formed stiffener near its intersection with the ring stiffener. The finite element solution demonstrated the very localized nature of the strain field near the ring/formed stiffener intersection.In an attempt to reduce analysis costs, a small portion of the 1:8-scale model immediately surrounding the ring/formed stiffener intersection was selected for further analysis. Two smaller models, a ring/formed stiffener intersection and a ring/circular stiffener intersection, were studied. The models were significantly smaller than the regions used previously. A comparison of the two intersection models showed that the circular stiffener is a more efficient configuration.     

Structural characterisation of apatite coatings

The current, most frequently employed, commercial route to produce hydroxyapatite prosthetic coatings is plasma spraying. However, this has several important limitations especially for textured surfaces. Low temperature methods of coating fabrication such as cathodic electrodeposition are attractive alternatives. However, quantitative characterisation of the phase composition of thin electrodeposited coatings can be problematic. An X-ray diffraction method, which provides quantitative compositional information without reference to external or internal standards, is introduced and validated. The method can also be applied when Bragg peaks from the supporting substrate are apparent within the data and preferred orientation can be tolerated. This method has been used to examine in detail the microstructure of electrodeposited coatings which are compared directly with those formed by a commercial plasma spraying process.We show that, unlike the plasma sprayed coatings, the electrodeposited material consists of a single crystalline phase (hydroxyapatite) and a significantly reduced amorphous phase. The electrodeposited coatings also possess significantly more microstrain and a smaller crystallite size than the corresponding plasma sprayed material.     

Characteristics of Milk Powders Produced by Spray Freeze Drying

Skim and whole milk powders were manufactured at lab scale by spray freeze drying (SFD), using liquid nitrogen as the cryogen. The polydispersity of droplet/particle sizes was limited using an encapsulator nozzle to atomize the feed. Particle morphology was examined using a scanning electron microscope. Samples were compared with equivalent spray-dried powders in tests of wettability and dissolution in water. The spray freeze-dried powders were found to be highly porous, with a uniform structure of pores throughout the entire particles. When tested in water, SFD skim milk powders wetted roughly three times as fast as industrially spray-dried agglomerated skim milk powders and were observed to dissolve rapidly by breaking down into smaller particles.     

System requirements for Ka-band Earth-satellite propagation data

Accurate estimates of the propagation impairments that affect link quality and availability and determine signal interference fields are essential for the reliable design of telecommunication systems and the efficient use of the electromagnetic spectrum. Recent announcements by commercial entities of their intent to use Ka-band spectrum to supply satellite services have heightened interest in propagation data and models for these frequencies. This paper provides a brief overview of Ka-band Earth-satellite systems and requirements in relation to the need for specific types of propagation data     

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.