Comet-like mineralogy of olivine crystals in an extrasolar proto-Kuiper belt.

Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets. Collisions between such bodies produce small dust particles, the spectral features of which reveal their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg(2-2x)Fe(2x)SiO(4)) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids (x ≈ 0.29). In the cold outskirts of the ß Pictoris system, an analogue to the young Solar System, olivine crystals were detected but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets. Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of ß Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 ± 0.001) and show that they make up 3.6 ± 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System, even though ß Pictoris is more massive and more luminous and has a different planetary system architecture.

Digital vs traditional: Are diagnostic accuracy rates similar for glass slides vs whole slide images in a non-gynaecological external quality assurance setting?

INTRODUCTION: The Royal College of Pathologists of Australasia Quality Assurance Programs introduced virtual microscopy cases into its cytopathology non-gynaecological programme after a short pilot phase, to address the challenges of providing a purely glass slide-based external quality assurance programme to multiple participants both locally and internationally. The use of whole slide image (WSI) cases has facilitated a more robust programme in relation to standardised material and statistical analysis, with access to a wider variety of specimen types and diagnostic entities. METHOD: Diagnostic accuracy rates on 56 WSI were assessed against the reference diagnosis. A portion (12) of these WSI slides had been used in glass slide format in previous external quality assurance surveys, and the results of these were compared to the responses received as glass slide cases. RESULTS: Overall diagnostic accuracy for the 56 WSI cases was acceptable in comparison to the reference diagnosis. When these 12 cases were analysed individually, for seven of the 12 cases, virtual format was found to be not inferior to glass slides for diagnostic accuracy. For one case, accuracy using WSI for diagnosis was superior to glass format. CONCLUSION: Diagnostic accuracy, using WSI for cases in our external quality assurance programme is acceptable. As the use of digital microscopy in a large scale external quality assurance programme offers extensive advantages over a glass slide-based format, our results encourage future comparison of diagnostic accuracy for virtual compared to glass slide format at a point in time where pathologists are becoming increasingly familiar with virtual microscopy in everyday practice.

Technical proficiency in cytopathology: assessment through external quality assurance.

OBJECTIVE: To assess both the feasibility and value of conducting an external quality assurance programme concerning technical aspects of cytopathology laboratory practice, and the interest by laboratories in enrolling in such a programme. METHODS: Six technical surveys, comprising staining exercises and questionnaires relating to laboratory practice, were distributed over a 4-year period to the approximately 220 laboratories enrolled in the RCPAQAP Cytopathology slide survey modules. Staining exercises using the Papanicolaou and Romanowsky techniques, the preparation of urine and body fluid specimens and immunocytochemistry on the cell block material were assessed. Accompanying relevant questionnaires were included, and one survey comprised a questionnaire alone concerning the collection of urinary tract and body fluid samples. RESULTS: Provision of an external cytopathology technical module was feasible for the RCPAQAP and participation rates (maximum of 87% per survey; average 68% for stained slides and 66% for questionnaires) were commendable, particularly considering these were optional undertakings with some exercises not applicable to all laboratories. The great majority of submitted slides were scored as satisfactory, and there was an especially high standard for the immunocytochemical staining exercise with 95% considered satisfactory, including 50.6% with a perfect score. Reasons for suboptimal scores were provided for potential quality improvement for interested laboratories. A wealth of information relating to laboratory practice was provided to the RCPAQAP which was collated and summarised for laboratory use. CONCLUSIONS: The provision of a technical module in cytopathology is both a feasible and valuable undertaking of interest to laboratories which should become standard practice for cytopathology external quality assurance providers.

Reduction of spectral interferences using ultraclean gold nanowire arrays in the LDI-MS analysis of a model peptide.

The surface chemistry of gold nanowires (AuNWs) has been systematically assessed in terms of contamination and cleaning processes. The nanomaterial's surface quality was correlated to its performance in the matrix-free laser desorption ionization mass spectrometry (LDI-MS) analysis of low molecular weight analytes. Arrays of AuNWs were deposited on glass slides by means of the lithographically patterned nanowire electrodeposition technique. AuNWs were then characterized in terms of surface chemical composition and morphology using X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. AuNWs were subjected to a series of well-known cleaning procedures with the aim of producing the best performing surfaces for the LDI-MS detection of leucine enkephalin, chosen as a model analyte with a molar mass below 1,000 g/mol. Prolonged cyclic voltammetry in 2 M sulfuric acid and, most of all, oxygen plasma cleaning for 5 min provided the best results in terms of simpler (interference-free) and more intense mass spectrometry spectra of the reference compound. The analyte always ionized as the sodiated adduct, and leucine enkephalin limits of detection of 0.5 and 2.5 pmol were estimated for the positive and negative analysis modes, respectively. This study points out the tight correlation existing between the chemical status of the nanostructure surface and the AuNW-assisted LDI-MS performance in terms of reproducibility of spectra, intensity of analyte ions and reduction of interferences.

Defining excellence in anaesthesia: the role of personal qualities and practice environment.

BACKGROUND: Calls for reform to postgraduate medical training structures in the UK have included suggestions that training should foster excellence and not simply ensure competence. METHODS: We conducted a modified Delphi-type survey starting with an e-mail request to specialist anaesthetists involved in education, asking them to identify the attributes of an excellent anaesthetist. In focused group interviews, their coded and categorized responses were ranked, and suggestions were made for incorporation into anaesthesia education. We also compared the findings with currently available professional and educational guidance. RESULTS: Our expert group strongly expressed the view that while superior knowledge and skills, associated with exceptional performance in clinical work, were fundamental to the excellent practitioner, they were not sufficient in themselves. A group of attributes that were personal qualities and functions of personality were also considered essential. The defining characteristic of excellence was, perhaps, the continuing urge to seek challenges and learn from them. Other high-ranking characteristics included clinical skills, interest in teaching, conscientiousness, innovation/originality, communication skills, and good relationships with patients. Knowledge for its own sake (personal involvement in research) was not rated highly, but applied knowledge was judged to underlie many of the most important categories. CONCLUSIONS: The achievement of excellence in anaesthesia is likely to depend on the successful interplay of individuals' personal qualities and the environment in which they work. Thus, not only trainees but also educational supervisors, heads of departments, and those responsible for organizing training systems all have a part to play in the encouragement of excellence.

Beyond competence: defining and promoting excellence in anaesthesia.

Recent trends in medical training have tended to focus on competence, in the sense of adequate performance, rather than excellence. This article reviews published literature and relevant concepts relating to excellence and professionalism from within anaesthesia, from medicine more generally and from outside the profession. A number of conceptual frameworks are presented that could be adapted for the promotion of excellence, and some of the necessary prerequisites for this promotion discussed.

Sunglint patterns: unusual dark patches.

Anomalous dark areas in sunglint patterns are occasionally seen in photographs taken by the Applications Technology Sattellte. These dark areas appear to be caused by relatively calm surface conditions against a background of higher sea states. Evidence of cold water temperatures suggest the presence of upwelling. These sightings may thus be of importance to the fishing industry.

Supporting practice teachers to identify failing students.

The subject of identifying and supporting failing students in community nursing education programmes has been largely overlooked in the literature, yet is of great concern to practice teachers. This article discusses the views on the topic of a group of practice teachers in the light of existing, related research and proposes a number of indicators for good practice. It is suggested that of central importance is the need for higher education institutions and practice teachers to work together in identifying students causing concern at an early stage in their studies, based on both objective and subjective observations, and to have in place documented procedures to be followed when such situations arise.

Hyaluronic acid content of effusions as a diagnostic aid for malignant mesothelioma.

A high-performance liquid chromatographic technique, using a size exclusion column (TSK-5000PW), has been developed for the quantification of hyaluronic acid (HA) in pleural and peritoneal effusions. Sample preparation requires only a 100-fold dilution of the exudate with phosphate buffer prior to analysis. Chromatographic conditions are: 0.05 M phosphate buffer (pH, 5.0) mobile phase at a flow rate of 1.0 ml/min, ultraviolet absorbance detection at 200 nm. The method resolves HA from all other glycosaminoglycans. The presence of HA is confirmed by the removal of the HA peak (retention time, approx. 5.3 min) by incubation of a second sample aliquot with hyaluronidase. Effusions of 13 of 14 patients with confirmed malignant mesothelioma contained HA in the 0.3 to 11.1 mg/ml range. In only one case was no HA detected. None of the effusions from 56 control patients with various other primary tumors contained detectable HA, i.e., there were no false positives. An unidentified peak, not susceptible to hyaluronidase appeared in 11% (6 of 56) of the controls. A single mesothelioma case was correctly identified in a group of 10 coded samples. It is suggested that an effusion with an HA concentration greater than 0.25 mg/ml, confirmed by hyaluronidase susceptibility, is an indication of the presence of malignant mesothelioma. The test is simple and rapid, and it is recommended that any effusion of uncertain etiology be screened for the presence of HA.

Estimation of diffuse and point source microbial pollution in the ribble catchment discharging to bathing waters in the north west of England.

Achieving compliance with the mandatory standards of the 1976 Bathing Water Directive (76/160/EEC) is required at all U.K. identified bathing waters. In recent years, the Fylde coast has been an area of significant investments in 'point source' control, which have not proven, in isolation, to satisfactorily achieve compliance with the mandatory, let alone the guide, levels of water quality in the Directive. The potential impact of riverine sources of pollution was first confirmed after a study in 1997. The completion of sewerage system enhancements offered the potential for the study of faecal indicator delivery from upstream sources comprising both point sources and diffuse agricultural sources. A research project to define these elements commenced in 2001. Initially, a desk study reported here, estimated the principal infrastructure contributions within the Ribble catchment. A second phase of this investigation has involved acquisition of empirical water quality and hydrological data from the catchment during the 2002 bathing season. These data have been used further to calibrate the 'budgets' and 'delivery' modelling and these data are still being analysed. This paper reports the initial desk study approach to faecal indicator budget estimation using available data from the sewerage infrastructure and catchment sources of faecal indicators.

Influence of dexaminoglutethimide, an optical isomer of aminoglutethimide, on the disposition of estrone sulfate in postmenopausal breast cancer patients.

Aminoglutethimide (AG) has been the most widely used aromatase inhibitor in breast cancer patients to date. Commercially, AG (Orimeten) is available as a racemate (DL-AG). Previous studies suggested the stereoisomers of AG (D-AG and L-AG) to differ considerably in their affinities and potencies to inhibit different cytochrome P-450-dependent enzymes, with D-AG being the potent aromatase inhibitor. DL-AG, apart from being an aromatase inhibitor, is known to enhance the metabolism of plasma estrone sulfate (E1S). In the present study we compared the effects of D-AG (500 mg daily) and DL-AG (1000 mg daily) on plasma estrogen levels and estrone (E1) and E1S clearance rates, determined after the injection of [14C]E1 and [3H]E1S, in a cross-over study involving 12 postmenopausal breast cancer patients. Treatment with DL-AG and D-AG suppressed plasma E1S to 18.6% and 15.0% of pretreatment levels, whereas E1 and estradiol E2 levels fell to 18.6% and 23.4% of their pretreatment levels during treatment with DL-AG and to 17.7% and 23.4% during treatment with D-AG, respectively. Thus, both treatment options suppressed all estrogens measured to a similar extent. The clearance rate of E1S increased from a mean pretreatment value of 5.9 to 14.0 and 10.0 L/h during treatment with DL-AG and D-AG, respectively (P < 0.05, comparing the two on-treatment situations), whereas the production rate of E1S decreased from a pretreatment value of 1.44 to 0.64 nmol/h with DL-AG and 0.36 nmol/h with D-AG (P < 0.05, comparing on-treatment values). These findings are consistent with the hypothesis that the D- as well as the L-form of AG may enhance the clearance rate of E1S. The finding of a higher estrogen production rate during treatment with DL-AG compared to D-AG probably reflects an increased plasma level of the estrogen precursor androstenedione (mean levels of androstenedione of 2.54 and 1.27 nmol/L during treatment with D-AG and DL-AG, respectively; P < 0.05).

Problems at social re-integration of long-term cancer survivors.

To assess the long-term consequences of cancer for everyday life, a postal survey in the Netherlands was done among 849 ex-cancer patients. Almost all responders were self-supporting to a large extent. Compared with the period before diagnosis, the socioeconomic position had not changed in 62%. 28% of the responders who were employed at the time of diagnosis (10% of all responders), were now housekeepers (99% female). Absence from work at survey did not differ significantly from absence in the year before diagnosis. A history of cancer tended to have a negative impact on promotional prospects and income. Ex-cancer patients were often confronted with problems when they tried to take out insurance or to modify an existing policy. The psychological well-being of the responders was low, compared to the average Dutch population.

Evaluation of field desorption mass spectrometry for the analysis of polyethylene.

Field desorption mass spectrometry (FD-MS) has been evaluated for the analysis of low molecular weight polyethylene by using samples in the molecular weight range 600-2000 u as determined by gel permeation chromatography. The repeat units and end groups were characterized by FD-MS, but it was demonstrated that accurate molecular weight distribution data cannot be obtained for polyethylene by FD-MS because there is mass discrimination against the higher molecular weight polymers.

Correlation between electron capture negative chemical ionization mass spectrometric fragmentation and calculated internal energies for polychlorinated biphenyls.

Correlationbse tween molecular structure and fragmentation observed in electron capture negative chemical ionization mass spectra (moderator gas = methane) of 49 selected tetrachlorinated, pentachlorinated, and hexachlorinated biphenyls have been investigated by using molecular modeling. The semiempirical general molecular orbital program MOPAC was used to calculate molecular properties for biphenyl and the 209 polychlorinated biphenyls. The mass spectrometric ionization and fragmentation processes were found to be linked to the number of chlorine atoms present on the biphenyl, and to the number of those chlorine atoms in the ortho (2, 2', 6, and 6') positions. The intensity of molecular ions increased with the number of chlorine atoms present, but this was counteracted by enhanced fragmentation as the number of ortho position chlorine atoms increased. The molecular parameters that were most closely linked with the number of ortho chlorine atoms were the twist angle between the phenyl rings and the energy of the lowest unoccupied molecular orbital (LUMO). It is suggested that fragmentation occurs when the energy of the ionizing electron exceeds the energy difference between the LUMO and LlJMO + 1 orbitals.

Polybrominated biphenyls in model and environmentally contaminated human blood: protein binding and immunotoxicological studies.

A review and summary is given of analytical, biochemical, and immunological studies made following an immunodiagnostic investigation which revealed significant decreases in the numbers, and changes in the functional integrity, of both T-and B-lymphocytes in a group of Michigan dairy farmers exposed to polybrominated biphenyls (PBB) which had been inadvertently introduced into the food chain in 1973. A quantification technique based on selected ion monitoring of bromine anions, obtained in negative chemical ionization, permitted determination of 10-35 pg of individual PBB congener per mL serum, a 20-fold improvement over electron capture gas chromatography. An in vitro spiked system was established and shown to be a representative model of environmentally contaminated blood. Immunoprecipitation followed by mass spectrometric quantification determined that the distribution of PBB among plasma, erythrocytes, mononucleocytes and polymorphonucleocytes was 89:9:less than 1:less than 1. In plasma 80% of the PBB was bound to apolipoproteins B and A in a 3:1 ratio. No preferential absorption of PBB congeners was found in the blood compartments suggesting that changes in the relative abundances of PBB congeners observed in longitudinal studies on Michigan subjects reflect differences in excretion rates or metabolism. A repeat in 1981 of the immunodiagnostic tests conducted in 1976 revealed a virtually complete persistence of the immune dysfunctions in the Michigan farmers exposed to PBB a decade ago.

A comparison of gastro-oesophageal reflux in volunteers assessed by ambulatory pH and gamma monitoring after treatment with either Liquid Gaviscon or Algicon Suspension.

This study was designed to compare the effectiveness of single doses of either Liquid Gaviscon or Algicon Suspension in the suppression of food and acid reflux into the oesophagus after a test meal in volunteers. After the pH electrode and gamma detector were positioned 5 cm above the cardia, the volunteers received a refluxogenic radiolabelled meal. The subjects then remained untreated, or thirty minutes later they were given a dose of unlabelled Algicon Suspension, or Liquid Gaviscon and a recording was made for a minimum of 3 hours. Allocation to the treatment group was randomized with the cross-overs performed 1 week apart. Liquid Gaviscon suppressed gastro-oesophageal reflux of both food and acid whereas only an insignificant reduction in reflux was seen after Algicon Suspension. The oesophageal pH remained below 4 for 3.21 +/- 0.92% (S.E.M.) of the recording period in the control study, 0.88 +/- 0.33 after Gaviscon and 2.91 +/- 0.68 after Algicon. The reflux of food was reduced from 17,070 x 10(3) +/- 4713 x 10(3) counts in the control study to 224 x 10(3) +/- 93 x 10(3) counts after the Gaviscon and 16,080 x 10(3) +/- 7131 x 10(3) counts after Algicon. The suppression of reflux by Liquid Gaviscon was significantly better than that produced by Algicon Suspension.

Scintigraphic assessment of the intragastric distribution and gastric emptying of an encapsulated drug: the effect of feeding and of a proton pump inhibitor.

BACKGROUND: Local delivery of therapeutic agents to the stomach may be a useful strategy in the treatment of Helicobacter pylori infection. We aimed to see whether the intragastric distribution and gastric retention of a therapeutic agent could be improved, either by giving omeprazole or by dosing after a meal. METHODS: Twelve healthy volunteers took part in this double-blind placebo-controlled crossover study comparing the effects of omeprazole 20 mg twice daily for 5 days with placebo, and the fasted with the fed state, on the gastric emptying and intragastric distribution of a soluble scintigrapic marker contained in a drug capsule. RESULTS: Dosing after food profoundly prolonged gastric residence of the drug label, prolonging mean time to 50% emptying (T50) from 0.5 +/- 0.1 h in the fasted state to 2.0 +/- 0.2 h when given after food. Food also improved intragastric distribution by increasing delivery to the body and fundus. Omeprazole enhanced the effect of food, prolonging T50 to 2.9 +/- 0.3 h, but had no effect in fasted subjects. CONCLUSIONS: Dosing after food markedly improves the aspects of local drug delivery to the stomach investigated in this study, and omeprazole enhances this effect. Post-prandial dosing may, therefore, be useful for improving delivery of some anti-Helicobacter agents.

Infant diarrhoea due to Escherichia coli 091 K? H7.

A small outbreak of infective diarrhoea occurred among babies in hospital at Winchester, England. The causal agent was found to be a strain of Escherichia coli 091 K? H7 which was resistant to several antibiotics. Epidemic diarrhoea due to E. coli 091 has previously been reported from south Germany.