Bridging the gap between policy aspirations and the ability of regulators to deliver robust evidence-based tools within affordable and realistic time-scales presents major challenges to the science community. Lake-MImAS (Morphological Impact Assessment System) is a hydromorphological classification and decision-support tool adaptable to any setting, developed in response to the EC Water Framework Directive (WFD) requirement to classify all surface waters in the European Union and achieve at least good ecological status by 2015. Lake-MImAS provides a transparent and consistent risk-assessment framework to assess the impact of hydromorphological pressures on ecologically relevant lake features and associated processes. Underpinned by expert-judgement, the tool quantifies lost 'system capacity' (%) relative to pristine, or un-impacted condition and does so on a type-specific basis. Morphological condition limits (MCLs) separate 'lost capacity' into five condition classes ranging from near natural to severely altered. Near natural (<5% capacity loss) corresponds directly with high ecological status of the WFD and provides the basis to define reference conditions. The calibrated tool was tested against independent judgement made by expert practitioners from UK environment and conservation agencies. The same condition class was assigned in 84% of Scottish lochs (n=40), in 58% of lakes in England and Wales (n=28) and in 57% of loughs in Northern Ireland (n=27). The overall agreement was 68% and 98% of all comparisons lay within one condition class. In most cases where different classes were assigned the explanation lay in local experts underestimating the extent of water level regulation. Whilst further work is required to strengthen the evidence base linking hydromorphological alteration and ecological response, Lake-MImAS provides the foundation for a pragmatic risk-assessment scheme to support WFD classification and related regulatory activity. The modular nature of the tool means it adaptive to new locations, lake type and pressure combinations and it has wider applications including physical condition monitoring for conservation sites, impact assessment arising from new developments and supporting remediation programmes.

We have investigated the use of amphiphilic diblock copolymers of poly (N-vinyl-2-pyrrolidone) and poly-(d,l-lactide), PVP-PLA, to dissolve propofol inside micelles (30–60 nm) – Propofol-PM. We compared the pharmacokinetics (PK) of propofol in blood and plasma when administered as 1% Diprivan and as three 1% solutions reconstituted from Propofol-PM 7, 10 and 12% respectively. We also undertook a preliminary pharmacodynamic (PD) study. Forty male Sprague–Dawley rats (325 ± 10 g) were randomly allocated to one of eight groups (five rats/group). Ten rats were used for each of the four propofol formulations: five rats for the collection of whole blood and five for plasma. The rats were anaesthetised with isoflurane and both jugular veins exposed. Isoflurane was then discontinued. When the animals responded to a hind paw pinch, they received propofol 10 mg.kg−1 (1 ml.kg−1 over 1 min) via the jugular vein. Blood samples were collected at 1, 3, 5, 7.5, 10, 15, 30, 60 and 75 min after injection. A PK model was constructed using nonmem software. Animal weight, sample matrix (blood or plasma) and propofol formulation (Diprivan, Propofol-PM 7, 10 and 12%) were evaluated as model covariates. In a separate small PD study, the times of the recovery endpoints (leg withdrawal, first movement, righting) were compared for the four propofol formulations. All experiments were conducted in accordance with guidelines from the Canadian Council on Animal Care and the Use of Laboratory Animals, and a certificate of conformity granted. The optimal PK model had two compartments and incorporated sample matrix and propofol formulation as dichotomous covariates (Fig. 1). Sample matrix was applied to all structural parameters. An influence of propofol formulation was observed for all structural model parameters (excluding distributional clearance) but only when plasma was used as the sample matrix. The effect of formulation was not apparent when whole blood concentrations of propofol were measured. The average model predicted profiles. Error bars show ± 1 SD. The whole blood PK of Propofol-PM did not differ from that observed with Diprivan. We observed lower propofol concentrations in plasma samples after Propofol-PM administration than after Diprivan but the quantity of the copolymer in the Propofol-PM formulations did not influence the PK. Although there was no statistically significant difference in any of the recovery endpoints, the number of animals in the PD study was small (n = 4–6 per formulation) and there was a high degree of variability. Hence, the PD study was likely underpowered to detect small differences and must be regarded as preliminary.

BACKGROUND:As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations.METHODS:Propofol (99.7%) was added directly to an aqueous solution of poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide)copolymers (PVP-PLA) block copolymers and stirred in order to obtain a clear solution. This formulation was filtered sterile and then lyophilized to its solid form Propofol-PM (propofol polymeric micelle) which reconstitutes to a propofol 1%w/v (10 mg ml(-1)) clear aqueous solution of 30-60 nm propofol-containing micelles. Population pharmacokinetic data from whole blood and plasma were obtained by administering reconstituted Propofol-PM formulations and a 1% oil in water formulation, Diprivan to male Sprague-Dawley rats (n = 40) at a dose of 10 mg kg(-1). Preliminary recovery data were obtained from a further small study.RESULTS:The pharmacokinetics were best described using a two-compartment mamillary population model, which incorporated sample matrix (blood or plasma) and propofol formulation (Diprivan) or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation was observed for all parameters (excluding distributional clearance) but only when plasma was used for propofol quantification. In this preliminary pharmacodynamic study, there was no statistically significant difference in the timing of the recovery endpoints between the Propofol-PM formulation and Diprivan groups.CONCLUSIONS:Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan.

Mannitol is often added to the cardiopulmonary bypass pump prime to reduce the incidence of renal dysfunction, but studies so far have been inconclusive. Urinary excretion of microalbumin and retinol binding protein are more sensitive than routine biochemical tests of renal function after cardiac surgery. We performed a double-blind, randomised, controlled trial in cardiac surgical patients with pre-operative plasma creatinine < 130 micromol x l(-1). Twenty patients received 0.5 g x kg(-1) of mannitol in the pump prime, whereas 20 control patients received an equivalent volume of Hartmann's solution. Blood and urine samples were taken on the day before surgery and daily for 5 days postoperatively for measurement of plasma urea and creatinine, urinary creatinine, retinol binding protein and microalbumin. We found no differences between the mannitol and control patients for any measured variable, and conclude that mannitol has little impact on renal function in patients with normal pre-operative plasma creatinine concentrations.

Ultra-high pressure metamorphic rocks have been found worldwide. The volume and areal extent of an exhumed UHPM domain are important for understanding the geodynamic mechanisms responsible for the high pressure and relatively medium temperature conditions needed for their creation. We report here Raman microspectroscopical data that prove the existence of microdiamonds at the Svartberget Fe-Ti type peridotite locality in the Western Gneiss Region of Norway. Raman microscopy of two carbon microinclusions belonging to polyphase inclusion assemblages included in garnets from a garnet-phlogopite websterite vein yielded a sharp, narrow, intense peak at 1332 cm(-1), characteristic of diamond. The diamond is associated with polyphase solid inclusions possibly originating from supercritical, dense, H-C-N-O-F-P-S-Cl fluids. Lithological, textural and geochronological evidence points towards a Caledonian origin of the trapped fluid and subsequent diamond formation.

BACKGROUND AND OBJECTIVES:Pirfenidone is an orally available antifibrotic agent that has shown benefit in animal models of pulmonary and renal fibrosis and in clinical trials of pulmonary fibrosis, multiple sclerosis, and hepatic cirrhosis. Our objective was to determine whether pirfenidone slows the loss of renal function in focal segmental glomerulosclerosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:An open-label trial was performed to evaluate the safety and efficacy of pirfenidone in patients with idiopathic and postadaptive focal segmental glomerulosclerosis. The monthly change in estimated GFR, expressed as ml/min per 1.73 m2, was compared between the baseline period and the treatment period. During both periods, patients received angiotensin antagonist therapy if tolerated. Twenty-one patients were enrolled, and 18 patients completed a median of 13 mo of pirfenidone treatment. RESULTS:The monthly change in GFR improved from a median of -0.61 ml/min per 1.73 m2 (interquartile range -1.31 to -0.41) during the baseline period to -0.45 ml/min per 1.73 m2 (interquartile range -0.78 to -0.16) with pirfenidone therapy. This change represents a median of 25% improvement in the rate of decline (P < 0.01). Pirfenidone had no effect on BP or proteinuria. Adverse events attributed to therapy included dyspepsia, sedation, and photosensitive dermatitis. CONCLUSIONS:It is concluded that pirfenidone is an attractive candidate for placebo-controlled trials in patients with progressive chronic kidney disease.

This study investigates Information Systems (IS) personnel turnover in South Africa. The results indicate that there is significant positive correlation between job satisfaction, career satisfaction and organisational commitment, whereby individuals experiencing job satisfaction are more likely to be committed to their organisation and experience career satisfaction. In addition, job satisfaction, career satisfaction and organisational commitment were all found to be negatively related to turnover intention. Based on these findings it is clear that organisations seeking a reduction in IS personnel turnover should consider the individual wants of employees and facilitate more appropriate matches between employees and jobs.

In two experiments, we studied the recall of missing items. Short lists of common words were presented once and were followed immediately by a random permutation of all but one of the presented items. The task of the subject was to recall the missing item--that is, the item present in the study set but missing from the probe set. Experiment 1 replicated the high accuracy with five-item lists originally reported by Yntema and Trask (1963) and showed that the latencies were quite short (about 750 msec). Experiment 2 varied list length unpredictably and showed that accuracy was a function of both list length (four, five, or six items) and serial position. Latency was again quite short but was essentially independent of list length and serial position. It was possible to simulate most of the effects with the power set model with no free parameters (i.e., parameters that varied with the experimental manipulations). The results seemed to be more consistent with a direct access model (the power set model of TODAM; Murdock, 1995) than with a simple search or serial-scanning model.

The majority of novel anticancer drugs developed to date are intended for parenteral administration. Paradoxically, most of these drugs are water-insoluble, delaying their clinical development. A common approach to confering water solubility to drugs is to use amphiphilic, solubilizing agents, such as polyethoxylated castor oil (e.g., Cremophor EL, CrmEL). However, these vehicles are themselves associated with a number of pharmacokinetic and pharmaceutical concerns. The present work is aimed at evaluating a novel polymeric solubilizer for anticancer drugs, i.e., poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA). This copolymer self-assembles in water to yield polymeric micelles (PM) that efficiently solubilize anticancer drugs, such as paclitaxel (PTX), docetaxel (DCTX), teniposide (TEN) and etoposide (ETO). A PM-PTX formulation was evaluated, both, in vitro on three different cancer cell lines and in vivo for its safety, pharmacokinetics, biodistribution and antitumor activity. In vitro, cytotoxicity studies revealed that the drug-loaded PM formulation was equipotent to the commercial PTX formulation (Taxol). In the absence of drug, PVP-b-PDLLA with 37% DLLA content was less cytotoxic than CrmEL. In vivo, acute toxicity was assessed in mice after a single injection of escalating dose levels of formulated PTX. PM-PTX was well tolerated and the maximum tolerated dose (MTD) was not reached even at 100 mg/kg, whereas the MTD of Taxol was established at 20 mg/kg. At 60 mg/kg, PM-PTX demonstrated greater in vivo antitumor activity than Taxol injected at its MTD. Finally, it was shown in mice and rabbits that the areas under the plasma concentration-time curves were inversely related to PM drug loading.

Fluoronyboite, ideally NaNa2(Al2Mg3)(Si7Al)O22F2, has been found in the Jianchang eclogite pod, Su-Lu coesite-eclogite province, China. It has been approved as a new mineral by the IMA. Single-crystal structure refinement and electron microprobe analysis were used for characterization: C2/m, with a = 9.666(4), b = 17.799(6), c = 5.311(2) Angstrom, beta = 104.10(3)degrees, V - 886.2(8) Angstrom(3), Z = 2, formula: (A)(Na-0.78 K-0.06)Sigma(0.84) (B)(Na1.53C a(0.47))(Sigma2.00) (C)( Fe-0.89(2+) Mg-2.55 Mn0.01Zn0.01Fe0.323+Al1.21Ti0.01)(Sigma5.00) T(Si7.14Al0.86)(Sigma8.00)O-22(X)(OH0.84F1.16)(Sigma2.00).Fluoronyboite formed during UHPM conditions, and is preserved in the retrograded kyanite-bearing eclogite sample DJ102 together with clinopyroxene (Jd(70)Ae(20)Di(10)), garnet (Alm(60)PrP(21)Grs(17)SPS(02)), and rutile. Lower-pressure minerals are also present (fluoro-alumino-magnesiotaramite, apatite, paragonite), and symplectitic rims were also developed around clinopyroxene crystals. Cation ordering and the structural and physical properties of fluoronyboite are reported and discussed with reference to those of F-free nyboite from the type locality at Nybo in Norway, for which some as yet unpublished mineral data are also reported. Relations between composition and petrogenetic conditions of these rare high-pressure amphiboles are discussed.

The use of teams within organisations is becoming more prevalent as teams have been identified as an efficient work unit of human capital. This research identified 17 team effectiveness characteristics and, using a sample of local project team members, attempted to ascertain which of these factors distinguished highly performing IS teams from lower performing ones. A web-based survey was conducted and valid data collected from 62 IS professionals working in project teams. The results suggested that Goal Setting, Conflict Management, Skill Diversity/Heterogeneity, Commitment, Quality and Performance, Mutual Accountability, Trust and Support were significant characteristics in segregating high performance IS teams from those who achieved lower performance levels. These findings are of use to IS project managers who need to focus on all the 17 characteristics whilst placing particular emphasis on the 6 characteristics reported above.

All too often managers invest a lot of time and energy in trying to do the right thing. They attempt to create a vision. They try to communicate the strategic direction. They look to set up teams to get people involved in improving work processes and overall quality. They define jobs, set up compensation systems but focus rarely gets to behaviour, that is, what people do and say everyday in order to get the work done.

TODAM is a theory of distributed associative memory based on the convolution-correlation formalism of A. Borsellino and T. Poggio (1973, Kybernetik, 122, 113-122), and TODAM2 is a revised version which includes context, auto-associations for binding, a dual basis for item information, and mediators for associative information. It can explain some complex interactions (differential forgetting and differential attention) between item and associative information. In this paper we derive the basic expressions for the memory-probe dot product for the 2x2 cases (item and pair study crossed with item and pair probe), and then we apply these expressions to judgments of frequency (JOF) and judgments of recency (JOR). We report an experiment which tests both JOF and JOR for single items with post-cuing to control for encoding strategies and suggest an attenuation factor for repetition to improve the fits. With attenuation, TODAM2 can fit the JOR data, but the JOF fits, while not too bad, consistently predict too much dependence between item and associative information. Copyright 2001 Academic Press.

This geologic mapping and interpretation of the Pea Ridge iron mine, Missouri, is part of a cooperative effort between the U.S. Geological Survey (USGS) and the Missouri Department of Natural Resources, Division of Geology and Land Survey (DGLS), under the auspices of the USGS Midcontinent Strategic and Critical Minerals Project. The goal of the Pea Ridge study is to compare the Middle Proterozoic iron deposits of Missouri with the Middle Proterozoic Olympic Dam deposit and similar deposits of the Stuart Shelf, South Australia. This effort developed from work by Sims and others (1987), who recognized the many similarities between the St. Francois terrane in southeastern Missouri and the Stuart Shelf and also the potential for Olympic Dam-type deposits in the Middle Proterozoic granite-rhyolite terranes of the Midcontinent. Detailed descriptions of the map units are given in Nuelle and others (1992). Results of stable-isotope, fluid-inclusion, and traceelement studies that focus on the origin of the ore deposit are presented in Day and others (1991, 1992, and 1993), Sidder and others (1991, 1993a, b), and Cordell and others (1993). The Pea Ridge Iron Ore Company granted access to the mine for purposes of geologic mapping and for topical studies to determine ore genesis and to investigate the potential for mineral commodities other than iron, such as rareearth elements and gold. Additional information for underground areas and mine levels was obtained from generalized maps and logs of developmental drill core by the late Jack Emery, former mine geologist with the Pea Ridge Iron Ore Company. Mine level designations are those used by the company; sublevels indicate workings accessible only by declines from other levels. All levels are measured in depth from the shaft collar.

An in-house calibration laboratory for the Biomedical Instrumentation Maintenance Services of the hospitals in the West of Scotland was established in 1993. This paper describes the development of this calibration service in the context of an overall quality system and also estimates its costs. Not only does the in-house service have many advantages but it is shown to be cost effective for workloads exceeding 260 items per annum.

B. Cong (ed). Ultrahigh-Pressure Metamorphic Rocks in the Dabieshan–Sulu Region of China. Dordrecht (Kluwer Academic Publishers), 1996, ISBN 0 7923-4163-5, and Beijing (Science Press) 1996, viii + 224 pp. Price £75.00 - Volume 62 Issue 4