Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

Background Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. Methods In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients. Results In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity. Conclusion Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

Marketing secondhand goods in late medieval England

Purpose – The purpose of this paper is to identify the main practitioners, goods, customers and locations of secondhand marketing activities in late medieval England. It questions how important was the economic role played by such markets and what was the interaction with more formal market structures?

Design/methodology/approach – A broad range of evidence was examined, covering the period from 1200 to 1500: regulations, court rolls, wills, manorial accounts, literature, and even archaeology. Such material often provided mere scraps of information about marginal marketing activity and it was important to recognise the severe limitations of the evidence. Nevertheless, a wide survey of the available sources can give us an insight into medieval attitudes towards such trade, as well as reminding us that much marketing activity occurred beyond the reach of the surviving documentation.

Findings – Late medieval England had numerous outlets for secondhand items, from sellers of used clothes and furs who wandered the marketplaces to craftsmen who recycled and mended old materials. Secondhand marketing was an important part of the medieval makeshift economy, serving not only the needs of the lower sectors of society but also those aspiring to a higher status. However, it is unlikely that such trade generated much profit and the traders were often viewed as marginal, suspicious and even fraudulent.

Originality/value – There is a distinct lack of research into the extent of and significance of medieval secondhand marketing, which existed in the shadowy margins of formal markets and is thus poorly represented in the primary sources. A broad-based approach to the evidence can highlight a variety of important issues, which impact upon the understanding of the medieval English economy.

Characterisation of the Thermal, Spectroscopic and Drug Dissolution Properties of Mefenamic Acid and Polyoxyethylene–Polyoxypropylene Solid Dispersions

The aim of this study was to investigate the solubility of mefenamic acid (MA), a highly cohesive, poorly water-soluble drug in a copolymer of polyoxyethylene–polyoxypropylene (Lutrol F681), and to understand the effect drug polymer solubility has on in vitro dissolution of MA. Solid dispersions (SD) of MA were prepared by a hot melt method, using Lutrol F681 as a thermoplastic polymeric platform. High-speed differential scanning calorimetry (Hyper-DSC), Raman spectroscopy, powder X-ray diffractometry (PXRD) and hot-stage/?uorescence microscopy were used to assess the solubility of the drug in molten and solid polymer. Drug dissolution studies were subsequently conducted on single-phase solid solutions and biphasic SD using phosphate buffer pH 6.8 as dissolution media. Solubility investigations using Hyper-DSC, Raman spectroscopy and hot-stage microscopy suggested MA was soluble in molten Lutrol F681 up to a concentration of 35% (w/w). Conversely, the solubility in the solidstate matrix was limited to<15% (w/w); determined by Raman spectroscopy, PXRD and ?uorescence microscopy. As expected the dissolution properties of MA were signi?cantly in?uenced by the solubility of the drug in the polymer matrix. At a concentration of 10% (w/w) MA (a single phase solid solution) dissolution of MA in phosphate buffer 6.8 was rapid, whereas at a concentration of 50% (w/w) MA (biphasic SD) dissolution was signi?cantly slower. This study has clearly demonstrated the complexity of drug– polymer binary blends and in particular de?ning the solubility of a drug within a polymeric platform. Moreover, this investigation has demonstrated the signi?cant effect drug solubility within a polymeric matrix has upon the in vitro dissolution properties of solid polymer/drug binary blends.

Metals in the Exosphere of the Highly Irradiated Planet WASP-12b

We present near-UV transmission spectroscopy of the highly irradiated transiting exoplanet WASP-12b, obtained with the Cosmic Origins Spectrograph on the Hubble Space Telescope. The spectra cover three distinct wavelength ranges: NUVA (2539-2580 Å), NUVB (2655-2696 Å), and NUVC (2770-2811 Å). Three independent methods all reveal enhanced transit depths attributable to absorption by resonance lines of metals in the exosphere of WASP-12b. Light curves of total counts in the NUVA and NUVC wavelength ranges show a detection at a 2.5s level. We detect extra absorption in the Mg II ??2800 resonance line cores at the 2.8s level. The NUVA, NUVB, and NUVC light curves imply effective radii of 2.69 ± 0.24 R J , 2.18 ± 0.18 R J , and 2.66 ± 0.22 R J respectively, suggesting the planet is surrounded by an absorbing cloud which overfills the Roche lobe. We detect enhanced transit depths at the wavelengths of resonance lines of neutral sodium, tin, and manganese, and at singly ionized ytterbium, scandium, manganese, aluminum, vanadium, and magnesium. We also find the statistically expected number of anomalous transit depths at wavelengths not associated with any known resonance line. Our data are limited by photon noise, but taken as a whole the results are strong evidence for an extended absorbing exosphere surrounding the planet. The NUVA data exhibit an early ingress, contrary to model expectations; we speculate this could be due to the presence of a disk of previously stripped material.

Forensic Geology in Environmental Crime: Illegal Waste Movement Burial in Northern Ireland

The illegal burial of waste often occurs in locations where loose, transferable material is abundant, allowing covert pits to be dug or filled. The transfer of waste material onto suspects and their vehicles during loading, unloading, and burial is common, as is the case during other criminal activities such as the burial of murder victims. We use two case studies to show that the established principles of using geological materials in excluding or linking suspects can be applied to illegal waste disposal. In the first case, the layering of different geological materials on the tailgate of a container used to transport toxic waste demonstrated where the vehicle had been and denied the owner's alibi, associating him with an illegal dumpsite. In the second case, an unusual suite of minerals, recovered from a suspect's trousers, provided the intelligence that led environmental law enforcement officers to an illegal waste burial site.

Supercritical fluids: A route to palladium-aerogel nanocomposites

Supercritical carbon dioxide (scCO(2)) is used to prepare novel silica aerogel composites containing nanoparticles of palladium. The material produced has been found to exhibit a Pd loading of 8% by wt. The particles deposited fit within two discrete size ranges of

Clean preparation of nanoparticulate metals in porous supports: a supercritical route

Here we present the synthesis of nanometre sized silver particles which have been trapped within porous substrates; poly( styrene-divinylbenzene) beads and silica aerogels. This is the first time that supercritical carbon dioxide has been used to impregnate such porous materials with silver coordination complexes. In this paper we demonstrate that control over the resultant nanoparticles with respect to size, loading and distribution in the support material has been achieved by simple choice of the precursor complex. The solubility of the precursor complexes in the supercritical solvent is shown to be one of the key parameters in determining the size of the nanoparticles, their distribution and their homogeneity within the support matrix. Moreover, we demonstrate that the same methodology can be applied to two very different substrate materials. In the particular case of aerogels, conventional organic solvents could not be used to prepare nanoparticles because the surface tension of the solvent would lead to fracturing of the aerogel structure.

Confirming the Existence of Gaps and Depletions in the Irish Oak Tree-Ring Record

In the course of building the 7000 year Belfast long oak chronology a series of depletion problems were encountered. These problems were overcome by 1984 when the completion of the long chronology was announced. The solution to the bridging of the various ‘gaps’ in the Irish chronology lay in the use of long sections of oak chronology from Britain. Now that a quarter of a century has elapsed and large numbers of additional oak samples, and site assemblages, have been accumulated it seems reasonable to review the ‘gaps’ in order to see if the Irish chronology could now be constructed without the use of British material. That is, are the depletion periods in the Irish chronology still evident, and if so, what might they imply about past conditions and human populations? The perhaps surprising conclusion is that the original depletions are still evident after 25 years of quasi-random sampling by archaeologists and palaeoecologists throughout Ireland.

Finite element analysis of an embankment on a soft estuarine deposit using an elastic–viscoplastic soil model

A new elastic–viscoplastic (EVP) soil model has been used to simulate the measured deformation response of a soft estuarine soil loaded by a stage-constructed embankment. The simulation incorporates prefabricated vertical drains installed in the foundation soils and reinforcement installed at the base of the embankment. The numerical simulations closely matched the temporal changes in surface settlement beneath the centerline and shoulder of the embankment. More importantly, the elastic–viscoplastic model simulated the pattern and magnitudes of the lateral deformations beneath the toe of the embankment — a notoriously difficult aspect of modelling the deformation response of soft soils. Simulation of the excess pore-water pressure proved more difficult because of the heterogeneous nature of the estuarine deposit. Excess pore-water pressures were, however, mapped reasonably well at three of the six monitoring locations. The simulations were achieved using a small set of material constants that can easily be obtained from standard laboratory tests. This study validates the use of the EVP model for problems involving soft soil deposits beneath loading from a geotechnical structure.

Explicit argumentation as a supervisory tool for decision making in child protection cases involving human rights issues

This paper addresses the problems often faced by social workers and their supervisors in decision making where human rights considerations and child protection concerns collide. High profile court cases in the United Kingdom and Europe have consistently called for social workers to convey more clarity when justifying their reasons for interfering with human rights in child protection cases. The themes emerging from these case law decisions imply that social workers need to be better at giving reasons and evidence in more explicit ways to support any actions they propose which cause interference with Convention Rights. Toulmin (1958, 1985) offers a structured approach to argumentation which may have relevance to the supervision of child protection cases when social workers and managers are required to balance these human rights considerations. One of the key challenges in this balancing act is the need for decision makers to feel confident that any interventions resulting in the interference of human rights are both justified and proportionate. Toulmin’s work has already been shown to have relevance for assisting social workers navigate pathways through cases involving competing ethical and moral demands (Osmo and Landau, 2001) and more recently to human rights and decision making in child protection (Duffy et al, 2006). Toulmin’s model takes the practitioner through a series of stages where any argument or proposed recommendation (claim) is subjected to intense critical analysis involving exposition of its strengths and weaknesses. The author therefore proposes that explicit argumentation (Osmo and Landau, 2001) may help supervisors and practitioners towards safer and more confident decision making in child protection cases involving the interference of the human rights of children and parents. In addition to highlighting the broader context of human rights currently permeating child protection decision making, the paper will include case material to practically demonstrate the application of Toulmin’s model of argumentation to the supervision context. In this way the paper adopts a strong practice approach in helping to assist practitioners with the problems and dilemmas they may come up against in decision making in complex cases.

Compressed Metal Powders that Remain Superhydrophobic After Abrasion

Superhydrophobic “lotus effect” materials are typically not sufficiently robust for most real world applications because their small surface features are both easily damaged and vulnerable to fouling. Here, a method for preparing a new type of superhydrophobic (? > 162°) composite material by compression of superhydrophobic metal particles is reported. This material, which has no natural analogue, has low-surface-energy microstructures extending throughout its whole volume. Removing its outer layer by abrasion or cutting deep into it does not result in loss of superhydrophobicity because it merely exposes a fresh portion of the underlying superhydrophobic material. The high contact angle is therefore retained even after accidental damage, and vigorous abrasion can be used to restore hydrophobicity after fouling.