Open Air Laboratories (OPAL): a community-driven research programme

OPAL is an English national programme that takes scientists into the community to investigate environmental issues. Biological monitoring plays a pivotal role covering topics of: i) soil and earthworms; ii) air, lichens and tar spot on sycamore; iii) water and aquatic invertebrates; iv) biodiversity and hedgerows; v) climate, clouds and thermal comfort. Each survey has been developed by an interdisciplinary team and tested by voluntary, statutory and community sectors. Data are submitted via the web and instantly mapped. Preliminary results are presented, together with a discussion on data quality and uncertainty. Communities also investigate local pollution issues, ranging from nitrogen deposition on heathlands to traffic emissions on roadside vegetation. Over 200,000 people have participated so far, including over 1000 schools and 1000 voluntary groups. Benefits include a substantial, growing database on biodiversity and habitat condition, much from previously unsampled sites particularly in urban areas, and a more engaged public.

Pyrene-Modified quartz crystal microbalance for the detection of polynitroaromatic compounds

The synthesis of a dithiol-functionalized pyrene derivative is reported, together with studies of interactions between this receptor (and other related pyrenes) and nitroaromatic compounds (NACs), in both solution and in the solid state. Spectroscopic analysis in solution and X-ray crystallographic analysis of cocrystals of pyrene and NACs in the solid state indicate that supramolecular interactions lead to the formation of defined pi-pi stacked complexes. The dithiolfunctionalized pyrene derivative can be used to modify the surface of a gold quartz crystal microbalance (QCM) to create a unique π-electron rich surface, which is able to interact with electron poor aromatic compounds. For example, exposure of the modified QCM surface to the nitroaromatic compound 2,4-dinitrotoluene (DNT) in solution results in a reduction in the resonant frequency of the QCM as a result of supramolecular interactions between the electron-rich pyrenyl surface layer and the electron-poor DNT molecules. These results suggest the potential use of such modified QCM surfaces for the detection of explosive NACs.

PINCER trial: a cluster randomised trial comparing the effectiveness and cost-effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors in general practice are an important source of potentially preventable morbidity and mortality. Building on previous descriptive, qualitative and pilot work, we sought to investigate the effectiveness, cost-effectiveness and likely generalisability of a complex pharm acist-led IT-based intervention aiming to improve prescribing safety in general practice. Objectives: We sought to: • Test the hypothesis that a pharmacist-led IT-based complex intervention using educational outreach and practical support is more effective than simple feedback in reducing the proportion of patients at risk from errors in prescribing and medicines management in general practice. • Conduct an economic evaluation of the cost per error avoided, from the perspective of the National Health Service (NHS). • Analyse data recorded by pharmacists, summarising the proportions of patients judged to be at clinical risk, the actions recommended by pharmacists, and actions completed in the practices. • Explore the views and experiences of healthcare professionals and NHS managers concerning the intervention; investigate potential explanations for the observed effects, and inform decisions on the future roll-out of the pharmacist-led intervention • Examine secular trends in the outcome measures of interest allowing for informal comparison between trial practices and practices that did not participate in the trial contributing to the QRESEARCH database. Methods Two-arm cluster randomised controlled trial of 72 English general practices with embedded economic analysis and longitudinal descriptive and qualitative analysis. Informal comparison of the trial findings with a national descriptive study investigating secular trends undertaken using data from practices contributing to the QRESEARCH database. The main outcomes of interest were prescribing errors and medication monitoring errors at six- and 12-months following the intervention. Results: Participants in the pharmacist intervention arm practices were significantly less likely to have been prescribed a non-selective NSAID without a proton pump inhibitor (PPI) if they had a history of peptic ulcer (OR 0.58, 95%CI 0.38, 0.89), to have been prescribed a beta-blocker if they had asthma (OR 0.73, 95% CI 0.58, 0.91) or (in those aged 75 years and older) to have been prescribed an ACE inhibitor or diuretic without a measurement of urea and electrolytes in the last 15 months (OR 0.51, 95% CI 0.34, 0.78). The economic analysis suggests that the PINCER pharmacist intervention has 95% probability of being cost effective if the decision-maker’s ceiling willingness to pay reaches £75 (6 months) or £85 (12 months) per error avoided. The intervention addressed an issue that was important to professionals and their teams and was delivered in a way that was acceptable to practices with minimum disruption of normal work processes. Comparison of the trial findings with changes seen in QRESEARCH practices indicated that any reductions achieved in the simple feedback arm were likely, in the main, to have been related to secular trends rather than the intervention. Conclusions Compared with simple feedback, the pharmacist-led intervention resulted in reductions in proportions of patients at risk of prescribing and monitoring errors for the primary outcome measures and the composite secondary outcome measures at six-months and (with the exception of the NSAID/peptic ulcer outcome measure) 12-months post-intervention. The intervention is acceptable to pharmacists and practices, and is likely to be seen as costeffective by decision makers.

Prediction of processed cheese instrumental texture and meltability by mid-infrared spectroscopy coupled with chemometric tools

The objective of this study was to determine the potential of mid-infrared spectroscopy coupled with multidimensional statistical analysis for the prediction of processed cheese instrumental texture and meltability attributes. Processed cheeses (n = 32) of varying composition were manufactured in a pilot plant. Following two and four weeks storage at 4 degrees C samples were analysed using texture profile analysis, two meltability tests (computer vision, Olson and Price) and mid-infrared spectroscopy (4000-640 cm(-1)). Partial least squares regression was used to develop predictive models for all measured attributes. Five attributes were successfully modelled with varying degrees of accuracy. The computer vision meltability model allowed for discrimination between high and low melt values (R-2 = 0.64). The hardness and springiness models gave approximate quantitative results (R-2 = 0.77) and the cohesiveness (R-2 = 0.81) and Olson and Price meltability (R-2 = 0.88) models gave good prediction results. (c) 2006 Elsevier Ltd. All rights reserved..

Application of mid-infrared spectroscopy to the prediction of maturity and sensory texture attributes of cheddar cheese

The objective of this study was to determine the potential of mid-infrared spectroscopy in conjunction with partial least squares (PLS) regression to predict various quality parameters in cheddar cheese. Cheddar cheeses (n = 24) were manufactured and stored at 8 degrees C for 12 mo. Mid-infrared spectra (640 to 4000/cm) were recorded after 4, 6, 9, and 12 mo storage. At 4, 6, and 9 mo, the water-soluble nitrogen (WSN) content of the samples was determined and the samples were also evaluated for 11 sensory texture attributes using descriptive sensory analysis. The mid-infrared spectra were subjected to a number of pretreatments, and predictive models were developed for all parameters. Age was predicted using scatter-corrected, 1st derivative spectra with a root mean square error of cross-validation (RMSECV) of 1 mo, while WSN was predicted using 1st derivative spectra (RMSECV = 2.6%). The sensory texture attributes most successfully predicted were rubbery, crumbly, chewy, and massforming. These attributes were modeled using 2nd derivative spectra and had, corresponding RMSECV values in the range of 2.5 to 4.2 on a scale of 0 to 100. It was concluded that mid-infrared spectroscopy has the potential to predict age, WSN, and several sensory texture attributes of cheddar cheese..

Direct iminization of PEEK

Semi-crystalline poly(ether ketone)s are important high-temperature engineering thermoplastics, but are difficult to characterize at the molecular level because of their insolubility in conventional organic solvents. Here we report that polymers of this type, including PEEK, react cleanly at high temperatures with low-volatility aralkyl amines to afford stable, noncrystalline poly(ether-imine)s, which are readily soluble in solvents such as chloroform, THF and DMF and so characterizable by conventional size-exclusion chromatography.

Deception-detection and machine intelligence in practical Turing tests

Deception-detection is the crux of Turing’s experiment to examine machine thinking conveyed through a capacity to respond with sustained and satisfactory answers to unrestricted questions put by a human interrogator. However, in 60 years to the month since the publication of Computing Machinery and Intelligence little agreement exists for a canonical format for Turing’s textual game of imitation, deception and machine intelligence. This research raises from the trapped mine of philosophical claims, counter-claims and rebuttals Turing’s own distinct five minutes question-answer imitation game, which he envisioned practicalised in two different ways: a) A two-participant, interrogator-witness viva voce, b) A three-participant, comparison of a machine with a human both questioned simultaneously by a human interrogator. Using Loebner’s 18th Prize for Artificial Intelligence contest, and Colby et al.’s 1972 transcript analysis paradigm, this research practicalised Turing’s imitation game with over 400 human participants and 13 machines across three original experiments. Results show that, at the current state of technology, a deception rate of 8.33% was achieved by machines in 60 human-machine simultaneous comparison tests. Results also show more than 1 in 3 Reviewers succumbed to hidden interlocutor misidentification after reading transcripts from experiment 2. Deception-detection is essential to uncover the increasing number of malfeasant programmes, such as CyberLover, developed to steal identity and financially defraud users in chatrooms across the Internet. Practicalising Turing’s two tests can assist in understanding natural dialogue and mitigate the risk from cybercrime.

Simultaneous bridge-localized and mixed-valence character in diruthenium radical cations featuring diethynylaromatic bridging ligands

A series of bimetallic ruthenium complexes [{Ru(dppe)Cp*}2(μ-C≡CArC≡C)] featuring diethynylaromatic bridging ligands (Ar = 1,4-phenylene, 1,4-naphthylene, 9,10-anthrylene) have been prepared and some representative molecular structures determined. A combination of UV–vis–NIR and IR spectroelectrochemical methods and density functional theory (DFT) have been used to demonstrate that one-electron oxidation of compounds [{Ru(dppe)Cp*}2(μ-C≡CArC≡C)](HC≡CArC≡CH = 1,4-diethynylbenzene; 1,4-diethynyl-2,5-dimethoxybenzene; 1,4-diethynylnaphthalene; 9,10-diethynylanthracene) yields solutions containing radical cations that exhibit characteristics of both oxidation of the diethynylaromatic portion of the bridge, and a mixed-valence state. The simultaneous population of bridge-oxidized and mixed-valence states is likely related to a number of factors, including orientation of the plane of the aromatic portion of the bridging ligand with respect to the metal d-orbitals of appropriate π-symmetry.

Conformational modulation of sequence recognition in synthetic macromolecules

The different triplet sequences in high molecular weight aromatic copolyimides comprising pyromellitimide units ("I") flanked by either ether-ketone ("K") or ether-sulfone residues ("S") show different binding strengths for pyrene-based tweezer-molecules. Such molecules bind primarily to the diimide unit through complementary π-π-stacking and hydrogen bonding. However, as shown by the magnitudes of 1H NMR complexation shifts and tweezer-polymer binding constants, the triplet "SIS" binds tweezer-molecules more strongly than "KIS" which in turn bind such molecules more strongly than "KIK". Computational models for tweezer-polymer binding, together with single-crystal X-ray analyses of tweezer-complexes with macrocyclic ether-imides, reveal that the variations in binding strength between the different triplet sequences arise from the different conformational preferences of aromatic rings at diarylketone and diarylsulfone linkages. These preferences determine whether or not chain-folding and secondary π−π-stacking occurs between the arms of the tweezermolecule and the 4,4'-biphenylene units which flank the central diimide residue.

Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers of progression: an exploratory study.

BACKGROUND: Due to the heterogeneity in the biological behavior of prostate cancer, biomarkers that can reliably distinguish indolent from aggressive disease are urgently needed to inform treatment choices. METHODS: We employed 8-plex isobaric Tags for Relative and Absolute Quantitation (iTRAQ), to profile the proteomes of two distinct panels of isogenic prostate cancer cells with varying growth and metastatic potentials, in order to identify novel biomarkers associated with progression. The LNCaP, LNCaP-Pro5, and LNCaP-LN3 panel of cells represent a model of androgen-responsive prostate cancer, while the PC-3, PC-3M, and PC-3M-LN4 panel represent a model of androgen-insensitive disease. RESULTS: Of the 245 unique proteins identified and quantified (>or=95% confidence; >or=2 peptides/protein), 17 showed significant differential expression (>or=+/-1.5), in at least one of the variant LNCaP cells relative to parental cells. Similarly, comparisons within the PC-3 panel identified 45 proteins to show significant differential expression in at least one of the variant PC-3 cells compared with parental cells. Differential expression of selected candidates was verified by Western blotting or immunocytochemistry, and corresponding mRNA expression was determined by quantitative real-time PCR (qRT-PCR). Immunostaining of prostate tissue microarrays for ERp5, one of the candidates identified, showed a significant higher immunoexpression in pre-malignant lesions compared with non-malignant epithelium (P < 0.0001, Mann-Whitney U-test), and in high Gleason grade (4-5) versus low grade (2-3) cancers (P < 0.05). CONCLUSIONS: Our study provides proof of principle for the application of an 8-plex iTRAQ approach to uncover clinically relevant candidate biomarkers for prostate cancer progression.