Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea

Rationale: Anticipatory nausea (AN) is a poorly controlled side-effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, significant sedative effects, and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. Objectives: To assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Methods: Male Lister hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-supressed feeding (NSF) tests. Results: CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. Conclusions: CBDA is very well tolerated and devoid of the sedative side-effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.

The Mesolithic-Neolithic transition in the Channel Islands: maritime and terrrestrial perspectives

This paper investigates the Mesolithic-Neolithic transition in the Channel Islands. It presents a new synthesis of all known evidence from the islands c. 5000-4300 BC, including several new excavations as well as find spot sites that have not previously been collated. It also summarises – in English – a large body of contemporary material from north-west France. The paper presents a new high-resolution sea level model for the region, shedding light on the formation of the Channel Islands from 9000-4000 BC. Through comparison with contemporary sites in mainland France, an argument is made suggesting that incoming migrants from the mainland and the small indigenous population of the islands were both involved in the transition. It is also argued that, as a result of the fact the Channel Islands witnessed a very different trajectory of change to that seen in Britain and Ireland c. 5000-3500 BC, this small group of islands has a great deal to tell us about the arrival of the Neolithic more widely.

In vitro osteogenesis on fluorcanasite glass-ceramic with three different chemical compositions

This study aimed at investigating in vitro osteogenesis on three fluorcanasite glass-ceramic compositions with different solubilities (K3, K5, and K8). Osteoblastic cells were obtained from human alveolar bone fragments and cultured under standard osteogenic condition until subconfluence. First passage cells were cultured on K3, K5, and K8 and on Bioglass (R) 45S5 (45S5-control). Cell adhesion was evaluated at 24 h. For proliferation and viability, cells were cultured for 1, 4, and 10 days. Total protein content and alkaline phosphatase (ALP) activity were measured at 7, 14, and 21 days. Cultures were stained with Alizarin red at 21 days, for detection of mineralized matrix. Data were compared by ANOVA followed by Duncan`s test. Cell adhesion, cell proliferation, viability, total protein content, and ALP activity were not affected by fluorcanasite glass-ceramic composition and solubility. Bone-like formation was similar on all fluorcanasite-glass ceramics and was reduced compared to 45S5. The changes in the chemical composition and consequently solubility of the fluorcanasite glass-ceramics tested here did not significantly alter the in vitro osteogenesis. Further modifications of the chemical composition of the fluorcanasite glass-ceramic would be required to improve bone response, making this biomaterial a good candidate to be employed as a bone substitute.

Global properties of `ordinary` early-type galaxies: photometry and spectroscopy of stars and globular clusters in NGC 4494

We present a comprehensive analysis of the spatial, kinematic and chemical properties of stars and globular clusters (GCs) in the `ordinary` elliptical galaxy NGC 4494 using data from the Keck and Subaru telescopes. We derive galaxy surface brightness and colour profiles out to large galactocentric radii. We compare the latter to metallicities derived using the near-infrared Calcium Triplet. We obtain stellar kinematics out to similar to 3.5 effective radii. The latter appear flattened or elongated beyond similar to 1.8 effective radii in contrast to the relatively round photometric isophotes. In fact, NGC 4494 may be a flattened galaxy, possibly even an S0, seen at an inclination of similar to 45 degrees. We publish a catalogue of 431 GC candidates brighter than i(0) = 24 based on the photometry, of which 109 are confirmed spectroscopically and 54 have measured spectroscopic metallicities. We also report the discovery of three spectroscopically confirmed ultra-compact dwarfs around NGC 4494 with measured metallicities of -0.4 less than or similar to [Fe/H] less than or similar to -0.3. Based on their properties, we conclude that they are simply bright GCs. The metal-poor GCs are found to be rotating with similar amplitude as the galaxy stars, while the metal-rich GCs show marginal rotation. We supplement our analysis with available literature data and results. Using model predictions of galaxy formation, and a suite of merger simulations, we find that many of the observational properties of NGC 4494 may be explained by formation in a relatively recent gas-rich major merger. Complete studies of individual galaxies incorporating a range of observational avenues and methods such as the one presented here will be an invaluable tool for constraining the fine details of galaxy formation models, especially at large galactocentric radii.

Metallicity gradients at large galactocentric radii using the near-infrared Calcium triplet

We describe a new spectroscopic technique for measuring radial metallicity gradients out to large galactocentric radii. We use the DEep Imaging Multi-Object Spectrograph (DEIMOS) on the Keck telescope and the galaxy spectrum extraction technique of Proctor et al. We also make use of the metallicity sensitive near-infrared Calcium ii triplet (CaT) features together with single stellar population models to obtain metallicities. Our technique is applied as a pilot study to a sample of three relatively nearby (< 30 Mpc) intermediate-mass to massive early-type galaxies. Results are compared with previous literature inner region values and generally show good agreement. We also include a comparison with profiles from dissipational disc-disc major merger simulations. Based on our new extended metallicity gradients combined with other observational evidence and theoretical predictions, we discuss possible formation scenarios for the galaxies in our sample. The limitations of our new technique are also discussed.

Probing the 2D kinematic structure of early-type galaxies out to three effective radii

We detail an innovative new technique for measuring the two-dimensional (2D) velocity moments (rotation velocity, velocity dispersion and Gauss-Hermite coefficients h(3) and h(4)) of the stellar populations of galaxy haloes using spectra from Keck DEIMOS (Deep Imaging Multi-Object Spectrograph) multi-object spectroscopic observations. The data are used to reconstruct 2D rotation velocity maps. Here we present data for five nearby early-type galaxies to similar to three effective radii. We provide significant insights into the global kinematic structure of these galaxies, and challenge the accepted morphological classification in several cases. We show that between one and three effective radii the velocity dispersion declines very slowly, if at all, in all five galaxies. For the two galaxies with velocity dispersion profiles available from planetary nebulae data we find very good agreement with our stellar profiles. We find a variety of rotation profiles beyond one effective radius, i.e. rotation speed remaining constant, decreasing and increasing with radius. These results are of particular importance to studies which attempt to classify galaxies by their kinematic structure within one effective radius, such as the recent definition of fast- and slow-rotator classes by the Spectrographic Areal Unit for Research on Optical Nebulae project. Our data suggest that the rotator class may change when larger galactocentric radii are probed. This has important implications for dynamical modelling of early-type galaxies. The data from this study are available on-line.

Evolutionary model trees for handling continuous classes in machine learning

Model trees are a particular case of decision trees employed to solve regression problems. They have the advantage of presenting an interpretable output, helping the end-user to get more confidence in the prediction and providing the basis for the end-user to have new insight about the data, confirming or rejecting hypotheses previously formed. Moreover, model trees present an acceptable level of predictive performance in comparison to most techniques used for solving regression problems. Since generating the optimal model tree is an NP-Complete problem, traditional model tree induction algorithms make use of a greedy top-down divide-and-conquer strategy, which may not converge to the global optimal solution. In this paper, we propose a novel algorithm based on the use of the evolutionary algorithms paradigm as an alternate heuristic to generate model trees in order to improve the convergence to globally near-optimal solutions. We call our new approach evolutionary model tree induction (E-Motion). We test its predictive performance using public UCI data sets, and we compare the results to traditional greedy regression/model trees induction algorithms, as well as to other evolutionary approaches. Results show that our method presents a good trade-off between predictive performance and model comprehensibility, which may be crucial in many machine learning applications. (C) 2010 Elsevier Inc. All rights reserved.

Workplace "bargaining" and the wages/working time nexus: counting the cost of decentralisation

The impact of deregulation on dispersion of earnings in Victoria has been
acknowledged in the findings of the recent task force enquiry into industrial relations in Victoria. This paper argues that the link between hours worked and rates of pay has played a significant role in this increased dispersion. Drawing upon detailed analysis of hours and wages in Victorian agreements, data is presented on declining take-home pay flowing from the loss of penalty rates. This, we argue, is attributable to
the lack of substantive and procedural protections available to Victorian workers under schedule 1A of the Workplace Relations Act, and formerly under the Victorian Employee Relations Act, 1992. We contrast these findings with collective agreements trading off penalty rates certified by the Australian Industrial Relations Commission, and Australian Workplace Agreements approved by the Office of the Employment
Advocate. We conclude by suggesting there is a scale of fair outcomes attached to the wages/hours trade-off, directly attributable to the various institutional mechanisms now influencing Australian wage determination.

Effect of membrane stress on surface roughness changes in sheet forming

Friction plays an important role in sheet metal forming (SMF) and the roughness of the surface of the sheet is a major factor that influences friction. In finite element method (FEM) models of metal forming, the roughness has usually been assumed to be constant; even though it is commonly observed that sheet drawn under tension over a tool radius results in the surface becoming shiny, indicating a major change in surface morphology. An elastic–plastic FEM model for micro-contact between a flat surface and a single roughness peak has been developed. The model was used to investigate the effect of the membrane stress in the sheet on the deformation of an artificial roughness peak. From the simulation results, the change in asperity, or deformation of the local peak, for a given nominal tool contact stress is significantly influenced by the local substrate stress. The height of the asperity decreases with increasing substrate stress and the local pressure is much higher than the nominal pressure. In addition, the local contact stress decreases with an increase in the substrate stress levels.

Monitoring the total phenolic/antioxidant levels in wine using flow injection anaylsis with acidic potassium permanganate chemiluminescence detection

Flow injection methodology is described for the estimation of the total phenolic content of wine using acidic potassium permanganate chemiluminescence detection. Selected simple phenolic compounds including quercetin, rutin, catechin, epicatechin, ferulic acid, caffeic acid, gallic acid, 4-hydroxycinnamic acid and vanillin elicited analytically useful chemiluminescence with detection limits ranging between 4×10⁻¹⁰ and 7×10⁻⁷ M. A comparison between the chemiluminescence methodology and other total phenol/antioxidant assays, used by the food and beverage industry, resulted in a good correlation. The chemiluminescence detection was found to be selective with minimal interferences being observed from the non-phenolic components in wine. Analysis of 12 different wines showed that the chemiluminescence method was a rapid way to estimate their antioxidant or total phenolic content.

Family law in Australia: re Patrick and the matter of Child A

In Re Patrick, Guest J of the Family Court of Australia dealt with the issue of whether a gay sperm donor, known to the lesbian mother of the child, had a right under Australian law to regular contact with the child. Justice Guest held that the sperm donor was allowed contact with the child to the extent that this was in the child's best interests. His Honour did, however, find that due to the way in which particular provisions of Australia's Family Law Act 1975 (Cth) are drafted, a sperm donor cannot be regarded as the 'parent' of the child, and accordingly called for legislative reform to recognise the rights of known sperm donors wanting involvement with the child. In this article, we discuss the matter of Re Patrick, comparing it with the strikingly similar matter of Pursuer Against Defender in the Case of Child A, decided recently by Sheriff Laura Duncan in the Glasgow Sheriff Court. We will then outline a proposal to amend the Family Law Act 1975 so that sperm donors can apply for an order to be a 'parent' for the purposes of the law, and therefore have the same rights and responsibilities as any other parent. In response to the tragic ending to the matter of Re Patrick, we conclude by stressing the need for an educational programme to be established, so that lesbian women who are considering parenthood may do so in the knowledge that the sperm donor does have the status of 'father', and in some jurisdictions 'parent', rather than merely being a 'donor'.

Rosencrantz and Guildenstern are nevertheless dead: the hypothetical adolescence of Prince Hamlet and the contested remorselessness of young offenders

A young man stabs a defenceless elderly man to death, and remarks “I’ll lug the guts into the neighbour room.” Martha Grace Duncan has argued that such apparent remorselessness and other forensic features must be interpreted differently in children and young people as compared to adult defendants, because of developmental effects. Professor Duncan discusses a range of fictional as well as real examples in pressing her claim, and also appeals to psychiatric, psychological and psychoanalytic expertise. In order to examine the general validity of her argument, it is hypothesised here that a Duncanian adolescence defense has been presented for Prince Hamlet who, miraculously revived, now stands his trial for murder. It is argued that the “adolescence defense” is unsound in principle and that children and youth (whether or not as superannuated as the Prince of Denmark) should be treated in the same forensic manner as adults. If we respect children and youth, we must respect their autonomy however uncomfortable for us this may be: “So young, my lord, and true.”

Elastic bending of steel-polymer-steel (SPS) laminates to a constant curvature

The shear strain of the interlayer in the elastic regime for a Steel-Polymer-Steel (SPS) laminate material has been studied during bending to a constant curvature. An analytical model is developed and the influence of process parameters are analyzed. The tension in the cover sheets is also determined and, finally, a moment diagram is calculated. The results show that the moment in the SPS laminate is nonuniform along the bent strip even though the curvature is constant because of the tension and compression forces introduced in the cover sheets by the shear reaction force of the interlayer material.

Robust control applied to metal spraying for rapid tooling

The spray forming process is a novel method of rapidly manufacturing tools and dies for stamping and injection operations. The process sprays molten tool steel from a set of arc spray guns onto a ceramic former to build up a thick steel shell. The volumetric contraction that occurs as the steel cools is offset by a volumetric expansion taking place within the sprayed steel, which allows the dimensional accurate tools to be produced. To ensure that the required phase transformation takes place, the temperature of the steel is regulated during spraying. The sprayed metal acts both as a source of mass and a source of heat and by adjusting the rate at which metal is sprayed; the surface temperature profile over the surface of the steel can be controlled. The temperature profile is measured using a thermal imaging camera and regulated by adjusting the rate at which the guns spray the steel. Because the temperature is regulated by adjusting the feed rate to an actuator that is moving over the surface, this is an example of mobile control, which is a class of distributed parameter control. The dynamic system has been controlled using a PI controller before. The paper describes the application of H∞ tracking type controller as the desire was for the average temperature to follow a desired profile. A study on the controllability of the underlying system was aimed at.