Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo

Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the anti-epileptiform and anti-seizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01-100 muM) effects were assessed in vitro using the Mg(2+)-free and 4-aminopyridine (4-AP) models of status epilepticus-like epileptiform activity in hippocampal brain slices via multi-electrode array (MEA) recordings. In the Mg(2+)-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude (in CA1 and dentate gyrus (DG) regions) and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1, only at 100 muM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10 and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole (PTZ) model of generalised seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality in comparison to vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB(1) receptors and displayed no agonist activity in [(35)S]GTPgammaS assays in cortical membranes. These findings suggest that CBD acts to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel anti-epileptic drug (AED) in the unmet clinical need associated with generalised seizures.

Dynamic load balancing for the distributed mining of molecular structures

In molecular biology, it is often desirable to find common properties in large numbers of drug candidates. One family of methods stems from the data mining community, where algorithms to find frequent graphs have received increasing attention over the past years. However, the computational complexity of the underlying problem and the large amount of data to be explored essentially render sequential algorithms useless. In this paper, we present a distributed approach to the frequent subgraph mining problem to discover interesting patterns in molecular compounds. This problem is characterized by a highly irregular search tree, whereby no reliable workload prediction is available. We describe the three main aspects of the proposed distributed algorithm, namely, a dynamic partitioning of the search space, a distribution process based on a peer-to-peer communication framework, and a novel receiverinitiated load balancing algorithm. The effectiveness of the distributed method has been evaluated on the well-known National Cancer Institute’s HIV-screening data set, where we were able to show close-to linear speedup in a network of workstations. The proposed approach also allows for dynamic resource aggregation in a non dedicated computational environment. These features make it suitable for large-scale, multi-domain, heterogeneous environments, such as computational grids.

High performance subgraph mining in molecular compounds

Structured data represented in the form of graphs arises in several fields of the science and the growing amount of available data makes distributed graph mining techniques particularly relevant. In this paper, we present a distributed approach to the frequent subgraph mining problem to discover interesting patterns in molecular compounds. The problem is characterized by a highly irregular search tree, whereby no reliable workload prediction is available. We describe the three main aspects of the proposed distributed algorithm, namely a dynamic partitioning of the search space, a distribution process based on a peer-to-peer communication framework, and a novel receiver-initiated, load balancing algorithm. The effectiveness of the distributed method has been evaluated on the well-known National Cancer Institute’s HIV-screening dataset, where the approach attains close-to linear speedup in a network of workstations.

Historicizing counterurbanization: in-migration and the reconstruction of rural space in Berkshire (UK), 1901-51

This article uses census data for Berkshire to argue that large-scale counterurbanization began much earlier than is generally recognized in some parts of southern England. This was not just movement down the urban hierarchy, which as Pooley and Turnbull have demonstrated was a long-term feature of England’s settlement system, but in some cases at least amenity-driven migration to rural areas of the kind increasingly recognized as a core component of recent counterurbanization. Despite a reduction of acreage Berkshire’s rural districts saw a 54% rise in population between 1901 and 1951. The sub-regional pattern of growth is assessed to gauge whether ‘clean break’ migration to the remote west of the county (which remained effectively out of commuting range from London throughout the period) was taking place, or whether counterurbanization was confined to the more accessible eastern districts. However, whilst population did increase in both west and east, it was in fact the central districts that grew most impressively. Three case study parishes are investigated in order to gauge the nature and consequences of counterurbanization at a local level. Professional and business migrants figure prominently, seeking to preserve and promote the rural attributes of their new communities, without however cutting their ties to urban centres. It is argued that migration to rural Berkshire in the first half of the twentieth century cannot adequately be described either as a form of extended suburbanization or an anti-metropolitan ‘clean break’. Rather, early counterurbanization marks the first stage on the long road to a post-productivist countryside, in which countryside becomes detached from agriculture, there is socio-economic convergence between town and country, and the ‘rural’ increasingly becomes defined by landscape and identity rather than economic function.

Competing edge networks

We introduce a model for a pair of nonlinear evolving networks, defined over a common set of vertices, sub ject to edgewise competition. Each network may grow new edges spontaneously or through triad closure. Both networks inhibit the other’s growth and encourage the other’s demise. These nonlinear stochastic competition equations yield to a mean field analysis resulting in a nonlinear deterministic system. There may be multiple equilibria; and bifurcations of different types are shown to occur within a reduced parameter space. This situation models competitive peer-to-peer communication networks such as BlackBerry Messenger displacing SMS; or instant messaging displacing emails.

Distribution of esterase activity in porcine ear skin, and the effects of freezing and heat separation

Porcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin. Using an esterase staining kit, esterase activity was found to be localised in the stratum corneum and viable epidermis. Under frozen storage and a common heating protocol of epidermal sheet separation, esterase staining in the skin visibly diminished. This was confirmed by a quantitative assay using HPLC to monitor the hydrolysis of aspirin, in freshly excised, frozen or heated porcine ear skin. Compared to vehicle-only control, the rate of aspirin hydrolysis was approximately three-fold higher in the presence of freshly excised skin, but no different in the presence of frozen or heated skin. Therefore, frozen and heat-separated porcine ear skin should not be used to study the permeation of ester-containing permeants, in particular co-drugs and pro-drugs, whose hydrolysis or degradation can be modulated by skin esterases.

Gap junction-mediated spontaneous Ca(2+) waves in differentiated cholinergic SN56 cells

Neuronal gap junctions are receiving increasing attention as a physiological means of intercellular communication, yet our understanding of them is poorly developed when compared to synaptic communication. Using microfluorimetry, we demonstrate that differentiation of SN56 cells (hybridoma cells derived from murine septal neurones) leads to the spontaneous generation of Ca(2+) waves. These waves were unaffected by tetrodotoxin (1microM), but blocked by removal of extracellular Ca(2+), or addition of non-specific Ca(2+) channel inhibitors (Cd(2+) (0.1mM) or Ni(2+) (1mM)). Combined application of antagonists of NMDA receptors (AP5; 100microM), AMPA/kainate receptors (NBQX; 20microM), nicotinic AChR receptors (hexamethonium; 100microM) or inotropic purinoceptors (brilliant blue; 100nM) was also without effect. However, Ca(2+) waves were fully prevented by carbenoxolone (200microM), halothane (3mM) or niflumic acid (100microM), three structurally diverse inhibitors of gap junctions, and mRNA for connexin 36 was detected by PCR. Whole-cell patch-clamp recordings revealed spontaneous inward currents in voltage-clamped cells which we inhibited by Cd(2+), Ni(2+) or niflumic acid. Our data suggest that differentiated SN56 cells generated spontaneous Ca(2+) waves which are propagated by intercellular gap junctions. We propose that this system can be exploited conveniently for the development of neuronal gap junction modulators.

Speech therapy after stroke: trial shows only that practice varies

Bowen and colleagues’ methods and conclusions raise concerns.1 At best, the trial evaluates the variability in current practice. In no way is it a robust test of treatment. Two communication impairments (aphasia and dysarthria) were included. In the post-acute stage spontaneous recovery is highly unpredictable, and changes in the profile of impairment during this time are common.2 Both impairments manifest in different forms,3 which may be more or less responsive to treatment. A third kind of impairment, apraxia of speech, was not excluded but was not targeted in therapy. All three impairments can and do co-occur. Whether randomised controlled trial designs can effectively cope with such complex disorders has been discussed elsewhere.4 Treatment was defined within terms of current practice but was unconstrained. Therefore, the treatment group would have received a variety of therapeutic approaches and protocols, some of which may indeed be ineffective. Only 53% of the contact time with a speech and language therapist was direct (one to one), the rest was impairment based therapy. In contrast, all of the visitors’ time was direct contact, usually in conversation. In both groups, the frequency and length of contact time varied. We already know that the transfer from impairment based therapy to functional communication can be limited and varies across individuals.5 However, it is not possible to conclude from this trial that one to one impairment based therapy should be replaced. For that, a well defined impairment therapy protocol must be directly compared with a similarly well defined functional communication therapy, with an attention control.

Climate and more sustainable cities: climate information for improved planning and management of cities (producers/capabilities perspective)

In the last two decades substantial advances have been made in the understanding of the scientific basis of urban climates. These are reviewed here with attention to sustainability of cities, applications that use climate information, and scientific understanding in relation to measurements and modelling. Consideration is given from street (micro) scale to neighbourhood (local) to city and region (meso) scale. Those areas where improvements are needed in the next decade to ensure more sustainable cities are identified. High-priority recommendations are made in the following six strategic areas: observations, data, understanding, modelling, tools and education. These include the need for more operational urban measurement stations and networks; for an international data archive to aid translation of research findings into design tools, along with guidelines for different climate zones and land uses; to develop methods to analyse atmospheric data measured above complex urban surfaces; to improve short-range, high-resolution numerical prediction of weather, air quality and chemical dispersion through improved modelling of the biogeophysical features of the urban land surface; to improve education about urban meteorology; and to encourage communication across scientific disciplines at a range of spatial and temporal scales.

Challenges in communicating and using ensembles in operational flood forecasting.

Following trends in operational weather forecasting, where ensemble prediction systems (EPS) are now increasingly the norm, flood forecasters are beginning to experiment with using similar ensemble methods. Most of the effort to date has focused on the substantial technical challenges of developing coupled rainfall-runoff systems to represent the full cascade of uncertainties involved in predicting future flooding. As a consequence much less attention has been given to the communication and eventual use of EPS flood forecasts. Drawing on interviews and other research with operational flood forecasters from across Europe, this paper highlights a number of challenges to communicating and using ensemble flood forecasts operationally. It is shown that operational flood forecasters understand the skill, operational limitations, and informational value of EPS products in a variety of different and sometimes contradictory ways. Despite the efforts of forecasting agencies to design effective ways to communicate EPS forecasts to non-experts, operational flood forecasters were often skeptical about the ability of forecast recipients to understand or use them appropriately. It is argued that better training and closer contacts between operational flood forecasters and EPS system designers can help ensure the uncertainty represented by EPS forecasts is represented in ways that are most appropriate and meaningful for their intended consumers, but some fundamental political and institutional challenges to using ensembles, such as differing attitudes to false alarms and to responsibility for management of blame in the event of poor or mistaken forecasts are also highlighted. Copyright © 2010 Royal Meteorological Society.

Capturing meaning construction in financial disclosure

Our study takes as its motivation common concerns across a variety of disciplines regarding an understanding of the linguistic, rhetorical and argumentative functions of the narrative aspects of financial disclosures, however with one significant alteration. This is that we do not restrict our investigation to the textual aspects but also consider the discursive nature of numbers. Numbers and narratives are simply alternative, and complementary, media to be used in disclosure, and many of the linguistic, and all of the rhetorical and argumentative, considerations apply to both, and need to be addressed and analysed. For complete version of the "long abstract" see attached full text pdf or the link in "Related URLs" field.

Pause for thought

The recent slowdown (or 'pause') in global surface temperature rise is a hot topic for climate scientists and the wider public. We discuss how climate scientists have tried to communicate the pause and suggest that 'many-to-many' communication offers a key opportunity to directly engage with the public.

Customer engagement planning emerging from the “individualist-collectivist”-framework: an empirical examination in China and UK

Purpose – Today marketers operate in globalised markets, planning new ways to engage with domestic and foreign customers alike. While there is a greater need to understand these two customer groups, few studies examine the impact of customer engagement tactics on the two customer groups, focusing on their perceptual differences. Even less attention is given to customer engagement tactics in a cross-cultural framework. In this research, the authors investigate customers in China and UK, aiming to compare their perceptual differences on the impact of multiple customer engagement tactics. Design/methodology/approach – Using a quantitative approach with 286 usable responses from China and the UK obtained through a combination of person-administered survey and computer-based survey screening process, the authors test a series of hypotheses to distinguish across-cultural differences. Findings – Findings show that the collectivists (Chinese customers) perceive customer engagement tactics differently than the individualists (UK customers). The Chinese customers are more sensitive to price and reputation, whereas the UK customers respond more strongly to service, communication and customisation. Chinese customers’ concerns with extensive price and reputation comparisons may be explained by their awareness towards face (status), increased self-expression and equality. Practical implications – The findings challenge the conventional practice of using similar customer engagement tactics for a specific market place with little concern for multiple cultural backgrounds. The paper proposes strategies for marketers facing challenges in this globalised context. Originality/value – Several contributions have been made to the literatures. First, the study showed the effects of culture on the customers’ perceptual differences. Second, the study provided more information to clarify customers’ different reactions towards customer engagement tactics, highlighted by concerns towards face and status. Third, the study provided empirical evidence to support the use of multiple customer engagement tactics to the across cultural studies.

A pilot study investigating the effects of a single dose of a flavonoid-rich blueberry drink on memory in 8-10 year old children

Recent evidence from animal and adult human subjects has demonstrated potential benefits to cognition from flavonoid supplementation. This study aimed to investigate whether these cognitive benefits extended to a sample of school-aged children. Using a cross-over design, with a wash out of at least seven days between drinks, fourteen 8-10 year old children consumed either a flavonoid-rich blueberry drink or matched vehicle. Two hours after consumption, subjects completed a battery of five cognitive tests comprising the Go-NoGo, Stroop, Rey’s Auditory Verbal Learning Task, Object Location Task, and a Visual N-back. In comparison to vehicle, the blueberry drink produced significant improvements in the delayed recall of a previously learned list of words, showing for the first time a cognitive benefit for acute flavonoid intervention in children. However, performance on a measure of proactive interference indicated that the blueberry intervention led to a greater negative impact of previously memorised words on the encoding of a set of new words. There was no benefit of our blueberry intervention for measures of attention, response inhibition or visuo-spatial memory. While findings are mixed, the improvements in delayed recall found in this pilot study suggest that, following acute flavonoid-rich blueberry interventions, school aged children encode memory items more effectively.

Understanding consumer evaluations of personalised nutrition services in terms of the privacy calculus: a qualitative study

Background: Personalised nutrition (PN) may provide major health benefits to consumers. A potential barrier to the uptake of PN is consumers’ reluctance to disclose sensitive information upon which PN is based. This study adopts the privacy calculus to explore how PN service attributes contribute to consumers’ privacy risk and personalisation benefit perceptions. Methods: Sixteen focus groups (n = 124) were held in 8 EU countries and discussed 9 PN services that differed in terms of personal information, communication channel, service provider, advice justification, scope, frequency, and customer lock-in. Transcripts were content analysed. Results: The personal information that underpinned PN contributed to both privacy risk perception and personalisation benefit perception. Disclosing information face-to-face mitigated the perception of privacy risk and amplified the perception of personalisation benefit. PN provided by a qualified expert and justified by scientific evidence increased participants’ value perception. Enhancing convenience, offering regular face-to face support, and employing customer lock-in strategies were perceived as beneficial. Conclusion: This study suggests that to encourage consumer adoption, PN has to account for face-to-face communication, expert advice providers, support, a lifestyle-change focus, and customised offers. The results provide an initial insight into service attributes that influence consumer adoption of PN.