Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB 1 receptor-independent mechanism

BACKGROUND AND PURPOSE Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB 1 receptors. EXPERIMENTAL APPROACH The anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg −1 ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB 1 receptors was evaluated using displacement binding assays. KEY RESULTS CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg −1 ) and audiogenic seizure models (≥87 mg·kg −1 ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg −1 ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ 9 -tetrahydrocannabinol and Δ 9 -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB 1 cannabinoid receptors than purified CBDV. CONCLUSIONS AND IMPLICATIONS CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB 1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

Development of convection along the SPCZ within a Madden-Julian oscillation

A subtropical Rossby-wave propagation mechanism is proposed to account for the poleward and eastward progression of intraseasonal convective anomalies along the South Pacific convergence zone (SPCZ) that is observed in a significant proportion of Madden–Julian oscillations (MJOs). Large-scale convection, associated with an MJO, is assumed to be already established over the Indonesian region. The latent heating associated with this convection forces an equatorial Rossby-wave response with an upper-tropospheric anticyclone centred over, or slightly to the west of, the convection. Large potential-vorticity (PV) gradients, associated with the subtropical jet and the tropopause, lie just poleward of the anticyclone, and large magnitude PV air is advected equatorwards on the eastern side of the anticyclone. This ‘high’ PV air, or upper-tropospheric trough, is far enough off the equator that it has associated strong horizontal temperature gradients, and it induces deep ascent on its eastern side, at a latitude of about 15–30°. If this deep ascent is over a region susceptible to deep convection, such as the SPCZ, then convection may be forced or triggered. Hence convection develops along the SPCZ as a forced response to convection over Indonesia. The response mechanism is essentially one of subtropical Rossby-wave propagation. This hypothesis is based on a case study of a particularly strong MJO in early 1988, and is tested by idealized modelling studies. The mechanism may also be relevant to the existence of the mean SPCZ, as a forced response to mean Indonesian convection.

Development and exploitation of a controlled vocabulary in support of climate modelling

There are three key components for developing a metadata system: a container structure laying out the key semantic issues of interest and their relationships; an extensible controlled vocabulary providing possible content; and tools to create and manipulate that content. While metadata systems must allow users to enter their own information, the use of a controlled vocabulary both imposes consistency of definition and ensures comparability of the objects described. Here we describe the controlled vocabulary (CV) and metadata creation tool built by the METAFOR project for use in the context of describing the climate models, simulations and experiments of the fifth Coupled Model Intercomparison Project (CMIP5). The CV and resulting tool chain introduced here is designed for extensibility and reuse and should find applicability in many more projects.

The agile governance of business IT projects

Organisations typically define and execute their selected strategy by developing and managing a portfolio of projects. The governance of this portfolio has proved to be a major challenge, particularly for large organisations. Executives and managers face even greater pressures when the nature of the strategic landscape is uncertain. This paper explores approaches for dealing with different levels of certainty in business IT projects and provides a contingent governance framework. Historically business IT projects have relied on a structured sequential approach, also referred to as a waterfall method. There is a distinction between the development stages of a solution and the management stages of a project that delivers the solution although these are often integrated in a business IT systems project. Prior research has demonstrated that the level of certainty varies between development projects. There can be uncertainty on what needs to be developed and also on how this solution should be developed. The move to agile development and management reflects a greater level of uncertainty often on both dimensions and this has led the adoption of more iterative approaches. What has been less well researched is the impact of uncertainty on the governance of the change portfolio and the corresponding implications for business executives. This paper poses this research question and proposes a govemance framework to address these aspects. The governance framework has been reviewed in the context of a major anonymous organisation, FinOrg. Findings are reported in this paper with a focus on the need to apply different approaches. In particular, the governance of uncertain business change is contrasted with the management approach for defined IT projects. Practical outputs from the paper include a consideration of some innovative approaches that can be used by executives. It also investigates the role of the business change portfolio group in evaluating and executing the appropriate level of governance. These results lead to recommendations for executives and also proposed further research.

An investigation of the role of business analysts in IS development

Business analysis has developed since the early 1990s as an IS discipline that is concerned with understanding business problems, defining requirements and evaluating relevant solutions. However, this discipline has had limited recognition within the academic community and little research has been conducted into the practices and standards employed by business analysts. This paper reports on a study into business analysis that considered the activities conducted and the outcomes experienced on IS projects. Senior business analysts were interviewed in order to gain insights into the business analyst role and the techniques and approaches applied when conducting this work. The Context, Content, Process, Outcomes framework was adopted as a basis for developing the interview questions. The data collected was analysed using the template analysis technique and the template was based upon this framework. Additional themes concerning aspects of business analysis that may contribute to IS success emerged during data analysis. These included the key business analysis activities and the skills business analysts require to perform these activities. The organisational attitude was also identified as a key factor in enabling the use and contribution of business analysis.

Community projects: an experimental analysis of a fair implementation process

We define and experimentally test a public provision mechanism that meets three basic ethical requirements and allows community members to influence, via monetary bids, which of several projects is implemented. For each project, participants are assigned personal values, which can be positive or negative. We provide either public or private information about personal values. This produces two distinct public provision games, which are experimentally implemented and analyzed for various projects. In spite of the complex experimental task, participants do not rely on bidding their own personal values as an obvious simple heuristic whose general acceptance would result in fair and efficient outcomes. Rather, they rely on strategic underbidding. Although underbidding is affected by projects’ characteristics, the provision mechanism mostly leads to the implementation of the most efficient project.

The co-development of technology and new buildings: incorporating building integrated photovoltaics

Current approaches for the reduction of carbon emissions in buildings are often predicated on the integration of renewable technologies into building projects. Building integrated photovoltaics (BIPV) is one of these technologies and brings its own set of challenges and problems with a resulting mutual articulation of this technology and the building. A Social Construction of Technology (SCOT) approach explores how negotiations between informal groups of project actors with shared interests shape the ongoing specification of both BIPV and the building. Six main groups with different interests were found to be involved in the introduction of BIPV (Cost Watchers, Design Aesthetes, Green Guardians, Design Optimizers, Generation Maximizers and Users). Their involvement around three sets of issues (design changes from lack of familiarity with the technology, misunderstandings from unfamiliar interdependencies of trades and the effects of standard firm procedure) is followed. Findings underline how BIPV requires a level of integration that typically spans different work packages and how standard contractual structures inhibit the smooth incorporation of BIPV. Successful implementation is marked by ongoing (re-)design of both the building and the technology as informal fluid groups of project actors with shared interests address the succession of problems which arise in the process of implementation.

Impact of externalities on sustainable development: evidence from public-private partnerships in Kazakhstan and Russia

Purpose – This paper aims to investigate the influence of public-private partnerships (PPPs) on social and economic conditions in Kazakhstan and Russia from a public economics perspective, namely, through the lens of a market failure and PPPs’ negative externalities. Design/methodology/approach – Drawing on the concept of a market failure and using the externalities perspective, the paper investigates whether partnerships are instrumental in solving market problems, which is illustrated by the evidence from ongoing PPP projects in Kazakhstan and Russia. Findings – Results show that citizens face expansion of monopolistic trends in the service provision and decreased availability of public services. Additionally, the government support to partnerships recreates a negative externality in the form of a higher risk premium on loan interest rates that banks use to finance PPPs. The partnerships’ impact on sustainable development often appears detrimental, as they significantly intensify the struggle between sub-national governments for increased transfers from the national budget. Practical implications – The government agencies must incorporate the appraisal of the PPP externalities and their effects on the society in the decision-making regarding the PPP formation. Originality/value – The authors suggest that, although government is interested in PPPs’ positive externalities, in reality many negative externalities may offset the positive spillover effects. As a result, the partnerships’ contributions to economic and social sustainability remain controversial. Extending the value-for-money concept to incorporate the assessment of PPP externalities might significantly enhance the partnership conceptualisation by more comprehensive and accurate assessment of PPPs’ economic and social value.