Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults

This article describes the pharmacology of the novel atypical antidepressant drug agomelatine, critically reviews and evaluates its clinical use for the treatment of major depression, and suggests areas for further research. Agomelatine is a synthetic analog of the hormone melatonin. It stimulates the activity of melatonin MT1 and MT2 receptors and inhibits the activity of serotonin 5HT-2C receptor subtypes. Three acute trials demonstrated clinically modest, but statistically significant benefits over placebo. Three acute trials did not find agomelatine more effective than placebo. A meta-analysis of these six trials demonstrated a small, statistically significant, marginally clinically relevant difference between agomelatine and placebo. The only placebo-controlled study in elderly patients did not demonstrate a significant benefit for agomelatine. It was more effective than placebo in only one of two relapse prevention studies. Agomelatine was generally well tolerated compared to placebo. Its side-effect profile is different than and compares favorably to other antidepressant drugs. The overall tolerability of agomelatine in head-to-head comparisons was not substantially better than active drug comparators. Agomelatine is contraindicated in patients with impaired liver function and in patients taking drugs that potently inhibit CYP-1A2 metabolic enzymes. Because elevated liver enzymes are common, and there is a rare risk of more serious liver reactions, routine laboratory monitoring of liver function is recommended periodically throughout treatment. Agomelatine does not have clinically significant advantages compared to other antidepressant drugs, and it has certain limitations and disadvantages. Because of its unique pharmacology and relatively benign tolerability profile, however, it may be a useful alternative for patients who do not respond to or cannot tolerate other antidepressant drugs. © 2009 Howland, publisher and licensee Dove Medical Press Ltd

Doing voices: reading language as craft in black British poetry

This is the author's final draft post-refereeing as published in The Journal of Commonwealth Literature published online 14 April 2014 DOI:10.1177/0021989414529121. The online version of this article can be found at: http://jcl.sagepub.com/content/early/2014/04/11/0021989414529121This essay offers a detailed exploration and comparative reading of two poems published 20 years apart: John Agard’s “Listen Mr Oxford Don” (1985), and Daljit Nagra’s “Kabba Questions the Ontology of Representation, the Catch-22 for ‘Black’ Writers…” (2007). The former poem is well-known, being regarded by a range of scholars as the acme of (and often, shorthand for) self-reflexively dialogic black British voice poetry, as it emerged in the 1980s, that plays off the friction between writing and speech. The latter is a complex and satirical take on poetic convention and canonicity – including the legacies of 1980s black British poetry – that exploits a tension between written poetic convention and artifice on the one hand, and the idea of the voiced poem as conveying “presence” or “authenticity” on the other. Both poems direct us towards a structuring paradox in which the embodied immediacy of human voice is mediated through the graphic conventions of written poetry. Reading these poems together, the essay considers on the one hand, how ideas about poetic form, language, and voice emerge out of particular historical junctures; and on the other, how such attentiveness to context can help us to develop techniques of a postcolonial “close reading”, eschewing totalizing formulae or summative evaluations of linguistic dissidence

The anatomy of interatrial communications - what does the interventionist need to know?

Increasingly, the interventional cardiologist is seeking to close interatrial communications by inserting devices by means of catheterisation. So as to optimise these procedures, it is adavantageous to have a firm grasp of the anatomy of the normal atrial septal structures, this then providing the basis to understand the morphology of the holes which can exist between the chambers, not all of which are true septal defects.A true septal structure can be removed without exiting from the cavities of the heart. It is the flap valve of the oval fossa, along with the anterior rim of the fossa, which fulfill this criterion. The remainder of the extensive rim of the normal fossa is no more than an infolding between the walls of the right and left atriums and their venous tributaries, and has different dimensions at various points around the ircumference. The so-called muscular atrioventricular “septum” is a sandwich incorporating a layer of epicardial fibro-adipose tissue. True defects of the atrial septum, therefore, exist because of deficiency, perforation, or absence of the flap valve. Most of these defects will prove suitable for interventional closure, but potential caveats include multiple defects, aneurysm of the flap valve, or adjacency of the fossa to the venous orifices. The other interatrial communications, namely the sinus venosus, coronary sinus, and “ostium primum” defects are outside the confines of the oval fossa. Recognition of this feature is the key to their diagnosis, and their ifferentiation from true atrial septal defects. Of these defects, only the coronary sinus defect is likely to be suitable for device closure, and then only in the very rare circumstances when it is seen in isolatio

Magnetic resonance imaging: a tool for pork pie development

The traditional British pork pie consists of roughly chopped pork cooked in a hot water pastry crust. Due to shrinkage of the meat during cooking, the gap formed around the meat is usually sealed using a gelatin based jelly to exclude air and thus help to preserve the pie. The properties of the jelly are such that it will ingress into the pastry crust causing undesirable softening. The jelly is traditionally produced by simmering pig trotters with seasoning for several hours. In this work we demonstrate the potential of magnetic resonance imaging (MRI) as a tool for investigating the conditions required for producing jellies with different properties and present two examples of this use. Firstly we demonstrate that MRI can determine the ability of water to diffuse through the jelly which is critical in minimizing the amount of moisture moving from the jelly to the crust. Secondly, the impact of jelly temperature on the penetration length into the crust is investigated. These examples highlight the power of MRI as a tool for food assessment

Current barriers and possible solutions to effective project team formation and deployment within a large construction organisation

The characteristics of the construction industry present an extremely challenging context for effective human resource management (HRM). The dynamic project-based nature of the industry results in extreme fluctuations in organisations’ workloads and requires teams to form, develop and disband relatively quickly. Thus, the importance of efficient management of employee resourcing activities cannot be understated. This paper reports on the findings of research which explored employee resourcing practices within large UK construction firms. The results suggest that managers currently attempt to carry out some strategic planning with regards to employee resourcing, but that this does not necessarily translate into effective operational practice which simultaneously takes account of organisational, project and individual employee needs. A new approach for more effective employee resourcing decision-making, based on encouraging the involvement of the employees in the deployment process, is put forward as a management tool which informs effective team formation and deployment. However, this will require the acceptance of both decision-support technology and of employee input into what is currently a tacit, management-oriented decision process

Psychological contract expectations of construction project managers

The past 20 years have seen a period of fundamental change for many construction businesses as they have restructured, downsized, de-layered, merged and de-merged to survive turbulent markets and rapidly changing demand cycles. Such change places significant new pressures, challenges and constraints on the employer/employee relationship. This paper argues that these changes are likely to have reconstituted employee expectations of the less formal aspects of the employment relationship, known collectively as the psychological contract. Explores this inductive research which examines the psychological contract of 30 construction project managers

Anatomic-electrophysiological correlations concerning the pathways for atrioventricular conduction.

The remarkable success of radiofrequency ablation in recent decades in curing atrioventricular nodal reentrant tachycardias has intensified efforts to provide a solid theoretical basis for understanding the mechanisms of atrioventricular transmission. These efforts, which were made by both anatomists and electrophysiologists, frequently resulted in seemingly controversial observations. Quantitatively and qualitatively, our understanding of the mysteries of propagation through the inhomogeneous and extremely complex atrioventricular conduction axis is much deeper than it was at the beginning of the past century. We must go back to the initial sources, nonetheless, in an attempt to provide a common ground for evaluating the morphological and electrophysiological principles of junctional arrhythmias. In this review, we provide an account of the initial descriptions, which still provide an appropriate foundation for interpreting recent electrophysiological findings