Microemulsions as topical delivery vehicles for the anti-melanoma prodrug, temozolomide hexyl ester (TMZA-HE)

A prodrug, temozolomide acid hexyl ester (TMZA-HE), was identified as a skin-deliverable congener for temozolomide (TMZ) to treat skin cancers. Poor solubility and instability of TMZA-HE rendered a serious challenge for formulation of a topical preparation. Microemulsions (ME) were chosen as a potential vehicle for TMZA-HE topical preparations. ME systems were constructed with either oleic acid (OA) or isopropyl myristate (IPM) as the oil phase and tocopheryl (vitamin E) polyethylene glycol 1000 succinate (VE-TPGS) as a surfactant. Topical formulations of OA and IPM ME systems demonstrated beneficial solubilising ability and provided a stable environment for the prodrug, TMZA-HE. Significant differences between the microstructures of OA and IPM ME systems were revealed by freeze fracture electron microscopy (FFEM) and different loading abilities and permeation potencies between the two systems were also identified. In permeation studies, IPM ME systems, with inclusion of isopropyl alcohol (IPA) as a co-surfactant, significantly increased TMZA-HE permeation through silicon membranes and rat skin resulting in less drug retention within the skin, while OA ME systems demonstrated higher solubilising ability and a higher concentration of TMZA-HE retained within the skin. Therefore IPM ME systems are promising for transdermal delivery of TMZA-HE and OA ME systems may be a suitable choice for a topical formulation of TMZA-HE. © 2007 The Authors.

'He was like a zombie':off-label prescription of antipsychotic drugs in dementia

This paper explores the legal position of the off-label prescription of antipsychotic medications to people with dementia who experience behavioural and psychological symptoms of dementia (BPSD). Dementia is a challenging illness, and BPSD can be very difficult for carers to manage, with evidence that this contributes to carer strain and can result in the early institutionalisation of people with dementia. As a result, the prescription of antipsychotic and other neuroleptic medications to treat BPSD has become commonplace, in spite of these drugs being untested and unlicensed for use to treat older people with dementia. In recent years, it has become apparent through clinical trials that antipsychotic drugs increase the risk of cerebrovascular accident (stroke) and death in people with dementia. In addition, these types of medication also have other risk factors for people with dementia, including over-sedation and worsening of cognitive function. Drawing on recent questionnaire (n = 185), focus group (n = 15), and interview (n = 11) data with carers of people with dementia, this paper explores the law relating to off-label prescription, and the applicability of medical negligence law to cases where adverse events follow the use of antipsychotic medication. It is argued that the practice of off-label prescribing requires regulatory intervention in order to protect vulnerable patients. © The Author [2012]. Published by Oxford University Press; all rights reserved.

'Only in the leap from the lion's head will he prove his worth':natural law and international relations

This article argues the benefits of including a theological interpretation of natural law morality within the normative discourses of international politics. It challenges the assumption of a Grotian secular natural law arguing that practical reason, in a Thomist interpretation, is better suited to the demands of international political theory. It engages with themes of agency, practical reason, and community in order to enhance the content of the post-territorial community evidenced in ethical cosmopolitan debates. Likewise, it envisions a simultaneously enhancing a rapprochement among cosmopolitan and communitarian discourses of international politics facilitated through an institutional design guided by the morality of natural law.

Anisotropic model of kinetic roughening:he strong-coupling regime

We study the strong coupling (SC) limit of the anisotropic Kardar-Parisi-Zhang (KPZ) model. A systematic mapping of the continuum model to its lattice equivalent shows that in the SC limit, anisotropic perturbations destroy all spatial correlations but retain a temporal scaling which shows a remarkable crossover along one of the two spatial directions, the choice of direction depending on the relative strength of anisotropicity. The results agree with exact numerics and are expected to settle the long-standing SC problem of a KPZ model in the infinite range limit. © 2007 The American Physical Society.

Work-based HE pathways for the electrical power engineering industry

Aston University has been working closely with key companies from within the electricity industry for several years, initially in the development and delivery of an employer-led foundation degree programme in electrical power engineering, and more recently, in the development of a progression pathway for foundation degree graduates to achieve a Bachelors-level qualification. The Electrical Power Engineering foundation degree was developed in close consultation with the industry such that the programme is essentially owned by the sector. Programme delivery has required significant shifts away from traditional HE teaching patterns whilst maintaining the quality requirement and without compromise of the academic degree standard. Block teaching (2-week slots), partnership delivery, off-site student support and work-based learning have all presented challenges as we have sought to maximise the student learning experience and to ensure that the graduates are fit-for purpose and "hit the ground running" within a defined career structure for sponsoring companies. This paper will outline the skills challenges facing the sector; describe programme developments and delivery challenges; before articulating some observations and conclusions around programme effectiveness, impact of foundation degree graduates in the workplace and the significance of the close working relationship with key sponsoring companies. Copyright © 2012, September.

French linguistics research and teaching in UK and Irish HE institutions

Introduction: The research and teaching of French linguistics in UK higher education (HE) institutions have a venerable history; a number of universities have traditionally offered philology or history of the language courses, which complement literary study. A deeper understanding of the way that the phonology, syntax and semantics of the French language have evolved gives students linguistic insights that dovetail with their study of the Roman de Renart, Rabelais, Racine or the nouveau roman. There was, in the past, some coverage of contemporary French phonetics but little on sociolinguistic issues. More recently, new areas of research and teaching have been developed, with a particular focus on contemporary spoken French and on sociolinguistics. Well supported by funding councils, UK researchers are also making an important contribution in other areas: phonetics and phonology, syntax, pragmatics and second-language acquisition. A fair proportion of French linguistics research occurs outside French sections in psychology or applied linguistics departments. In addition, the UK plays a particular role in bringing together European and North American intellectual traditions and methodologies and in promoting the internationalisation of French linguistics research through the strength of its subject associations, and that of the Journal of French Language Studies. The following sections treat each of these areas in turn. History of the French Language There is a long and distinguished tradition in Britain of teaching and research on the history of the French language, particularly, but by no means exclusively, at the universities of Cambridge, Manchester and Oxford.