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.

Disabled volunteers : an analysis of the experiences of wheelchair-users who volunteer

Following grounded-theory methodology, this thesis provides an analysis of the volunteering experiences of 47 wheelchair-users. It challenges the traditional image of volunteering which tends to conceptualise non-disabled people as the instigators of voluntary action (the helpers) and disabled people as the recipients of volunteerism (the helped). It also begins to fill a notable gap in academic knowledge about the volunteering experiences of disabled people. The literature review showed that contemporary conceptualisations of disability were unsuitable for this thesis. Thus, an organising framework is proposed which acknowledges that disabled peoples’ experiences may be influenced by medically and socially constructed factors – or by a combination of both acting simultaneously (medical-social factors). Having conceptualised disability for the purposes of the study, the thesis then provides an account of the research methodology used. This is followed by a presentation of research findings. An analysis of the volunteers’ demographic, epidemiological and background characteristics is provided and their perceptions of the benefits of, and barriers to, volunteering highlighted. This is followed by an analysis of their volunteering experiences. Theory is developed in order to explain the volunteers’ experiences from the approach outlined within the organising framework. The final part of the thesis adopts a reflexive approach to contextualise the research processes from the writer’s own perspective as a disabled person conducting research into the lived experiences of other disabled people. The thesis concludes by highlighting the implications of the study for future social research.

Incorporation and release of macromolecules from biodegradable polymer vehicles

The initial objective of this work was to evaluate and introduce fabrication techniques based on W/0/W double emulsion and 0/W single emulsion systems with solvent evaporation for the incorporation of a surrogate macromolecule (BSA) into microspheres and microcapsules fabricated using P(HB-HV}, PEA and their blends. Biodegradation, expressed as changes in the gross and ultrastructural morphology of BSA loaded microparticulates with time was monitored using SEM concomitant with BSA release. Spherical microparticulates were successfully fabricated using both the W/0/W and 0/W emulsion systems. Both microspheres and microcapsules released BSA over a period of 24 to 26 days. BSA release from P(HB-HV)20% PCL 11 microcapsules increased steadily with time, while BSA release from all other microparticulates was characterised by an initial lag phase followed by exponential release lasting 6-11 days. Microcapsules were found to biodegrade more rapidly than microspheres fabricated from the same polymer. The incubation of microparticulates in newborn calf serum; synthetic gastric juice and pancreatin solution showed that microspheres and microcapsules were susceptible to enzymatic biodegradation. The in vitro incubation of microparticulates in Hank's buffer demonstrated limited biodegradation of microspheres and microcapsules by simple chemical hydrolysis. BSA release was thought to ocurr as a result of the macromolecule diffusing through either inherent micropores or via pores and channels generated in situ by previously dissolved BSA. However, in all cases, irrespective of percentage loading or fabrication polymer, low encapsulation efficiencies were obtained with W/0/W and 0/W techniques (4.2±0.9%- 15.5±0.5%,n=3), thus restricting the use of these techniques for the generation of microparticulate sustained drug delivery devices. In order to overcome this low encapsulation efficiency, a W/0 single emulsion technique was developed and evaluated in an attempt to minimise the loss of the macromolecule into the continuous aqueous phase and increase encapsulation efficiency. Poly(lactide-co-glycolide) [PLCG] 75:25 and 50:50, PEA alone and PEA blended with PLCG 50:50 to accelerate biodegradation, were used to microencapsulate the water soluble antibiotic vancomycin, a putative replacement for gentamicin in the control of bacterial infection in orthopaedic surgery especially during total hip replacement. Spherical microspheres (17.39±6.89~m,n=74-56.5±13.8~m,n=70) were successfully fabricated with vancomycin loadings of 10, 25 and 50%, regardless of the polymer blend used. All microspheres remained structurally intact over the period of vancomycin release and exhibited high percentage yields( 40. 75±2 .86%- 97.16±4.3%,n=3)and encapsulation efficiencies (47.75±9.0%- 96.74±13.2%,n=12). PLCG 75:25 microspheres with a vancomycin loading of 50% were judged to be the most useful since they had an encapsulation efficiency of 96.74+13.2%, n=12 and sustained therapeutically significant vancomycin release (15-25μg/ml) for up to 26 days. This work has provided the means for the fabrication of a spectrum of prototype biodegradable microparticulates, whose biodegradation has been characterised in physiological media and which have the potential for the sustained delivery of therapeutically useful macromolecules including water soluble antibiotics for orthopaedic applications.

But it’s not all about the sex:mothering, normalisation and young learning disabled people

This paper is about mothering, young learning disabled people, their sexualised and relationship lives and normalisation - not through the lens of the disabled person, but via a mothers perspective and theoretical discussion. As a mother who has a learning disabled daughter, a feminist and an academic, my own mothering experience, my PhD research and social theory are woven throughout this paper with the intention of opening up debate about sex, intimacy, normalisation, and how this impacts upon young learning disabled people. I suggest that the relationship between sex, reproduction, intimacy and intellectual impairment, and a project to decipher what it means to be human, in all its dirty glory are also part of the discourse that needs to be discussed experientially and theoretically. So much so that the messy world within which we all live can be variously and differently constructed.

Wireless power charger for light electric vehicles

Wireless power transmission technology is gaining more and more attentions in city transportation applications due to its commensurate power level and efficiency with conductive power transfer means. In this paper, an inductively coupled wireless charging system for 48V light electric vehicle is proposed. The power stages of the system is evaluated and designed, including the high frequency inverter, the resonant network, full bridge rectifier, and the load matching converter. Small signal modeling and linear control technology is applied to the load matching converter for input voltage control, which effectively controls the wireless power flow. The prototype is built with a dsPIC digital signal controller; the experiments are carried out, and the results reveal nature performances of a series-series resonant inductive power charger in terms of frequency, air-gap length, power flow control, and efficiency issues.

Enabling long journeys in electric vehicles:design and demonstration of an infrastructure location model

This research develops a methodology and model formulation which suggests locations for rapid chargers to help assist infrastructure development and enable greater battery electric vehicle (BEV) usage. The model considers the likely travel patterns of BEVs and their subsequent charging demands across a large road network, where no prior candidate site information is required. Using a GIS-based methodology, polygons are constructed which represent the charging demand zones for particular routes across a real-world road network. The use of polygons allows the maximum number of charging combinations to be considered whilst limiting the input intensity needed for the model. Further polygons are added to represent deviation possibilities, meaning that placement of charge points away from the shortest path is possible, given a penalty function. A validation of the model is carried out by assessing the expected demand at current rapid charging locations and comparing to recorded empirical usage data. Results suggest that the developed model provides a good approximation to real world observations, and that for the provision of charging, location matters. The model is also implemented where no prior candidate site information is required. As such, locations are chosen based on the weighted overlay between several different routes where BEV journeys may be expected. In doing so many locations, or types of locations, could be compared against one another and then analysed in relation to siting practicalities, such as cost, land permission and infrastructure availability. Results show that efficient facility location, given numerous siting possibilities across a large road network can be achieved. Slight improvements to the standard greedy adding technique are made by adding combination weightings which aim to reward important long distance routes that require more than one charge to complete.

Impact of electric vehicles on GB electricity demand and associated benefits for system control

This paper investigates the impact that electric vehicle uptake will have on the national electricity demand of Great Britain. Data from the National Travel Survey, and the Coventry and Birmingham Low Emissions Demonstration (CABLED) are used to model an electrical demand profile in a future scenario of significant electric vehicle market penetration. These two methods allow comparison of how conventional cars are currently used, and the resulting electrical demand with simple substitution of energy source, with data showing how electric vehicles are actually being used at present. The report finds that electric vehicles are unlikely to significantly impact electricity demand in GB. The paper also aims to determine whether electric vehicles have the potential to provide ancillary services to the grid operator, and if so, the capacity for such services that would be available. Demand side management, frequency response and Short term Operating Reserve (STOR) are the services considered. The report finds that electric cars are unlikely to provide enough moveable demand peak shedding to be worthwhile. However, it is found that controlling vehicle charging would provide sufficient power control to viably act as frequency response for dispatch by the transmission system operator. This paper concludes that electric vehicles have technical potential to aid management of the transmission network without adding a significant demand burden. © 2013 IEEE.

Who gives a damn about intellectually disabled people and their families? Care-less spaces personified in the case of LB

On 5 October 2015 the inquest into Connor Sparrowhawk’s death began. A young autistic man, aged 18, died in the bath on 4 July 2013. He had a seizure. The rolling tweets from @LBInquest are harrowing to say the least. Unimaginable torture for Sara and Richard (his mother and step-father), as well as his siblings and others caring. Comments from the inquest such as ‘I felt that Connor should be checked on every 5 or 10 minutes when he was in the bath because of his epilepsy’ and ‘ensuring someone was outside the door when he was bathing was basic nursing care’ sound all the alarm bells for lack of care, because allegedly this did not happen. Clearly there was no one person looking out for him when he needed it the most. On 16 October 2015 the inquest jury found Connor’s death was contributed by neglect. This article will explore the absence of care in a care-less system.

Meeting 2050 CO2 emissions reduction targets:The potential for electric vehicles

This chapter explores the potential for electric vehicles to contribute to decarbonising surface transport. Decarbonising transport is a major global challenge-meeting CO2 emissions reduction targets for 2050, with a rapidly growing, and urbanising global population.

New SR drive with integrated charging capacity for plug-in hybrid electric vehicles (PHEVs)

Plug-in hybrid electric vehicles (PHEVs) provide much promise in reducing greenhouse gas emissions and, thus, are a focal point of research and development. Existing on-board charging capacity is effective but requires the use of several power conversion devices and power converters, which reduce reliability and cost efficiency. This paper presents a novel three-phase switched reluctance (SR) motor drive with integrated charging functions (including internal combustion engine and grid charging). The electrical energy flow within the drivetrain is controlled by a power electronic converter with less power switching devices and magnetic devices. It allows the desired energy conversion between the engine generator, the battery, and the SR motor under different operation modes. Battery-charging techniques are developed to operate under both motor-driving mode and standstill-charging mode. During the magnetization mode, the machine's phase windings are energized by the dc-link voltage. The power converter and the machine phase windings are controlled with a three-phase relay to enable the use of the ac-dc rectifier. The power converter can work as a buck-boost-type or a buck-type dc-dc converter for charging the battery. Simulation results in MATLAB/Simulink and experiments on a 3-kW SR motor validate the effectiveness of the proposed technologies, which may have significant economic implications and improve the PHEVs' market acceptance.

New integrated multilevel converter for switched reluctance motor drives in plug-in hybrid electric vehicles with flexible energy conversion

This paper presents an integrated multilevel converter of switched reluctance motors (SRMs) fed by a modular front-end circuit for plug-in hybrid electric vehicle (PHEV) applications. Several operating modes can be achieved by changing the on-off states of the switches in the front-end circuit. In generator driving mode, the battery bank is employed to elevate the phase voltage for fast excitation and demagnetization. In battery driving mode, the converter is reconfigured as a four-level converter, and the capacitor is used as an additional charge capacitor to produce multilevel voltage outputs, which enhances the torque capability. The operating modes of the proposed drive are explained and the phase current and voltage are analyzed in details. The battery charging is naturally achieved by the demagnetization current in motoring mode and by the regenerative current in braking mode. Moreover, the battery can be charged by the external AC source or generator through the proposed converter when the vehicle is in standstill condition. The SRM-based PHEV can operate at different speeds by coordinating the power flow between the generator and battery. Simulation in MATLAB/Simulink and experiments on a three-phase 12/8 SRM confirm the effectiveness of the proposed converter topology.

Design and flux-weakening control of an interior permanent magnet synchronous motor for electric vehicles

Permanent magnet synchronous motors (PMSMs) provide a competitive technology for EV traction drives owing to their high power density and high efficiency. In this paper, three types of interior PMSMs with different PM arrangements are modeled by the finite element method (FEM). For a given amount of permanent magnet materials, the V shape interior PMSM is found better than the U-shape and the conventional rotor topologies for EV traction drives. Then the V shape interior PMSM is further analyzed with the effects of stator slot opening and the permanent magnet pole chamfering on cogging torque and output torque performance. A vector-controlled flux-weakening method is developed and simulated in matlab to expand the motor speed range for EV drive system. The results show good dynamic and steady-state performance with a capability of expanding speed up to 4 times of the rated. A prototype of the V shape interior PMSM is also manufactured and tested to validate the numerical models built by the finite element method.

Care-less spaces and identity construction:transition to secondary school for disabled children

There is a growing body of literature which marks out a feminist ethics of care and it is within this framework we understand transitions from primary to secondary school education can be challenging and care-less, especially for disabled children. By exploring the narratives of parents and professionals, we investigate transitions and self-identity, as a meaningful transition depends on the care-full spaces pupils inhabit. These education narratives are all in the context of privileging academic attainment and a culture of testing and examinations. Parents and professionals, as well as children are also surveyed. Until there are care-full education processes, marginalisation will remain, impacting on disabled children’s transition to secondary school and healthy identity construction. Moreover, if educational challenges are not addressed, their life chances are increasingly limited. Interdependent caring work enables engagement in a meaningful education and positive identity formation. In school and at home, care-full spaces are key in this process.