Accessibility-by-design: a framework for delivery-context-aware personalised media content re-purposing

This paper describes a framework architecture for the automated re-purposing and efficient delivery of multimedia content stored in CMSs. It deploys specifically designed templates as well as adaptation rules based on a hierarchy of profiles to accommodate user, device and network requirements invoked as constraints in the adaptation process. The user profile provides information in accordance with the opt-in principle, while the device and network profiles provide the operational constraints such as for example resolution and bandwidth limitations. The profiles hierarchy ensures that the adaptation privileges the users' preferences. As part of the adaptation, we took into account the support for users' special needs, and therefore adopted a template-based approach that could simplify the adaptation process integrating accessibility-by-design in the template.

Profiling management for personalised multimedia delivery on-demand within the AXMEDIS framework

Media content distribution on-demand becomes more complex when performed on a mass scale involving various channels with distinct and dynamic network characteristics, and, deploying a variety of terminal devices offering a wide range of capabilities. It is practically impossible to create and prepackage various static versions of the same content to match all the varying demand parameters of clients for various contexts. In this paper we present a profiling management approach for dynamically personalised media content delivery on-demand integrated with the AXMEDIS Framework. The client profiles comprise the representation of User, Device, Network and Context of content delivery based on MPEG-21:DIA. Although the most challenging proving ground for this personalised content delivery has been the mobile testbed i.e. the distribution to mobile handsets, the framework described here can be deployed for disribution, by the AXMEDIS PnP module, through other channels e.g. satellite, Internet to a range of client terminals e.g. desktops, kiosks, IPtv and other terrminals whose baseline terminal capabilities can be made availabe by the manufacturers as is normal.

A nipple shield delivery system for oral drug delivery to breastfeeding infants : Microbicide delivery to inactivate HIV

A new drug delivery method for infants is presented which incorporates an active pharmaceutical ingredient (API)-loaded insert into a nipple shield delivery system (NSDS). The API is released directly into milk during breastfeeding. This study investigates the feasibility of using the NSDS to deliver the microbicide sodium dodecyl sulfate (SDS), with the goal of preventing mother-to-child transmission (MTCT) of HIV during breastfeeding in low-resource settings, when there is no safer alternative for the infant but to breastfeed. SDS has been previously shown to effectively inactivate HIV in human milk. An apparatus was developed to simulate milk flow through and drug release from a NSDS. Using this apparatus milk was pulsed through a prototype device containing a non-woven fiber insert impregnated with SDS and the microbicide was rapidly released. The total SDS release from inserts ranged from 70 to 100% of the average 0.07 g load within 50 ml (the volume of a typical breastfeed). Human milk spiked with H9/HIVIIIB cells was also passed through the same set-up. Greater than 99% reduction of cell-associated HIV infectivity was achieved in the first 10 ml of milk. This proof of concept study demonstrates efficient drug delivery to breastfeeding infants is achievable using the NSDS.

Fine sediment delivery and transfer in lowland catchments: modelling suspended sediment concentrations in response to hydrological forcing

Fine sediment delivery to and storage in stream channel reaches can disrupt aquatic habitats, impact river hydromorphology, and transfer adsorbed nutrients and pollutants from catchment slopes to the fluvial system. This paper presents a modelling toot for simulating the time-dependent response of the fine sediment system in catchments, using an integrated approach that incorporates both land phase and in-stream processes of sediment generation, storage and transfer. The performance of the model is demonstrated by applying it to simulate in-stream suspended sediment concentrations in two lowland catchments in southern England, the Enborne and the Lambourn, which exhibit contrasting hydrological and sediment responses due to differences in substrate permeability. The sediment model performs well in the Enborne catchment, where direct runoff events are frequent and peak suspended sediment concentrations can exceed 600 mg l(-1). The general trends in the in-stream concentrations in the Lambourn catchment are also reproduced by the model, although the observed concentrations are low (rarely exceeding 50 mg l(-1)) and the background variability in the concentrations is not fully characterized by the model. Direct runoff events are rare in this highly permeable catchment, resulting in a weak coupling between the sediment delivery system and the catchment hydrology. The generic performance of the model is also assessed using a generalized sensitivity analysis based on the parameter bounds identified in the catchment applications. Results indicate that the hydrological parameters contributing to the sediment response include those controlling (1) the partitioning of runoff between surface and soil zone flows and (2) the fractional loss of direct runoff volume prior to channel delivery. The principal sediment processes controlling model behaviour in the simulations are the transport capacity of direct runoff and the in-stream generation, storage and release of the fine sediment fraction. The in-stream processes appear to be important in maintaining the suspended sediment concentrations during low flows in the River Enborne and throughout much of the year in the River Lambourn. Copyright (c) 2007 John Wiley & Sons, Ltd.

Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery

Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term ‘co-drug’ refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum corneum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stability by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availability of compatible moieties and physicochemical properties of the overall molecule.

Topical delivery of a naproxen-dithranol co-drug: in vitro skin penetration, permeation, and staining

Purpose This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties. Method Freshly excised, full-thickness porcine ear skin was dosed with saturated solutions of the compounds. After 24 h, the skin was recovered and used to prepare comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining. Results Depth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of dithranol degradation products in the skin. Furthermore, significantly less naproxen from hydrolysed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 ± 0.03 nmol cm-² and 180 ± 60 nmol cm-², respectively). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to dithranol. Conclusions Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol.

Formulation and delivery of the bacterial antagonist Bacillus subtilis for management of lentil vascular wilt caused by Fusarium oxysporum f. sp lentis

Different formulations of Bacillus subtilis were prepared using standard laboratory protocols. Bacillus subtilis survived in glucose and talc powders at 8.6 and 7.8 log(10) CFU/g, respectively, for 1 year of storage at room temperature compared with 3.5 log(10) CFU/g on a peat formulation. Glasshouse experiments using soil and seed treatments were conducted to test the efficacy of B. subtilis for protecting lentil against the wilt disease caused by Fusariumoxysporum f. sp. lentis. Seed treatments with formulations of B. subtilis on glucose, talc and peat significantly enhanced its biocontrol activity against Fusarium compared with a treatment in which spores were applied directly to seed. The formulations decreased disease severity by reducing colonization of plants by the pathogen, promoting their growth and increased the dry weight of lentil plants. Of these treatments the glucose and talc-based powder formulations were more effective than the peat formulation and the spore application without a carrier. It was shown that the B. subtilis spores applied with glucose were viable for longer than those applied with other carriers. Seed treatment with these formulated spores is an effective delivery system that can provide a conducive environment for B. subtilis to suppress vascular wilt disease on lentil and has the potential for utilization in commercial field application.

A platform for supporting micro-collaborations in a diverse device environment

Collaborative software is usually thought of as providing audio-video conferencing services, application/desktop sharing, and access to large content repositories. However mobile device usage is characterized by users carrying out short and intermittent tasks sometimes referred to as 'micro-tasking'. Micro-collaborations are not well supported by traditional groupware systems and the work in this paper seeks out to address this. Mico is a system that provides a set of application level peer-to-peer services for the ad-hoc formation and facilitation of collaborative groups across a diverse mobile device domain. The system builds on the Java ME bindings of the JXTA P2P protocols, and is designed with an approach to use the lowest common denominators that are required for collaboration between varying degrees of mobile device capability. To demonstrate how our platform facilitates application development, we built an exemplary set of demonstration applications and include code examples here to illustrate the ease and speed afforded when developing collaborative software with Mico.

Generation of anti-complement "prodrugs": cleavable reagents for specific delivery of complement regulators to disease sites

Expression of biologically active molecules as fusion proteins with antibody Fc can substantially extend the plasma half-life of the active agent but may also influence function. We have previously generated a number of fusion proteins comprising a complement regulator coupled to Fc and shown that the hybrid molecule has a long plasma half-life and retains biological activity. However, several of the fusion proteins generated had substantially reduced biological activity when compared with the native regulator or regulator released from the Fc following papain cleavage. We have taken advantage of this finding to engineer a prodrug with low complement regulatory activity that is cleaved at sites of inflammation to release active regulator. Two model prodrugs, comprising, respectively, the four short consensus repeats of human decay accelerating factor (CD55) linked to IgG4 Fc and the three NH2-terminal short consensus repeats of human decay accelerating factor linked to IgG2 Fc have been developed. In each, specific cleavage sites for matrix metalloproteinases and/or aggrecanases have been incorporated between the complement regulator and the Fc. These prodrugs have markedly decreased complement inhibitory activity when compared with the parent regulator in vitro. Exposure of the prodrugs to the relevant enzymes, either purified, or in supernatants of cytokine-stimulated chondrocytes or in synovial fluid, efficiently cleaved the prodrug, releasing active regulator. Such agents, having negligible systemic effects but active at sites of inflammation, represent a paradigm for the next generation of anti-C therapeutics.

Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-β1

TGF-beta1 levels increase after vascular injury and promote vascular smooth muscle cell (VSMC) proliferation. We define a nonviral gene delivery system that targets alphavbeta3 and alpha5beta1 integrins that are expressed on proliferating VSMCs and strongly induced by TGF-beta1. A 15-amino acid RGDNP-containing peptide from American Pit Viper venom was linked to a Lys(16) peptide as vector (molossin vector) and complexed with Lipofectamine or fusogenic peptide for delivery of luciferase or beta-galactosidase reporter genes to primary cultures of human, rabbit, and rat VSMCs. Preincubation of VSMCs with TGF-beta1 for 24 h, but not with PDGF-BB, interferon-gamma, TNF-alpha, nor PMA, increased alphavbeta3 and alpha5beta1 expressions on VSMCs and enhanced gene delivery of molossin vector. Thus beta-galactosidase activity increased from 35 +/- 5% (controls) to 75 +/- 5% after TGF-beta1 treatment, and luciferase activity increased fourfold over control values. Potential use of this system in vessel bypass surgery was examined in an ex vivo rat aortic organ culture model after endothelial damage. Molossin vector system delivered beta-galactosidase to VSMCs in the vessel wall that remained for up to 12 days posttransfection. The molossin vector system, when combined with TGF-beta1, enhances gene delivery to proliferating VSMCs and might have clinical applications for certain vasculoproliferative diseases.

Dendrimers: a new class of nanoscopic containers and delivery devices

Dendrimers and hyperbranched polymers are a relatively new class of materials with unique molecular architectures and dimensions in comparison to traditional linear polymers. This review details recent notable advances in the application of these new polymers in terms of the development of new polymeric delivery systems. Although comparatively young, the developing field of hyperbranched drug delivery devices is a rapidly maturing area and the key discoveries in drug-conjugate systems amongst others are highlighted. As a consequence of their ideal hyperbranched architectures, the utilisation of host-guest chemistries in dendrimers has been included within the scope of this review. (C) 2003 Elsevier Ltd. All rights reserved.