Developing system models to help Great Britain's railways embrace innovative technologies with confidence

Railways are under pressure to become more efficient and cut their costs; innovation has a part to play in achieving these goals. The railway is, however, a complex and closely coupled system, making it difficult in the early stages of development, to be clear what the system-wide impact of innovation will be. The research covered in this paper stems from the idea that computer-based models of existing systems can help overcome this problem, by providing a baseline framework against which the impact of innovation can be identified. The paper describes development of a repeatable modelling methodology, which elicits\ud objective system data from Railway Group Standards and integrates it using CORE®, a powerful system modelling tool, to create system models. The ability of such models to help identify impacts is verified, using as an example the introduction of RailBAM (a new technology that acoustically monitors the health of rolling stock axle bearings) into the existing hot axle bearing detection system

Tertiary and carboniferous magmatism around Lundy Island and the outer Bristol Channel - a geophysical and geochemical perspective

The British Tertiary Volcanic Province comprises central volcanic complexes with positive gravity and magnetic anomalies, some centres associated with both large volumes of continental flood basalts and regional dyke swarms. The Lundy Island is the southern most expression of Tertiary volcanism and consists of granite intruded by around 200 dykes and associated with positive gravity and magnetic anomalies. The Lundy Dyke Swarm comprises basalt/dolerite and trachyte to rhyolite intrusions within host Tertiary granite (58.7 ± 1.6 Ma) and Devonian sediments. Outcrops of dykes are confined to coastal exposures on Lundy as they are veneered by peat over most of the island. Dykes present paired magnetic anomaly profiles, which allows their trends tobe determined by proton magnetometry. The dykes have a radial disposition superimposed on a ENE-WSW regional trend. Anisotropy of magnetic susceptibility studies indicate that magma for the radial component was emplaced at shallow to moderate inclinations, suggesting a relatively shallow origin near to the western border of Lundy Island. The regional component was emplaced at shallow to sub-horizontalangles, suggesting lateral movement of magma from a possible source 12 km to the northwest.Geochemical signatures indicate that the Lundy Dyke Swarm was transitional between plume-related magmatism and partial melting of the lithospheric mantle, the magma being stored in several small storage bodies at differing depths in the upper continental crust, rather than in one large magma chamber. Basic dykes at Lee Bay (60 ± 0.6 to 63.1 ± 0.7 Ma) pre-date the Lundy Dyke Swarm and were derived from a discrete magma chamber, possibly near to Morte Point. Conversely, other dykes in North Devon (Fremington dyke - 292.4 ± 1.7 Ma; Horse-Shoe Rocks - 339.6 ± 7.4 Ma) are not directly related to Tertiary magmatism, even though the Horse-Shoe Rocks have a Tertiary palaeomagnetic overprint.The Lundy Igneous Complex (comprising granite, dykes and sub-surface basic rocks) is situated close to the intersection of the Variscan Front and the Welsh Caledonides massif where the continental thickness is between 25 and 27 km. Emplacement of magma was assisted by the heavily fractured nature of the host sediments. However, a large positive gravity anomaly to the northwest of Lundy Island does not have a corresponding magnetic anomaly and so is interpreted as the response to relatively dense uplifted basement in the Lundy Horst rather than a large volume of basic rocks.Thus, the Lundy Igneous Complex probably did not produce sub-aerial volcanic activity, as pressure in the magma chamber would not have exceeded the overlying litho static load, despite the fractured nature of the host rocks

An augmented delivery of the anticancer agent, curcumin, to the colon

This work describes the formulation aspects of an orally viable curcumin-containing mucoadhesive nanoparticulate system for management of colon cancer. Curcumin is documented to possess anticancer properties whilst modified citrus pectin yields a galactose functionality capable of inhibiting the growth and proliferation of colon cancer cells due to antagonism to galectin-3 (Gal-3). A successfully formulated curcumin containing chitosan-modified citrus pectinate nanoparticles (MCPCNPs) registered a z-average of 178 nm (± 0.896) and a positive surface charge of + 35.7 mV (± 1.41). The MCPCNPs presented high mucoadhesion propensity in the colonic region/ media and minimal at pH 1.2 (stomach). There was approximately 18 % curcumin release at pH 1.2 over 2 h and up to 68% release in the 33% (w/v) caecal medium over 24 h. The data obtained strongly suggests that the formulated MCPCNPs have the potential to be applied as an orally deliverable colon cancer formulation alternative in the treatment of colon cancer

Antifungal and mucoadhesive properties of an orally administered chitosan-coated amphotericin B 1 nanostructured lipid carrier (NLC)

Surface - modified nanostructured lipid carriers (NLC) is a promising formulation to prolong the retention time of the therapeutic agent at the site of absorption. Chitosan-coated AmpB-loaded NLC (ChiAmpB NLC) were developed showing particle size of 394.4 ± 6.4 nm, encapsulation efficiency of 86.0 ± 0.3 % and a drug loading of 11.0 ± 0.1 %. ChiAmpB NLC showed biphasic release behaviour with no significant change in its physical properties upon exposure to conditions simulating the gastrointestinal tract. Compared to pure AmpB, ChiAmpB NLC observed not only a comparable antifungal behaviour but showed superior safety profiles, with two times lesser toxicity to the red blood cells and ten times safer to the HT-29 cell line. It was also successfully observed a translation of the in vitro mucoadhesion result to the ex vivo animal study in which ChiAmpB NLC results in higher percentage of retention in the small intestine compared to uncoated formulation. Together, the data strongly offered the possibility of having a non-toxic yet effective oral treatment for systemic fungal infections

Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B

This study describes the properties of an amphotericin B-containing mucoadhesive nanostructured lipid carrier (NLC), with the intent to maximize uptake within the gastrointestinal tract. We have reported previously that lipid nanoparticles can significantly improve the oral bioavailability of amphotericin B (AmpB). On the other hand, the aggregation state of AmpB within the NLC has been ascribed to some of the side effects resulting from IV administration. In the undissolved state, AmpB (UAmpB) exhibited the safer monomeric conformation in contrast to AmpB in the dissolved state (DAmpB), which was aggregated. Chitosan-coated NLC (ChiAmpB NLC) presented a slightly slower AmpB release profile as compared to the uncoated formulation, achieving 26.1 % release in 5 hours. Furthermore, the ChiAmpB NLC formulation appeared to prevent the expulsion of AmpB upon exposure to simulated gastrointestinal pH media, whereby up to 63.9 % of AmpB was retained in the NLC compared to 56.1 % in the uncoated formulation. The ChiAmpB NLC demonstrated mucoadhesive properties in pH 5.8 and 6.8. Thus, the ChiAmpB NLC formulation is well-primed for pharmacokinetic studies to investigate whether delayed gastrointestinal transit may be exploited to improve the systemic bioavailability of AmpB, whilst simultaneously addressing the side-effect concerns of AmpB

The Development of Facial Prosthetics and Adhesives in Plastic and Reconstructive Surgery. A study in the application of prosthetic materials and devices used in plastic and reconstructive surgery together with tissue adhesives as an alternative to conventional ligation.

Various silicone elastomers have been evaluated for use in the prosthetic reconstruction of facial defects. Their strength, texture, flexibility, hardness, ease of preparation, pigment receptivity and retention, and their resistance to cleaning were compared and the data consulted when an elastomer was chosen to restore defects, improve aesthetics and reestablish the confidence of a selection of patients. Detailed case reports are provided, together with information on the adhesives or mechanical methods available for retaining the facial prosetheses. Cyanoacrylate adhesives for use on skin surfaces and as tissue adhesives have been studied in detail. A novel n-butyl 413 cyanoacrylate has been developed with a viscosity, haemostatic property and stability to make it particularly suitable for use in skin grafting and tissue repair. It has already been used with good results on patients with severe burns. An improved formulation, containing a fluorescent dye, can be precisely applied through a specially constructed foot-controlled dispenser illuminated by a fibre-optic supplying UV-light. Cyanoacrylates are already being used as tissue adhesives in place of the conventional but potentially disfiguring suture. The availability of improved, imperceptible adhesives and a precision applicator, which can be used in a modern operating theatre, will extend their effectiveness and satisfy some of the needs of Plastic, and Oral and Maxillo-Facial Surgeons. Portable applicators have potential use in battlefield and in veterinary surgery and overcome the imprecision characteristic of earlier methods.Loctite U

Development of an in vitro system to study the interactions of aerosolized drugs with pulmonary mucus

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Mucus is the first biological component inhaled drugs encounter on their journey towards their pharmacological target in the upper airways. Yet, how mucus may influence drug disposition and efficacy in the lungs has been essentially overlooked. In this study, a simple in vitro system was developed to investigate the factors promoting drug interactions with airway mucus in physiologically relevant conditions. Thin layers of porcine tracheal mucus were prepared in Transwell® inserts and initially, the diffusion of various fluorescent dyes across those layers was monitored over time. A deposition system featuring a MicroSprayer® aerosolizer was optimized to reproducibly deliver liquid aerosols to multiple air-facing layers and then exploited to compare the impact of airway mucus on the transport of inhaled bronchodilators. Both the dyes and drugs tested were distinctly hindered by mucus with high logP compounds being the most affected. The diffusion rate of the bronchodilators across the layers was in the order: ipratropium ≈ glycopyronnium > formoterol > salbutamol > indacaterol, suggesting hydrophobicity plays an important role in their binding to mucus but is not the unique parameter involved. Testing of larger series of compounds would nevertheless be necessary to better understand the interactions of inhaled drugs with airway mucus