The application of monolayer studies in the understanding of liposomal formulations

The study of surfactant monolayers is certainly not a new technique, but the application of monolayer studies to elucidate controlling factors in liposome design remains an underutilised resource. Using a Langmuir-Blodgett trough, pure and mixed lipid monolayers can be investigated, both for their interactions within the monolayer, and for interfacial interactions with drugs in the aqueous sub-phase. Despite these monolayers effectively being only half a bilayer, with a flat rather than curved structure, information from these studies can be effectively translated into liposomal systems. Here we outline the background, general protocols and application of Langmuir studies with a focus on their application in liposomal systems. A range of case studies are discussed which show how the system can be used to support its application in the development of liposome drug delivery. Examples include investigations into the effect of cholesterol within the liposome bilayer, understanding effective lipid packaging within the bilayer to promote water soluble and poorly soluble drug retention, the effect of alkyl chain length on lipid packaging, and drug-monolayer electrostatic interactions that promote bilayer repackaging.

Chloride resistance and durability of cement paste and concrete containing metakaolin

Metakaolin (MK), a calcined clay, was included as a partial cement replacement material, at up to 20% by weight of binder, in cement pastes and concrete, and its influence on the resistance to chloride ingress investigated. Reductions in effective chloride diffusion coefficients through hardened cement paste were obtained for binary blends and by combining OPC, MK and a second cement replacement material of pulverised fuel ash or ground granulated blast furnace slag. Steady state oxygen diffusion measurements through hardened cement pastes measured using an electrochemical cell showed that the interaction between charged species and the pore surfaces is a major factor in determining chloride diffusion rate. Rheology of the binder, particularly at high MK replacement levels, was found to have a dramatic influence on the diffusion performance of cement pastes. It was concluded that plasticising admixtures are essential for adequate dispersion of MK in cement pastes. Chloride concentration profile analysis of the concrete cylinders, exposed to sodium chloride solution for one year, was employed to obtain apparent chloride diffusion coefficients for concrete specimens. MK was found to reduce the depth of chloride penetration into concrete when compared with that of unblended mixes. Corrosion rate and corrosion potential measurements were taken on steel bars embedded in concrete exposed to a saline environment under conditions of cyclic wetting and drying. The initiation time for corrosion was found to be significantly longer for MK blended mixes than for plain OPC systems. The aggregate-paste interfacial zone of MK blended systems was investigated by steady state diffusion of chloride ions through mortar containing glass beads as model aggregate. For the model aggregate specimens tested the work confirmed the hypothesis that properties of the bulk paste are the controlling factors in ionic diffusion through mortar.

The factors affecting the optimal performance of eddy-current machines

This thesis presents an examination of the factors which influence the performance of eddy-current machines and the way in which they affect optimality of those machines. After a brief introduction to the types of eddy-current machine considered, the applications to which these machines are put are examined. A list of parameters by which to assess their performance is obtained by considering the machine as part of a system. in this way an idea of what constitutes an optimal machine is obtained. The third chapter then identifies the factors which affects the performance and makes a quantitative evaluation of the effect. Here the various alternative configurations and components are compared with regard to their influence on the mechanical, electromagnetic, and thermal performance criteria of the machine. Chapter four contains a brief review of the methods of controlling eddy-current machines by electronic methods using thyristors or transistors as the final control element. Where necessary, the results of previous workers in the field of electrical machines have been extended or adapted to increase the usefulness of this thesis.

Psychological risk factors for chronic post-surgical pain after inguinal hernia repair surgery:a prospective cohort study.

A significant proportion of patients experience chronic post-surgical pain (CPSP) following inguinal hernia surgery. Psychological models are useful in predicting acute pain after surgery, and in predicting the transition from acute to chronic pain in non-surgical contexts. This is a prospective cohort study to investigate psychological (cognitive and emotional) risk factors for CPSP after inguinal hernia surgery. Participants were asked to complete questionnaires before surgery and 1 week and 4 months after surgery. Data collected before surgery and 1 week after surgery were used to predict pain at 4 months. Psychological risk factors assessed included anxiety, depression, fear-avoidance, activity avoidance, catastrophizing, worry about the operation, activity expectations, perceived pain control and optimism. The study included 135 participants; follow-up questionnaires were returned by 119 (88.1%) and 115 (85.2%) participants at 1 week and 4 months after surgery respectively. The incidence of CPSP (pain at 4 months) was 39.5%. After controlling for age, body mass index and surgical variables (e.g. anaesthetic, type of surgery and mesh type used), lower pre-operative optimism was an independent risk factor for CPSP at 4 months; lower pre-operative optimism and lower perceived control over pain at 1 week after surgery predicted higher pain intensity at 4 months. No emotional variables were independently predictive of CPSP. Further research should target these cognitive variables in pre-operative psychological preparation for surgery. © 2011 European Federation of International Association for the Study of Pain Chapters.

Endogenous ownership structure:factors affecting the post-privatisation equity in largest Hungarian firms

Using a data set for the 162 largest Hungarian firms during the period of 1994-1999, this paper explores the determinants of equity shares held by both foreign investors and Hungarian corporations. Evidence is found for a post-privatisation evolution towards more homogeneous equity structures, where dominant categories of Hungarian and foreign owners aim at achieving controlling stakes. In addition, focusing on firm-level characteristics we find that exporting firms attract foreign owners who acquire controlling equity stakes. Similarly, firm-size measurements are positively associated with the presence of foreign investors. However, they are negatively associated with 100% foreign ownership, possibly because the marginal costs of acquiring additional equity are growing with the size of the assets. The results are interpreted within the framework of the existing theory. In particular, following Demsetz and Lehn (1985) and Demsetz and Villalonga (2001) we argue that equity should not be treated as an exogenous variable. As for specific determinants of equity levels, we focus on informational asymmetries and (unobserved) ownership-specific characteristics of foreign investors and Hungarian investors.

Factors preventing myopia progression with orthokeratology correction

PURPOSE: To examine which baseline measurements constitute predictive factors for axial length growth over 2 years in children wearing orthokeratology contact lenses (OK) and single-vision spectacles (SV). METHODS: Sixty-one children were prospectively assigned to wear either OK (n = 31) or SV (n = 30) for 2 years. The primary outcome measure (dependent variable) was axial length change at 2 years relative to baseline. Other measurements (independent variables) were age, age of myopia onset, gender, myopia progression 2 years before baseline and baseline myopia, anterior chamber depth, corneal power and shape (p value), and iris and pupil diameters as well as parental refraction. The contribution of all independent variables to the 2-year change in axial length was assessed using univariate and multivariate regression analyses. RESULTS: After univariate analyses, smaller increases in axial length were found in the OK group compared to the SV group in children who were older, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had less myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had lower levels of parental myopia (all p < 0.05). In multivariate analyses, older age and greater corneal power were associated with smaller increases in axial length in the OK group (both p < 0.05), whereas in SV wearers, smaller iris diameter was associated with smaller increases in axial length (p = 0.021). CONCLUSIONS: Orthokeratology is a successful treatment option in controlling axial elongation compared to SV in children of older age, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had lower myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris and pupil diameters, and had lower levels of parental myopia. © American Academy of Optometry.

The design of contact lens based ocular drug delivery systems for single-day use:part (I) structural factors, surrogate ophthalmic dyes and passive diffusion studies

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.