A study of the effects of orally administered female hormones on the volume and composition of lacrimal fluid related to the toleration of corneal contact lenses

This study was designed to evaluate the effects of certain orally active contraceptive steroids on the eye, related to the tolerance of a corneal contact lens. An oestrogen, ethinyloestradiol BP. 0.05 mg, a progestogen, norethisterone acetate BP. 2.50 mg and a control tablet (vitamin C, 50 mg) were utilised. The effect of these preparations on corneal curvature, lacrimal fluid volume and protein composition and directly on corneal lens tolerance was monitored in a group of 23 volunteer patients. The progestogen was found to produce a significant (P≥ 0.05) decrease in tear volume as measured by a 3 minute Schirmer test. A smaller volume reduction was observed with ethinyloestradiol. A normal cornea appears unaffected, within the measurement limits available, by the use of either hormone. However, in the presence of a corneal lens, oestrogen was found to induce substantial corneal steepening, indicative of tissue oedema, during the initial 2-3 weeks of medication. Progestogen occasionally produced a similar effect, which could recur with either hormone shortly after the end of the treatment period. A new method of acrylamide gel electrophoresis was developed for examination of the protein concentration and composition of lacrimal fluid. This allowed much greater resolution of microquantities of unconcentrated fluid than anything previously reported. Quantitation by densitometry has permitted the recording of medication and lens-induced changes in the protein pattern. Tear albumin has been shown to differ from serum albumin and to consist of up to 3 subfractions, 7 further protein fractions may also be resolved. The concentration and probable origin of these proteins have been established and the overall effects of hormone administration described. Individual idiosyncratic responses are also discussed. The study has established tbenature of some effects of contraceptive steroids on the anterior eye, and the probable reasons for resultant corneal lens intolerance.

The measurement and decomposition of economy-wide productivity growth:Assessing the accuracy and selecting between different approaches

Productivity at the macro level is a complex concept but also arguably the most appropriate measure of economic welfare. Currently, there is limited research available on the various approaches that can be used to measure it and especially on the relative accuracy of said approaches. This thesis has two main objectives: firstly, to detail some of the most common productivity measurement approaches and assess their accuracy under a number of conditions and secondly, to present an up-to-date application of productivity measurement and provide some guidance on selecting between sometimes conflicting productivity estimates. With regards to the first objective, the thesis provides a discussion on the issues specific to macro-level productivity measurement and on the strengths and weaknesses of the three main types of approaches available, namely index-number approaches (represented by Growth Accounting), non-parametric distance functions (DEA-based Malmquist indices) and parametric production functions (COLS- and SFA-based Malmquist indices). The accuracy of these approaches is assessed through simulation analysis, which provided some interesting findings. Probably the most important were that deterministic approaches are quite accurate even when the data is moderately noisy, that no approaches were accurate when noise was more extensive, that functional form misspecification has a severe negative effect in the accuracy of the parametric approaches and finally that increased volatility in inputs and prices from one period to the next adversely affects all approaches examined. The application was based on the EU KLEMS (2008) dataset and revealed that the different approaches do in fact result in different productivity change estimates, at least for some of the countries assessed. To assist researchers in selecting between conflicting estimates, a new, three step selection framework is proposed, based on findings of simulation analyses and established diagnostics/indicators. An application of this framework is also provided, based on the EU KLEMS dataset.

Commentary : comparison of historical medical spending patterns among the BRICS and G7

A commentary on "Comparison of historical medical spending patterns among the BRICS and G7" by Jakovljevic, M.M. (2015). J.Med.Econ. 19, 70–76, doi:10.3111/13696998.2015.1093493

External audit in the National Health Service in England and Wales:a study of an oversight body's control of auditor remuneration

In the National Health Service (NHS) in England and Wales an oversight body, the Audit Commission (AC), defines the scope of the external auditors’ work, appoints the auditors and has oversight of their fees and audit quality. This heavily regulated audit regime mitigates some of the deficiencies observed in high profile corporate failures. Independence, it has been argued, is influenced by the total auditor remuneration paid by the client. In this study we examine total auditor remuneration in a regulated market which seeks to ensure audit independence and audit quality. In particular we undertake rigorous analysis of auditor remuneration by the type of auditor: We place emphasis on the differentiation between private sector firms and the AC’s in-house auditors (District Audit). Individual private audit firms charge premiums (up to 16%) for particular audit work in identified locations, but no premiums were found when we examined total auditor remuneration. The regime appears to permit efficient operation of the audit market while safeguarding both audit independence and standards.

Accounting and the emergence of care pathways in the National Health Service

This paper examines the effects of New Public Management reforms on the information infrastructure underpinning the work of public service professionals. Focussing on the case of the British National Health Service (NHS), the paper argues that hospital accounting reforms played a significant role in the emergence of standardised models of clinical practice. The paper moreover argues that, under the label “care pathways”, such standardised models of clinical practice became embedded in the information infrastructure of the NHS and concludes by discussing their implications for the work of doctors and hospital accountants.

Protein deposition at polymer surfaces:the bulk and surface structure-property effects of hydrogels

The primary objective of this research has been to investigate the interfacial phenomenon of protein adsorption in relation to the bulk and surface structure-property effect s of hydrogel polymers. In order to achieve this it was first necessary to characterise the bulk and surface properties of the hydrogels, with regard to the structural chemistry of their component monomers. The bulk properties of the hydrogels were established using equilibrium water content measurements, together with water-binding studies by differential scanning calorimetry (D.S.C.). Hamilton and captive air bubble-contact angle techniques were employed to characterise the hydrogel-water interface and from which by a mathematical derivation, the interfacial free energy (ðsw) and the surface free energy components (ð psv, ðdsv, ðsv) were obtained. From the adsorption studies using the radio labelled iodinated (125I) proteins of human serum albumin (H.S.A.) and human fibrinogen (H.Fb.), it was Found that multi-layered adsorption was occurring and that the rate and type of this adsorption was dependent on the physico-chemical behaviour of the adsorbing protein (and its bulk concentration in solution), together with the surface energetics of the adsorbent polymer. A potential method for the invitro evaluation of a material's 'biocompatibility' was also investigated, based on an empirically observed relationship between the adsorption of albumin and fibrinogen and the 'biocompatibility' of polymeric materials. Furthermore, some consideration was also given to the biocompatibility problem of proteinaceous deposit formation on hydrophilic soft' contact lenses and in addition a number of potential continual wear contact lens formulations now undergoing clinical trials,were characterised by the above techniques.

The use of Meteosat satellite data for spatial rainfall estimations and hydrological simulations

Satellite information, in combination with conventional point source measurements, can be a valuable source of information. This thesis is devoted to the spatial estimation of areal rainfall over a region using both the measurements from a dense and sparse network of rain-gauges and images from the meteorological satellites. A primary concern is to study the effects of such satellite assisted rainfall estimates on the performance of rainfall-runoff models. Low-cost image processing systems and peripherals are used to process and manipulate the data. Both secondary as well as primary satellite images were used for analysis. The secondary data was obtained from the in-house satellite receiver and the primary data was obtained from an outside source. Ground truth data was obtained from the local Water Authority. A number of algorithms are presented that combine the satellite and conventional data sources to produce areal rainfall estimates and the results are compared with some of the more traditional methodologies. The results indicate that the satellite cloud information is valuable in the assessment of the spatial distribution of areal rainfall, for both half-hourly as well as daily estimates of rainfall. It is also demonstrated how the performance of the simple multiple regression rainfall-runoff model is improved when satellite cloud information is used as a separate input in addition to rainfall estimates from conventional means. The use of low-cost equipment, from image processing systems to satellite imagery, makes it possible for developing countries to introduce such systems in areas where the benefits are greatest.

The development and operation of the effective interpersonal relationship skills relevant to career development problems from staff assessment at an industrial research laboratory

This study concerns the application of a model of effective interpersonal relationships to problems arising from staff assessment at I.C.I. Ltd. Corporate Laboratory between 1972 and 1974. In collaboration with academic and industrial supervision, the study commenced with a survey of management and supervisor opinions about the effectiveness of current staff (work) relationships, with particular reference to the problem of recognising and developing creative potential. This survey emphasised a need to improve the relationships between staff in the staff assessment context. A survey of research into creativity emphasised the importance of the interpersonal environment for obtaining creative behaviour in an organisation context. A further survey of theories of how inter­personal behaviour related to personal creativity (therapeutic psychology) provided a model of effective interpersonal behaviour (Carkhuff, 1969) that could be applied to the organisation context of staff assessment. The objective of the project was redefined as a need to improve the conditions of interpersonal behaviour in relation to certain (career development) problems arising from staff assessment practices. In order to demonstrate the application of the model of effective interpersonal behaviour, the research student recorded interviews between himself and members of staff designed to develop and operate the dimensions of the model. Different samples of staff were used to develop the 'facilitative' and the 'action oriented' dimensions of bahaviour, and then for the operation of a helping programme (based on vocational guidance tests). These interactions have been analysed, according to the scales of measurement in the model ana the results are presented in case study form in this thesis. At each stage of the project, results and conclusions were presented to the sponsoring organisation (e.g. industrial supervisor) in order to assess their (subjective) opinion of relevance to the organ­ isation. Finally, recommendations on further actions towards general improvement of the work relationships in the laboratory were presented in a brief report to the sponsor.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

Validation of the food allergy quality of life:parental burden questionnaire in the UK

Purpose - Food allergy can have a profound effect on quality of life (QoL) of the family. The Food Allergy Quality of Life—Parental Burden Questionnaire (FAQL-PB) was developed on a US sample to assess the QoL of parents with food allergic children. The aim of this study was to examine the reliability and validity of the FAQL-PB in a UK sample and to assess the effect of asking about parental burden in the last week compared with parental burden in general, with no time limit for recall given. Methods - A total of 1,200 parents who had at least one child with food allergy were sent the FAQL-PB and the Child Health Questionnaire (CHQ-PF50); of whom only 63 % responded. Results - Factor analysis of the FAQL-PB revealed two factors: limitations on life and emotional distress. The total scale and the two sub-scales had high internal reliability (all a > 0.85). There were small to moderate but significant correlations between total FAQL-PB scores and health and parental impact measures on the CHQ-PF50 (p < 0.01). Significantly greater parental burden was reported for the no-time limited compared with the time-limited version (p < 0.01). Conclusions - The FAQL-PB is a reliable and valid measure for use in the UK. The scale could be used in clinic to assess the physical and emotional quality of life in addition to the impact on total quality of life.

The study and measurements of the behaviour and characteristics of electromagnetic relays

The thesis presents a theoretical and practical study of the dynamic behaviour of electromagnetic relays. After discussing the problem of solving the dynamicc equations analytically and presenting a historical survey of the earlier works in the relay and its dynamics, the simulation of a relay on the analogue computer is discussed. It is shown that the simulation may be used to obtain specific solutions to the dynamic equations. The computer analysis provides the dynamic characteristics for design purposes and may be used in the study of bouncing, rebound oscillations and stability of the armature motion. An approximate analytical solution to the two dynamic equations is given based on the assumption that the dynamic variation of the pull with the position of the armature is linear. The assumption is supported by the Computer-aided analysis and experimental results. The solution is intended to provide a basis for a rational design. A rigorous method of analysing the dynamic performance by using Ahlberg's theory is also presented. This method may be justified to be the extension of Ahlberg's theory by taking the mass and frictional damping forces into account. While calculating the armature motion mathematically, Ahlberg considers the equilibrium of two kinds of forces, namely pull and load, and disregards the mass and friction forces, whereas the present method deals with the equilibrium of all four kinds of forces. It is shown how this can be utilised to calculate the dynamic characteristics for a specific design. The utility of this method also extends to the study of stability, contact bounce and armature rebound. The magnetic circuit and other related topics which are essential to the study of relay dynamics are discussed and some necessary experimental results are given.

Phytochemical mediated-modulation of the expression and transporter function of breast cancer resistance protein at the blood-brain barrier:an in-vitro study

Clinical translation of BCRP inhibitors have failed due to neurotoxicity and novel approaches are required to identify suitable modulators of BCRP to enhance CNS drug delivery. In this study we examine 18 compounds, primarily phytochemicals, as potential novel modulators of AhR-mediated regulation of BCRP expression and function in immortalised and primary porcine brain microvascular endothelial cells as a mechanism to enhance CNS drug delivery. The majority of modulators possessed a cellular viability IC50 > 100 µM in both cell systems. BCRP activity, when exposed to modulators for 1 hour, was diminished for most modulators through significant increases in H33342 accumulation at < 10 µM with 2,6,4-trimethoflavone increasing H33342 intracellular accumulation by 3.7–6.6 fold over 1–100 µM. Western blotting and qPCR identified two inducers of BCRP (quercetin and naringin) and two down-regulators (17-β-estradiol and curcumin) with associated changes in BCRP efflux transport function further confirmed in both cell lines. siRNA downregulation of AhR resulted in a 1.75 ± 0.08 fold change in BCRP expression, confirming the role of AhR in the regulation of BCRP. These findings establish the regulatory role AhR of in controlling BCRP expression at the BBB and confirm quercetin, naringin, 17-β-estradiol, and curcumin as novel inducers and down-regulators of BCRP gene, protein expression and functional transporter activity and hence potential novel target sites and candidates for enhancing CNS drug delivery.

A quantitative analysis of optic nerve axons in elderly control subjects and patients with Alzheimer's disease

Objective: To study the density and cross-sectional area of axons in the optic nerve in elderly control subjects and in cases of Alzheimer's disease (AD) using an image analysis system. Methods: Sections of optic nerves from control and AD patients were stained with toluidine blue to reveal axon profiles. Results: The density of axons was reduced in both the center and peripheral portions of the optic nerve in AD compared with control patients. Analysis of axons with different cross-sectional areas suggested a specific loss of the smaller sized axons in AD, i.e., those with areas less that 1.99 μm2. An analysis of axons >11 μm2 in cross-sectional area suggested no specific loss of the larger axons in this group of patients. Conclusions: The data suggest that image analysis provides an accurate and reproducible method of quantifying axons in the optic nerve. In addition, the data suggest that axons are lost throughout the optic nerve with a specific loss of the smaller-sized axons. Loss of the smaller axons may explain the deficits in color vision observed in a significant proportion of patients with AD.