Evaluation of modern intraocular lenses

Accommodating Intraocular Lenses (IOLs), multifocal IOLs (MIOLs) and toric IOLs are designed to provide a greater level of spectacle independency post cataract surgery. All of these IOLs are reliant on the accurate calculation of intraocular lens power determined through reliable ocular biometry. A standardised defocus area metric and reading performance index metric were devised for the evaluation of the range of focus and the reading ability of subjects implanted with presbyopic correcting IOLs. The range of clear vision after implantation of an MIOL is extended by a second focal point; however, this results in the prevalence of dysphotopsia. A bespoke halometer was designed and validated to assess this photopic phenomenon. There is a lack of standardisation in the methods used for determining IOL orientation and thus rotation. A repeatable, objective method was developed to allow the accurate assessment of IOL rotation, which was used to determine the rotational and positional stability of a closed loop haptic IOL. A new commercially available biometry device was validated for use with subjects prior to cataract surgery. The optical low coherence reflectometry instrument proved to be a valid method for assessing ocular biometry and covered a wider range of ocular parameters in comparison with previous instruments. The advantages of MIOLs were shown to include an extended range of clear vision translating into greater reading ability. However, an increased prevalence of dysphotopsia was shown with a bespoke halometer, which was dependent on the MIOL optic design. Implantation of a single optic accommodating IOL did not improve reading ability but achieved high subjective ratings of near vision. The closed-loop haptic IOL displayed excellent rotational stability in the late period but relatively poor rotational stability in the early period post implantation. The orientation error was compounded by the high frequency of positional misalignment leading to an extensive overall misalignment of the IOL. This thesis demonstrates the functionality of new IOL lens designs and the importance of standardised testing methods, thus providing a greater understanding of the consequences of implanting these IOLs. Consequently, the findings of the thesis will influence future designs of IOLs and testing methods.

HbA1c - changing units

Measurement of glycated haemoglobin A (HbA) provides an indication of longer-term glycaemic control. Standardisation of this test between laboratories is difficult to achieve, and most assays are currently calibrated to the values used in the Diabetes Control and Complications Trial (DCCT-aligned). With the availability of more specific reference standards it is now proposed that HbA is expressed as mmol HbA per mol of non-glycated haemoglobin. An HbA of 7% is approximately equal to 53 mmol/mol.

The formulation of artificial reference standards for use within the ELISPOT assay

Whether to assess the functionality of equipment or as a determinate for the accuracy of assays, reference standards are essential for the purposes of standardisation and validation. The ELISPOT assay, developed over thirty years ago, has emerged as a leading immunological assay in the development of novel vaccines for the assessment of efficacy. However, with its widespread use, there is a growing demand for a greater level of standardisation across different laboratories. One of the major difficulties in achieving this goal has been the lack of definitive reference standards. This is partly due to the ex vivo nature of the assay, which relies on cells being placed directly into the wells. Thus, the aim of this thesis was to produce an artificial reference standard using liposomes, for use within the assay. Liposomes are spherical bilayer vesicles with an enclosed aqueous compartment and therefore are models for biological membranes. Initial work examined pre-design considerations in order to produce an optimal formulation that would closely mimic the action of the cells ordinarily placed on the assay. Recognition of the structural differences between liposomes and cells led to the formulation of liposomes with increased density. This was achieved by using a synthesised cholesterol analogue. By incorporating this cholesterol analogue in liposomes, increased sedimentation rates were observed within the first few hours. The optimal liposome formulation from these studies was composed of 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and brominated cholesterol (Brchol) at a 16:4:12 µMol ratio, based on a significantly higher (p<0.01) sedimentation (as determined by a percentage transmission of 59 ± 5.9 % compared to the control formulation at 29 ± 12 % after four hours). By considering a range of liposome formulations ‘proof of principle’ for using liposomes as ELISPOT reference standards was shown; recombinant IFN? cytokine was successfully entrapped within vesicles of different lipid compositions, which were able to promote spot formation within the ELISPOT assay. Using optimised liposome formulations composed of phosphatidylcholine with or without cholesterol (16 µMol total lipid) further development was undertaken to produce an optimised, scalable protocol for the production of liposomes as reference standards. A linear increase in spot number by the manipulation of cytokine concentration and/or lipid concentrations was not possible, potentially due to the saturation that occurred within the base of wells. Investigations into storage of the formulations demonstrated the feasibility of freezing and lyophilisation with disaccharide cryoprotectants, but also highlighted the need for further protocol optimisation to achieve a robust reference standard upon storage. Finally, the transfer of small-scale production to a medium lab-scale batch (40 mL) demonstrated this was feasible within the laboratory using the optimised protocol.

Retinal vessel analysis:flicker reproducibility, methodological standardisations and practical limitations

The Retinal Vessel Analyser (RVA) is a commercially available ophthalmoscopic instrument capable of acquiring vessel diameter fluctuations in real time and in high temporal resolution. Visual stimulation by means of flickering light is a unique exploration tool of neurovascular coupling in the human retina. Vessel reactivity as mediated by local vascular endothelial vasodilators and vasoconstrictors can be assessed non-invasively, in vivo. In brief, the work in this thesis • deals with interobserver and intraobserver reproducibility of the flicker responses in healthy volunteers • explains the superiority of individually analysed reactivity parameters over vendorgenerated output • links in static retinal measures with dynamic ones • highlights practical limitations in the use of the RVA that may undermine its clinical usefulness • provides recommendations for standardising measurements in terms of vessel location and vessel segment length and • presents three case reports of essential hypertensives in a -year follow-up. Strict standardisation of measurement procedures is a necessity when utilising the RVA system. Agreement between research groups on implemented protocols needs to be met, before it could be considered a clinically useful tool in detecting or predicting microvascular dysfunction.

Defining an OWL ontology that could be used to integrate mental-health risk information within a decision support system

In the field of mental health risk assessment, there is no standardisation between the data used in different systems. As a first step towards the possible interchange of data between assessment tools, an ontology has been constructed for a particular one, GRiST (Galatean Risk Screening Tool). We briefly introduce GRiST and its data structures, then describe the ontology and the benefits that have already been realised from the construction process. For example, the ontology has been used to check the consistency of the various trees used in the model. We then consider potential uses in integration of data from other sources. © 2009 IEEE.

Translation practices in political institutions:a comparison of national, supranational, and non-governmental organisations

This article explores the settings and practices of translation at three types of political institutions, i.e. national, supranational, and non-governmental organisations. The three institutions are the translation service of the German Foreign Office, the translation department of the European Central Bank, and translation provision by the non-governmental organisation Amnesty International. The three case studies describe the specific translation practices in place at these institutions and illustrate some characteristic translation strategies. In this way, we reflect on how different translation practices can impact on translation agency and how these practices in turn are influenced by the type of institution and its organisational structure. The article also aims to explore to which extent the characteristics of collectivity, anonymity and standardisation, and of institutional translation as self-translation are applicable to the institutions under discussion.

Validation of protein carbonyl measurement:a multi-centre study

Protein carbonyls are widely analysed as a measure of protein oxidation. Several different methods exist for their determination. A previous study had described orders of magnitude variance that existed when protein carbonyls were analysed in a single laboratory by ELISA using different commercial kits. We have further explored the potential causes of variance in carbonyl analysis in a ring study. A soluble protein fraction was prepared from rat liver and exposed to 0, 5 and 15 min of UV irradiation. Lyophilised preparations were distributed to six different laboratories that routinely undertook protein carbonyl analysis across Europe. ELISA and Western blotting techniques detected an increase in protein carbonyl formation between 0 and 5 min of UV irradiation irrespective of method used. After irradiation for 15 min, less oxidation was detected by half of the laboratories than after 5 min irradiation. Three of the four ELISA carbonyl results fell within 95% confidence intervals. Likely errors in calculating absolute carbonyl values may be attributed to differences in standardisation. Out of up to 88 proteins identified as containing carbonyl groups after tryptic cleavage of irradiated and control liver proteins, only seven were common in all three liver preparations. Lysine and arginine residues modified by carbonyls are likely to be resistant to tryptic proteolysis. Use of a cocktail of proteases may increase the recovery of oxidised peptides. In conclusion, standardisation is critical for carbonyl analysis and heavily oxidised proteins may not be effectively analysed by any existing technique.

Floatingline estimation in FHR signal analysis

Cardiotocography provides significant information on foetal oxygenation linked to characteristics of foetal heart rate signals. Among most important we can mention foetal heart rate variability, whose spectral analysis is recognised like useful in improving diagnosis of pathologic conditions. However, despite its importance, a standardisation of definition and estimation of foetal heart rate variability is still searched. Some guidelines state that variability refers to fluctuations in the baseline free from accelerations and decelerations. This is an important limit in clinical routine since variability in correspondence of these FHR alterations has always been regarded as particularly significant in terms of prognostic value. In this work we compute foetal heart rate variability as difference between foetal heart rate and floatingline and we propose a method for extraction of floatingline which takes into account accelerations and decelerations. © 2011 Springer-Verlag Berlin Heidelberg.

GPs' perspectives on managing the NHS Health Check in primary care:a qualitative evaluation of implementation in one area of England

OBJECTIVES: To evaluate the implementation of the National Health Service (NHS) Health Check programme in one area of England from the perspective of general practitioners (GPs). DESIGN: A qualitative exploratory study was conducted with GPs and other healthcare professionals involved in delivering the NHS Health Check and with patients. This paper reports the experience of GPs and focuses on the management of the Heath Check programme in primary care. SETTING: Primary care surgeries in the Heart of Birmingham region (now under the auspices of the Birmingham Cross City Clinical Commissioning Group) were invited to take part in the larger scale evaluation. This study focuses on a subset of those surgeries whose GPs were willing to participate. PARTICIPANTS: 9 GPs from different practices volunteered. GPs served an ethnically diverse region with areas of socioeconomic deprivation. Ethnicities of participant GPs included South Asian, South Asian British, white, black British and Chinese. METHODS: Individual semistructured interviews were conducted with GPs face to face or via telephone. Thematic analysis was used to analyse verbatim transcripts. RESULTS: Themes were generated which represent GPs' experiences of managing the NHS Health Check: primary care as a commercial enterprise; 'buy in' to concordance in preventive healthcare; following protocol and support provision. These themes represent the key issues raised by GPs. They reveal variability in the implementation of NHS Health Checks. GPs also need support in allocating resources to the Health Check including training on how to conduct checks in a concordant (or collaborative) way. CONCLUSIONS: The variability observed in this small-scale evaluation corroborates existing findings suggesting a need for more standardisation. Further large-scale research is needed to determine how that could be achieved. Work needs to be done to further develop a concordant approach to lifestyle advice which involves tailored individual goal setting rather than a paternalistic advice-giving model.

Evaluation of low vision services on the quality of life of individuals with age-related macular degeneration

Background: Age-related macular degeneration (ARMD) is a major cause of irreversible visual loss in the elderly and a significant threat to their quality of life. Although low vision services often improve the functional outcomes of individuals with macular disease, it remains unclear whether or not they have any impact on quality of life. The principal aim of this study was to determine the effect of a hospital-based low vision clinic on the quality of life of individuals with ARMD. Methods: Forty patients with ARMD attended the low vision clinic at Milton Keynes University Hospital. Quality of life was measured with the vision-specific Low Vision Quality of Life (LVQOL) questionnaire and the general health EuroQol (EQ-5D-5L) questionnaire. Measures were completed at baseline (time zero, T0), and at three- (T3) and six-month (T6) follow-up visits. Results: The near visual acuity of individuals attending the low vision clinic for the first time improved significantly between visits T0 and T3 (p=0.005), reflecting the practiced use of their newly-dispensed low vision aids. As expected, there was no significant change in near acuity over this time period for existing patients. For both new and existing patients, a significant increase in LVQOL score was evident between visits T0 and T3, with a further significant improvement between T3 and T6. Similarly, there was a significant decrease in EQ-5D-5L questionnaire scores between visits T0 and T6. Conclusions: The higher LVQOL scores obtained at the end of the study period (T6) provide evidence that low vision services at Milton Keynes University Hospital served to improve patient quality of life. The reduction in EQ-5D-5L scores over the same time period suggests that low vision services also provide for an improvement in general health-related quality of life. Impact: The findings support the cause of low vision services to improve not only the vision and functional outcomes of individuals with macular disease but also their quality of life. Moreover, the findings suggest that a more efficient allocation of resources at low vision clinics may be possible through the standardisation of patient follow-up frequency.