Exploratory data analysis with non-linear and missing data in geochemistry

Exploratory analysis of data seeks to find common patterns to gain insights into the structure and distribution of the data. In geochemistry it is a valuable means to gain insights into the complicated processes making up a petroleum system. Typically linear visualisation methods like principal components analysis, linked plots, or brushing are used. These methods can not directly be employed when dealing with missing data and they struggle to capture global non-linear structures in the data, however they can do so locally. This thesis discusses a complementary approach based on a non-linear probabilistic model. The generative topographic mapping (GTM) enables the visualisation of the effects of very many variables on a single plot, which is able to incorporate more structure than a two dimensional principal components plot. The model can deal with uncertainty, missing data and allows for the exploration of the non-linear structure in the data. In this thesis a novel approach to initialise the GTM with arbitrary projections is developed. This makes it possible to combine GTM with algorithms like Isomap and fit complex non-linear structure like the Swiss-roll. Another novel extension is the incorporation of prior knowledge about the structure of the covariance matrix. This extension greatly enhances the modelling capabilities of the algorithm resulting in better fit to the data and better imputation capabilities for missing data. Additionally an extensive benchmark study of the missing data imputation capabilities of GTM is performed. Further a novel approach, based on missing data, will be introduced to benchmark the fit of probabilistic visualisation algorithms on unlabelled data. Finally the work is complemented by evaluating the algorithms on real-life datasets from geochemical projects.

Effect of contact surfaces on the thermal and photoxidation of dehydrated castor oil

The effect of stainless steel, glass, zirconium and titanium enamel surfaces on the thermal and photooxidative toughening mechanism of dehydrated castor oil films deposited on these surfaces was investigated using different analytical and spectroscopic methods. The conjugated and non-conjugated double bonds were identified and quantified using both Raman spectroscopy and 1D and 2D NMR spectroscopy. The disappearance of the double bonds in thermally oxidised oil-on-surface films was shown to be concomitant with the formation of hydroperoxides (determined by iodometric titration). The type of the surface had a major effect on the rate of thermal oxidation of the oil, but all of the surfaces examined had resulted in a significantly higher rate of oxidation compared to that of the neat oil. The highest effect was exhibited by the stainless steel surface followed by zirconium enamel, titanium enamel and glass. The rate of thermal oxidation of the oil-on-steel surface (at 100 °C, based on peroxide values) was more than five times faster than that of oil-on-glass and more than 21 times faster than the neat oil when compared under similar thermal oxidative conditions. The rate of photooxidation at 60 °C of oil-on-steel films was found to be about one and half times faster than their rate of thermal oxidation at the same temperature. Results from absorbance reflectance infrared microscopy with line scans taken across the depth of thermally oxidised oil-on-steel films suggest that the thermal oxidative toughening mechanism of the oil occurs by two different reaction pathways with the film outermost layers, i.e. furthest away from the steel surface, oxidising through a traditional free radical oxidation process involving the formation of various oxygenated products formed from the decomposition of allylic hydroperoxides, whereas, in the deeper layers closer to the steel surface, crosslinking reactions predominate.

Addressing missing data in geochemistry: a non-linear approach

Exploratory analysis of petroleum geochemical data seeks to find common patterns to help distinguish between different source rocks, oils and gases, and to explain their source, maturity and any intra-reservoir alteration. However, at the outset, one is typically faced with (a) a large matrix of samples, each with a range of molecular and isotopic properties, (b) a spatially and temporally unrepresentative sampling pattern, (c) noisy data and (d) often, a large number of missing values. This inhibits analysis using conventional statistical methods. Typically, visualisation methods like principal components analysis are used, but these methods are not easily able to deal with missing data nor can they capture non-linear structure in the data. One approach to discovering complex, non-linear structure in the data is through the use of linked plots, or brushing, while ignoring the missing data. In this paper we introduce a complementary approach based on a non-linear probabilistic model. Generative topographic mapping enables the visualisation of the effects of very many variables on a single plot, while also dealing with missing data. We show how using generative topographic mapping also provides an optimal method with which to replace missing values in two geochemical datasets, particularly where a large proportion of the data is missing.

Predicting success with silicone-hydrogel contact lenses in new wearers

Purpose: to evaluate changes in tear metrics and ocular signs induced by six months of silicone-hydrogel contact lens wear and the difference in baseline characteristics between those who successfully continued in contact lens wear compared to those that did not. Methods: Non-invasive Keratograph, Tearscope and fluorescein tear break-up times (TBUTs), tear meniscus height, bulbar and limbal hyperaemia, lid-parallel conjunctival folds (LIPCOF), phenol red thread, fluorescein and lissamine-green staining, and lid wiper epitheliopathy were measured on 60 new contact lens wearers fitted with monthly silicone-hydrogels (average age 36 ± 14 years, 40 females). Symptoms were evaluated by the Ocular Surface Disease Index (OSDI). After six months full time contact lens wear the above metrics were re-measured on those patients still in contact lens wear (n= 33). The initial measurements were also compared between the group still wearing lenses after six months and those who had ceased lens wear (n= 27). Results: There were significant changes in tear meniscus height (p= 0.031), bulbar hyperaemia (p= 0.011), fluorescein TBUT (p= 0.027), corneal (p= 0.007) and conjunctival (p= 0.009) staining, LIPCOF (p= 0.011) and lid wiper epitheliopathy (p= 0.002) after six months of silicone-hydrogel wear. Successful wearers had a higher non-invasive (17.0 ± 8.2. s vs 12.0 ± 5.6. s; p= 0.001) and fluorescein (10.7 ± 6.4. s vs 7.5 ± 4.7. s; p= 0.001) TBUT than drop-outs, although OSDI (cut-off 4.2) was also a strong predictor of success. Conclusion: Silicone-hydrogel lenses induced significant changes in the tear film and ocular surface as well as lid margin staining. Wettability of the ocular surface is the main factor affecting contact lens drop-out. © 2013 British Contact Lens Association.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

Specialist contact lens fitting

What is meant by the term ‘specialist contact lens fitting’? Or put another way, what would be considered non-specialist contact lens fitting? Is there such a thing as routine contact lens fitting? Soft or silicone hydrogel fitting for daily wear would probably be considered as routine contact lens fitting, but would extended or flexible wear remain in the same category or would they be considered a specialist fit? Different eras will classify different products as being ‘specialist’. Certainly twenty years ago soft toric contact lenses were considered as being speciality lenses but today would be thought of as routine lenses. Conversely, gas permeable lenses were thought of as mainstream twenty years ago but now are considered as speciality lenses. Although this would not be the same globally, as in some countries (such as Netherlands, France and Japan) gas permeable lens fitting remains popular and is not on the decline as in other countries (Canada, Australia and Sweden) [1]. Bandage soft lenses applied after surface laser refractive procedures would be considered as therapeutic lenses but in reality they are just plano thin hydrogel lenses worn constantly for 3–4 days to allow the underlying epithelium to convalesce and are then removed [2]. Some patients find that wearing hydrogel lenses during periods when they suffer from seasonal allergies actually improves their ocular comfort as the contact lens acts as a barrier to the allergen [3] and [4]. Scleral lenses have long been considered speciality lenses, apart from a time when they were the only lenses available but at that time all contact lens work would have been considered speciality practice! Nowadays we see the advent of mini-scleral designs and we see large diameter gas permeable lenses too. It is possible that these lenses increase the popularity of gas permeable lenses again and they become more main stream. So it would seem that the lines between routine and speciality contact lens fitting are not clear. Whether a lens is classed a specialist fit or not would depend on the lens type, why it was fitted, where in the world the fitting was being done and even the era in which it was fitted. This begs the question as to what would be considered entry level knowledge in contact lens fitting. This may not be an issue for most BCLA members or CLAE readers but certainly would be for bodies such as the College of Optometrists (UK) or the Association of British Dispensing Opticians when they are planning the final registration examinations for budding practitioners or when planning the level of higher level qualifications such as College Certificates or Diplomas. Similarly for training institutions when they are planning their course content. This becomes even trickier when trying to devise a qualification that spans across many countries, like the European Diploma in Optometry and Optics. How do we know if the training and examination level is correct? One way would be to analyse things when they go wrong and if patterns of malpractice are seen then maybe that could be used as an indicator to more training being needed. There were 162 Fitness to Practice Hearing at the General Optical Council between 2001 and 2010. Forty-seven of these were clinically related case, 39 fraud related, and 76 others. Of the clinical ones only 3 were contact lens related. So it would appear that as whole, in the profession, contact lens clinical skills are not being questioned too often (although it seems a few of us can’t keep our hands out the cookie jar!).

The Aston Medication Adherence Study:mapping the adherence patterns of an inner-city population

Background: The Aston Medication Adherence Study was designed to examine non-adherence to prescribed medicines within an inner-city population using general practice (GP) prescribing data. Objective: To examine non-adherence patterns to prescribed oralmedications within three chronic disease states and to compare differences in adherence levels between various patient groups to assist the routine identification of low adherence amongst patients within the Heart of Birmingham teaching Primary Care Trust (HoBtPCT). Setting: Patients within the area covered by HoBtPCT (England) prescribed medication for dyslipidaemia, type-2 diabetes and hypothyroidism, between 2000 and 2010 inclusively. HoBtPCT's population was disproportionately young,with seventy per cent of residents fromBlack and Minority Ethnic groups. Method: Systematic computational analysis of all medication issue data from 76 GP surgeries dichotomised patients into two groups (adherent and non-adherent) for each pharmacotherapeutic agent within the treatment groups. Dichotomised groupings were further analysed by recorded patient demographics to identify predictors of lower adherence levels. Results were compared to an analysis of a self-reportmeasure of adherence [using the Modified Morisky Scale© (MMAS-8)] and clinical value data (cholesterol values) from GP surgery records. Main outcome: Adherence levels for different patient demographics, for patients within specific longterm treatment groups. Results: Analysis within all three groups showed that for patients with the following characteristics, adherence levels were statistically lower than for others; patients: younger than 60 years of age; whose religion is coded as "Islam"; whose ethnicity is coded as one of the Asian groupings or as "Caribbean", "Other Black" and "African"; whose primary language is coded as "Urdu" or "Bengali"; and whose postcodes indicate that they live within the most socioeconomically deprived areas of HoBtPCT. Statistically significant correlations between adherence status and results from the selfreport measure of adherence and of clinical value data analysis were found. Conclusion: Using data fromGP prescribing systems, a computerised tool to calculate individual adherence levels for oral pharmacotherapy for the treatment of diabetes, dyslipidaemia and hypothyroidism has been developed.The tool has been used to establish nonadherence levels within the three treatment groups and the demographic characteristics indicative of lower adherence levels, which in turn will enable the targeting of interventional support within HoBtPCT. © Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2013.

A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis

Allergic eye disease encompasses a group of hypersensitivity disorders which primarily affect the conjunctiva and its prevalence is increasing. It is estimated to affect 8% of patients attending optometric practice but is poorly managed and rarely involves ophthalmic assessment. Seasonal allergic conjunctivitis (SAC) is the most common form of allergic eye disease (90%), followed by perennial allergic conjunctivitis (PAC; 5%). Both are type 1 IgE mediated hypersensitivity reactions where mast cells play an important role in pathophysiology. The signs and symptoms are similar but SAC occurs periodically whereas PAC occurs year round. Despite being a relatively mild condition, the effects on the quality of life can be profound and therefore they demand attention. Primary management of SAC and PAC involves avoidance strategies depending on the responsible allergen(s) to prevent the hypersensitivity reaction. Cooled tear supplements and cold compresses may help bring relief. Pharmacological agents may become necessary as it is not possible to completely avoid the allergen(s). There are a wide range of anti-allergic medications available, such as mast cell stabilisers, antihistamines and dual-action agents. Severe cases refractory to conventional treatment require anti-inflammatories, immunomodulators or immunotherapy. Additional qualifications are required to gain access to these medications, but entry-level optometrists must offer advice and supportive therapy. Based on current evidence, the efficacy of anti-allergic medications appears equivocal so prescribing should relate to patient preference, dosing and cost. More studies with standardised methodologies are necessary elicit the most effective anti-allergic medications but those with dual-actions are likely to be first line agents. © 2011 British Contact Lens Association.

Clinical performance of daily disposable soft contact lenses using sustained release technology

Purpose: Polyvinyl alcohol (PVA) is a successful tear film stabiliser and is widely used in comfort drops and some soft contact lens materials. A PVA-containing lens, nelfilcon A has been modified to include additional (non-functional) PVA in order to provide improved comfort. This study aims to examine the clinical performance of this nelfilcon A lens with AquaRelease™ (AquaRelease). Methods: Two contralateral, investigator masked, open label, subjective and objective evaluations were conducted. The first examined the effect of adding increased molecular weight PVA to nelfilcon A (n = 5), and the second compared this AquaRelease lens to ocufilcon B (n = 34). The principal measures were non-invasive break-up time (NIBUT) and subjective comfort, which were assessed at the beginning and end of a week of daily wear, and three times throughout 1 day at 8, 12 and 16 h. Results: All subjects successfully completed the daily wearing schedule of 16 h. On initial insertion, subjective comfort and NIBUT improved for AquaRelease than original nelfilcon A lenses (p < 0.05). Initial comfort was better for AquaRelease compared to ocufilcon B lenses (p = 0.01); however, NIBUT was not statistically different (11.7 ± 15.6 s versus 8.4 ± 6.8 s; p = 0.26). Subjective comfort decreased with time (p < 0.001), but there was no significant difference between AquaRelease and ocufilcon B lenses (p = 0.16). NIBUT was not significantly affected by time (p = 0.56) or between lenses (p = 0.33). At the end of a weeks' wear, subjective initial, end-of-day, overall comfort and vision were rated significantly better with AquaRelease than ocufilcon B (p < 0.01). Conclusions: Release of additional non-functionalised PVA from the nelfilcon A lenses appears to enhance comfortable contact lens wear. © 2006 British Contact Lens Association.

Customer loyalty among daily disposable contact lens wearers

Background: Optometric practices offer contact lenses as cash sale items or as part of monthly payment plans. With the contact lens market becoming increasingly competitive, patients are opting to purchase lenses from supermarkets and Internet suppliers. Monthly payment plans are often implemented to improve loyalty. This study aimed to compare behavioural loyalty between monthly payment plan members and non-members. Methods: BBR Optometry Ltd offers a monthly payment plan (Eyelife™) to their contact lens wearers. A retrospective audit of 38 Eyelife™ members (mean. ±. SD: 42.7. ±. 15.0 years) and 30 non-members (mean. ±. SD: 40.8. ±. 16.7 years) was conducted. Revenue and profits generated, service uptake and product sales between the two groups were compared over a fixed period of 18 months. Results: Eyelife™ members generated significantly higher professional fee revenue ( P<. 0.001), £153.96 compared to £83.50, and profits ( P<. 0.001). Eyelife™ members had a higher uptake of eye examinations ( P<. 0.001). The 2 groups demonstrated no significant difference in spectacle sales by volume ( P= 0.790) or value ( P= 0.369). There were also no significant differences in contact lens revenue ( P= 0.337), although Eyelife™ members did receive a discount. The Eyelife™ group incurred higher contact lens costs ( P= 0.037), due to a greater volume of contact lens purchases, 986 units compared to 582. Conclusions: Monthly payment plans improve loyalty among contact lens wearers, particularly service uptake and volume of lens purchases. Additionally the greater professional fees generated, render monthly payment plans an attractive business model and practice builder.

The influence of end of day silicone hydrogel daily disposable contact lens fit on ocular comfort, physiology and lens wettability

Purpose: To quantify the end-of-day silicone-hydrogel daily disposable contact lens fit and its influence of on ocular comfort, physiology and lens wettability. Methods: Thirty-nine subjects (22.1. ±. 3.5 years) were randomised to wear each of 3 silicone-hydrogel daily-disposable contact lenses (narafilcon A, delefilcon A and filcon II 3), bilaterally, for one week. Lens fit was assessed objectively using a digital video slit-lamp at 8, 12 and 16. h after lens insertion. Hyperaemia, non-invasive tear break-up time, tear meniscus height and comfort were also evaluated at these timepoints, while corneal and conjunctival staining were assessed on lens removal. Results: Lens fit assessments were not different between brands (P > 0.05), with the exception of the movement at blink where narafilcon A was more mobile. Overall, lag reduced but push-up speed increased from 8 to 12. h (P <. 0.05), but remained stable from 12 to 16. h (P > 0.05). Movement-on-blink was unaffected by wear-time (F = 0.403, P = 0.670). A more mobile lens fit with one brand did not indicate that person would have a more mobile fit with another brand (r = -0.06 to 0.63). Lens fit was not correlated with comfort, ocular physiology or lens wettability (P > 0.01). Conclusions: Among the lenses tested, objective lens fit changed between 8. h and 12. h of lens wear. The weak correlation in individual lens fit between brands indicates that fit is dependent on more than ocular shape. Consequently, substitution of a different lens brand with similar parameters will not necessarily provide comparable lens fit.

Diabetes and contact lens wear

The literature suggests that diabetic patients may have altered tear chemistry and tear secretion as well as structural and functional changes to the corneal epithelium, endothelium and nerves. These factors, together with a reported increased incidence of corneal infection, suggest that diabetic patients may be particularly susceptible to developing ocular complications during contact lens wear. Reports of contact lens-induced complications in diabetic patients do exist, although a number of these reports concern patients with advanced diabetic eye disease using lenses on an extended wear basis. Over the past decade or so, there have been published studies documenting the response of the diabetic eye to more modern contact lens modalities. The results of these studies suggest that contact lenses can be a viable mode of refractive correction for diabetic patients. Furthermore, new research suggests that the measurement of tear glucose concentration could, in future, be used to monitor metabolic control non-invasively in diabetic patients. This could be carried out using contact lenses manufactured from hydrogel polymers embedded with glucose-sensing agents or nanoscale digital electronic technology. The purpose of this paper is to review the literature on the anterior ocular manifestations of diabetes, particularly that pertaining to contact lens wear. © 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

Mapping and Merging of Anatomical Ontologies

This article presents the principal results of the Ph.D. thesis Intelligent systems in bioinformatics: mapping and merging anatomical ontologies by Peter Petrov, successfully defended at the St. Kliment Ohridski University of Sofia, Faculty of Mathematics and Informatics, Department of Information Technologies, on 26 April 2013.

Fitting an MSD (Mini Scleral Design) rigid contact lens in advanced keratoconus with INTACS

Keratoconus is a bilateral degenerative disease characterized by a non-inflammatory, progressive central corneal ectasia (typically asymmetric) and decreased vision. In its early stages it may be managed with spectacles and soft contact lenses but more commonly it is managed with rigid contact lenses. In advanced stages, when contact lenses can no longer be fit, have become intolerable, or corneal damage is severe, a penetrating keratoplasty is commonly performed. Alternative surgical techniques, such as the use of intra-stromal corneal ring segments (INTACS) have been developed to try and improve the fit of rigid contact lenses in keratoconic patients and avoid penetrating keratoplasties. This case report follows through the fitting of rigid contact lenses in an advanced keratoconic cornea after an INTACS procedure and discusses clinical findings, treatment options, and the use of mini-scleral and scleral lens designs as they relate to the challenges encountered in managing such a patient. Mini-scleral and scleral lenses are relatively easy to fit, and can be of benefit to many patients, including advanced keratoconic patients, post-INTAC patients and post-penetrating keratoplasty patients. © 2011 British Contact Lens Association.

Investigating the utility of clinical assessments to predict success with presbyopic contact lens correction

PURPOSE: To determine the utility of a range of clinical and non-clinical indicators to aid the initial selection of the optimum presbyopic contact lens. In addition, to assess whether lens preference was influenced by the visual performance compared to the other designs trialled (intra-subject) or compared to participants who preferred other designs (inter-subject). METHODS: A double-masked randomised crossover trial of Air Optix Aqua multifocal, PureVision 2 for Presbyopia, Acuvue OASYS for Presbyopia, Biofinity multifocal and monovision was conducted on 35 presbyopes (54.3±6.2years). Participant lifestyle, personality, pupil characteristics and aberrometry were assessed prior to lens fitting. After 4 weeks of wear, high and low contrast visual acuity (VA) under photopic and mesopic conditions, reading speed, Near Activity Visual Questionnaire (NAVQ) rating, subjective quality-of-vision scoring, defocus curves, stereopsis, halometry, aberrometry and ocular physiology were quantified. RESULTS: After trialling all the lenses, preference was mixed (n=12 Biofinity, n=10 monovision, n=7 Purevision, n=4 Air Optix Aqua, n=2 Oasys). Lens preference was not dependent on personality (F=1.182, p=0.323) or the hours spent working at near (p=0.535) or intermediate (p=0.759) distances. No intersubject or strong intrasubject relationships emerged between lens preference and reading speed, NAVQ rating, halo size, aberrometry or ocular physiology (p>0.05). CONCLUSIONS: Participant lifestyle and personality, ocular optics, contact lens visual performance and ocular physiology provided poor indicators of the preferred lens type after 4 weeks of wear. This is confounded by the wide range of task visual demands of presbyopes and the limited optical differences between current multifocal contact lens designs.