Useful ideas for exploiting time to engineer representations

Commentary on target article "From simple associations to systematic reasoning: a connectionist representation of rules, variables, and dynamic bindings using temporal synchrony", by L. Shastri and V. Ajjangadde, pp. 417-494

Developing a complex intervention to reduce time to presentation with symptoms of lung cancer

Background - Lung cancer is the commonest cause of cancer in Scotland and is usually advanced at diagnosis. Median time between symptom onset and consultation is 14 weeks, so an intervention to prompt earlier presentation could support earlier diagnosis and enable curative treatment in more cases. Aim - To develop and optimise an intervention to reduce the time between onset and first consultation with symptoms that might indicate lung cancer. Design and setting - Iterative development of complex healthcare intervention according to the MRC Framework conducted in Northeast Scotland. Method - The study produced a complex intervention to promote early presentation of lung cancer symptoms. An expert multidisciplinary group developed the first draft of the intervention based on theory and existing evidence. This was refined following focus groups with health professionals and high-risk patients. Results - First draft intervention components included: information communicated persuasively, demonstrations of early consultation and its benefits, behaviour change techniques, and involvement of spouses/partners. Focus groups identified patient engagement, achieving behavioural change, and conflict at the patient–general practice interface as challenges and measures were incorporated to tackle these. Final intervention delivery included a detailed self-help manual and extended consultation with a trained research nurse at which specific action plans were devised. Conclusion -The study has developed an intervention that appeals to patients and health professionals and has theoretical potential for benefit. Now it requires evaluation.

Analytical techniques for the study of soft contact lens spoilation

Soft contact lens wear has become a common phenomenon in recent times. The contact lens when placed in the eye rapidly undergoes change. A film of biological material builds up on and in the lens matrix. The long term wear characteristics of the lens ultimately depend on this process. With time distinct structures made up of biological material have been found to build up on the lens. A fuller understanding of this process and how it relates to the lens chemistry could lead to contact lenses that are better tolerated by the eye. The tear film is a complex biological fluid, it is this fluid that bathes the lens during wear. It is reasonable to suppose that it is material derived from this source that accumulates on the lens. To understand this phenomenon it was decided to investigate the make up and conformation of the protein species that are found on and in the lens. As inter individual variations in tear fluid composition have been found it is important to be able to study the proteins on a single lens. Many of the analytical techniques used in bio research are not suitable for this study because of the lack of sensitivity. Work with poly acrylamide electrophoresis showed the possibility of analyzing the proteins extracted from a single lens. The development of a biotin avidin electro-blot and an enzyme linked aniibody electro-blot, lead to the high sensitivity detection and identification of the proteins present. The extraction of proteins from a lens is always incomplete. A method that analyses the proteins in situ would be a great advancement. Fourier transform infra red microscopy was developed to a point where a thin section of a contact lens could yield information about the proteins present and their conformation. The three dimensional structure of the gross macroscopic structures termed white spots was investigated using confocal laser microscopy.

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!).

Ocular motor triad with single vision contact lenses compared to spectacle lenses

Aim: Theoretically myopes are required to exert more accommodation and vergence when wearing single vision contact lenses compared to glasses and hypermetropes less. This study aims to quantify the effects clinically. Method: Thirty subjects (21 female, nine male, average age 21.0 ± 2.2 years) with a range of refractive errors (-7.87 D to +3.50 D) viewed in a random order, static targets at 0.1, 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 D accommodative demand that were matched for angular subtense. The subjects were fully corrected with spectacles and daily disposable contact lenses to their full prescription. Accommodation was monitored objectively with the PowerRefractor and Shin-Nippon SRW5000 and vergence and pupil size with the PowerRefractor. Results: Myopes exerted greater accommodative effort for viewing near targets with contact lenses than glasses and hypermetropes less (r2 = 0.35, p = 0.001 PowerRefractor). Myopes also exerted greater vergence effort for viewing near targets with contact lenses than glasses and hypermetropes less (r2 = 0.22, p < 0.01). Conclusion: Theoretical calculation of the accommodative and vergence requirements with glasses compared to contact lenses reflect clinical findings, although there is reasonable variability between individuals. © 2006 British Contact Lens Association.

Impact in contact lenses and the anterior eye:challenges prevailing in 2015

As we settle into a new year, this second issue of Contact Lens and Anterior Eye allows us to reflect on how new research in this field impacts our understanding, but more importantly, how we use this evidence basis to enhance our day to day practice, to educate the next generation of students and to construct the research studies to deepen our knowledge still further. The end of 2014 saw the publication of the UK governments Research Exercise Framework (REF) which ranks Universities in terms of their outputs (which includes their paper, publications and research income), environment (infrastructure and staff support) and for the first time impact (defined as “any effect on, change or benefit to the economy, society, culture, public policy or services, health, the environment or quality of life, beyond academia” [8]). The REF is a process of expert review, carried out in 36 subject-based units of assessment, of which our field is typically submitted to the Allied Health, Dentistry, Nursing and Pharmacy panel. Universities that offer Optometry did very well with Cardiff, Manchester and Aston in the top 10% out of the 94 Universities that submitted to this panel (Grade point Average ranked order). While the format of the new exercise (probably in 2010) to allocate the more than £2 billion of UK government research funds is yet to be determined, it is already rumoured that impact will contribute an even larger proportion to the weighting. Hence it is even more important to reflect on the impact of our research. In this issue, Elisseef and colleagues [5] examine the intriguing potential of modifying a lens surface to allow it to bind to known wetting agents (in this case hyaluronic acid) to enhance water retention. Such a technique has the capacity to reduced friction between the lens surface and the eyelids/ocular surface, presumably leading to higher comfort and less reason for patients to discontinue with lens wear. Several papers in this issue report on the validity of new high precision, fast scanning imaging and quantification equipment, utilising techniques such as Scheimpflug, partial coherence interferometry, aberrometry and video allowing detailed assessment of anterior chamber biometry, corneal topography, corneal biomechanics, peripheral refraction, ocular aberrations and lens fit. The challenge is how to use this advanced instrumentation which is becoming increasingly available to create real impact. Many challenges in contact lenses and the anterior eye still prevail in 2015 such as: -While contact lens and refractive surgery complications are relatively rare, they are still too often devastating to the individual and their quality of life (such as the impact and prognosis of patients with Acanthmoeba Keratitis reported by Jhanji and colleagues in this issue [7]). How can we detect those patients who are going to be affected and what modifications do we need to make to contact lenses and patient management prevent this occurring? -Drop out from contact lenses still occurs at a rapid rate and symptoms of dry eye seem to be the leading cause driving this discontinuation of wear [1] and [2]. What design, coating, material and lubricant release mechanism will make a step change in end of day comfort in particular? -Presbyopia is a major challenge to hassle free quality vision and is one of the first signs of ageing noticed by many people. As an emmetrope approaching presbyopia, I have a vested interest in new medical devices that will give me high quality vision at all distances when my arms won’t stretch any further. Perhaps a new definition of presbyopia could be when you start to orientate your smartphone in the landscape direction to gain the small increase in print size needed to read! Effective accommodating intraocular lenses that truly mimic the pre-presbyopic crystalline lenses are still a way off [3] and hence simultaneous images achieved through contact lenses, intraocular lenses or refractive surgery still have a secure future. However, splitting light reaching the retina and requiring the brain to supress blurred images will always be a compromise on contrast sensitivity and is liable to cause dysphotopsia; so how will new designs account for differences in a patient's task demands and own optical aberrations to allow focused patient selection, optimising satisfaction? -Drug delivery from contact lenses offers much in terms of compliance and quality of life for patients with chronic ocular conditions such as glaucoma, dry eye and perhaps in the future, dry age-related macular degeneration; but scientific proof-of-concept publications (see EIShaer et al. [6]) have not yet led to commercial products. Part of this is presumably the regulatory complexity of combining a medical device (the contact lens) and a pharmaceutical agent. Will 2015 be the year when this innovation finally becomes a reality for patients, bringing them an enhanced quality of life through their eye care practitioners and allowing researchers to further validate the use of pharmaceutical contact lenses and propose enhancements as the technology matures? -Last, but no means least is the field of myopia control, the topic of the first day of the BCLA's Conference in Liverpool, June 6–9th 2015. The epidemic of myopia is a blight, particularly in Asia, with significant concerns over sight threatening pathology resulting from the elongated eye. This is a field where real impact is already being realised through new soft contact lens optics, orthokeratology and low dose pharmaceuticals [4], but we still need to be able to better predict which technique will work best for an individual and to develop new techniques to retard myopia progression in those who don’t respond to current treatments, without increasing their risk of complications or the treatment impacting their quality of life So what will your New Year's resolution be to make 2015 a year of real impact, whether by advancing science or applying the findings published in journals such as Contact Lens and Anterior Eye to make a real difference to your patients’ lives?

Optical quality for keratoconic eyes with conventional RGP lens and simulated, customised contact lens corrections:a comparison

Purpose: To compare monochromatic aberrations of keratoconic eyes when uncorrected, corrected with spherically-powered RGP (rigid gas-permeable) contact lenses and corrected using simulations of customised soft contact lenses for different magnitudes of rotation (up to 15°) and translation (up to 1mm) from their ideal position. Methods: The ocular aberrations of examples of mild, moderate and severe keratoconic eyes were measured when uncorrected and when wearing their habitual RGP lenses. Residual aberrations and point-spread functions of each eye were simulated using an ideal, customised soft contact lens (designed to neutralise higher-order aberrations, HOA) were calculated as a function of the angle of rotation of the lens from its ideal orientation, and its horizontal and vertical translation. Results: In agreement with the results of other authors, the RGP lenses markedly reduced both lower-order aberrations and HOA for all three patients. When compared with the RGP lens corrections, the customised lens simulations only provided optical improvements if their movements were constrained within limits which appear to be difficult to achieve with current technologies. Conclusions: At the present time, customised contact lens corrections appear likely to offer, at best, only minor optical improvements over RGP lenses for patients with keratoconus. If made in soft materials, however, these lenses may be preferred by patients in term of comfort. © 2012 The College of Optometrists.

The significance of hand wash compliance on the transfer of dermal lipids in contact lens wear

Aim: The aim of this study was to assess the impact of hand washing regimes on lipid transference to contact lenses. The presence of lipids on contact lenses can affect visual acuity and enhance spoilation. Additionally, they may even mediate and foster microbial transfer and serve as a marker of potential dermal contamination. Methods and materials: A social hand wash and the Royal College of Nursing (RCN) hand wash were investigated. A 'no-wash regime' was used as control. The transfer of lipids from the hand was assessed by Thin Layer Chromatography (TLC). Lipid transference to the contact lenses was studied through fluorescence spectroscopy (FS). Results: Iodine staining, for presence of lipids, on TLC plates indicated the 'no-wash regime' score averaged at 3.4 ± 0.8, the social wash averaged at 2.2 ± 0.9 and the RCN averaged at 1.2 ± 0.3 on a scale of 1-4. The FS of lipids on contact lenses for 'no washing' presented an average of 28.47 ± 10.54 fluorescence units (FU), the social wash presented an average of 13.52 ± 11.12. FU and the RCN wash presented a much lower average 6.47 ± 4.26. FU. Conclusions: This work demonstrates how the method used for washing the hands can affect the concentration of lipids, and the transfer of these lipids onto contact lenses. A regime of hand washing for contact lens users should be standardised to help reduce potentially transferable species present on the hands. © 2011 British Contact Lens Association.

Environmental scanning electron microscopy offers real-time morphological analysis of liposomes and niosomes

Liposomes have been imaged using a plethora of techniques. However, few of these methods offer the ability to study these systems in their natural hydrated state without the requirement of drying, staining, and fixation of the vesicles. However, the ability to image a liposome in its hydrated state is the ideal scenario for visualization of these dynamic lipid structures and environmental scanning electron microscopy (ESEM), with its ability to image wet systems without prior sample preparation, offers potential advantages to the above methods. In our studies, we have used ESEM to not only investigate the morphology of liposomes and niosomes but also to dynamically follow the changes in structure of lipid films and liposome suspensions as water condenses on to or evaporates from the sample. In particular, changes in liposome morphology were studied using ESEM in real time to investigate the resistance of liposomes to coalescence during dehydration thereby providing an alternative assay of liposome formulation and stability. Based on this protocol, we have also studied niosome-based systems and cationic liposome/DNA complexes. Copyright © Informa Healthcare.

Ablative pyrolysis of biomass

The primary objectives of this work were to design, construct, test and operate a novel ablative pyrolysis reactor and product recovery system. Other key objectives included the development of an ablative pyrolysis reactor design methodology, mathematical modelling of the ablation process and measurement of empirical ablation rate data at 500°C. The constructed reactor utilised a rotating blade approach to achieve particle ablation in a 258mm internal diameter reactor. By fulfilling the key requirements of high relative motion and high contact pressure, pine wood particles of maximum size 6.35 mm were successfully ablated.Sixteen experiments were carried out: five initial commissioning experiments were used to test the rotating blade concept and to solve char separation problems. Mass balances were obtained for the other eleven experiments with good closures. Based on ablatively pyrolysed dry wood, a maximum organic liquid yield of 65.9 wt% was achieved with corresponding yields of 12.4 wt% char, 11.5 wt% water and 9.2 wt% non-condensable gas. Reactor throughputs of 2 kg/h dry ablated wood were achieved at 600°C. The theoretical ablative pyrolysis reactor design methodology was simplified and improved based upon empirical data derived from wood rod ablation experiments. Yields of chemicals were qualitatively similar to those of other fast pyrolysis processes.The product recovery system, comprising hot char removal, liquids collection in two ice-cooled condensers followed by gas filtration and drying, gave good mass balance closures. The most significant problem was char separation and removal from the reactor. This was solved by using a nitrogen blow line. In general, the reactor and product collection systems performed well.Future development of the reactor would involve modification of the reactor feed tube to allow the reactor residence time to be reduced and testing of the rotating blade approach with different blade angles, configurations and numbers of blades.

The ecology of percolating filters containing a plastic filter medium in relation to their efficiency in The treatment of domestic sewage

The suitability of a new plastic supporting medium for biofiltration was tested over a three year period. Tests were carried out on the stability, surface properties, mechanical strength, and dimensions of the medium. There was no evidence to suggest that the medium was deficient in any of these respects. The specific surface (320m2m-3) and the voidage (94%) of the new medium are unlike any other used in bio-filtration and a pilot plant containing two filters was built to observe its effects on ecology and performance. Performance was estimated by chemical analysis and ecology studied by film examination and fauna counts. A system of removable sampling baskets was designed to enable samples to be obtained from two intermediate depths of filter. One of the major operating problems of percolating filters is excessive accumulation of film. The amount of film is influenced by hydraulic and organic load and each filter was run at a different loading. One was operated at 1.2m3m-3day-1 (DOD load 0.24kgm-3day-1) judged at the time to be the lowest filtration rate to offer advantages over conventional media. The other filter was operated at more than twice this loading (2.4m3m-3day-lBOD load 0.55kgm-3day-1) giving a roughly 2.5x and 6x the conventional loadings recommended for a Royal Commission effluent. The amount of film in each filter was normally low (0.05-3kgm(3 as volatile solids) and did not affect efficiency. The evidence collected during the study indicated that the ecology of the filters was normal when compared with the data obtained from the literature relating to filters with mineral media. There were indications that full ecological stability was yet to be reached and this was affecting the efficiency of the filters. The lower rate filter produced an average 87% BOD removal giving a consistent Royal Commission effluent during the summer months. The higher rate filter produced a mean 83% BOD removal but at no stage a consistent Royal Commission effluent. From the data on ecology and performance the filters resembled conventional filters rather than high rate filters.

Time and professional work in public sector organisations: an examination of four occupational groups in education and medicine

The aim of this thesis is to examine the experience of time of four professional occupational groups working in public sector organisations and the factors affecting this experience. The literature on time and work is examined to delineate the key parameters of research in this area. A broad organisation behaviour approach to the experience of time and work is developed in which individual, occupational, organisational and socio-political factors are inter-related. The experience of secondary school teachers, further education lecturers, general medical practitioners and hosoital consultants is then examined. Multiple methods of data collection are used: open-ended interviews, a questionnaire survey and the analysis of key documents relating to the institutional settings in which the four groups work. The research aims to develop our knowledge of working time by considering the dimensions of the experience of time at work, the contexts in wlhich this experience is generated and the constraints these contexts give rIse to. By developing our understanding of time as a key feature of work experience we also extend our knowledge of organisation behaviour in general. In conclusion a model of the factors relating the experience of time to the negotiation of time at work is presented.

The metamorphic environments of the Strontian, Foyers and Dalbeattie intrusions, Scotland

Three metamorphic aureoles around intrusions of the Caledonian 'Newer Granite' suite are described. Each represents a different orogenic environment. The Strontian complex is intruded into sillimanite grade Moinian metasediments at the core of the orogen. The aureole comprises three zones; a transitional muscovite + sillimanite + K-feldspar zone, a sillimanite + K-feldspar zone and an inner cordierite + K-feldspar zone. Contact migmatization occurs in the inner part of the aureole. Zoning profiles from garnets in both regional and aureole assemblages show retrograde Mn-rich rims. Fe and Mg compositions are re-equilibrated to contact conditions. Apparent re-equilibration of Ca compositions results from increasingly ideal solid solution behaviour of Ca in plagioclase and garnet with increasing temperature. Temperatures of 690°C at 4.1 kbar (XH2O = 0.53) are estimated in the cordierite + K-feldspar zone, dropping to 630°C (XH2O = 0.69) at the sillimanite + K-feldspar isograd. The zones increase in width to the east, influenced by the regional thermal gradient at the time of intrusion. The timer-scale of the contact event, t2, relative to the regional, tl, - is estimated as t2/t1 = 101.1+ -0.7 and is consistent with Intrusion at an early stage of regional uplift and cooling. The Foyers complex intrudes Moinian rocks at a higher structural level. Regional assemblages range from garnet to sillimanite grade. Three contact zones are recognised; a sillimanite zone, a sillimanite + K-feldspar zone and an inner cordierite + K-feldspar zone. The limit of the aureole is marked by the breakdown of garnet which shows disequilibrium, both texturally, and in complex zoning profiles, within it. Temperatures of 660°C at 3.9 kbar (XH20 = 0.14) are estimated in the cordierite + K-feldspar zone? The Dalbeattie complex is at the margin of the orogen, intruded into low grade Silurian metasediments. Two zones are recognised; a biotite zone and an inner hornblende zone. Cordierite and diopside are present in the inner zone.

Dynamic ocular thermography

The ability to measure ocular surface temperature (OST) with thermal imaging offers potential insight into ocular physiology that has been acknowledged in the literature. The TH7102MX thermo-camera (NEC San-ei, Japan) continuously records dynamic information about OST without sacrificing spatial resolution. Using purpose-designed image analysis software, it was possible to select and quantify the principal components of absolute temperature values and the magnitude plus rate of temperature change that followed blinking. The techniques was examined for repeatability, reproducibility and the effects of extrinsic factors: a suitable experimental protocol was thus developed. The precise source of the measured thermal radiation has previously been subject toe dispute: in this thesis, the results of a study examining the relationships between physical parameters of the anterior eye and OST, confirmed a principal role for the tear film in OST. The dynamic changes in OST were studied in a large group of young subjects: quantifying the post-blink changes in temperature with time also established a role for tear flow dynamics in OST. Using dynamic thermography, the effects of hydrogel contact lens wear on OST were investigated: a model eye for in vivo work, and both neophyte and adapted contact lens wearers for in vivo studies. Significantly greater OST was observed in contact lens wearers, particularly with silicone hydrogel lenses compared to etafilcon A, and tended to be greatest when lenses had been worn continuously. This finding is important to understanding the ocular response to contact lens wear. In a group of normal subjects, dynamic thermography appeared to measure the ocular response to the application of artificial tear drops: this may prove to be a significant research and clinical tool.