Autonomic, biometric and oculomotor correlates of myopia in young adults

The principal work reported in this thesis is the examination of autonomic profile of ciliary muscle innervation as a risk factor in myopia development. Deficiency in sympathetic inhibitory control of accommodation has been proposed as a contributory factor in the development of late onset myopia (LOM). Complementary measurements of ocular biometry, oculomotor function and dynamic accommodation response were carried out on the same subject cohort, thus allowing cross-correlation of these factors with. autonomic profile. Subjects were undergraduate and postgraduate students of Aston University. A 2.5 year longitudinal study of refractive error progression in 40 subjects revealed the onset of LOM in 10, initially emmetropic, young adult subjects (age range 18-24 years) undertaking substantial amounts of near work. A controlled, double blind experimental protocol was conducted concurrently to measure post-task open-loop accommodative regression following distance (0 D) or near (3 D above baseline tonic accommodation) closed-loop tasks of short (10 second) or long (3 minute) duration. Closed-loop tasks consisted of observation of a high contrast Maltese cross target; open-loop conditions were imposed by observation of a 0.2 c/deg Difference of Gaussian target. Accommodation responses were recorded continuously at 42 Hz using a modified Shin-Nippon SRW-5000 open-view infra-red optometer. Blockade of the sympathetic branch of accommodative control was achieved by topical instillation of the non-selective b-adrenoceptor antagonist timolol maleate. Betaxolol hydrochloride (non-selective b1-adrenoceptor antagonist) and normal saline were employed as control agents. Retarded open-loop accommodative regression under b2 blockade following the 3 minute near task indicated the presence of sympathetic facility. Sympathetic inhibitory facility in accommodation control was found in similar proportions between LOM and stable emmetropic subjects. A cross-sectional study (N=60) of autonomic profile showed that sympathetic innervation of ciliary muscle is present in similar proportions between emmetropes, early-, and late-onset myopes. Sympathetic facility was identified in 27% of emmetropes, 21% of EOMs and 29% of LOMs.

Sympathetic innervation of ciliary muscle and oculomotor function in emmetropic and myopic young adults

Purpose: Evidence exists for an additional inhibitory accommodative control system mediated by the sympathetic branch of the autonomic nervous system (ANS). This work aims to show the relative prevalence of sympathetic inhibition in young emmetropic and myopic adults, and to evaluate the effect of sympathetic facility on accommodative and oculomotor function. Methods: Profiling of ciliary muscle innervation was carried out in 58 young adult subjects (30 emmetropes, 14 early onset myopes, 14 late onset myopes) by examining post-task open-loop accommodation responses, recorded continuously by a modified open-view infrared optometer. Measurements of amplitude of accommodation, tonic accommodation, accommodative lag at near, AC/A ratio, and heterophoria at distance and near were made to establish a profile of oculomotor function. Results: Evidence of sympathetic inhibitory facility in ciliary smooth muscle was observed in 27% of emmetropes, 21% of early-onset myopes and 29% of late-onset myopes. Twenty-six percent of all subjects demonstrated access to sympathetic facility. Closed-loop oculomotor function did not differ significantly between subjects with sympathetic facility, and those with sympathetic deficit. Conclusions: Emmetropic and myopic groups cannot be distinguished in terms of the relative proportions having access to sympathetic inhibition. Presence of sympathetic innervation does not have a significant effect on accommodative function under closed-loop viewing conditions. © 2005 Elsevier Ltd. All rights reserved.

Autonomic correlates of ocular accommodation and cardiovascular function

PURPOSE: To evaluate the hypothesis that objective measures of open- and closed-loop ocular accommodation are related to systemic cardiovascular function, and ipso facto autonomic nervous system activity. METHODS: Sixty subjects (29 male; 31 female) varying in age from 18 to 33 years (average: 20.3 +/- 2.9 years) with a range of refractive errors [mean spherical equivalent (MSE): -7.12 to +1.82 D] participated in the study. Five 20-s continuous objective recordings of the accommodative response, measured with an open-view IR autorefractor (Shin-Nippon SRW-5000), were obtained for a variety of open- and closed-loop accommodative demands while simultaneous continuous measurement of heart rate was recorded with a finger-mounted piezo-electric pulse transducer for 5 min. Fast Fourier Transformation of cardiovascular function allowed the absolute and relative power of the autonomic components to be assessed in the frequency-domain, whereas heart period gave an indication of the time-domain response. RESULTS: Increasing closed-loop accommodative demand led to a concurrent increase in heart rate of approximately 2 beats/min for a 4.0 D increase in accommodative demand. The increase was attributable to a reduction in the absolute (p < 0.05) and normalised (p < 0.001) input of the systemic parasympathetic nervous system, and was unaffected by refractive group. The interaction with refractive group failed to reach significance. CONCLUSIONS: For sustained accommodation effort, the data demonstrate covariation between the oculomotor and cardiovascular systems which implies that a near visual task can significantly influence cardiovascular behaviour. Accommodative effort alone, however, is not a sufficient stimulus to induce autonomic differences between refractive groups. The data suggest that both the oculomotor and cardiovascular systems are predominantly attributable to changes in the systemic parasympathetic nervous system.

Intermediate pyrolysis:a sustainable biomass-to-energy concept-biothermal valorisation of biomass (BtVB) process

Wastewater treatment coupled with energy crop cultivation provides an attractive source of cheap feedstock. This study reviews an advanced, closed-loop bioenergy conversion process [biothermal valorisation of biomass (BtVB)], in which pyroformer is coupled to a gasifier. BtVB process was developed at European Bioenergy Research Institute (EBRI), Aston University, UK and demonstrates an improved method for thermal conversion of ash-rich biomass.

Controlled release in inhalation

Increasingly complicated medication regimens associated with the necessity of the repeated dosing of multiple agents used in treating pulmonary disease has been shown to compromise both disease management and patient convenience. In this study the viability of spray drying to introduce controlled release vectors into dry powders for inhalation was investigated. The first experimental section highlights the use of leucine in producing highly respirable spray dried powders, with in vitro respirable fractions (Fine particle fraction, FPF: F < 5µm) exceeding 80% of the total dose. The second experimental chapter introduces the biocompatible polymer chitosan (mw 190 – 310 kDa) to formulations containing leucine with findings of increased FPF with increasing leucine concentration (up to 82%) and the prolonged release of the active markers terbulataline sulfate (up to 2 hours) and beclometasone dipropionate (BDP: up to 12 hours) with increasing chitosan molecular weight. Next, the thesis details the use of a double emulsion format in delivering the active markers salbutamol sulfate and BDP at differing rates; using the polymers poly-lactide co-glycolide (PLGA 50:50 and PLGA 75:25) and/or chitosan incorporating leucine as an aerosolisation enhancer the duration of in vitro release of both agents reaching 19 days with FPF exceeding 60%. The final experimental chapter involves dual aqueous and organic closed loop spray drying to create controlled release dry powders for inhalation with in vitro sustained release exceeding 28 days and FPF surpassing 55% of total loaded dose. In conclusion, potentially highly respirable sustained release dry powders for inhalation have been produced by this research using the polymers chitosan and/or PLGA as drug release modifiers and leucine as an aerosolisation enhancer.

Oculomotor responses in emmetropia and myopia

It has been proposed that early-onset myopia (EOM) i.e. myopia onset before the age of 15 is primarily inherited whereas late-onset myopia (LOM) i.e. myopia onset after the age of 16 is induced by environmental factors, principally sustained near vision. No consensus exists as to which aspect of the near vision response; accommodation, vergence or their synergistic cross links promotes LOM development. Furthermore, the mechanism by which near vision could induce elongation of posterior chamber is obscure although there is evidence to show that ciliary muscle tone plays an important role. By comparing accommodation and vergence responses of emmetropes (EMMs), EOMs and LOMs under both open- and closed-loop conditions, this thesis aims to define further the oculomotor correlates of myopic development. A Canon Autoref R-1 optometer was used to measure accommodation responses while an Apple IIe controlled the flashed Maddox Rod sequence used when measuring vergence. Both techniques permitted open- and closed-loop measures to be obtained. The results presented demonstrate that it is unlikely that those individuals susceptible to LOM can be distinguished with regard to oculomotor responses or innervational characteristics of the ciliary muscle. The aetiology of LOM may be associated with ciliary muscle function but account needs to be taken of interactions between the ciliary muscle, choriod, sclera and introcular pressure and further research is necessary before those EMMs susceptible to LOM can be identified.

Synkinesis of accommodation and vergence during sustained rear vision

It is well established that a synkinetic relationship exists between the accommodation and vergence components of the oculomotor near response such that increased accommodation will initiate a vergence response (i.e. accommodative convergence) and conversely increased vergence will drive accommodation (i.e. convergent accommodation) . The synkinesis associated with sustained near-vision was examined in a student population consisting of emmetropes, late-onset myopes (LOMs) i.e. myopia onset at 15 years of age or later and early-onset myopes (EOMs) i.e. myopia onset prior to 15 years of age. Oculomotor synkinesis was investigated both under closed-loop conditions and with either accommodation or vergence open-loop. Objective measures of the accommodative response were made using an infra-red optometer. Differences in near-response characteristics were observed between LOMs and EOMs under both open- and closed-loop conditions. LOMs exhibit significantly higher levels of disparity-induced accommodation (accommodation driven by vergence under closed-loop conditions) and lower response accommodative convergence/accommodation (AC/A) ratios when compared with EOMs. However no difference in convergent accommodation/convergence (CA/C) ratios were found between the three refractive groups. Accommodative adaptation was examined by comparing the pre- to post-task shift in dark focus (DF) following near-vision tasks. Accommodative adaptation was observed following tasks as brief as 15s. Following a 45s near-vision task, subjects having pre-task DF greater than +0.750 exhibited a marked negative shift in post-task DF which was shown to be induced by beta-adrenergic innervation to the ciliary muscle. However no evidence was found to support the proposal of reduced adrenergic innervation to the ciliary muscle in LOMs. Disparity-vergence produced a reduction in accommodative adaptation suggesting that oculomotor adaptation was not driven by the output of the near-response crosslinks. In order to verify this proposition, the effect of vergence adaptation on CA/C was investigated and it was observed that prism adaptation produced no significant change in the CA/C ratio. This would indicate that in a model of accommodation-vergence interaction, the near response cross-links occur after the input to the adaptive components of the oculomotor response rather than before the adaptive elements as reported in previous literature. The findings of this thesis indicate differences in the relative composition of the aggregate accommodation and vergence responses in the three refractive groups examined. They may also have implications with regard to the aetiology of late-onset myopia.

An investigation into the relationship between pupil and accommodation responses during near vision

A Hamamatsu Video Area Analyser has been coupled with a modified Canon IR automatic optometer. This has allowed simultaneous recording of pupil diameter and accommodation response to be made both statically and continuously, a feature not common in previous studies. Experimental work concerned pupil and accommodation responses during near vision tasks under a variety of conditions. The effects of sustained near vision tasks on accommodation have usually been demonstrated by taking post-task measures under darkroom conditions. The possibility of similar effects on pupil diameter was assessed using static and continuous recordings following a near vision task. Results showed that is luminance levels remained unchanged by using a pre-and post-task bright-empty field then, although accommodation regressed to pre-task levels,pupil diameter remained for several minutes at the contstricted level induced by the task. An investigation into the effect of a sinusoidally-modulated blur-only accommodative stimulus on pupil response demonstrated that response may be reduced or absent despite robust accommodation responses. This suggests that blur-driven acommodation alone may not be sufficient to produce a pupil near response and that the presence of other cues may be necessary. Pupil response was investigated using a looming stimulus which produced an inferred-proximity cue. It was found that a pupil response could be induced which was in synchrony with the stimulus while closed-loop accommodation response was kept constant by the constraints of optical blur. The pupil diameter of young and elderly subjects undertaking a 5 minute reading task was measured to assess the contribution of pupil constriction to near vision function in terms of depth-of-focus. Results showed that in the young subjects pupil diameter was too large to have a significant effect on depth-of-focus although it may be increased in the elderly subjects. Pupil and accommodation reponses to a temporally-modulated stimulus containing all cues present in a normal visual environment was assessed and results showed that as stimulus temporal frequency increased, pupil response showed increasing phase lag relative to closed-loop accommodation. The results of this study suggest that it may be necessary to change the accepted view of the function of pupil response as part of the near vision triad and that further study would be of benefit in particular to designers of vision aids such as, for example, bifocal contact lenses.

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.

Bifurcation study for a vertical channel with constant flux and large aspect ratio

Using suitable coupled Navier-Stokes Equations for an incompressible Newtonian fluid we investigate the linear and non-linear steady state solutions for both a homogeneously and a laterally heated fluid with finite Prandtl Number (Pr=7) in the vertical orientation of the channel. Both models are studied within the Large Aspect Ratio narrow-gap and under constant flux conditions with the channel closed. We use direct numerics to identify the linear stability criterion in parametric terms as a function of Grashof Number (Gr) and streamwise infinitesimal perturbation wavenumber (making use of the generalised Squire’s Theorem). We find higher harmonic solutions at lower wavenumbers with a resonance of 1:3exist, for both of the heating models considered. We proceed to identify 2D secondary steady state solutions, which bifurcate from the laminar state. Our studies show that 2D solutions are found not to exist in certain regions of the pure manifold, where we find that 1:3 resonant mode 2D solutions exist, for low wavenumber perturbations. For the homogeneously heated fluid, we notice a jump phenomenon existing between the pure and resonant mode secondary solutions for very specific wavenumbers .We attempt to verify whether mixed mode solutions are present for this model by considering the laterally heated model with the same geometry. We find mixed mode solutions for the laterally heated model showing that a bridge exists between the pure and 1:3 resonant mode 2D solutions, of which some are stationary and some travelling. Further, we show that for the homogeneously heated fluid that the 2D solutions bifurcate in hopf bifurcations and there exists a manifold where the 2D solutions are stable to Eckhaus criterion, within this manifold we proceed to identify 3D tertiary solutions and find that the stability for said 3D bifurcations is not phase locked to the 2D state. For the homogeneously heated model we identify a closed loop within the neutral stability curve for higher perturbation wavenumubers and analyse the nature of the multiple 2D bifurcations around this loop for identical wavenumber and find that a temperature inversion occurs within this loop. We conclude that for a homogeneously heated fluid it is possible to have abrup ttransitions between the pure and resonant 2D solutions, and that for the laterally heated model there exist a transient bifurcation via mixed mode solutions.

Modelling of wastewater treatment plants:how far shall we go with sophisticated modelling tools?

Several levels of complexity are available for modelling of wastewater treatment plants. Modelling local effects rely on computational fluid dynamics (CFD) approaches whereas activated sludge models (ASM) represent the global methodology. By applying both modelling approaches to pilot plant and full scale systems, this paper evaluates the value of each method and especially their potential combination. Model structure identification for ASM is discussed based on a full-scale closed loop oxidation ditch modelling. It is illustrated how and for what circumstances information obtained via CFD (computational fluid dynamics) analysis, residence time distribution (RTD) and other experimental means can be used. Furthermore, CFD analysis of the multiphase flow mechanisms is employed to obtain a correct description of the oxygenation capacity of the system studied, including an easy implementation of this information in the classical ASM modelling (e.g. oxygen transfer). The combination of CFD and activated sludge modelling of wastewater treatment processes is applied to three reactor configurations, a perfectly mixed reactor, a pilot scale activated sludge basin (ASB) and a real scale ASB. The application of the biological models to the CFD model is validated against experimentation for the pilot scale ASB and against a classical global ASM model response. A first step in the evaluation of the potential of the combined CFD-ASM model is performed using a full scale oxidation ditch system as testing scenario.

Technology in Parkinson's disease:challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

Picosecond soliton control using nonlinear optical loop mirrors

We show that by inserting nonlinear optical loop mirrors into an optical fibre transmission line, that 1.5 ps solitons may be transmitted over at least 750 km, with amplifiers spaced at 15 km intervals.

Picosecond soliton control using nonlinear optical loop mirrors

We show that by inserting nonlinear optical loop mirrors into an optical fibre transmission line, that 1.5 ps solitons may be transmitted over at least 750 km, with amplifiers spaced at 15 km intervals.

Length, lexicality, and articulatory suppression in immediate recall:evidence against the articulatory loop

Influential models of short-term memory have attributed the fact that short words are recalled better than longer words in serial recall (the length effect) to articulatory rehearsal. Crucial for this link is the finding that the length effect disappears under articulatory suppression. We show, instead, that, under suppression, the length effect is abolished or reversed for real words but remains robust for nonwords. The latter finding is demonstrated in a variety of conditions: with lists of three and four nonwords, with nonwords drawn from closed and open sets, with spoken and written presentation, and with written and spoken output. Our interpretation is that the standard length effect derives from the number of phonological units to be retained. The length effect is abolished or reversed under suppression because this condition encourages reliance on lexical-semantic representations. Using these representations, longer words can more easily be reconstructed from degraded phonology than shorter words. © 2005 Elsevier Inc. All rights reserved.