Effect of β-adrenoceptor antagonists on autonomic control of ciliary smooth muscle

Purpose: Pharmacological intervention with peripheral sympathetic transmission at ciliary smooth muscle neuro-receptor junctions has been used against a background of controlled parasympathetic activity to investigate the characteristics of autonomic control of ocular accommodation. Methods: A continuously recording infrared optometer was used to measure accommodation on a group of five visually normal emmetropic subjects under open- and closed-loop conditions. A double-blind protocol between saline, timolol and betaxolol was used to differentiate between the localised action on ciliary smooth muscle and effects induced by changes in stimulus conditions. Data were collected before and 45 min following the instillation of saline, timolol or betaxolol. Open-loop post-task decay was investigated following 3 min sustained near fixation of a stimulus placed 3 D above the subject's pre-task tonic accommodation level. Closed-loop dynamic responses were recorded for each treatment condition while subjects viewed sinusoidally (0.05-0.6 Hz) or stepwise vergence-modulated targets over a 2 D range (2-4 D). Results: Open-loop data demonstrate a rapid post-task regression to pre-task tonic accommodation levels for saline and betaxolol control conditions. A slow positive post-task shift was induced by timolol indicating that sympathetic inhibition contributes to accommodative adaptation during sustained near vision. Closed-loop accommodation responses to temporally modulated sinusoidal stimuli showed characteristic features for both saline and betaxolol control conditions. Timolol induced a reduced gain for low- and mid-temporal frequencies (< 0.3 Hz) but did not affect the response at higher temporal frequencies. Response times to stepwise stimuli increased following the instillation of timolol for the near-to-far fixation condition compared with the controls and was related to the period of sustained prior fixation. Conclusions: Modulation of accommodation under open- and closed-loop conditions by a non-selective β-blocker is consistent with the temporal and inhibitory features of sympathetic innervation to ciliary smooth muscle. Although parasympathetic innervation predominates there is evidence to support a role for sympathetic innervation in the control of ocular accommodation. © 2002 The College of Optometrists.

Modelling and control of a hybrid stepping motor

The integration of a microprocessor and a medium power stepper motor in one control system brings together two quite different disciplines. Various methods of interfacing are examined and the problems involved in both hardware and software manipulation are investigated. Microprocessor open-loop control of the stepper motor is considered. The possible advantages of microprocessor closed-loop control are examined and the development of a system is detailed. The system uses position feedback to initiate each motor step. Results of the dynamic response of the system are presented and its performance discussed. Applications of the static torque characteristic of the stepper motor are considered followed by a review of methods of predicting the characteristic. This shows that accurate results are possible only when the effects of magnetic saturation are avoided or when the machine is available for magnetic circuit tests to be carried out. A new method of predicting the static torque characteristic is explained in detail. The method described uses the machine geometry and the magnetic characteristics of the iron types used in the machine. From this information the permeance of each iron component of the machine is calculated and by using the equivalent magnetic circuit of the machine, the total torque produced is predicted. It is shown how this new method is implemented on a digital computer and how the model may be used to investigate further aspects of the stepper motor in addition to the static torque.

Automatic control of attenuation in a digital communication network

This thesis describes the investigation of an adaptive method of attenuation control for digital speech signals in an analogue-digital environment and its effects on the transmission performance of a national telecommunication network. The first part gives the design of a digital automatic gain control, able to operate upon a P.C.M. signal in its companded form and whose operation is based upon the counting of peaks of the digital speech signal above certain threshold levels. A study was ma.de of a digital automatic gain control (d.a.g.c.) in open-loop configuration and closed-loop configuration. The former was adopted as the means for carrying out the automatic control of attenuation. It was simulated and tested, both objectively and subjectively. The final part is the assessment of the effects on telephone connections of a d.a.g.c. that introduces gains of 6 dB or 12 dB. This work used a Telephone Connection Assessment Model developed at The University of Aston in Birmingham. The subjective tests showed that the d.a.g.c. gives advantage for listeners when the speech level is very low. The benefit is not great when speech is only a little quieter than preferred. The assessment showed that, when a standard British Telecom earphone is used, insertion of gain is desirable if speech voltage across the earphone terminals is below an upper limit of -38 dBV. People commented upon the presence of an adaptive-like effect during the tests. This could be the reason why they voted against the insertion of gain at level only little quieter than preferred, when they may otherwise have judged it to be desirable. A telephone connection with a d.a.g.c. in has a degree of difficulty less than half of that without it. The score Excellent plus Good is 10-30% greater.

Simulation and control of a stepping motor

Open-loop operatlon of the stepping motor exploits the inherent advantages of the machine. For near optimum operation: in this mode, however, an accurate system model is required to facilitate controller design. Such a model must be comprehensive and take account of the non-linearities inherent in the system. The result is a complex formulation which can be made manageable with a computational aid. A digital simulation of a hybrid type stepping motor and its associated drive circuit is proposed. The simulation is based upon a block diagram model which includes reasonable approximations to the major non-linearities. The simulation is shown to yield accurate performance predictions. The determination of the transfer functions is based upon the consideration of the physical processes involved rather than upon direct input-outout measurements. The effects of eddy currents, saturation, hysteresis, drive circuit characteristics and non-linear torque displacement characteristics are considered and methods of determining transfer functions, which take account of these effects, are offered. The static torque displacement characteristic is considered in detail and a model is proposed which predicts static torque for any combination of phase currents and shaft position. Methods of predicting the characteristic directly from machine geometry are investigated. Drive circuit design for high efficiency operation is considered and a model of a bipolar, bilevel circuit is proposed. The transfers between stator voltage and stator current and between stator current and air gap flux are complicated by the effects of eddy currents, saturation and hysteresis. Frequency response methods, combined with average inductance measurements, are shown to yield reasonable transfer functions. The modelling procedure and subsequent digital simulation is concluded to be a powerful method of non-linear analysis.

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.

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.

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.

Sympathetic control of accommodation:evidence for inter-subject variation

Autonomic innervation of ciliary smooth muscle is mediated principally by the parasympathetic nervous system and is supplemented by the sympathetic nervous system. Previous drug and nerve stimulation experiments on humans and animals have demonstrated that sympathetic innervation is inhibitory (via β-2 adrenoceptors), relatively small, slow and augmented by concurrent levels of background parasympathetic activity. These characteristics are pertinent to the sympathetic system having a specific role in our ability to adapt successfully to sustained near vision tasks and, given the clear association between near vision and the onset and development of myopia, to a putative aetiological role in myopia development in pre-disposed individuals. A fifth characteristic, namely the variation between individuals in access to an inhibitory sympathetic facility is therefore of particular interest. A novel method for continuous recording of accommodation, currently employed in a large sample longitudinal study of myopia in young adults, was used following topical instillation of non-selective (timolol) and selective (betaxolol) sympathetic β-adrenoceptor antagonists. Measures of post-task accommodative hysteresis were taken with reference to the time-course of regression of accommodation when open-loop (Difference of Gaussian) conditions were immediately imposed following short (10 s) and long (3 min) duration far (0D) and near (3D above tonic level) tasks viewed through a Badal system. Data confirm earlier informal experimental observations that only one in three individuals are likely to have access to a sympathetic inhibitory facility during sustained near vision. © 2002 The College of Optometrists.

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.

Regenerative Fourier transformation for dual-quadrature regeneration of multilevel rectangular QAM

We propose a new nonlinear optical loop mirror based configuration capable of regenerating regular rectangular quadrature amplitude modulated (QAM) signals. The scheme achieves suppression of noise distortion on both signal quadratures through the realization of two orthogonal regenerative Fourier transformations. Numerical simulations show the performance of the scheme for high constellation complexities (including 256-QAM formats).