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Pedro M Serra, Michael J Cox, Catharine M Chisholm Bradford School of Optometry and Vision Sciences, University of Bradford, Bradford, UK Objective: Astigmatism produces meridional variations in the retinal blur pattern, thus interacting with object spatial detail and altering visual performance as the axis changes. This study investigates the influence of astigmatic axis orientation on visual acuity (VA) for four alphabets used worldwide. Methods: Visual acuity was measured monocularly in 25 Roman alphabet users (mean age: 25.6±7.5 years) using computer-presented logarithm of the minimum angle of resolution (logMAR) charts with letters from four different alphabets (Arabic, Chinese, Roman, and Tamil). VA was assessed under the effect of four optical conditions: best distance correction and three astigmatic conditions (using a +2.00 cylindrical diopter trial case lens with its axis oriented at 180, 45, or 90 degrees). For each alphabet, single optotypes were presented on a monitor viewed from a distance of 4.0 m, and a matching technique was used to identify the letters. Results: The degradation in VA with astigmatic defocus was influenced by the alphabet used (p

Bacterial porins often exhibit ion conductance and gating behavior which can be modulated by pH. However, the underlying control mechanism of gating is often complex, and direct inspection of the protein structure is generally insufficient for full mechanistic understanding. Here we describe Pretzel, a computational framework that can effectively model loop-based gating events in membrane proteins. Our method combines Monte Carlo conformational sampling, structure clustering, ensemble energy evaluation, and a topological gating criterion to model the equilibrium gating state under the pH environment of interest. We discuss details of applying Pretzel to the porin outer membrane protein G (OmpG).

Nanopore sensing is a powerful lab-on-a-chip technique that allows for the analysis of biomarkers present in small sample sizes. In general, nanopore clogging and low detection accuracy arise when the sample becomes more and more complex such as in blood or lysate. To address this, we developed an OmpG nanopore that distinguishes among not only different proteins in a mixture but also protein homologs. Here, we describe this OmpG-based nanopore system that specifically analyzes targets biomarkers in complex mixtures.

Membrane protein pores have emerged as powerful nanopore sensors for single-molecule detection. OmpG, a monomeric nanopore, is comprised of fourteen β-strands connected by seven flexible extracellular loops. The OmpG nanopore exhibits pH-dependent gating as revealed by planar lipid bilayer studies. Current evidence strongly suggests that the dynamic movement of loop 6 is responsible for the gating mechanism. In this work, we have shown that enhancing the electrostatic repulsion forces between extracellular loops suppressed the pH-dependent gating. Our mutant containing additional negative charges in loop 6 and loop 1 exhibited minimal spontaneous gating and reduced sensitivity to pH changes compared to the wild type OmpG. These results provide new evidence to support the mechanism of OmpG gating controlled by the complex electrostatic network around the gating loop 6. The pH-independent quiet OmpG pores could potentially be used as a sensing platform that operates at a broad range of pH conditions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: TGF-β plays a dual role in breast carcinogenesis, acting at early stages as tumor-suppressors and later as tumor-promoters. TGF-β isoforms are expressed in breast tissues and secreted in milk, suggesting that analysis of levels in milk might be informative for breast cancer risk. Accordingly, we assessed TGF-β2 levels in milk from women who had undergone a breast biopsy and related the concentrations to diagnosis., Methods: Milk donated by women who had undergone or were scheduled for a breast biopsy was shipped on ice for processing and testing. Breast cancer risk factors were obtained through a self-administered questionnaire, and biopsy diagnoses were extracted from pathology reports. TGF-β2 levels in milk, assessed as absolute levels and in relation to total protein, were analyzed in bilateral samples donated by 182 women. Linear regression was used to estimate relationships of log-transformed TGF-β2 levels and TGF-β2/ total protein ratios to biopsy category., Results: Milk TGF-β2 levels from biopsied and non-biopsied breasts within women were highly correlated (r (2) = 0.77). Higher mean TGF-β2 milk levels (based on average of bilateral samples) were marginally associated with more severe breast pathological diagnosis, after adjusting for duration of nursing current child (adjusted p trend = 0.07)., Conclusions: Our exploratory analysis suggests a borderline significant association between higher mean TGF-β2 levels in breast milk and more severe pathologic diagnoses. Further analysis of TGF-β signaling in milk may increase understanding of postpartum remodeling and advance efforts to analyze milk as a means of assessing risk of breast pathology.

The effects of glaucoma on binocular visual sensitivity for the detection of various stimulus attributes are investigated at the fovea and in four paracentral retinal regions. The study employed a number of visual stimuli designed to isolate the processing of various stimulus attributes. We measured absolute contrast detection thresholds and functional contrast sensitivity by using Landolt ring stimuli. This psychophysical Landolt C-based contrast test of detection and gap discrimination allowed us to test parafoveally at 6 ° from fixation and foveally by employing interleaved testing locations. First-order motion perception was examined by using moving stimuli embedded in static luminance contrast noise. Red/green (RG) and yellow/blue (YB) colour thresholds were measured with the Colour Assessment and Diagnosis (CAD) test, which utilises random dynamic luminance contrast noise (± 45 %) to ensure that only colour and not luminance signals are available for target detection. Subjects were normal controls (n = 65) and glaucoma patients with binocular visual field defects (n = 15) classified based on their Humphrey Field Analyzer mean deviation (MD) scores. The impairment of visual function varied depending on the stimulus attribute and location tested. Progression of loss was noted for all tests as the degree of glaucoma increased. For subjects with mild glaucoma (MD -0.01 dB to -6.00 dB) significantly more data points fell outside the normal age-representative range for RG colour thresholds than for any other visual test, followed by motion thresholds. This was particularly the case for the parafoveal data compared with the foveal data. Thus, a multifaceted measure of binocular visual performance, incorporating RG colour and motion test at multiple locations, might provide a better index for comparison with quality of life measures in glaucoma.

Purpose: This study describes the axial and peripheral dimensions of myopic and emmetropic eyes in a wide range of retinal locations using a non-contact optical biometer (Zeiss IOLMaster) based upon the principle of partial coherence interferometry. Understanding the optical properties of the peripheral eye may provide insight into myopia development and the possible effects on off-axis visual performance., Methods: Fifty-two myopes (spherical equivalent between -2.00 and -9.62 D) and 27 emmetropes (spherical equivalent between -0.50 and +0.50 D) with astigmatism less than 0.75 D, participated in this study. Axial length and peripheral cornea to retina lengths were measured using partial coherence interferometry at the fovea and up to ± 30° eccentricity along the horizontal and vertical meridian in 10° steps. Relative cornea to retina length was calculated by subtracting the axial length from that obtained at each peripheral location., Results: Our results showed significant differences between refractive groups for both horizontal (p < 0.001) and vertical (p < 0.001) meridians, illustrating that the retinal shape profile is significantly different between myopes and emmetropes. Myopic eyes exhibited a greater rate of change in cornea to retina lengths with increasing eccentricity than emmetropic eyes, with the temporal portion of the retina exhibiting the steepest shift. In addition, significant nasal-temporal asymmetry was observed, which was more pronounced in myopic eyes., Conclusions: Axial and peripheral cornea to retina dimension measurements, using partial coherence interferometry, suggest that myopic eyes tend toward an ellipsoid shape compared to the spherical emmetropic eyes., (Ophthalmic & Physiological Optics © 2012 The College of Optometrists.)

Purpose: The study of peripheral refractive error is of growing interest as degradation of the retinal image quality in the periphery is known to affect central refractive error development and ocular shape in animal models. The purpose of this study was to measure peripheral refraction across the horizontal, vertical, and two oblique meridians in a group of myopic and emmetropic adults and to investigate retinal asymmetry in the human retina., Methods: Thirty-one myopes (spherical equivalent between -2.00 and -9.62 D) and 20 emmetropes (spherical equivalent between -0.50 and +0.50 D) with astigmatism less than -0.75 D, participated in the project. Noncycloplegic peripheral refraction measurements were captured with an autorefractor (NVision K-5001; Shin-Nippon, Tokyo, Japan) at the fovea and up to 30° eccentricity in the horizontal, vertical, and two oblique meridians in 10° steps. RPR was calculated by subtracting the foveal spherical equivalent refraction from that obtained at each eccentric location., Results: Along all measured meridians, myopic eyes showed a relative hyperopic shift in the periphery, with the superior-temporal portion of the retina exhibiting the smallest shift. Emmetropic eyes, however, exhibited a relatively consistent refractive profile across all meridians and eccentricities, confirming a spherical retinal shape for this group. In addition, off-axis astigmatism increased with eccentricity in all meridians., Conclusions: These results suggest that the myopic eye tends toward an ellipsoid shape, rather than the globular shape of an emmetropic eye.

Purpose: Interest in peripheral refraction measurement has grown in recent years in response to the insight it may provide into myopia development. In light of the likely increase in the clinical use of open-field autorefractors for peripheral refraction measurements, the question of instrument alignment and its impact on the accuracy of refraction measurements is raised. The aim of this study was to investigate the accuracy and precision when an open-field device was moved away from alignment with the corneal reflex towards the pupil margins, and to determine the optimum alignment position for peripheral refraction measurements., Methods: Autorefractions were performed on the right eyes of 10 healthy participants using the Shin-Nippon NVision-K 5001 autorefractor. At least five measurements were taken with the subject fixating a distance target in the primary position of gaze, and then four peripheral fixation targets located along the horizontal meridian (10° and 20° eccentricities in the nasal and temporal retina). Measurements were taken at seven alignment positions across the pupil for each fixation angle. Refraction was recorded as the spherical and cylindrical power., Results: The central objective refraction achieved under cycloplegia based on the autorefraction result for the whole sample, ranged between -5.62 D and +1.85 D for the value of sphere, with a maximum astigmatism of -1.00 D. Acceptable alignment position range varied with fixation angle but was -1.0 to +1.0 mm in width across the pupil. Peripheral refraction measurements centred on the entrance pupil were as reliable as those centred on the corneal reflex., Conclusions: Our data suggest that for peripheral refraction measurements, there is a range of acceptable positions and operators can be confident of the validity of results obtained if aligned half way between the pupil centre and corneal reflex. The alignment becomes more critical at greater eccentricities., (Ophthalmic & Physiological Optics © 2011 The College of Optometrists.)

Purpose: Myopia is known to degrade visual performance with both optical and retinal changes implicated. Whether contact lenses or spectacles provide better visual performance for myopes is still under debate. The purpose of this study was to examine central and peripheral visual function in myopic subjects corrected with contact lenses versus spectacles., Methods: Size thresholds were measured at 13 locations for 20 myopic subjects (mean spherical equivalent refractive error (SE): -6.43±1.22 D and cylinder power: -0.23±0.22 D) corrected with contact lenses (new etafilcon A contact lens, fitted 15 min prior to measurements) versus spectacles. Measurements were taken at both low (δl/l=14%) and high (δl/l=100%) contrast levels. The data were analysed using one way repeated-measures ANOVA., Results: Size thresholds increased with eccentricity in a similar manner for both forms of optical correction. Repeated-measures ANOVA showed no statistically significant difference in central and peripheral visual performance between the two forms of correction for both low and high contrast tasks. The outcome remained the same following correction for spectacle magnification., Conclusion: Eye care practitioners can be confident that modern soft contact lenses do not impair visual performance compared to spectacle lenses for the majority of myopes., (Copyright © 2011 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Background: Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT)., Methodology/principal Findings: The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of 'point-of-regard' of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect., Conclusions/significance: Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive.

Inclusion of public service professions in the UK Disability Discrimination Act in 2004 prompted a review of occupational colour vision requirements for police officers. Changes in the regulations which existed prior to 2003 were proposed. The aim of this study was to obtain the views of serving police officers in Northern Ireland on the importance of good colour discrimination in everyday police work and on the recruitment regulations for patrol constables introduced in 2003 in mainland UK. These views were obtained by means of a questionnaire and informal discussions. More than 65% of police officers who responded to the questionnaire considered that good colour vision was very important for effective policing. Fewer than 2% considered that colour vision was unimportant. Experienced police officers agreed that the employment of colour-deficient patrol constables, as permitted in the new regulations, would lead to reduced efficiency and organisational difficulties at the local level. A number of everyday activities were described which showed the need for accurate colour discrimination. The change in recruitment policy and the lack of clarity in the new regulations show inadequate appreciation of the needs of the occupation, of different types of colour vision anomalies and of the diagnostic function of colour vision tests. Failure to provide guidance on appropriate colour vision tests, examination procedures and counselling services is likely to result in inconsistent employment policies in different police forces. It is recommended that the colour vision standard in place prior to 2003 is reinstated at the recruitment stage. The Ishihara test should be used for screening, and colour-deficient applicants further examined with the Farnsworth D15 test as a replacement for the City University Test 2nd edition.

Background: The binocular Esterman visual field test (EVFT) is the current visual field test for driving in the UK. Merging of monocular field tests (Integrated Visual Field, IVF) has been proposed as an alternative for glaucoma patients., Aims: To examine the level of agreement between the EVFT and IVF for patients with binocular paracentral scotomata, caused by either ophthalmological or neurological conditions, and to compare outcomes with useful field of view (UFOV) performance, a test of visual attention thought to be important in driving., Methods: 60 patients with binocular paracentral scotomata but normal visual acuity (VA) were recruited prospectively. Subjects completed and were classified as "pass" or "fail" for the EVFT, IVF and UFOV., Results: Good agreement occurred between the EVFT and IVF in classifying subjects as "pass" or "fail" (kappa = 0.84). Classifications disagreed for four subjects with paracentral scotomata of neurological origin (three "passed" IVF yet "failed" EVFT). Mean UFOV scores did not differ between those who "passed" and those who "failed" both visual field tests (p = 0.11). Agreement between the visual field tests and UFOV was limited (EVFT kappa = 0.22, IVF kappa 0.32)., Conclusions: Although the IVF and EVFT agree well in classifying visual fields with regard to legal fitness to drive in the UK, the IVF "passes" some individuals currently classed as unfit to drive due to paracentral scotomata of non-glaucomatous origin. The suitability of the UFOV for assessing crash risk in those with visual field loss is questionable.

Background: All forms of corneal refractive surgery can sometimes cause an increase in optical aberrations and scattered light, which can affect visual performance. The purpose of this study was to develop a suitable test that was sensitive to retinal image degradation in subjects who have undergone excimer laser refractive surgery and that was also relevant to visual demands in commercial aviation., Methods: Assessment of the visual environment and the tasks involved in piloting a commercial aircraft formed the basis for the selection of the test parameters. The new contrast acuity assessment (CAA) test covers a functional visual field of +/-5 degrees and is based on minimum spatial vision requirements for commercial pilots., Results: Data measured in 100 normal subjects were used to define the 'standard normal observer' and the range of variation for the parameters of the test. This approach makes it possible to quickly establish whether a given subject's performance falls within the range of the standard normal observer. The test is also administered under low ambient illumination since flying at night involves mesopic levels of light adaptation when the pupil size is large and the effects of aberrations and scattered light are therefore more pronounced., Conclusion: The results of the test are simple to interpret and reveal visual performance that falls outside the normal range as a result of either significant degradation of retinal image quality (caused by increased aberrations and scattered light) or abnormal processing of visual information in the retina and/or the visual pathway.