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Purpose: To describe and evaluate an iOS application suppression test, Worth 4 Dot App (W4DApp), which was designed and developed to assess size and depth of suppression., Methods: Characteristics of sensory fusion were evaluated in 25 participants (age 12-69 years) with normal (n = 6) and abnormal (n = 19) binocular vision. Suppression zone size and classification of fusion were determined by W4DApp and by flashlight Worth 4 Dot (W4D) responses from 33 cm to 6 m. Measures of suppression depth were compared between the W4DApp, the flashlight W4D with neutral density filter bar and the dichoptic letters contrast balance index test., Results: There was high agreement in classification of fusion between the W4DApp method and that derived from flashlight W4D responses from 33 cm to 6 m (α = 0.817). There were no significant differences in success rates or in reliability between the W4DApp or the flashlight W4D methods for determining suppression zone size. W4DApp suppression zone size strongly correlated to that determined with the flashlight W4D (rho = 0.964, P < 0.001). W4DApp depth of suppression measures showed significantly higher success rates (χ 2 = 5.128, P = 0.043) and reliability (intraclass correlation analysis = 0.901) but no significant correlation to the depth of suppression calculated by flashlight W4D and neutral density bar (rho = 0.301, P = 0.399) or contrast balance index (rho = -0.018, P = 0.958)., Conclusions: The W4DApp has potential clinical benefit in measuring suppression zone size; however, further modifications are required to improve validity of suppression depth measures., Translational Relevance: W4DApp iOS application will be a convenient tool for clinical determination of suppression characteristics., Competing Interests: Disclosure: A.L. Webber, None; T.R. Mandall, None; D.T. Molloy, None; L.J. Lister, None; E.E. Birch, None, (Copyright 2020 The Authors.)

Purpose: To assess the effects of changing computer monitor pixel density on visual acuity measurements made using Sloan optotypes., Methods: Acuity was measured on 10 participants aged 19 to 38 years (mean 27.9 ± 7.0) measured binocularly wearing their best spectacle correction. Stimuli were eight lines of five Sloan letter optotypes in logarithmic progression, ranging in size from -0.4 to 0.3 logMAR. Test distance was varied so that pixels on the monitor ranged in size from 0.125 mins of arc to 1.97 mins of arc. Two sampling approaches were used: (1) unfiltered sampling, with each pixel rendered either black or white; and (2) filtered sampling with pixel luminance averaged across a pixel aperture, giving grey-scale smoothing of letter edges., Results: A broken line fit was made to each data set, with acuity being stable at an asymptotic threshold VA as for small pixels sizes, with thresholds increasing linearly when pixel sizes exceeded a critical pixel size P crit . For unfiltered stimuli, P crit averaged 1.1 mins of arc and for unfiltered stimuli averaged 0.69 mins of arc. For filtered stimuli, P crit was 1.79xVA as , and for unfiltered P crit was 1.05xVA as ., Conclusion: The results show that grey-scale filtering makes acuity measurement more resistant to the effects of pixellation. Based on a conservative interpretation of these findings, we make the recommendation that charts be constructed with, for filtered optotypes, a maximum pixel size of 0.6 x of the smallest MAR used and, for unfiltered optotypes, 0.35 x the smallest MAR used., (© 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.)

Purpose: To determine the corneal surfaces and lens contributions to ocular aberrations., Methods: There were 61 healthy participants with ages ranging from 20 to 55 years and refractions -8.25 diopters (D) to +3.25 D. Anterior and posterior corneal topographies were obtained with an Oculus Pentacam, and ocular aberrations were obtained with an iTrace aberrometer. Raytracing through models of corneas provided total corneal and surface component aberrations for 5-mm-diameter pupils. Lenticular contributions were given as differences between ocular and corneal aberrations. Theoretical raytracing investigated influence of object distance on aberrations., Results: Apart from defocus, the highest aberration coefficients were horizontal astigmatism, horizontal coma, and spherical aberration. Most correlations between lenticular and ocular parameters were positive and significant, with compensation of total corneal aberrations by lenticular aberrations for 5/12 coefficients. Anterior corneal aberrations were approximately three times higher than posterior corneal aberrations and usually had opposite signs. Corneal topographic centers were displaced from aberrometer pupil centers by 0.32 ± 0.19 mm nasally and 0.02 ± 0.16 mm inferiorly; disregarding corneal decentration relative to pupil center was significant for oblique astigmatism, horizontal coma, and horizontal trefoil. An object at infinity, rather than at the image in the anterior cornea, gave incorrect aberration estimates of the posterior cornea., Conclusions: Corneal and lenticular aberration magnitudes are similar, and aberrations of the anterior corneal surface are approximately three times those of the posterior surface. Corneal decentration relative to pupil center has significant effects on oblique astigmatism, horizontal coma, and horizontal trefoil. When estimating component aberrations, it is important to use correct object/image conjugates and heights at surfaces.

Purpose: We determined whether human ocular lens position is influenced by gravity., Methods: Anterior chamber depth (ACD) and lens thickness (LT) were determined with a Haag-Streit Lenstar LS900 for right eyes of participants in two age groups, with a young group of 13 participants aged 18 to 21 years (mean, 21 years; SD, 1 year) and an older group of 10 participants aged 50 to 63 years (mean, 58 years; SD, 4 years). There were two sessions for each participant separated by at least 48 hours, with one session for the usual upright head position and one session for a downwards head position. In a session, testing was done for minimum accommodation followed by testing at maximum accommodation. A drop of 2% pilocarpine nitrate was instilled, and testing was repeated after 30 minutes under minimum and maximum accommodation conditions., Results: Gravity, manipulated through head posture, affected ACD for young adult and older adult groups but mean effects were only small, ranging from 0.04 to 0.12 mm, and for the older group required the instillation of an accommodation-stimulating drug. Gravity had a weakly significant effect on LT for the young group without accommodation or a drug, but the effect was small at 0.04 ± 0.06 mm (mean ± SD, P = 0.04)., Conclusions: There is a small but real effect of gravity on crystalline lens position, manifested as reduction in ACD at high levels of accommodative effort with the head in a downwards position. This provides evidence of the ability of zonules to slacken during strong accommodation.

It is important to understand the aetiology of interactive mixtures effects (i.e. synergism and antagonism) if results from known cases are to be extrapolated to untested combinations. The key role of toxicokinetics in determining internal concentrations at target sites means that understanding chemical uptake in mixtures is an essential requirement for mechanistic understanding of interactions. In this paper, a combined approach using mixture toxicity testing, toxicokinetic studies and modelling has been used to address the link between joint toxicity and internal concentration. The study is conducted in Lumbricid earthworms with a binary mixture of a metal (nickel) and an organophosphate insecticide (chlorpyrifos) not a priori expected to show interactive toxicity. As expected from their dissimilar modes of action and detoxification, exposure to combinations of nickel and chlorpyrifos resulted in additive toxicity. Measurement of internal concentrations indicated that both chemicals were rapidly accumulated (within 3 days) to equilibrium. When exposed as a mixture, Ni uptake followed the same pattern as found for the single chemical. This was not the case for chlorpyrifos which showed a faster rate of uptake and elimination and a slightly higher equilibrium concentration in a mixture. That the difference in chlorpyrifos kinetics in the mixture did not result in interactive toxicity highlights the need to assess chemical toxicodynamics as well as toxicokinetics. Measurement of chlorpyrifos-oxon identified the presence of this toxic form but implementation of more complex approaches encompassing toxicogenomics and epigenetics are ultimately needed to resolve the toxicokinetic to toxicodynamic link for these chemicals., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Intensive agriculture can require the simultaneous use of more than one pesticide, resulting in the presence of mixtures in soils and waters. To assess mixture effects, concentration addition (CA) for similar acting chemicals and independent action (IA) for dissimilar acting chemicals are the most frequently used models. While the mechanistic basis for the selection of CA and IA for a given mixture appears appealing (similar vs dissimilar action), it has not yet been established how similar chemicals need to be in their effect before CA should be viewed as the most appropriate model. Here this is investigated in studies of the toxicity of binary mixtures of five different pesticides from three classes that have the same putative mode of action (neuroexcitation) but different molecular mechanisms in binary mixture tests with the nematode Caenorhabditis elegans. Effects of exposure on nematode survival were limited at the concentrations tested. Data analysis, therefore, focused on reproductive toxicity. Both CA and IA were found to be valid models for prediction of the toxicity of the 10 mixtures, although for seven CA provided a mathematically better fit. Both models could describe the toxicity for four mixtures; however, evidence for interaction was found in the remaining six cases. Where interactions occurred, these could be explained by information on the potential mechanisms of compound toxicokinetics-particularly when mixtures comprised a metabolically activated and a metabolically deactivated chemical and/or cases where the relative potencies of the two tested chemicals differed greatly. It is concluded, therefore, that detailed analysis of toxicokinetics and toxicodynamics can aid further understanding of interactions in mixtures., (Copyright (c) 2010 SETAC.)

The combined effect of a chemical (fluoranthene) and a nonchemical stress (reduced soil moisture content) to the widely distributed earthworm Lumbricus rubellus were investigated in a laboratory study. Neither fluoranthene (up to 500 microg/g) nor low soil moisture (15% below optimal) had a significant effect on the survival of the exposed worms, but a significant effect on reproduction (cocoon production rate) was found for both stressors (p < 0.001 in both cases). The response of cocoon production to each stressor could be well described by a logistic model; this suggested that the joint effects may be applicable to description using the independent action (IA) model that is widely used in pharmacology and chemical mixture risk assessment. Fitting of the IA model provided a good description of the combined stressor data (accounting for 53.7% of total variation) and was the most parsimonious model describing joint effect (i.e., the description of the data was not improved by addition of further parameters accounting for synergism or antagonism). Thus, the independent action of the two responses was further supported by measurement of internal fluoranthene exposure. The chemical activity of fluoranthene in worm tissue was correlated only with soil fluoranthene concentration and not with soil moisture content. Taken together these results suggest that the IA model can help interpret the joint effects of chemical and nonchemical stressors. Such analyses should, however, be done with caution since the literature data set suggests that there may be cases where interactions between stressors result in joint effects that differ significantly from IA predictions.

Ecological risk assessments must increasingly consider the effects of chemical mixtures on the environment as anthropogenic pollution continues to grow in complexity. Yet testing every possible mixture combination is impractical and unfeasible; thus, there is an urgent need for models that can accurately predict mixture toxicity from single-compound data. Currently, two models are frequently used to predict mixture toxicity from single-compound data: Concentration addition and independent action (IA). The accuracy of the predictions generated by these models is currently debated and needs to be resolved before their use in risk assessments can be fully justified. The present study addresses this issue by determining whether the IA model adequately described the toxicity of binary mixtures of five pesticides and other environmental contaminants (cadmium, chlorpyrifos, diuron, nickel, and prochloraz) each with dissimilar modes of action on the reproduction of the nematode Caenorhabditis elegans. In three out of 10 cases, the IA model failed to describe mixture toxicity adequately with significant or antagonism being observed. In a further three cases, there was an indication of synergy, antagonism, and effect-level-dependent deviations, respectively, but these were not statistically significant. The extent of the significant deviations that were found varied, but all were such that the predicted percentage effect seen on reproductive output would have been wrong by 18 to 35% (i.e., the effect concentration expected to cause a 50% effect led to an 85% effect). The presence of such a high number and variety of deviations has important implications for the use of existing mixture toxicity models for risk assessments, especially where all or part of the deviation is synergistic.

Background: Natural contamination and anthropogenic pollution of soils are likely to be major determinants of functioning and survival of keystone invertebrate taxa. Soil animals will have both evolutionary adaptation and genetically programmed responses to these toxic chemicals, but mechanistic understanding of such is sparse. The clitellate annelid Lumbricus rubellus is a model organism for soil health testing, but genetic data have been lacking., Results: We generated a 17,000 sequence expressed sequence tag dataset, defining ~8,100 different putative genes, and built an 8,000-element transcriptome microarray for L. rubellus. Strikingly, less than half the putative genes (43%) were assigned annotations from the gene ontology (GO) system; this reflects the phylogenetic uniqueness of earthworms compared to the well-annotated model animals. The microarray was used to identify adult- and juvenile-specific transcript profiles in untreated animals and to determine dose-response transcription profiles following exposure to three xenobiotics from different chemical classes: inorganic (the metal cadmium), organic (the polycyclic aromatic hydrocarbon fluoranthene), and agrochemical (the herbicide atrazine). Analysis of these profiles revealed compound-specific fingerprints which identify the molecular responses of this annelid to each contaminant. The data and analyses are available in an integrated database, LumbriBASE., Conclusion: L. rubellus has a complex response to contaminant exposure, but this can be efficiently analysed using molecular methods, revealing unique response profiles for different classes of effector. These profiles may assist in the development of novel monitoring or bioremediation protocols, as well as in understanding the ecosystem effects of exposure.

Transcriptional responses of a soil-dwelling organism (the earthworm Lumbricus rubellus) to three chemicals, cadmium (Cd), fluoranthene (FA), and atrazine (AZ), were measured following chronic exposure, with the aim of identifying the nature of any shared transcriptional response. Principal component analysis indicated full or partial separation of control and exposed samples for each compound but not for the composite set of all control and exposed samples. Partial least-squares discriminant analysis allowed separation of the control and exposed samples for each chemical and also for the composite data set, suggesting a common transcriptional response to exposure. Genes identified as changing in expression level (by the least stringent test for significance) following exposure to two chemicals indicated a substantial number of common genes (> 127). The three compound overlapping gene set, however, comprised only 25 genes. We suggest that the low commonality in transcriptional response may be linked to the chronic concentrations (approximately 10% EC50) and chronic duration (28 days) used. Annotations of the three compound overlapping gene set indicated that genes from pathways most often associated with responses to environmental stress, such as heat shock, phase I and II metabolism, antioxidant defense, and cation balance, were not represented. The strongest annotation signature was for genes important in mitochondrial function and energy metabolism.

This study investigated the short-term survival, reproduction and physiological (lysosomal membrane stability, metallothionein transcript copy number, body tissue metal concentrations) responses of Lumbricus rubellus exposed to metal contaminated field soils under different laboratory temperatures (10, 15 and 20 degrees C) and physiological responses of earthworms collected from the field in three different seasons (spring, autumn, winter). In the laboratory, metal contaminated soils had significant effects on reproduction (p<0.001), metallothionein-2 (MT-2) expression (p=0.033) and earthworm As (p=0.003), Cd (p=0.001), Pb (p<0.001) and Zn (p<0.001) concentration, but not lysosomal membrane stability and tissue Hg and Cu. No effect of temperature was found for any parameter. Principal component analysis of extractable and tissue metal concentrations indicated PC1 as a measure of metal stress. Both cocoon production (r=-0.75) and MT-2 induction (r=0.41) were correlated with PC1. A correlation was also found between cocoon production and MT-2 expression (r=-0.41). Neutral red retention and MT-2 measurements in worms collected from the field sites in three seasons confirmed the absence of a temperature effect on these responses.

Laboratory toxicity tests are usually conducted under stable ambient conditions, while exposures in ecosystems occur in a fluctuating climate. To assess how climate influences the toxicity of Cu and Cd for the earthworm Lumbricus rubellus, this study compared effects for life-cycle parameters (survival, reproduction), cellular status (lysosomal membrane stability), gene expression (transcript of the metal binding protein metallothionein-2) and tissue metal concentration measured under outdoor conditions, with the same responses under constant conditions as measured by Spurgeon et al. [Spurgeon, D.J., Svendsen, C., Weeks, J.M., Hankard, P.K., Stubberud, H.E., Kammenga, J.E., 2003. Quantifying copper and cadmium impacts on intrinsic rate of population increase in the terrestrial oligochaete Lumbricus rubellus. Environmental Toxicology and Chemistry 22, 1465-1472]. Both metals were found to significantly influence earthworm reproduction, compromise lysosomal membrane stability and induce MT-2 gene expression in the outdoor system. Comparison with physiological and life-cycle responses in the laboratory indicated similar response patterns and effect concentrations for Cu. For Cd, lysosomal membrane stability and MT-2 expression showed comparable responses in both exposures. Juvenile production rate, however, gave different dose response relationships, with the EC-(50) in the outdoor test approximately half that in the laboratory test. A difference in Cd accumulation was also seen. Overall, however, the comparison indicated only a marginal effect of environmental fluctuations typical for northern temperate Europe on earthworm sensitivity to the two metals.