697 resultados para toxicity effect


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Background/Aims: In an investigation of the functional impact of amblyopia on children, the fine motor skills, perceived self-esteem and eye movements of amblyopic children were compared with that of age-matched controls. The influence of amblyogenic condition or treatment factors that might predict any decrement in outcome measures was investigated. The relationship between indirect measures of eye movements that are used clinically and eye movement characteristics recorded during reading was examined and the relevance of proficiency in fine motor skills to performance on standardised educational tests was explored in a sub-group of the control children. Methods: Children with amblyopia (n=82; age 8.2 ± 1.3 years) from differing causes (infantile esotropia n=17, acquired strabismus n=28, anisometropia n=15, mixed n=13 and deprivation n=9), and a control group of children (n=106; age 9.5 ± 1.2 years) participated in this study. Measures of visual function included monocular logMAR visual acuity (VA) and stereopsis assessed with the Randot Preschool Stereoacuity test, while fine motor skills were measured using the Visual-Motor Control (VMC) and Upper Limb Speed and Dexterity (ULSD) subtests of the Brunicks-Oseretsky Test of Motor Proficiency. Perceived self esteem was assessed for those children from grade 3 school level with the Harter Self Perception Profile for Children and for those in younger grades (preschool to grade 2) with the Pictorial Scale of Perceived Competence and Acceptance for Young Children. A clinical measure of eye movements was made with the Developmental Eye Movement (DEM) test for those children aged eight years and above. For appropriate case-control comparison of data, the results from amblyopic children were compared with age-matched sub-samples drawn from the group of children with normal vision who completed the tests. Eye movements during reading for comprehension were recorded by the Visagraph infra-red recording system and results of standardised tests of educational performance were also obtained for a sub-set of the control group. Results Amblyopic children (n=82; age 8.2 ± 1.7 years) performed significantly poorer than age-matched control children (n=37; age 8.3 ± 1.3 years) on 9 of 16 fine motor skills sub-items and for the overall age-standardised scores for both VMC and ULSD items (p<0.05); differences were most evident on timed manual dexterity tasks. The underlying aetiology of amblyopia and level of stereoacuity significantly affected fine motor skill performance on both items. However, when examined in a multiple regression model that took into account the inter-correlation between visual characteristics, poorer fine motor skills performance was only associated with strabismus (F1,75 = 5.428; p =0. 022), and not with the level of stereoacuity, refractive error or visual acuity in either eye. Amblyopic children from grade 3 school level and above (n=47; age 9.2 ± 1.3 years), particularly those with acquired strabismus, had significantly lower social acceptance scores than age-matched control children (n=52; age 9.4 ± 0.5 years) (F(5,93) = 3.14; p = 0.012). However, the scores of the amblyopic children were not significantly different to controls for other areas related to self-esteem, including scholastic competence, physical appearance, athletic competence, behavioural conduct and global self worth. A lower social acceptance score was independently associated with a history of treatment with patching but not with a history of strabismus or wearing glasses. Amblyopic children from pre-school to grade 2 school level (n=29; age = 6.6 ± 0.6 years) had similar self-perception scores to their age-matched peers (n=20; age = 6.4 ± 0.5 years). There were no significant differences between the amblyopic (n=39; age 9.1 ± 0.9 years) and age-matched control (n = 42; age = 9.3 ± 0.38 years) groups for any of the DEM outcome measures (Vertical Time, Horizontal Time, Number of Errors and Ratio (Horizontal time/Vertical time)). Performance on the DEM did not significantly relate to measures of VA in either eye, level of binocular function, history of strabismus or refractive error. Developmental Eye Movement test outcome measures Horizontal Time and Vertical Time were significantly correlated with reading rates measured by the Visagraph for both reading for comprehension and naming numbers (r>0.5). Some moderate correlations were also seen between the DEM Ratio and word reading rates as recorded by Visagraph (r=0.37). In children with normal vision, academic scores in mathematics, spelling and reading were associated with measures of fine motor skills. Strongest effect sizes were seen with the timed manual dexterity domain, Upper Limb Speed and Dexterity. Conclusions Amblyopia may have a negative impact on a child’s fine motor skills and an older child’s sense of acceptance by their peers may be influenced by treatment that includes eye patching. Clinical measures of eye movements were not affected in amblyopic children. A number of the outcome measures of the DEM are associated with objective recordings of reading rates, supporting its clinical use for identification of children with slower reading rates. In children with normal vision, proficiency on clinical measures of fine motor skill are associated with outcomes on standardised measures of educational performance. Scores on timed manual dexterity tasks had the strongest association with educational performance. Collectively, the results of this study indicate that, in addition to the reduction in visual acuity and binocular function that define the condition, amblyopes have functional impairment in childhood development skills that underlie proficiency in everyday activities. The study provides support for strategies aimed at early identification and remediation of amblyopia and the co-morbidities that arise from abnormal visual neurodevelopment.

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We report numerical analysis and experimental observation of strongly localized plasmons guided by triangular metal wedges and pay special attention to the effect of smooth (nonzero radius) tips. Dispersion, dissipation, and field structure of such wedge plasmons are analyzed using the compact two-dimensional finite-difference time-domain algorithm. Experimental observation is conducted by the end-fire excitation and near-field scanning optical microscope detection of the predicted plasmons on 40°silver nanowedges with the wedge tip radii of 20, 85, and 125 nm that were fabricated by the focused-ion beam method. The effect of smoothing wedge tips is shown to be similar to that of increasing wedge angle. Increasing wedge angle or wedge tip radius results in increasing propagation distance at the same time as decreasing field localization (decreasing wave number). Quantitative differences between the theoretical and experimental propagation distances are suggested to be due to a contribution of scattered bulk and surface waves near the excitation region as well as the addition of losses due to surface roughness. The theoretical and measured propagation distances are several plasmon wavelengths and are useful for a range of nano-optical applications

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This study examines whether voluntary national governance codes have a significant effect on company disclosure practices. Two direct effects of the codes are expected: 1) an overall improvement in company disclosure practices, which is greater when the codes have a greater emphasis on disclosure; and 2) a leveling out of disclosure practices across companies (i.e., larger improvements in companies that were previously poorer disclosers) due to the codes new comply-or-explain requirements. The codes are also expected to have an indirect effect on disclosure practices through their effect on company governance practices. The results show that the introduction of the codes in eight East Asian countries has been associated with lower analyst forecast error and a leveling out of disclosure practices across companies. The codes are also found to have an indirect effect on company disclosure practices through their effect on board independence. This study shows that a regulatory approach to improving disclosure practices is not always necessary. Voluntary national governance codes are found to have both a significant direct effect and a significant indirect effect on company disclosure practices. In addition, the results indicate that analysts in Asia do react to changes in disclosure practices, so there is an incentive for small companies and family-owned companies to further improve their disclosure practices.

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Genetic polymorphisms in hepatically expressed UGT1A1 and UGT1A9 contribute to the interindividual variability i-n irinotecan disposition and toxicity. We screened UGT1A1 (UGT1A1*60, g.−3140G>A, UGT1A1*28 and UGT1A1*6) and UGT1A9 (g.−118(T)9>10 and I399C>T) genes for polymorphic variants in the promoter and coding regions, and the genotypic effect of UGT1A9 I399C>T polymorphism on irinotecan disposition in Asian cancer patients was investigated. Blood samples were collected from 45 patients after administration of irinotecan as a 90 min intravenous infusion of 375 mg/m2 once in every 3 weeks. Genotypic–phenotypic correlates showed that cancer patients heterozygous or homozygous for the I399C>T allele had approximately 2-fold lower systemic exposure to SN-38 (P<0.05) and a trend towards a higher relative extent of glucuronidation (REG) of SN-38 (P>0.05). UGT1A1–1A9 diplotype analysis showed that patients harbouring the H1/H2 (TG6GT10T/GG6GT9C) diplotype had 2.4-fold lower systemic exposure to SN-38 glucuronide (SN-38G) compared with patients harbouring the H1/H5 (TG6GT10T/GG6GT10C) diplotype (P=0.025). In conclusion, this in vivo study supports the in vitro findings of Girard et al. and suggests that the UGT1A9 I399C>T variant may be an important glucuronidating allele affecting the pharmacokinetics of SN-38 and SN-38G in Asian cancer patients receiving irinotecan chemotherapy.

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The present study examined the capacity of the mud crab, Scylla serrata to digest experimental diets that contained different animal and plant-based feed meals or different levels or types of starch. The apparent dry matter digestibility (ADMD) coefficients for all feed meals tested in the first part of this study, except meat meal, were similar (78–88%). Crude protein digestibility (ACPD) coefficients for all feed meals were relatively high, with values ranging from 86% to 96%. Cotton seed meal, poultry meal, canola meal, fishmeal, soybean meal and lupin meal had similar gross energy digestibility (AGED) values (P>0.05) ranging from 84% to 89%. In the second part of this study, the impact of selected starches on the digestibility of fishmeal-based formulated diets was assessed. The apparent starch digestibility (ASD) of wheat starch decreased significantly as the inclusion level was increased from 15% to 60%, however, there was no significant effect on ACPD values. At a 30% inclusion level, the ASD of diets containing different starches decreased in the order corn>wheat>potato=rice. Moreover, ACPD values were significantly higher (P<0.05) in the diets containing corn or rice starch than in those containing wheat or potato starches.

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Denaturation of extracellular matrix proteins exposes cryptic binding sites. It is hypothesized that binding of cell adhesion receptors to these cryptic binding sites regulates cellular behaviour during tissue repair and regeneration. To test this hypothesis, we quantify the adhesion of pre-osteoblastic cells to native (Col) and partially-denatured (pdCol) collagen I using single-cell force spectroscopy. During early stages of cell attachment (≤180 s) pre-osteoblasts (MC3T3-E1) adhered significantly stronger to pdCol compared to Col. RGD (Arg-Gly-Asp)-containing peptides suppressed this elevated cell adhesion. We show that the RGD-binding α5β1- and αv-integrins mediated pre-osteoblast adhesion to pdCol, but not to Col. On pdCol pre-osteoblasts had a higher focal adhesion kinase tyrosine-phosphorylation level that correlated with enhanced spreading and motility. Moreover, pre-osteoblasts cultured on pdCol showed a pronounced matrix mineralization activity. Our data suggest that partially-denatured collagen exposes RGD-motifs that trigger binding of α5β1- and αv-integrins. These integrins initiate cellular processes that stimulate osteoblast adhesion, spreading, motility and differentiation. Taken together, these quantitative insights reveal an approach for the development of alternative collagen I- based surfaces for tissue engineering applications.

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An extensive literature examines the dynamics of interest rates, with particular attention given to the positive relationship between interest-rate volatility and the level of interest rates—the so-called level effect. This paper examines the interaction between the estimated level effect and competing parameterisations of interest-rate volatility for the Australian yield curve. We adopt a new methodology that estimates elasticity in a multivariate setting that explicitly accommodates the correlations that exist between various yield factors. Results show that significant correlations exist between the residuals of yield factors and that such correlations do indeed impact on model estimates. Within the multivariate setting, the level of the short rate is shown to be a crucial determinant of the conditional volatility of all three yield factors. Measures of model fit suggest that, in addition to the usual level effect, the incorporation of GARCH effects and possible regime shifts is important

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Background: Mechanical forces either due to accommodation or myopia may stretch the retina and/or cause shear between the retina and choroid. This can be investigated by making use of the Stiles-Crawford effect (SCE), which is the phenomenon of light changing in apparent brightness as it enters through different positions in the pupil. The SCE can be measured by psychophysical and objective techniques, with the SCE parameters being directionality (rate of change across the pupil), and orientation (the location of peak sensitivity in the pupil). Aims: 1. To study the changes in foveal SCE with accommodation in emmetropes and myopes using a subjective (psychophysical) technique. 2. To develop and evaluate a quick objective technique of measuring the SCE using the multifocal electroretinogram. Methods: The SCE was measured in 6 young emmetropes and 6 young myopes for up to 8 D accommodation stimulus with a psychophysical technique and its variants. An objective technique using the multifocal electroretinogram was developed and evaluated with 5 emmetropes. Results: Using the psychophysical technique, the SCE directionality increased by similar amounts in both emmetropes and myopes as accommodation increased, with an increase of 15-20% with 6 D of accommodation. However, there were no significant orientation changes. Additional measurements showed that most of the change in the directionality was probably an artefact of optical factors such as higher-order aberrations and accommodative lag rather a true effect of accommodation. The multifocal technique demonstrated the presence of the SCE, but results were noisy and too variable to detect any changes in SCE directionality or orientation with accommodation. Conclusion: There is little true change in the SCE with accommodation responses up to 6 D in either emmetropes or myopes, although it is possible that substantial changes might occur at very high accommodation levels. The objective technique using the multifocal electroretinogram was quicker and less demanding for the subjects than the psychophysical technique, but as implemented in this thesis, it is not a reliable method of measuring the SCE.

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Purpose: Small red lights (one minute of arc or less) change colour appearance with positive defocus. We investigated the influence of longitudinal chromatic aberration and monochromatic aberrations on the colour appearance of small narrow band lights. Methods: Seven cyclopleged, trichromatic observers viewed a small light (one minute of arc, λmax = 510, 532, 550, 589, 620, 628 nm, approximately 19 per cent Weber contrast) centred within a black annulus (4.5 minutes of arc) and surrounded by a uniform white field (2,170 cd/m2). Pupil size was four millimetres. An optical trombone varied focus. Longitudinal chromatic aberration was controlled with a two component Powell achromatising lens that neutralises the eye’s chromatic aberration; a doublet that doubles and a triplet that reverses the eye’s chromatic aberration. Astigmatism and higher order monochromatic aberrations were corrected using adaptive optics. Results: Observers reported a change in appearance of the small red light (628 nm) without the Powell lens at +0.49 ± 0.21 D defocus and with the doublet at +0.62 ± 0.16 D. Appearance did not alter with the Powell lens, and five of seven observers reported the phenomenon with the triplet for negative defocus (-0.80 ± 0.47 D). Correction of aberrations did not significantly affect the magnitude at which the appearance of the red light changed (+0.44 ± 0.18 D without correction; +0.46 ± 0.16 D with correction). The change in colour appearance with defocus extended to other wavelengths (λmax = 510 to 620 nm), with directions of effects being reversed for short wavelengths relative to long wavelengths. Conclusions: Longitudinal chromatic aberrations but not monochromatic aberrations are involved in changing the appearance of small lights with defocus.

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Purpose: The classic study of Sumby and Pollack (1954, JASA, 26(2), 212-215) demonstrated that visual information aided speech intelligibility under noisy auditory conditions. Their work showed that visual information is especially useful under low signal-to-noise conditions where the auditory signal leaves greater margins for improvement. We investigated whether simulated cataracts interfered with the ability of participants to use visual cues to help disambiguate the auditory signal in the presence of auditory noise. Methods: Participants in the study were screened to ensure normal visual acuity (mean of 20/20) and normal hearing (auditory threshold ≤ 20 dB HL). Speech intelligibility was tested under an auditory only condition and two visual conditions: normal vision and simulated cataracts. The light scattering effects of cataracts were imitated using cataract-simulating filters. Participants wore blacked-out glasses in the auditory only condition and lens-free frames in the normal auditory-visual condition. Individual sentences were spoken by a live speaker in the presence of prerecorded four-person background babble set to a speech-to-noise ratio (SNR) of -16 dB. The SNR was determined in a preliminary experiment to support 50% correct identification of sentence under the auditory only conditions. The speaker was trained to match the rate, intensity and inflections of a prerecorded audio track of everyday speech sentences. The speaker was blind to the visual conditions of the participant to control for bias.Participants’ speech intelligibility was measured by comparing the accuracy of their written account of what they believed the speaker to have said to the actual spoken sentence. Results: Relative to the normal vision condition, speech intelligibility was significantly poorer when participants wore simulated catarcts. Conclusions: The results suggest that cataracts may interfere with the acquisition of visual cues to speech perception.

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Purpose: First-eye cataract surgery can reduce the rate of falls among older adults, yet the effect of second-eye surgery on the rate of falling remains unclear. The present study investigated the effect of monocular and binocular simulated cataract blur on postural stability among older adults. Methods: Postural stability was assessed on 34 healthy older adults (mean 68.2 years, SD 3.5) with normal vision, using a portable force platform (BT4, HUR Labs, Finland) which collected data on centre of pressure (COP) displacement. Stability was assessed on firm and foam surfaces under four binocular viewing conditions using Vistech filters to simulate cataract blur: [1] best-corrected vision both eyes; [2] blur over non-dominant eye, [3] blur over dominant eye and [4] blur over both eyes. Binocular logMAR visual acuity, Pelli-Robson contrast sensitivity and stereoacuity were also measured under these viewing conditions and ocular dominance measured using the hole-in-card test. Generalized estimating equations with an exchangeable correlation structure examined the effect of the surface and vision conditions on postural stability. Results: Visual acuity and contrast sensitivity were significantly reduced under monocular and binocular cataract blur compared to normal viewing. All blur conditions resulted in loss of stereoacuity. Binocular cataract blur significantly reduced postural stability compared to normal vision on the firm (COP path length; p=0.013) and foam surface (anterior-posterior COP RMS, COP path length and COP area; p<0.01). However, no significant differences in postural stability were found between the monocular blur conditions compared to normal vision, or between the dominant and non-dominant monocular blur conditions on either the firm or foam surfaces. Conclusions: Findings indicate that binocular blur significantly impairs postural stability, and suggests that improvements in postural stability may justify first-eye cataract surgery, particularly during somatosensory disruption. Postural stability was not significantly impaired in the monocular cataract blur conditions compared to the normal vision condition, nor was there any effect of ocular dominance on postural stability in the presence of monocular cataract blur.

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We investigate whether therewas a causal effect of income changes on the health satisfaction of East and West Germans in the years following reunification. Our data source is the German Socio-Economic Panel (GSOEP) between 1984 and 2002, and we fit a recently proposed fixed-effects ordinal estimator to our health measures and use a causal decomposition technique to account for panel attrition.We find evidence of a significant positive effect of income changes on health satisfaction, but the quantitative size of this effect is small. This is the case with respect to current income and a measure of ‘permanent’ income.