Behavioral Implications of Knockout for the Dyslexia-Risk Gene Dcdc2 in Mice

Several genetic linkage and epidemiological studies have provided strong evidence that DCDC2 is a candidate gene for developmental dyslexia, a disorder that impairs a person’s reading ability despite adequate intelligence, education, and socio-economic status. Studies investigating embryonic intra-ventricular RNA interference (RNAi) of Dcdc2, a rat homolog of the DCDC2 gene in humans, indicate disruptions in neuronal migration in the rat cortex during development. Interestingly, these anatomical anomalies are consistent with post mortem histological analysis of human dyslexic patients. Other rodent models of cortical developmental disruption have shown impairment in rapid auditory processing and learning maze tasks in affected subjects. The current study investigates the rapid auditory processing abilities of mice heterozygous for Dcdc2 (one functioning Dcdc2 allele) and mice with a homozygous knockout of Dcdc2 (no functioning Dcdc2 allele). It is important to note that this genetic model for behavioral assessment is still in the pilot stage. However, preliminary results suggest that mice with a genetic mutation of Dcdc2 have impaired rapid auditory processing, as well as non-spatial maze learning and memory ability, as compared to wildtypes. By genetically knocking out Dcdc2 in mice, behavioral features associated with Dcdc2 can be characterized, along with other neurological abnormalities that may arise due to the loss of the functioning gene.

Intercambio entre lectores. Un proyecto con mujeres y niños en contexto de encierro

El artículo expone algunas experiencias y resultados del proyecto "Lectura y escritura en la Unidad 33. Madres, niños e instituciones educativas" que se inició como proyecto de Extensión de la Universidad Nacional de La Plata en el año 2010. El proyecto implementa con mujeres y niños que viven en situación de encierro un conjunto de acciones con diferentes grados de formalización en torno a las culturas de lo escrito y otras formas de expresión, en tanto prácticas culturales que tienen derecho de ejercer y ampliar en diversas situaciones de interacción social. Se presentan los distintos espacios de trabajo y se sintetizan algunos resultados de un un taller denominado "la ronda: historia, poesías y canciones" Del análisis de las situaciones propuestas y los datos recogidos de un corpus de entrevistas semiestructuradas a un grupo de mujeres participantes, con edades entre 19 y 33 años, se destaca el sentido y valor de las lecturas e intercambios entre lectores literarios en la vida cotidiana del encierro

Intercambio entre lectores. Un proyecto con mujeres y niños en contexto de encierro

El artículo expone algunas experiencias y resultados del proyecto "Lectura y escritura en la Unidad 33. Madres, niños e instituciones educativas" que se inició como proyecto de Extensión de la Universidad Nacional de La Plata en el año 2010. El proyecto implementa con mujeres y niños que viven en situación de encierro un conjunto de acciones con diferentes grados de formalización en torno a las culturas de lo escrito y otras formas de expresión, en tanto prácticas culturales que tienen derecho de ejercer y ampliar en diversas situaciones de interacción social. Se presentan los distintos espacios de trabajo y se sintetizan algunos resultados de un un taller denominado "la ronda: historia, poesías y canciones" Del análisis de las situaciones propuestas y los datos recogidos de un corpus de entrevistas semiestructuradas a un grupo de mujeres participantes, con edades entre 19 y 33 años, se destaca el sentido y valor de las lecturas e intercambios entre lectores literarios en la vida cotidiana del encierro

Intercambio entre lectores. Un proyecto con mujeres y niños en contexto de encierro

El artículo expone algunas experiencias y resultados del proyecto "Lectura y escritura en la Unidad 33. Madres, niños e instituciones educativas" que se inició como proyecto de Extensión de la Universidad Nacional de La Plata en el año 2010. El proyecto implementa con mujeres y niños que viven en situación de encierro un conjunto de acciones con diferentes grados de formalización en torno a las culturas de lo escrito y otras formas de expresión, en tanto prácticas culturales que tienen derecho de ejercer y ampliar en diversas situaciones de interacción social. Se presentan los distintos espacios de trabajo y se sintetizan algunos resultados de un un taller denominado "la ronda: historia, poesías y canciones" Del análisis de las situaciones propuestas y los datos recogidos de un corpus de entrevistas semiestructuradas a un grupo de mujeres participantes, con edades entre 19 y 33 años, se destaca el sentido y valor de las lecturas e intercambios entre lectores literarios en la vida cotidiana del encierro

Visual-auditory integration during speech imitation in autism

Children with autistic spectrum disorder (ASD) may have poor audio-visual integration, possibly reflecting dysfunctional 'mirror neuron' systems which have been hypothesised to be at the core of the condition. In the present study, a computer program, utilizing speech synthesizer software and a 'virtual' head (Baldi), delivered speech stimuli for identification in auditory, visual or bimodal conditions. Children with ASD were poorer than controls at recognizing stimuli in the unimodal conditions, but once performance on this measure was controlled for, no group difference was found in the bimodal condition. A group of participants with ASD were also trained to develop their speech-reading ability. Training improved visual accuracy and this also improved the children's ability to utilize visual information in their processing of speech. Overall results were compared to predictions from mathematical models based on integration and non-integration, and were most consistent with the integration model. We conclude that, whilst they are less accurate in recognizing stimuli in the unimodal condition, children with ASD show normal integration of visual and auditory speech stimuli. Given that training in recognition of visual speech was effective, children with ASD may benefit from multi-modal approaches in imitative therapy and language training. (C) 2004 Elsevier Ltd. All rights reserved.

Socioeconomic position, cognitive function, and clustering of cardiovascular risk factors in adolescence: Findings from the Mater University Study of Pregnancy and its outcomes

Objectives: The objectives of this study were to examine the extent of clustering of smoking, high levels of television watching, overweight, and high blood pressure among adolescents and whether this clustering varies by socioeconomic position and Cognitive function. Methods: This study was a cross-sectional analysis of 3613 (1742 females) participants of an Australian birth cohort who were examined at age 14. Results: Three hundred fifty-three (9.8%) of the participants had co-occurrence of three or four risk factors. Risk factors clustered in these adolescents with a greater number of participants than would be predicted by assumptions of independence having no risk factors and three or four risk factors. The extent of clustering tended to be greater in those from lower-income families and among those with lower cognitive function. The age-adjusted ratio of observed to expected cooccurrence of three or four risk factors was 2.70 (95% confidence interval [Cl], 1.80-4.06) among those from low-income families and 1.70 (95% Cl, 1.34-2.16) among those from more affluent families. The ratio among those with low Raven's scores (nonverbal reasoning) was 2.36 (95% Cl, 1.69-3.30) and among those with higher scores was 1.51 (95% Cl, 1.19-1.92); similar results for the WRAT 3 score (reading ability) were 2.69 (95% Cl, 1.85-3.94) and 1.68 (95% Cl, 1.34-2.11). Clustering did not differ by sex. Conclusion: Among adolescents, coronary heart disease risk factors cluster, and there is some evidence that this clustering is greater among those from families with low income and those who have lower cognitive function.

Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score > 2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

Visual function and subjective quality of life compared in subjects with acquired macular disease

PURPOSE: To determine the objective measures of visual function that are most relevant to subjective quality of vision and perceived reading ability in patients with acquired macular disease. METHODS: Twenty-eight patients with macular disease underwent a comprehensive assessment of visual function. The patients also completed a vision-related quality-of-life questionnaire that included a section of general questions about perceived visual performance and a section with specific questions on reading. RESULTS: Results of all tests of vision correlated highly with reported vision-related quality-of-life impairment. Low-contrast tests explained most of the variance in self-reported problems with reading. Text-reading speed correlated highly with overall concern about vision. CONCLUSIONS: Reading performance is strongly associated with vision-related quality of life. High-contrast distance acuity is not the only relevant measure of visual function in relation to the perceived visual performance of a patient with macular disease. The results suggest the importance of print contrast, even over print size, in reading performance in patients with acquired macular disease.

Impaired balance in developmental dyslexia? A meta-analysis of the contending evidence

Background: Developmental dyslexia is typically defined by deficits in phonological skills, but it is also associated with anomalous performance on measures of balance. Although balance assessments are included in several screening batteries for dyslexia, the association between impairments in literacy and deficits in postural stability could be due to the high co-occurrence of dyslexia with other developmental disorders in which impairments of motor behaviour are also prevalent. Methods: We identified 17 published studies that compared balance function between dyslexia and control samples and obtained effect-sizes for each. Contrast and association analyses were used to quantify the influence of hypothesised moderator variables on differences in effects across studies. Results: The mean effect-size of the balance deficit in dyslexia was .64 (95% CI = .44-.78) with heterogeneous findings across the population of studies. Probable co-occurrence of other developmental disorders and variability in intelligence scores in the dyslexia samples were the strongest moderator variables of effect-size. Conclusions: Balance deficits are associated with dyslexia, but these effects are apparently more strongly related to third variables other than to reading ability. Deficits of balance may indicate increased risk of developmental disorder, but are unlikely to be uniquely associated with dyslexia.

Identification of candidate genes for dyslexia susceptibility on chromosome 18

Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. Methodology/Principal Findings: Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L). Conclusions: Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.

Visual comparison of multifocal contact lens to monovision

Purpose. To compare visual function with the Bausch & Lomb PureVision multifocal contact lens to monovision with PureVision single vision contact lenses. Methods. Twenty presbyopic subjects were fitted with either the PureVision multifocal contact lens or monovision with PureVision singlevision lenses. Aftera 1-month trial, the following assessments of visual function were made: (a) distance, intermediate, and near visual acuity (VA); (b) reading ability; (c) distance and near contrast sensitivity function (CSF); (d) near range of clear vision; (e) stereoacuity; and (f) subjective evaluation of near vision ability with a standardized questionnaire. Subjects were then refitted with the alternative correction and the procedure was repeated. All measurements were compared between the two corrections, whereas the ``low addition'' multifocal lens was also compared with the ``high addition'' alternative. Results. Distance and near VA were significantly better with monovision than with the multifocal option (p < 0.05). Intermediate VA (p = 0.13) was similar with both corrections, whereas there was also no significant difference in distance and near CSF (p = 0.29 on both occasions). Reading speeds (p = 0.48) and the critical print size (p = 0.90) were not significantly different between the two contact lens corrections, but stereoacuity (p < 0.01) and the near range of clear vision (p < 0.05) were significantly better with the multifocal option than with monovision. Subjective assessment of near ability was similar for both types of contact lens (p = 0.52). The high addition multifocal lens produced significantly poorer distance and near CSF, near VA, and critical print size compared with the low addition alternative. Conclusions. Monovision performed better than a center-near aspheric simultaneous vision multifocal contact lens of the same material for distance and near VA only. The multifocal option provides better stereoacuity and near range of clear vision, with little differences in CSF, so a better balance of real-world visual function may be achieved due to minimal binocular disruption. (Optom Vis Sci 2009;86:98-105)

Early cognitive profiles of emergent readers:a longitudinal study

This longitudinal study examined the contribution of phonological awareness, phonological memory, and visuospatial ability to reading development in 142 English-speaking children from the start of kindergarten to the middle of Grade 2. Partial cross-lagged analyses revealed significant relationships between early performance on block design and matching letter-like forms tasks and later reading ability. Rhyme awareness correlated with later reading ability during the earliest stages, but onset awareness did not emerge as important until after the children had started reading. Digit span correlated significantly with future reading ability at every stage. These findings indicate that although phonological awareness, phonological memory, and visuospatial ability are all necessary for emergent reading, their relative importance varies across the first 2 years of reading development.

Impaired sensitivity to dynamic stimuli in poor readers of a regular orthography

The mappings from grapheme to phoneme are much less consistent in English than they are for most other languages. Therefore, the differences found between English-speaking dyslexics and controls on sensory measures of temporal processing might be related more to the irregularities of English orthography than to a general deficit affecting reading ability in all languages. However, here we show that poor readers of Norwegian, a language with a relatively regular orthography, are less sensitive than controls to dynamic visual and auditory stimuli. Consistent with results from previous studies of English-readers, detection thresholds for visual motion and auditory frequency modulation (FM) were significantly higher in 19 poor readers of Norwegian compared to 22 control readers of the same age. Over two-thirds (68.4%) of the children identified as poor readers were less sensitive than controls to either or both of the visual coherent motion or auditory 2Hz FM stimuli. © 2003 Elsevier Science (USA). All rights reserved.

Separate influences of acoustic AM and FM sensitivity on the phonological decoding skills of impaired and normal readers

Developmental dyslexia is associated with deficits in the processing of basic auditory stimuli. Yet it is unclear how these sensory impairments might contribute to poor reading skills. This study better characterizes the relationship between phonological decoding skills, the lack of which is generally accepted to comprise the core deficit in reading disabilities, and auditory sensitivity to amplitude modulation (AM) and frequency modulation (FM). Thirty-eight adult subjects, 17 of whom had a history of developmental dyslexia, completed a battery, of psychophysical measures of sensitivity to FM and AM at different modulation rates, along with a measure of pseudoword reading accuracy and standardized assessments of literacy and cognitive skills. The subjects with a history of dyslexia were significantly less sensitive than controls to 2-Hz FM and 20-Hz AM only. The absence of a significant group difference for 2-Hz AM shows that the dyslexics do not have a general deficit in detecting all slow modulations. Thresholds for detecting 2-Hz and 240-Hz FM and 20-Hz AM correlated significantly with pseudoword reading accuracy. After accounting for various cognitive skills, however, multiple regression analyses showed that detection thresholds for both 2-Hz FM and 20-Hz AM were significant and independent predictors of pseudoword reading ability in the entire sample. Thresholds for 2-Hz AM and 240-Hz FM did not explain significant additional variance in pseudoword reading skill, it is therefore possible that certain components of auditory processing of modulations are related to phonological decoding skills, whereas others are not.

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.