A Descriptive Analysis of Eight Remedial Reading Students in the Sevier District Schools

Authorities have variously estimated the number of children with a reading disability to be between ten and fifteen percent of the total school population.1,2,3 Formerly, many children who had reading difficulties perhaps left school at an early age. Also, many children who might have had reading problems perhaps remained undetected before widespread group testing was initiated. Today, with the high premium placed upon high school and even college achievement, an education is, so to speak, a prerequisite to adult success. With reading unique in its being both a subject area and a tool necessary for the mastery of other subject areas, any disability is worthy of concern and consideration

Management of high-risk corneal grafts

MACMILLAN BUILDING,4 CRINAN ST, LONDON, ENGLAND, N1 9X

Social Pedagogy: An Approach Without Fixed Recipes

A historical and theoretical reconstruction of the specificity and peculiarity of the discipline of social pedagogy, as it has developed in Denmark. Social pedagogy takes its departure from the idea that the individual person and the community are complementary but at the same time opposed to each other, so the task of social pedagogy is rebalancing the dynamics between the two. Social pedagogy is also characterised as a discipline with three dimensions: a practical dimension, a theoretical dimension and a professional dimension. The professional’s task is neither to apply theory in practice nor to uphold the usual practice; it is to mediate between theory and practice. The specificity of the discipline gives rise to particular challenges and dilemmas that theorists make understandable and transparent and practitioners have to deal with. A big challenge for social pedagogy is the quest for evidence-based methods that overrides the specificity of the social pedagogical approach. Balancing different forms of knowledge implies that programmes and methods are used as inspiration that can be contained in a social pedagogical approach

Novel disease-causing variants and phenotypic features of X-linked megalocornea

Purpose: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families. // Methods: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain. // Results: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae). // Conclusion: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants

A comparison of keratoconus progression following collagen cross-linkage using standard or personalised keratometry thresholds

OBJECTIVE: To define how estimates of keratoconus progression following collagen cross-linking (CXL) vary according to the parameter selected to measure corneal shape. MATERIALS AND METHODS: We estimated progression following CXL in 1677 eyes. We compared standard definitions of keratoconus progression based on published thresholds for Kmax, front K2, or back K2, or progression of any two of these three parameters, with the option of an increased threshold for Kmax values ≥ 55D. As corneal thickness reduces unpredictably after CXL, it was excluded from the principal analysis. We then repeated the analysis using novel adaptive estimates of progression for Kmax, front K2, or back K2, developed separately using 6463 paired readings from keratoconus eyes, with a variation of the Bland–Altman method to determine the 95% regression-based limits of agreement (LoA). We created Kaplan-Meier survival plots for both standard and adaptive thresholds. The primary outcome was progression five years after a baseline visit 9–15 months following CXL. RESULTS: Progression rates were 8% with a standard (≥ 1.5D) threshold for K2 or 6% with the static multi-parameter definition. With a ≥ 1D threshold for Kmax, the progression was significantly higher at 29%. With adaptive Kmax or K2, the progression rates were similar (20%) but less than with the adaptive multi-parameter method (22%). CONCLUSIONS: Estimates of keratoconus progression following CXL vary widely according to the reference criteria. Using adaptive thresholds (LoA) to define the repeatability of keratometry gives estimates for progression that are markedly higher than with the standard multi-parameter method

Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene

BACKGROUND: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands. METHODS: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment included spectral domain optical coherence tomography (SD-OCT) of one individual with advanced disease, and SD-OCT and confocal microscopy of a child with early stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in each proband. A fasting serum lipid profile was measured in three probands. Paternity testing was performed in one family. RESULTS: A novel heterozygous c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband. In the second Czech proband, aged 6 years when first examined, a previously described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation in the heterozygous state. Previously reported heterozygous c.361C>T; p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white British families. Although crystalline deposits were present in all probands the affected area was small in some individuals. Corneal arcus and stromal haze were the most prominent phenotypical feature in two probands. In the Czech probands, SD-OCT confirmed accumulation of reflective material in the anterior stroma. Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia was found in all three individuals tested. CONCLUSION: Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children

IPSC-Derived Corneal Endothelial-like Cells Act as an Appropriate Model System to Assess the Impact of SLC4A11 Variants on Pre-mRNA Splicing

Purpose: To report molecular genetic findings in six probands with congenital hereditary endothelial dystrophy (CHED) variably associated with hearing loss (also known as Harboyan syndrome). Furthermore, we developed a cellular model to determine if disease-associated variants induce aberrant SLC4A11 pre-mRNA splicing. Methods: Direct sequencing of the entire SLC4A11 coding region was performed in five probands. In one individual, whole genome sequencing was undertaken. The effect of c.2240+5G>A on pre-mRNA splicing was evaluated in a corneal endothelial-like (CE-like) cell model expressing SLC4A11. CE-like cells were derived from autologous induced pluripotent stem cells (iPSCs) via neural crest cells exposed to B27, PDGF-BB, and DKK-2. Total RNA was extracted, and RT-PCR was performed followed by Sanger and a targeted next generation sequencing (NGS) approach to identify and quantify the relative abundance of alternatively spliced transcripts. Results: In total, 11 different mutations in SLC4A11 evaluated as pathogenic were identified; of these, c.1237G>A, c.2003T>C, c.1216+1G>A, and c.2240+5G>A were novel. The c.2240+5G>A variant was demonstrated to result in aberrant pre-mRNA splicing. A targeted NGS approach confirmed that the variant introduces a leaky cryptic splice donor site leading to the production of a transcript containing an insertion of six base pairs with the subsequent introduction of a premature stop codon (p.Thr747*). Furthermore, a subset of transcripts comprising full retention of intron 16 also were observed, leading to the same functionally null allele. Conclusions: This proof-of-concept study highlights the potential of using CE-like cells to investigate the pathogenic consequences of SLC4A11 disease-associated variants

Dihydropyridine receptors and type 1 ryanodine receptors constitute the molecular machinery for voltage-induced Ca2+ release in nerve terminals

Ca2+ stores were studied in a preparation of freshly dissociated terminals from hypothalamic magnocellular neurons. Depolarization from a holding level of -80 mV in the absence of extracellular Ca2+ elicited Ca2+ release from intraterminal stores, a ryanodine-sensitive process designated as voltage-induced Ca2+ release (VICaR). The release took one of two forms: an increase in the frequency but not the quantal size of Ca2+ syntillas, which are brief, focal Ca2+ transients, or an increase in global [Ca2+]. The present study provides evidence that the sensors of membrane potential for VICaR are dihydropyridine receptors (DHPRs). First, over the range of -80 to -60 mV, in which there was no detectable voltage-gated inward Ca2+ current, syntilla frequency was increased e-fold per 8.4 mV of depolarization, a value consistent with the voltage sensitivity of DHPR-mediated VICaR in skeletal muscle. Second, VICaR was blocked by the dihydropyridine antagonist nifedipine, which immobilizes the gating charge of DHPRs but not by Cd2+ or FPL 64176 (methyl 2,5 dimethyl-4[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate), a non-dihydropyridine agonist specific for L-type Ca2+ channels, having no effect on gating charge movement. At 0 mV, the IC50 for nifedipine blockade of VICaR in the form of syntillas was 214 nM in the absence of extracellular Ca2+. Third, type 1 ryanodine receptors, the type to which DHPRs are coupled in skeletal muscle, were detected immunohistochemically at the plasma membrane of the terminals. VICaR may constitute a new link between neuronal activity, as signaled by depolarization, and a rise in intraterminal Ca2+

Designing a large-scale track-based monitoring program to detect changes in species distributions in arid Australia.

Monitoring trends in animal populations in arid regions is challenging due to remoteness and low population densities. However, detecting species' tracks or signs is an effective survey technique for monitoring population trends across large spatial and temporal scales. In this study, we developed a simulation framework to evaluate the performance of alternative track-based monitoring designs at detecting change in species distributions in arid Australia. We collated presence-absence records from 550 2-ha track-based plots for 11 vertebrates over 13 years and fitted ensemble species distribution models to predict occupancy in 2018. We simulated plausible changes in species' distributions over the next 15 years and, with estimates of detectability, simulated monitoring to evaluate the statistical power of three alternative monitoring scenarios: (1) where surveys were restricted to existing 2-ha plots, (2) where surveys were optimized to target all species equally, and (3) where surveys were optimized to target two species of conservation concern. Across all monitoring designs and scenarios, we found that power was higher when detecting increasing occupancy trends compared to decreasing trends owing to the relatively low levels of initial occupancy. Our results suggest that surveying 200 of the existing plots annually (with a small subset resurveyed twice within a year) will have at least an 80% chance of detecting 30% declines in occupancy for four of the five invasive species modeled and one of the six native species. This increased to 10 of the 11 species assuming larger (50%) declines. When plots were positioned to target all species equally, power improved slightly for most compared to the existing survey network. When plots were positioned to target two species of conservation concern (crest-tailed mulgara and dusky hopping mouse), power to detect 30% declines increased by 29% and 31% for these species, respectively, at the cost of reduced power for the remaining species. The effect of varying survey frequency depended on its trade-off with the number of sites sampled and requires further consideration. Nonetheless, our research suggests that track-based surveying is an effective and logistically feasible approach to monitoring broad-scale occupancy trends in desert species with both widespread and restricted distributions