Computerised speechreading training for deaf children: A randomised controlled trial

Purpose: We developed and evaluated in a randomised controlled triala computerised speechreading training programme to determine a) whether it is possible to train speechreading in deaf children and b) whether speechreading training results in improvements in phonological and reading skills.Previous studies indicate a relationship between speechreading and reading skill and further suggest this relationshipmay be mediated by improved phonological representations. This is important since many deaf children find learning to read to be very challenging. Method: Sixty-six deaf 5-7 year olds were randomised into speechreading and maths training arms. Each training programme was comprised of10 minutesessionsa day, 4 days a week for 12 weeks. Children were assessed on a battery of language and literacy measures before training, immediately after training, 3 months and 10 months after training. Results: We found no significant benefits for participants who completed the speechreading training, compared to those who completed the maths training, on the speechreading primary outcome measure. However, significantly greater gains were observed in the speechreading training group on one of the secondary measures of speechreading. There was also some evidence of beneficial effects of the speechreading training on phonological representations, however these effects were weaker. No benefits were seen toword reading. Conclusions: Speechreading skill is trainable in deaf children. However, to support early reading, training may need to be longer or embedded in a broader literacy programme. Nevertheless, a training tool that can improve speechreading is likely to be of great interest to professionals working with deaf children

Artificial escape from XCI by DNA methylation editing of the CDKL5 gene.

A significant number of X-linked genes escape from X chromosome inactivation and are associated with a distinct epigenetic signature. One epigenetic modification that strongly correlates with X-escape is reduced DNA methylation in promoter regions. Here, we created an artificial escape by editing DNA methylation on the promoter of CDKL5, a gene causative for an infantile epilepsy, from the silenced X-chromosomal allele in human neuronal-like cells. We identify that a fusion of the catalytic domain of TET1 to dCas9 targeted to the CDKL5 promoter using three guide RNAs causes significant reactivation of the inactive allele in combination with removal of methyl groups from CpG dinucleotides. Strikingly, we demonstrate that co-expression of TET1 and a VP64 transactivator have a synergistic effect on the reactivation of the inactive allele to levels >60% of the active allele. We further used a multi-omics assessment to determine potential off-targets on the transcriptome and methylome. We find that synergistic delivery of dCas9 effectors is highly selective for the target site. Our findings further elucidate a causal role for reduced DNA methylation associated with escape from X chromosome inactivation. Understanding the epigenetics associated with escape from X chromosome inactivation has potential for those suffering from X-linked disorders

Speechreading, phonological skills and word reading ability in children

PURPOSE: The purpose of the present study was to investigate the relationship between speechreading ability, phonological skills, and word reading ability in typically developing children. METHOD: Sixty-six typically developing children (6–7 years old) completed tasks measuring word reading, speechreading (words, sentences, and short stories), alliteration awareness, rhyme awareness, nonword reading, and rapid automatized naming (RAN). RESULTS: Speechreading ability was significantly correlated with rhyme and alliteration awareness, phonological error rate, nonword reading, and reading ability (medium effect sizes) and RAN (small effect size). Multiple regression analyses showed that speechreading was not a unique predictor of word reading ability beyond the contribution of phonological skills. A speechreading error analysis revealed that children tended to use a phonological strategy when speechreading, and in particular, this strategy was used by skilled speechreaders. CONCLUSIONS: The current study provides converging evidence that speechreading and phonological skills are positively related in typically developing children. These skills are likely to have a reciprocal relationship, and children may benefit from having their attention drawn to visual information available on the lips while learning letter sounds or learning to read, as this could augment and strengthen underlying phonological representations

LRH-1 as a target for the development of new breast cancer therapies

Estrogen drives the growth and development of estrogen receptor alpha (ERα) positive breast cancer and ERα is the target for hormonal therapies that inhibit its activity. A substantial proportion of patients become resistant to these therapies, demonstrating a need for new therapies. Gene expression microarray studies have been performed with a view to identifying potential novel therapeutic targets, biomarkers or forming the basis of identifying a molecular signature for endocrine resistance. These studies have identified candidate genes whose expression is altered in models of endocrine resistance. Investigation of the molecular pathways particularly highlights cell survival and regulation of apoptosis and indicates that these pathways play a key role in the development of resistance. Microarray analysis also identified the liver receptor homolog 1 (LRH-1, NR5A2), a member of the nuclear receptor superfamily of transcription factors, as an estrogen regulated gene in MCF7 cells. Functional analysis showed that LRH-1 regulates breast cancer cell growth, acting in part by regulating ERα expression. Gene expression profiling of MCF-7 cells following RNAi for LRH-1 identified LRH-1 regulated genes. LRH-1 is known to regulate expression of CYP19A1 (aromatase), responsible for estrogen biosynthesis through the aromatisation of aromatase. Together, our findings identify LRH-1 as a potential therapeutic target for breast cancer treatment. Results of screening for small molecule inhibitors of LRH-1 will be presented, together with analysis of gene expression profiling for LRH-1 regulated genes.Open Acces

Deaf children with cochlear implants in Chile: A national analysis of health determinants and outcomes in the Latin American context

Deafness from birth represents a critical challenge for children’s communication, with substantial public health considerations. One intervention has been cochlear implants (CI) for children with severe to profound deafness. Since 2008, Chile has implemented regulations to provide a CI at an early age. However, wide variability exists in factors and expected outcomes without previous national studies. This study aimed to characterise deaf children with CI in Chile and evaluate the impact of CI on speech perception and production, social inclusion, and parental satisfaction. We conducted a prospective study using hospital clinical records and an online questionnaire with 107 deaf children under 15 who had received CIs from 2017 to 2019. We characterised factors and outcomes and investigated the relationship between demographic, audiological, and social determinants of health and outcomes, including communication at home, CAPII, SIR, Geers and Moog Scale, Social Inclusion, and Parental Satisfaction. Our study showed a national profile of deaf children with CI, representing 70% of those implanted from 2017 to 2019. CI beneficiaries lived in more developed boroughs (.54) compared to the national average (.37). Communication and speech perception outcomes varied and were concerning, yet more positive outcomes were presented for social inclusion and parental satisfaction. We found an association between the measured outcomes and children’s age, a socio-economic factor, CI use and CI training. This novel national study supports integrating public services close to each beneficiary’s borough to improve outcomes with the device. CI use and parental training might be crucial measures during rehabilitation treatment

Literacy outcomes for Deaf and Hard of Hearing primary school children: A cohort comparison study

Purpose: This study compared the language and literacy of two cohorts of children with severe-profound hearing loss, recruited 10 years apart, to determine whether outcomes had improved in line with the introduction of newborn hearing screening and access to improved hearing aid technology. Method: Forty-two deaf children, aged 5 -7 years with a mean unaided loss of 102 DB, were assessed on language, reading and phonological skills. Their performance was compared to that of a similar group of 32 deaf children assessed 10 years earlier, and also a group of 40 hearing children of similar single word reading ability. Results: English vocabulary was significantly higher in the new cohort, although it was still below chronological age. Phonological awareness and reading ability had not significantly changed over time. In both cohorts English vocabulary predicted reading but phonological awareness was only a significant predictor for the new cohort. Conclusions: The current results show that vocabulary knowledge of children with severe-profound hearing loss has improved over time but there has not been a commensurate improvement in phonological skills or reading. They suggest that children with severe-profound hearing loss will require continued support to develop robust phonological coding skills to underpin reading

Identifying Developmental Language Disorder in Deaf Children with Cochlear Implants: A Case Study of Three Children

(1) Background: While spoken language learning delays are assumed for deaf and hard of hearing (DHH) children after cochlear implant (CI), many catch up with their hearing peers. Some DHH children with CIs, however, show persistent delays in language, despite protective factors being in place. This suggests a developmental language disorder (DLD). However, at present there is little consensus on how to diagnose DLD in DHH children. (2) Methods: Given the lack of consensus in this area, a set of case studies provides an appropriate first step. The goal of this paper is to show the plausibility of a DLD diagnosis, following careful analysis of protective and risk factors. A retrospective case study review was conducted for three children. Their long-term language outcomes up to four years after CI were considered in the context of access to sound, speech sound discrimination, social skills and non-verbal cognition. (3) Results: It was possible to posit DLD in one child who had experienced good access to sound, alongside good speech discrimination abilities and social development, and normal non-verbal cognition, but who presented with severe language learning difficulties. (4) Conclusions: Finding markers for DLD in DHH children is important for diagnosis and intervention. The implications for clinical practice are discussed