Association of proximal elements of social disadvantage with children's language development at 2 years : an analysis of data from the Children in Focus (CiF) sample from the ALSPAC birth cohort

Background An association between social disadvantage and early language development is commonly reported in the literature, but less attention has been paid to the way that different aspects of social disadvantage affect both expressive and receptive language in the first 2 years of life. Aims To examine the contributions of gender, parental report of early language skills and proximal social variables (the amount of stimulation in the home, the resources available to the child and the attitudes/emotional status of the primary carer and the support available to him/her) controlling for distal social variables (family income and maternal education) to children's expressive and receptive language development at 2 years in a community ascertained population cohort. Methods & Procedures Data from 1314 children in the Children in Focus (CiF) sample from the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. Multivariable regression models identified the contribution of proximal (what parents do with their children) measures of social disadvantage adjusting for more distal (e.g., family income and material wealth) measures as well as early language development at 15 months to the development of verbal comprehension, expressive vocabulary and expressive grammar (word combinations) at 2 years of age. Outcome & Results In the final multivariable models gender, earlier language and proximal social factors, co‐varying for distal factors predicted 36% of the variance for expressive vocabulary, 22% for receptive language and 27% for word combinations at 2 years. Language development at 15 months remained a significant predictor of outcomes at 24 months. Environmental factors were associated with both expressive scales but the picture was rather more mixed for receptive language suggesting that there may be different mechanisms underlying the different processes. Conclusions & Implications This study supports the argument that social advantage makes a strong contribution to children's language development in the early years. The results suggest that what parents/carers do with their children is critical even when structural aspects of social disadvantage such as family income and housing have been taken into consideration although this relationship varies for different aspects of language. This has the potential to inform the targeting of public health interventions focusing on early language and pre‐literacy skills on the one hand and home learning environments on the other and, potentially, the two in combination

A method for generating coherent spatially explicit maps of seasonal palaeoclimates from site-based reconstructions

We describe a method for reconstructing spatially explicit maps of seasonal palaeoclimate variables from site-based reconstructions. Using a 3D-Variational technique, the method finds the best statistically unbiased, and spatially continuous, estimate of the palaeoclimate anomalies through combining the site-based reconstructions and a prior estimate of the palaeoclimate state. By assuming a set of correlations in the error of the prior, the resulting climate is smoothed both from month to month and from grid cell to grid cell. The amount of smoothing can be controlled through the choice of two length-scale values. The method is applied to a set of reconstructions of the climate of the Last Glacial Maximum (ca. 21,000 years ago, yr BP) for southern Europe derived from pollen data with a prior derived from results from the third phase of the Palaeoclimate Intercomparison Project (PMIP3). We demonstrate how to choose suitable values for the smoothing length scales from the datasets used in the reconstruction

Assessment and diagnosis of Developmental Language Disorder: The experiences of speech and language therapists

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Background: For many years research and practice have noted the impact of the heterogeneous nature of Developmental Language Disorder (also known as language impairment or specific language impairment) on diagnosis and assessment. Recent research suggests the disorder is not restricted to the language domain and against this background, the challenge for the practitioner is to provide accurate assessment and effective therapy. The language practitioner aims to support the child and their carers to achieve the best outcomes. However, little is known about the experiences of the language practitioner in the assessment process, in contrast to other childhood disorders, yet their expertise is central in the assessment and diagnosis of children with language disorder. Aims: This study aimed to provide a detailed qualitative description of the experiences of speech and language therapists involved in the assessment and diagnosis of children with Developmental Language Disorder. Methods & Procedures: The qualitative study included three focus groups to provide a credible and rich description of the experiences of speech and language therapists involved in the assessment of Developmental Language Disorder. The speech and language therapists who participated in the study were recruited from three NHS Trusts across the UK and all were directly involved in the assessment and diagnosis procedures. The lengths of practitioner experience ranged from 2 years to 38 years. The data was analysed using a thematic analysis in accordance with the principles set out by Braun & Clarke (2006). Outcomes & Results: The data showed a number of key themes concerning the experiences of speech and language therapists in assessing children with Developmental Language Disorder (DLD). These themes ranged from the participants’ experiences of the barriers to early referral, challenges for assessment and the concerns over continued future support. Conclusions & Implications: This study provides first-hand evidence from speech and language therapists in the assessment of children with Developmental Language Disorder, drawing together experiences from language practitioners from different regions. The findings provide insight to the barriers to referral, the potential variations in the assessment process, the role of practitioner expertise and the challenges faced them. The importance of early intervention, useful assessment tools and future support were expressed. Taken together, the results relate to some issues to be addressed on a practical level and a continuing need for initiatives to raise awareness of DLD in the public domain.Peer reviewe

Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1.

BackgroundOncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive immunity. HSV-1 also has a large capacity for the insertion of additional, potentially therapeutic, exogenous genes. Finally, HSV-1 has a proven safety and efficacy profile in patients with cancer, talimogene laherparepvec (T-VEC), an oncolytic HSV-1 which expresses GM-CSF, being the only oncolytic immunotherapy approach that has received FDA approval. As the clinical efficacy of oncolytic immunotherapy has been shown to be further enhanced by combination with immune checkpoint inhibitors, developing improved oncolytic platforms which can synergize with other existing immunotherapies is a high priority. In this study we sought to further optimize HSV-1 based oncolytic immunotherapy through multiple approaches to maximize: (i) the extent of tumor cell killing, augmenting the release of tumor antigens and danger-associated molecular pattern (DAMP) factors; (ii) the immunogenicity of tumor cell death; and (iii) the resulting systemic anti-tumor immune response.MethodsTo sample the wide diversity amongst clinical strains of HSV-1, twenty nine new clinical strains isolated from cold sores from otherwise healthy volunteers were screened across a panel of human tumor cell lines to identify the strain with the most potent tumor cell killing ability, which was then used for further development. Following deletion of the genes encoding ICP34.5 and ICP47 to provide tumor selectivity, the extent of cell killing and the immunogenicity of cell death was enhanced through insertion of a gene encoding a truncated, constitutively highly fusogenic form of the envelope glycoprotein of gibbon ape leukemia virus (GALV-GP-R-). A number of further armed derivatives of this virus were then constructed intended to further enhance the anti-tumor immune response which was generated following fusion-enhanced, oncolytic virus replication-mediated cell death. These viruses expressed GMCSF, an anti-CTLA-4 antibody-like molecule, CD40L, OX40L and/or 4-1BB, each of which is expected to act predominantly at the site and time of immune response initiation. Expression of these proteins was confirmed by ELISA and/or western blotting. Immunogenic cell death was assessed by measuring the levels of HMGB1 and ATP from cell free supernatants from treated cells, and by measuring the surface expression of calreticulin. GALV-GP-R- mediated cell to cell fusion and killing was tested in a range of tumor cell lines in vitro. Finally, the in vivo therapeutic potential of these viruses was tested using human A549 (lung cancer) and MDA-MB-231(breast cancer) tumor nude mouse xenograft models and systemic anti-tumor effects tested using dual flank syngeneic 4434 (melanoma), A20 (lymphoma) mouse tumor models alone and in combination with a murine anti-PD1 antibody, and 9 L (gliosarcoma) tumors in rats.ResultsThe twenty nine clinical strains of HSV-1 isolated and tested demonstrated a broad range of tumor cell killing abilities allowing the most potent strain to be identified which was then used for further development. Oncolytic ability was demonstrated to be further augmented by the expression of GALV-GP-R- in a range of tumor cell lines in vitro and in mouse xenograft models in nude mice. The expression of GALV-GP-R- was also demonstrated to lead to enhanced immunogenic cell death in vitro as confirmed by the increased release of HMGB1 and ATP and increased levels of calreticulin on the cell surface. Experiments using the rat 9 L syngeneic tumor model demonstrated that GALV-GP-R- expression increased abscopal uninjected (anenestic) tumor responses and data using mouse 4434 tumors demonstrated that virus treatment increased CD8+ T cell levels both in the injected and uninjected tumor, and also led to increased expression of PD-L1. A combination study using varying doses of a virus expressing GALV-GP-R- and mGM-CSF and an anti-murine PD1 antibody showed enhanced anti-tumor effects with the combination which was most evident at low virus doses, and also lead to immunological memory. Finally, treatment of mice with derivatives of this virus which additionally expressed anti-mCTLA-4, mCD40L, m4-1BBL, or mOX40L demonstrated enhanced activity, particularly in uninjected tumors.ConclusionThe new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R- and hGM-CSF) has entered clinical development alone and in combination with anti-PD1 therapy in a number of tumor types (NCT03767348)

Perspectives of Pre‐school children in England with speech and language needs in the development of evidence‐based activities

Background The existing evidence is limited in terms of perspectives of pre-school children with speech and language needs, and their views on activities used to support their needs. This paper discusses a stream of work from the interdisciplinary research programme known as [‘Child Talk’, based in England, UK. The overall purpose of this work stream was to gain the perspectives of pre-school children aged 2 to 5 years 11 months, with speech and language needs, to use in the development of an evidence-based framework of activities. Methods Twenty-four pre-schoolchildren with a variety of needs from diverse backgrounds took part. An observational methodology was used to capture children’s experiences. Children were filmed during a series of sessions, with innovative head mounted cameras worn by the children and supported by researcher field notes. Framework analysis was used to analyse the data based on the body movement, vocalisation and visual attention of the children during these sessions. Results and Conclusions. Results included that children expressed enjoyment and engagement in the activities. The children expressed themselves and demonstrated their focus ‘multimodally’ through combinations of body language, vocalisation, and visual attention. These modalities were present across all contexts and children. It highlights the importance of encouraging participation in pre-school children and consequently this innovative piece of work has national and international importance

Education and employment outcomes of young adults with a history of developmental language disorder

Background: Developmental language disorder (DLD) presents a considerable barrier for young adults to engage in further education and training. Early studies with young adults with DLD revealed poor educational achievement and lack of opportunities to progress in education. More recent studies have provided more positive findings. Relatively sparse data exist, however, on current cohorts and the factors that predict outcomes. Aims: To examine educational and employment outcomes in young adulthood in a sample of people with histories of DLD, compared with an age-matched peer group without DLD. We ask: How do educational pathways and early jobs compare between those with and without DLD? Are young adults with DLD receiving similar levels of income as their peers? To what extent are language and literacy abilities associated with outcomes? Methods & Procedures: Participants included 84 individuals with DLD (67% males) and 88 age-matched peers without DLD (56% males). Participants were on average 24 years of age. They completed a battery of psycholinguistic, literacy and nonverbal skills assessments. Data were also collected on educational qualifications, current educational status, extent of educational support received, employment status, history and support, as well as current income. Outcomes & Results: Those with DLD obtained lower academic and vocational qualifications. Higher educational/vocational qualifications were associated with better language, better reading and higher PIQ. There were few differences between the two groups in terms of engagement with education but the mean age at leaving education was significantly earlier in the participants with DLD. Substantially more participants with DLD reported receiving support or dispensation from their educational institution. There was no significant difference between groups in the proportion of young people currently employed, though a higher proportion of the age-matched peers was in work full-time. Participants with DLD were much more likely to be in non-professional occupations. However, when examining pay in relation to types of occupation, the groups’ incomes were broadly comparable. Conclusions & Implications: At the group level, young people with a history of DLD more commonly have less skilled employment and more rarely achieve professional roles. At the individual level, there is considerable variation with smaller but not trivial proportions of young adults with a history of DLD showing good educational and employment outcomes. There are positive aspects to early adult outcomes for some young people with a history of DLD

'It depends': Characterizing speech and language therapy for preschool children with developmental speech and language disorders

Background: A number of studies have suggested that practitioners hold speech and language therapy (SLT) practice as tacit and consequently it is difficult for the therapist to describe. The current study uses a range of knowledge elicitation (KE) approaches, a technique not used before in SLT, as a way of accessing this tacit knowledge. There is currently no agreed framework that establishes key factors underpinning practice for preschool children with speech and language disorders. This paper attempts to address that gap. Aims: The aim of this study was to develop a framework of speech and language therapists’ practice when working with preschool children with developmental speech and language disorders (DS&LD). Methods and Procedures: A mixed methods approach was adopted for this study. Data were collected iteratively, from 245 speech and language therapists with experience of working with preschool children with DS&LD across sites in England, by means of focus groups and national events. There were three stages of data collection; local sites, specific interest groups and two national events. KE techniques were used to gather data, with initial data being collected in local site focus groups. Findings from groups were taken to subsequent larger groups where a combination of concept mapping, teach-back and sorting exercises, generated a more detailed description of practice, using discussion of consensus and disagreement to stimulate further exploration and definition and provide validatory evidence. Outcomes and Results: This paper provides a high-level framework of therapy for preschool children with DS&LD that makes practice explicit in this area. The framework proposes that therapists’ aims for this group of children fall into three categories: addressing children’s areas of impairment and skills; achieving functionally meaningful skills and carryover; supporting adults to provide a supportive communication environment. The exact configuration is shaped by the child’s context and needs. Conclusions and Implications: The framework highlights themes that are well researched in the literature (e.g. speech) and others that have been little studied (e.g. adult understanding), indicating a disconnect between research evidence and practice. The research also highlights the complex nature of interventions for preschool children with DS&LD and the importance therapists attribute to tailoring therapy to individual needs. The framework provides a scaffold for speech and language therapists to focus their clinical practice and encourages us as a profession to better understand and explore the gaps between research evidence and clinical practice, for preschool children with DS&LD

Implementation fidelity of a computer-assisted intervention for children with speech sound disorders

© 2017 The Speech Pathology Association of Australia Limited Published by Informa UK Limited, trading as Taylor & Francis Group. Background: Implementation fidelity refers to the degree to which an intervention or programme adheres to its original design. This paper examines implementation fidelity in the Sound Start Study, a clustered randomised controlled trial of computer-assisted support for children with speech sound disorders (SSD). Method: Sixty-three children with SSD in 19 early childhood centres received computer-assisted support (Phoneme Factory Sound Sorter [PFSS]–Australian version). Educators facilitated the delivery of PFSS targeting phonological error patterns identified by a speech-language pathologist. Implementation data were gathered via (1) the computer software, which recorded when and how much intervention was completed over 9 weeks; (2) educators’ records of practice sessions; and (3) scoring of fidelity (intervention procedure, competence and quality of delivery) from videos of intervention sessions. Result: Less than one-third of children received the prescribed number of days of intervention, while approximately one-half participated in the prescribed number of intervention plays. Computer data differed from educators’ data for total number of days and plays in which children participated; the degree of match was lower as data became more specific. Fidelity to intervention procedures, competency and quality of delivery was high. Conclusion: Implementation fidelity may impact intervention outcomes and so needs to be measured in intervention research; however, the way in which it is measured may impact on data