Disabled People

In Defence of Welfare was published in early 2011 and brings together responses from social policy experts to a range of different aspects of the Coalition government's planned reforms of - and cuts to - to welfare provision

Disability research in the Nordic context – progress and challenges in investment welfare states 1970–2013

Disability research and disability studies in the twenty-first century are almost unrecognisable compared to, for example, work that was completed on disability only 20–30 years ago. Disability research and disability studies may still be constructed as different entities: disability research shading into medical and rehabilitation studies, while disability studies is almost entirely concerned with the social aspects of disability. However, the terrain is now firmly stamped by the imprint of sociology, social policy, psychology, social work and even economics. The rise of US disability studies has ensured that European disability studies and research engage with English, linguistics, philosophy and history. Indeed some might lament that disability studies has lost its character with this influx of inter and counter-disciplinary approaches to disability. I would argue that, on the contrary, disability studies is a more vibrant place to engage with the study of disability, impairment, disabling barriers and enabling systems. Nordic disability studies, although largely beginning after US and UK activities, has arguably reached a position of discursive maturity very quickly, one where impairment is recognized by many and social factors are central to many adopting what has broadly been framed as a relational approach to disability

Good practice for providing disabled people with reasonable access to the built environment : A comparative study of legislative provision

Purpose – By comparing the legislative regimes in different states, this paper aims to provide a platform upon which an agenda of “good practice” can be formulated and initiated in relation to the provision of access to the built environment for disabled people. Design/methodology/approach – The paper utilizes a desktop approach to examine the various regimes. Particular focus is placed upon the regimes in the European Union States of the UK, Malta, Ireland and France and these are contrasted with those in the non-European states of Australia and the USA. Findings – The paper shows how the UK, Malta and possibly Ireland have attempted to take a path of amicable cooperation and negotiation to establish the principle of “reasonable” adjustments to improve access to new and old buildings, whereas France and the USA have tended to adopt a prescriptive course of technical detail and legal compliance to enhance access. The paper also reveals how Australia follows an intermediate route of cooperation and human rights legislation to achieve the same goals. Practical implications – The paper places new insights into the public domain through the evaluation of the strengths and weakness of each approach. Originality/value – This paper uniquely recognizes a number of mistakes that have to be avoided in future legislation and makes tangible recommendations on how to make further progress in the quest to make the built environment more accessible to disabled people

Educational outcomes associated with persistent speech disorder

Background: Children with persistent speech disorder (PSD) are at higher risk of difficulties with literacy, with some evidence suggesting an association with poorer educational attainment. However, studies to date have either used small clinical samples, which exclude children who have not been referred to clinical services, or relied on parent/teacher report of children’s speech development. There is a need for an inclusive study to investigate the impact of PSD on educational outcomes using a population-based sample and robust measures of speech development. Aim: Using a large prospective UK population-based study – the Avon Longitudinal Study of Parents and Children (ALSPAC) – this study investigated: 1) how children identified with PSD at age 8 perform on educational attainment tests at ages 10-11 and 13-14 in comparison to children without PSD; and 2) whether children identified with PSD at age 8 are more likely to receive a label of special educational needs (SEN) in secondary school. Methods & Procedures: We examined the data for 263 children with PSD and 6399 controls who had speech assessed at age 8 in a research clinic. Educational attainment was measured using data from English school standard attainment tests. Data on special educational needs categorisation were obtained between 11 and 13 years of age. Children with PSD and controls were compared using regression analyses adjusted for biological sex, maternal age, verbal, performance and full-scale IQ. Outcomes & Results: Children with PSD at age 8 were more likely to: achieve lower attainment scores at ages 10-11 in English and mathematics and across all three subjects of English, mathematics and science at ages 13-14 after controlling for biological sex and maternal education; score below target levels for English at both time points after controlling for verbal IQ, and at ages 13-14 after controlling for performance IQ; and receive a label of SEN (typically for the category of cognition and learning needs or communication and interaction needs) in secondary school. Conclusions & Implications: PSD identified at age 8 is associated with poor educational attainment at ages 10-11 and 13-14 in the core subjects of English, mathematics and science. Children with PSD at age 8 are more likely to be identified with SEN at ages 11-13, particularly cognition and learning needs and communication and interaction needs. We need to be aware of the potential for long-term impact of PSD on educational attainment in providing appropriate and effective support throughout school

BRAF- and MEK-targeted small molecule inhibitors exert enhanced antimelanoma effects in combination with oncolytic reovirus through ER stress

Reovirus type 3 (Dearing) (RT3D) infection is selective for cells harboring a mutated/activated RAS pathway. Therefore, in a panel of melanoma cell lines (including RAS mutant, BRAF mutant and RAS/BRAF wild-type), we assessed therapeutic combinations that enhance/suppress ERK1/2 signaling through use of BRAF/MEK inhibitors. In RAS mutant cells, the combination of RT3D with the BRAF inhibitor PLX4720 (paradoxically increasing ERK1/2 signaling in this context) did not enhance reoviral cytotoxicity. Instead, and somewhat surprisingly, RT3D and BRAF inhibition led to enhanced cell kill in BRAF mutated cell lines. Likewise, ERK1/2 inhibition, using the MEK inhibitor PD184352, in combination with RT3D resulted in enhanced cell kill in the entire panel. Interestingly, TCID 50 assays showed that BRAF and MEK inhibitors did not affect viral replication. Instead, enhanced efficacy was mediated through ER stress-induced apoptosis, induced by the combination of ERK1/2 inhibition and reovirus infection. In vivo, combined treatments of RT3D and PLX4720 showed significantly increased activity in BRAF mutant tumors in both immune-deficient and immune-competent models. These data provide a strong rationale for clinical translation of strategies in which RT3D is combined with BRAF inhibitors (in BRAF mutant melanoma) and/or MEK inhibitors (in BRAF and RAS mutant melanoma)

Evidence-based intervention for preschool children with primary speech and language impairments: Child Talk - an exploratory mixed-methods study

BackgroundThe Child Talk study aimed to develop an evidence-based framework to support the decision-making of speech and language therapists (SLTs) as they design and plan interventions appropriate to the needs of individual children with primary speech and language impairments and their families. The need for early identification and effective intervention for these children continues to be a government policy priority because of the link between children’s early speech and language skills and their broader well-being and outcomes in later life. The first phase of Child Talk sought to map and describe current SLT practice for these children; identify and summarise the existing research evidence relating to practice; and investigate the perspectives of parents, early years practitioners, preschool children and ‘underserved’ communities on speech and language therapy. The second phase of Child Talk focused on the development of a toolkit – assessment tools, outcome measures and a data set – to support future service and economic evaluations of the framework.MethodsChild Talk adopted a mixed-methods design. Quantitative methods included surveys and investigated the prevalence and patterns of intervention usage; qualitative data collection methods included focus groups, interviews and reflection to investigate participants’ perspectives and understandings of interventions. Data analysis methods included descriptive and inferential statistics, thematic and content analysis and framework analysis. Participants were recruited nationally through six NHS sites, professional bodies, parent groups and advertising. Participants included SLTs (n = 677), parents (n = 84), preschool children (n = 24), early years practitioners (n = 31) and ‘underserved’ communities (n = 52).Key findingsSpeech and language therapy interventions were characterised in terms of nine themes, viewed as comprehensive and inclusive by practitioners. Relevant assessments, interventions and outcome domains were identified for the nine themes. Areas of tacit knowledge and underspecified processes contributed to variability in the detail of the framework. Systematic reviews identified 58 relevant and robust studies (from 55,271 papers retrieved from the initial literature search). The number of studies relevant to each theme varied from 1 to 33. Observational data on preschool children’s perspectives on speech and language therapy interventions revealed the dynamic nature of their interaction with different activities and people within therapy sessions. Parents’ experiences of speech and language therapy were generally positive although some reported that the rationale for therapy was not always clear. Parental perspectives in underserved communities suggested that, although parents were confident about how to support children’s language development, they were less informed about the nature of language impairments and the function of speech and language therapy. The availability of information regarding resources directed towards speech and language therapy services was poor. In particular, services lacked both a culture of collecting outcome data routinely and measures of professional input and costs associated with their activities.ConclusionA descriptive framework of SLT practice has been developed to support the discussions between therapists and families when making decisions regarding the selection of interventions and outcome measures. Further research is needed to address gaps in the intervention framework and evaluate its effectiveness and cost-effectiveness in improving outcomes for preschool children with primary speech and language impairments.Study registrationThis study is registered as PROSPERO CRD42013006369

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway

Background: reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. Methods: to test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. Results: correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. Conclusions: in summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue

Synergistic antitumour effects of rapamycin and oncolytic reovirus.

There are currently numerous oncolytic viruses undergoing clinical trial evaluation in cancer patients and one agent, Talimogene laherparepvec, has been approved for the treatment of malignant melanoma. This progress highlights the huge clinical potential of this treatment modality, and the focus is now combining these agents with conventional anticancer treatments or agents that enhance viral replication, and thereby oncolysis, in the tumour microenvironment. We evaluated the combination of reovirus with rapamycin in B16F10 cell, a murine model of malignant melanoma, based on potential mechanisms by which mTOR inhibitors might enhance viral oncolysis. Rapamycin was not immunomodulatory in that it had no effect on the generation of an antireovirus-neutralising antibody response in C57/black 6 mice. The cell cycle effects of reovirus (increase G0/G1 fraction) were unaffected by concomitant or sequential exposure of rapamycin. However, rapamycin attenuated viral replication if given prior or concomitantly with reovirus and similarly reduced reovirus-induced apoptotic cell death Annexin V/PI and caspase 3/7 activation studies. We found clear evidence of synergistic antitumour effects of the combination both in vitro and in vivo, which was sequence dependent only in the in vitro setting. In conclusion, we have demonstrated synergistic antitumour efficacy of reovirus and rapamycin combination