A clinical and cost effectiveness trial of a parent group intervention to manage challenging restricted and repetitive behaviours in young children with autism spectrum disorder: study protocol for a randomized controlled trial

Background Restricted and repetitive behaviours vary greatly across the autism spectrum, and although not all are problematic some can cause distress and interfere with learning and social opportunities. We have, alongside parents, developed a parent group based intervention for families of young children with autism, which aims to offer support to parents and carers; helping them to recognise, understand and learn how to respond to their child’s challenging restricted repetitive behaviours. Methods The study is a clinical and cost-effectiveness, multi-site randomised controlled trial of the Managing Repetitive Behaviours (MRB) parent group intervention versus a psychoeducation parent group Learning About Autism (LAA) (n = 250; 125 intervention/125 psychoeducation; ~ 83/site) for parents of young children aged 3–9 years 11 months with a diagnosis of autism. All analyses will be done under intention-to-treat principle. The primary outcome at 24 weeks will use generalised estimating equation (GEE) to compare proportion of children with improved RRB between the MRB group and the LAA group. The GEE model will account for the clustering of children by parent groups using exchangeable working correlation. All secondary outcomes will be analysed in a similar way using appropriate distribution and link function. The economic evaluation will be conducted from the perspective of both NHS costs and family access to local community services. A ‘within trial’ cost-effectiveness analysis with results reported as the incremental cost per additional child achieving at least the target improvement in CGI-I scale at 24 weeks. Discussion This is an efficacy trial to investigate the clinical and cost-effectiveness of a parent group based intervention designed to help parents understand and manage their child’s challenging RRB. If found to be effective, this intervention has the potential to improve the well-being of children and their families, reduce parental stress, greatly enhance community participation and potential for learning, and improve longer-term outcomes. Trial registration Trial ID: ISRCTN15550611 Date registered: 07/08/2018. Sponsor and Monitor: Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust R&D Manager Lyndsey Dixon, Address: St Nicholas Hospital, Jubliee Road, Gosforth, Newcastle upon Tyne NE3 3XT, [email protected], Tel: 0191 246 722

Disorders of sex development : insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46, XY DSD and 48 with 46, XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46, XY DSD. In patients with 46, XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes

Corporate Governance for Sustainability

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term

Global corporate citizenship: what does it mean?

This paper develops the basis for an analysis of the idea of ‘Global Corporate Citizenship’, providing conceptual and empirical clarification of this emergent concept. It deals with ways of establishing substantive corporate global democracy in international companies, and tackles issues associated with internal and external corporate governance

Getting to know the knowledge economy: ICTs, networks and governance

Do we live in a new information-based networked economy? This is the underlying issue raised in this article. Confronting the claims made that such an economy is in the making provides the opportunity to discuss some ideas about the reconfiguration of knowledge that the interaction of ICTs with networks is providing. The extent and importance of ICTs is analysed and their potential impact on the evolution of economic activity investigated. The question of how to 'govern' these interactions is also broached. Perhaps somewhat paradoxically, a key argument made is that the advent of ICTs is pressing networks into a deeper engagement with tacit knowledge and the reappraisal of the virtues of craft production

Between hierarchies and markets: the logic and limits of network organization

'Network' is a fashionable concept across the social sciences. This book analyses the nature and operations of networks as distinct from other forms of socio-economic governance and co-ordination. Questions whether there can be a particular logic to the network form of organization. Wide-ranging interdisciplinary approach

Religious fundamentalisms, territories and 'globalization'

Investigates what the fundamentalist variants of the three main monotheist religions (Christianity, Islam, Judaism) have had to say about globalization and territories. Looks at these in terms of the implications of their analytical formulations and operational practices for the continued relevance of a liberal international order. Deals with the possibility of continued governance of the international system as these forms of religious organization encourage a fractured and disordered futur

'Financial globalisation' and the 'crisis': a critical assessment and 'what is to be done'?

Do we have a genuine global financial system? This article challenges the strong notion that the recent financial crisis was global in scope. It argues the international financial system is quite differentiated, being made up of domestic-national, supranational regional and international aspects. The system is characterised by contagion, however, and the article goes on to consider the role of this in generating spill-overs into the wider economic mechanism. Given this characterisation of the financial system the implications for how to organise a regulatory response are pursued. Here the argument is that the principle of 'distributed preparedness for resilience' should guide this response not a new set of top-down global rules and norms organised once again by the institutions of global economic governance