"Older Adults with ASD: The Consequences of Aging." Insights from a series of special interest group meetings held at the International Society for Autism Research 2016-2017

A special interest group (SIG) entitled "Older Adults with ASD: The Consequences of Aging" was held at the International Society for Autism Research (INSAR) annual meetings in 2016 and 2017. The SIG and subsequent meetings brought together, for the first time, international delegates who were members of the autistic community, researchers, practitioners and service providers. Based on aging autism research that is already underway in UK, Europe, Australia and North America, discussions focussed on conceptualising the parameters of aging when referring to autism, and the measures that are appropriate to use with older adults when considering diagnostic assessment, cognitive factors and quality of life in older age. Thus, the aim of this SIG was to progress the research agenda on current and future directions for autism research in the context of aging. A global issue on how to define 'aging' when referring to ASD was at the forefront of discussions. The ‘aging’ concept can in principle refer to all developmental transitions. However, in this paper we focus on the cognitive and physical changes that take place from mid-life onwards. Accordingly, it was agreed that aging and ASD research should focus on adults over the age of 50 years, given the high rates of co-occurring physical and mental health concerns and increased risk of premature death in some individuals. Moreover, very little is known about the cognitive change, care needs and outcomes of autistic adults beyond this age. Discussions on the topics of diagnostic and cognitive assessments, and of quality of life and well-being were explored through shared knowledge about which measures are currently being used and which background questions should be asked to obtain comprehensive and informative developmental and medical histories. Accordingly, a survey was completed by SIG delegates who were representatives of international research groups across four continents, and who are currently conducting studies with older autistic adults. Considerable overlap was identified across different research groups in measures of both autism and quality of life, which pointed to combining data and shared learnings as the logical next step. Regarding the background questions that were asked, the different research groups covered similar topics but the groups differed in the way these questions were formulated when working with autistic adults across a range of cognitive abilities. It became clear that continued input from individuals on the autism spectrum is important to ensure that questionnaires used in ongoing and future are accessible and understandable for people across the whole autistic spectrum, including those with limited verbal abilities

Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy

Lentiviral vector genomic RNA requires sequences that partially overlap wild-type HIV-1 gag and env genes for packaging into vector particles. These HIV-1 packaging sequences constitute 19.6% of the wild-type HIV-1 genome and contain functional cis elements that potentially compromise clinical safety. Here, we describe the development of a novel lentiviral vector (LTR1) with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4.8% of the wildtype genome. This has been achieved by reconfiguring the vector to mediate reverse-transcription with a single strand transfer, instead of the usual two, and in which HIV-1 packaging sequences are not copied. We show that LTR1 vectors offer improved safety in their resistance to remobilization in HIV-1 particles and reduced frequency of splicing into human genes. Following intravenous luciferase vector administration to neonatal mice, LTR1 sustained a higher level of liver transgene expression than an equivalent dose of a standard lentivirus. LTR1 vectors produce reverse-transcription products earlier and start to express transgenes significantly quicker than standard lentiviruses after transduction. Finally, we show that LTR1 is an effective lentiviral gene therapy vector as demonstrated by correction of a mouse hemophilia B model

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries