Enhancing Social-Emotional Outcomes in Early Years (E-SEE): Randomized Pilot Study of Incredible Years Infant and Toddler Programs

Abstract: Social emotional development in infancy is a predictor of outcomes in later life, yet there is little evidence of effectiveness for parenting interventions designed to enhance social emotional wellbeing in infancy. An 18-month two-arm randomized controlled pilot trial evaluated the feasibility of a definitive trial of Incredible Years (IY) Infant and Toddler parent programs delivered in a proportionate universal model, called Enhancing Social-Emotional Health and Wellbeing in the Early Years (E-SEE) Steps. Intervention families received an IY Babies book (universal dose), followed by the IY Infant and/or the Toddler group-based programs, based on parent depression (PHQ-9) and/or child social emotional development (ASQ:SE-2) scores. Control parents received services as usual. Parents from two English local authorities with a child eight-weeks-old or younger participated, and were block randomized using a web-based system. Primary endpoints for the study were feasibility parameters relating to recruitment, retention, intervention fidelity and appropriateness of measures. 205 participants were randomized (152:53, intervention:control). Our target was 288 parents. Trial retention rate was higher than expected, with a completion rate of 88% (n = 181, 137:44) at follow-up 3; equating to 94% of 192 expected participants. Intervention uptake was lower than expected. Fidelity of delivery was acceptable and measures were deemed appropriate. A definitive trial is feasible with design amendments to include: introduction of a child screener for intervention eligibility; enhanced intervention material; revised sample size and random allocation ratio. Our internal pilot became an external pilot due to these changes

Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field