Protocol for the Process Evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) randomized controlled trial for children and young people.

BACKGROUND: Process evaluations are an important component in the interpretation and understanding of outcomes in trials. The Online Remote Behavioural Intervention for Tics (ORBIT) study is a randomized controlled trial evaluating the effectiveness of an Internet-delivered behavioural intervention (called BIP TIC) compared to an Internet-delivered education programme aimed at children and young people with tics. A process evaluation will be undertaken alongside the main trial to determine precisely how the behavioural intervention works and ascertain whether, and if so, how, the intervention could be successfully implemented in standard clinical practice. This protocol paper describes the rationale, aims, and methodology of the ORBIT trial process evaluation. METHODS: The process evaluation will have a mixed-methods design following the UK Medical Research Council 2015 guidelines, comprising both quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arm; purposively sampled, semi-structured interviews of parents and children, therapists and supervisors, and referring clinicians of the ORBIT trial, as well as analysis of qualitative comments put into the online therapy platform by participants at the end of treatment. Qualitative data will be analysed thematically. Quantitative and qualitative data will be integrated in a triangulation approach, to provide an understanding of how the intervention works, and what resources are needed for effective implementation, uptake and use in routine clinical care. DISCUSSION: This process evaluation will explore the experiences of participants, therapists and supervisors and referring clinicians of a complex online intervention. By contextualising trial efficacy results, this will help understand how and if the intervention worked and what may be required to sustain the implementation of the treatment long term. The findings will also aid in our understanding of factors that can affect the success of complex interventions. This will enable future researchers developing online behavioural interventions for children and young people with mental health and neurological disorders to gain invaluable information from this process evaluation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018. ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018.

Pluralism in mathematics.

We defend pluralism in mathematics, and in particular Errett Bishop's constructive approach to mathematics, on pragmatic grounds, avoiding the philosophical issues which have dissuaded many mathematicians from taking it seriously. We also explain the computational value of interval arithmetic.

Influence of environmental factors upon the survival of Aujeszky's disease virus.

The survival of Aujeszky's disease (pseudorabies) virus outside the living host was found to be dependent on pH level and temperature. Virus inactivation occurred at a rate varying from 0.04 log10 per day at 4 degrees C to 0.6 log10 per day at 37 degrees C at the optimum pH levels of 6 to 8. Fluctuation of the temperature between 4 degrees C and 37 degrees C had no apparent effect upon the titre of the virus. At a steady temperature of -13 degrees C, the virus was rapidly inactivated at all tested pH levels. For long-term storage it is recommended that the pH should be adjusted to between 6 and 7, that suspensions should be kept at -90 degrees C and that freezing and thawing should be rapid so as to pass through the just subzero temperature zone as quickly as possible. Drying, both on glass and on gelatin, caused inactivation of the virus at all pH levels, as did exposure to ultraviolet light.

Spontaneous shedding of pseudorabies virus from a clinically recovered postparturient sow.

Pseudorabies virus was shed by a sow that had been clinically infected 19 months earlier (when 1 month old) and had been in isolation for 3 1/2 months. The shedding was detected from the third to eighth days after farrowing and was confined to the nasal secretion. Two susceptible pigs in contact with the sow after farrowing were not infected.

Persistence of pseudorabies virus in infected swine.

The persistence of pseudorabies virus (PRV) in pigs clinically recovered from the disease was detected by culture of tissue fragments. Weanling pigs were infected by intranasal instillation of 200,000 plaque-forming units of a strain of PRV isolated from sick pigs in Iowa, and virus was recovered from them 6 weeks to 13 months later. Tonsil, trigeminal ganglia, or pooled trigeminal ganglia and olfactory and optic nerve tissue were most consistently the source of virus. The tissue-fragment culture technique was compared with a co-culture technique for detection of virus in tissue specimens from the recovered pigs. Use of these procedures provided the means to detect PRV in pigs for periods longer than previously recognized.