Applying behaviour change theory to parent-led language interventions for children in the early years.

BACKGROUND: The aim of many interventions used by speech and language therapists (SLTs) is to change behaviours related to communication and interaction. Parent-led language interventions for children in the early years (0-5 years) rely on SLTs supporting parents to change their behaviour in child-focused interactions to effect a change in the child's communication. Therapeutic techniques used by SLTs in parent-led language interventions are largely underspecified, impacting on intervention reporting, replication, trialling and development. The Behaviour Change Technique Taxonomy Version 1 (BCTTv1) offers a method of describing intervention techniques developed for use in public health interventions, but with several examples of its application to speech and language interventions. AIMS: To identify behaviour change techniques (BCTs) from the BCTTv1 occurring in parent-led language interventions for children in the early years. METHODS & PROCEDURES: A literature search identified relevant descriptions of parent-led language interventions. These were coded using the BCTTv1. A reliability check was carried out on 10% of the descriptions. To confirm the use of identified BCTs in clinical practice, results of the literature search were triangulated with an online survey of SLTs, and observations of SLTs delivering parent-led language intervention. OUTCOMES & RESULTS: A total of 84 papers containing descriptions of 45 interventions were coded; 62 SLTs responded to the survey and three SLTs were observed delivering parent-led language intervention. A total of 24 BCTs were identified in the literature search, replicated in the observations and verified by SLTs in the survey. BCTs were identified at two levels: Level 1 SLT implemented to change parent interactive behaviour; and Level 2 parent implemented to change child communicative behaviour. CONCLUSIONS & IMPLICATIONS: The BCTTv1 is a useful starting place for describing parent-led language interventions. With some additions and adjustments, BCTs identified in this study were immediately recognized by practitioners and can easily be adopted into practice. WHAT THIS PAPER ADDS: What is already known on this subject Techniques used in SLT interventions are often not clearly described. The BCTTv1 has been used to clarify technique descriptions with success in a small number of SLT disciplines, but not yet in parent-led language interventions for preschoola children. What this paper adds to the existing knowledge This paper constitutes the first research into quantifying the techniques used in parent-led language interventions using the BCTTv1. What are the potential or actual clinical implications of this work? This paper provides a clear list of techniques used by SLTs implementing interventions for preschool children, which can be immediately adopted and used in practice. It also highlights potential adjustments and gaps in the BCTTv1 in relation to SLT which can contribute to future iterations.

BAP1 Loss Is Associated with Higher ASS1 Expression in Epithelioid Mesothelioma: Implications for Therapeutic Stratification.

The nuclear deubiquitylase BRCA1-associated protein 1 (BAP1) is frequently inactivated in malignant pleural mesothelioma (MPM) and germline BAP1 mutation predisposes to cancers including MPM. To explore the influence on cell physiology and drug sensitivity, we sequentially edited a predisposition mutation (w-) and a promoter trap (KO) into human mesothelial cells. BAP1w-/KO MeT5A cells express less BAP1 protein and phenocopy key aspects of BAP1 loss in MPM. Stable isotope labeling with amino acids in cell culture-mass spectrometry revealed evidence of metabolic adaptation, with concomitant alteration of cellular metabolites. In MeT5A, BAP1 deficiency reduces glycolytic enzyme levels but increases enzymes involved in the tricarboxylic acid cycle and anaplerotic pathways. Notably both argininosuccinate synthase 1 (ASS1), essential for cellular synthesis of arginine, and its substrate aspartate, are elevated in BAP1w-/KO MeT5A cells. Likewise, ASS1 expression is higher in BAP1-altered MPM cell lines, and inversely correlates with BAP1 in The Cancer Genome Atlas MESO dataset. Elevated ASS1 is also evident by IHC staining in epithelioid MPM lacking nuclear BAP1 expression, with improved survival among patients with BAP1-negative/ASS1-expressing tumors. Alterations in arginine metabolism may sensitize cells to metabolic drugs and we find that BAP1-negative/ASS1-expressing MPM cell lines are more sensitive to ASS1 inhibition, although not to inhibition of purine synthesis by mizoribine. Importantly, BAP1w-/KO MeT5A become desensitized to arginine deprivation by pegylated arginine deiminase (ADI-PEG20), phenocopying BAP1-negative/ASS1-expressing MPM cell lines. IMPLICATIONS: Our data reveal an interrelationship between BAP1 and arginine metabolism, providing a potential means of identifying patients with epithelioid MPM likely to benefit from ADI-PEG20.

The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation.

Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors BAP1, NF2 and P16 may differentially sensitise tumours to treatments. We have established chick chorioallantoic membrane (CAM) xenograft models of low-passage MPM cell lines and protocols for evaluating drug responses. Ten cell lines, representing the spectrum of histological subtypes and tumour suppressor status, were dual labelled for fluorescence/bioluminescence imaging and implanted on the CAM at E7. Bioluminescence was used to assess viability of primary tumours, which were excised at E14 for immunohistological staining or real-time PCR. All MPM cell lines engrafted efficiently forming vascularised nodules, however their size, morphology and interaction with chick cells varied. MPM phenotypes including local invasion, fibroblast recruitment, tumour angiogenesis and vascular remodelling were evident. Bioluminescence imaging could be used to reliably estimate tumour burden pre- and post-treatment, correlating with tumour weight and Ki-67 staining. In conclusion, MPM-CAM models recapitulate important features of the disease and are suitable to assess drug targets using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, potentially offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies.