Fidelity of delivery and contextual factors influencing children’s level of engagement: Process evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) Trial (Preprint)

BACKGROUND: The Online Remote Behavioural Intervention for Tics (ORBIT) study was a multicentre randomized controlled trial of a complex intervention that consisted of an online behavioural intervention for children and young people (CYP) with tic disorders. In this first part of a two-stage process evaluation, we conducted a mixed-methods study exploring reach, dose, and fidelity of the intervention and contextual factors influencing engagement with the intervention. OBJECTIVE: This study aims to explore the fidelity of delivery and the contextual factors underpinning the ORBIT intervention. METHODS: Baseline study data and intervention usage metrics from participants in the intervention arm were used as quantitative implementation data (n=112). The experiences of being in the intervention were explored by semi-structured interviews with children (n=20) and parent (n=20) participants, therapists (n=4), and referring clinicians (n=6). A principal components analysis was used to create a comprehensive, composite measure of CYP’s engagement with the intervention. Engagement factor scores reflected relative uptake as assessed by a range of usage indices including chapters accessed, number of pages visited and number of logins. RESULTS: The intervention was implemented with high fidelity, and participants deemed the intervention acceptable and satisfactory. Engagement and adherence were high with child participants completing an average of 7.5/10 chapters and 100/112 (89.3%) participants completed a minimum of 4 chapters: the pre-defined threshold for effective dose. Compared to the total population of children with tic disorders, the sample tended to have more educated parents and live in more economically advantaged areas but socioeconomic factors were not related to engagement factor scores. Factors associated with higher engagement factor scores included participants enrolled at the London site vs. the Nottingham site (P=.011), self-referred vs. clinic-referred (P=.041), higher parental engagement as evidenced by number of parental chapters completed (ρ=0.73, n=111, P<.001) and more therapist time for parent (ρ=0.46, n=111, P<.001). A multiple linear regression indicated that parents’ chapter completion (β=.69, t110=10.18, P<.001) and therapist time for parent (β=.19, t110=2.95, P=.004) were the only significant independent predictors of engagement factor scores. CONCLUSIONS: Overall, the intervention had high fidelity of delivery and was evaluated positively by participants, although reach may have been constrained by the nature of the randomized controlled trial. Parental engagement and therapist time for parent were strong predictors of intervention implementation which has important implications for the design and implementation of digital therapeutic interventions into Child and Adolescent Mental Health Services. Clinical Trial: International Standard Randomized Controlled Trial Number (ISRCTN) 70758207; https://doi.org/10.1186/ISRCTN70758207 and ClinicalTrials.gov NCT03483493; https://clinicaltrials.gov/ct2/show/NCT0348349

Quantitative atom probe analysis of carbides

Compared to atom probe analysis of metallic materials, the analysis of carbide phases results in an enhanced formation of molecular ions and multiple events. In addition, many multiple events appear to consist of two or more ions originating from adjacent sites in the material. Due to limitations of the ion detectors measurements generally underestimate the carbon concentration. Analyses using laser-pulsed atom probe tomography have been performed on SiC, WC, Ti(C,N) and Ti 2 AlC grains in different materials as well as on large M 2 3C 6 precipitates in steel. Using standard evaluation methods, the obtained carbon concentration was 6-24% lower than expected from the known stoichiometry. The results improved remarkably by using only the 13 C isotope, and calculating the concentration of 12 C from the natural isotope abundance. This confirms that the main reason for obtaining a too low carbon concentration is the dead time of the detector, mainly affecting carbon since it is more frequently evaporated as multiple ions. In the case of Ti(C,N) andTi 2 AlC an additional difficulty arises from the overlap between C 2 + ,C 2+ 4 and Ti 2+ at the mass-to-charge 24 Da. \ua9 2010 Elsevier B.V

Factors influencing the efficacy of an online behavioural intervention for children and young people with tics: Process evaluation of a randomised controlled trial

The Online Remote Behavioural Intervention for Tics (ORBIT) trial found that an internet-delivered, therapist-supported, and parent-assisted Exposure and Response Prevention (ERP) intervention reduced tic severity and improved clinical outcomes. This process evaluation aimed to explore mechanisms of impact and factors influencing efficacy. Participants were 112 children with a tic disorder and their parents randomised to the active intervention arm of the ORBIT trial. Child engagement was assessed by usage metrics and parent engagement by chapter completion. Experiences of the digital intervention were explored by semi-structured interviews. Outcomes (3-months post randomisation) were change in tic severity and overall clinical improvement. Tic severity reduced from baseline to 3-month follow-up and 36% were rated as much improved clinically. Greater tic severity at baseline predicted reduction in tic severity. Parental engagement was the only independent predictor of clinical improvement. There were no statistically significant mediators or moderators of the relationship between level of child engagement and outcome. From the qualitative findings, child participants appreciated working together with parents on the intervention and participants found the intervention engaging. ORBIT may be an effective and acceptable intervention for children and young people with tic disorders, with parental engagement being a key factor in successful outcomes

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

BackgroundProcess 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.MethodsThe 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.DiscussionThis 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 registrationInternational Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018.ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018

Holocene environmental changes in southern Kamchatka, Far Eastern Russia, inferred from a pollen and testate amoebae peat succession record

© 2015. High resolution palaeoenvironmental records in Far-Eastern Russia are rare, and the Kamchatka Peninsula is among the least studied areas of the region. This paper describes a record spanning the last ca. 11,000. yr, obtained from a bog in the southern part of Kamchatka. The radiocarbon dated core was analysed for pollen, testate amoebae, charcoal and loss-on-ignition (LOI).The vegetation during the early Holocene was dominated by grasses (Poaceae), birch (Betula) and heath (Ericaceae p. p.). Around 10,300. cal. yr BP there was a substantial change in the vegetation cover to shrub alder (Alnus viridis s.l.) stands with sedges and ferns (Polypodiophyta) as well as herbs such as meadow rue (Thalictrum) in the understory. In the surroundings of Utka peatlands started to form. The variations in the vegetation cover were most probably caused by climatic changes. At the beginning of sediment accumulation, before 10,300. cal. yr BP, the composition of the vegetation points to cooler summers and/or decreased annual precipitation. Around 10,300. cal. yr BP, changes in vegetation occurred due to rising temperatures and/or changed water regimes. Increased abundancies of dry indicating testate amoebae after 9100 cal. yr BP point to intermediate to dry soil conditions. Between 8600 and 7700 cal. yr BP tree alder (Alnus incana) was widely spread at the site which probably indicates optimal environmental conditions. The tephra layer at 381-384.5. cm (ca. 8500 cal. yr BP) produces a strong impact on the testate amoebae assemblages. At 7700 cal. yr BP there was a sudden drop of A. incana in the local vegetation. From this time on, A. incana and also A. viridis decrease continuously whereas Betula gradually increases. The upper part of the sequence (after 6300 cal. yr BP) shows higher abundancies of meadowsweet (Filipendula) and sweet gale (Myrica) pollen. After 6300 cal. yr BP, changes in testate amoebae demonstrate variable soil moisture conditions at the site. Between 3700 and 1800 cal. yr BP, wet conditions dominate as dry indicating testate amoebae decrease. After 1800 cal. yr BP soil conditions become more variable again but this time with dry dominating testate amoebae. In contrast to surrounding regions, there is no evidence of trees such as spruce or larch growing in the surroundings of the site even though those trees are characteristic of many eastern Siberian sites. This difference might be because of the maritime influence of the Okhotsk Sea. Even dwarf pine (Pinus pumila), which is currently widely dispersed in northern Kamchatka, became part of the local vegetation only during the last 700 yr

The Role of Bile in the Regulation of Exocrine Pancreatic Secretion

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap

Widespread forest vertebrate extinctions induced by a mega hydroelectric dam in lowland Amazonia

Mega hydropower projects in tropical forests pose a major emergent threat to terrestrial and freshwater biodiversity worldwide. Despite the unprecedented number of existing, underconstruction and planned hydroelectric dams in lowland tropical forests, long-term effects on biodiversity have yet to be evaluated. We examine how medium and large-bodied assemblages of terrestrial and arboreal vertebrates (including 35 mammal, bird and tortoise species) responded to the drastic 26-year post-isolation history of archipelagic alteration in landscape structure and habitat quality in a major hydroelectric reservoir of Central Amazonia. The Balbina Hydroelectric Dam inundated 3,129 km2 of primary forests, simultaneously isolating 3,546 land-bridge islands. We conducted intensive biodiversity surveys at 37 of those islands and three adjacent continuous forests using a combination of four survey techniques, and detected strong forest habitat area effects in explaining patterns of vertebrate extinction. Beyond clear area effects, edge-mediated surface fire disturbance was the most important additional driver of species loss, particularly in islands smaller than 10 ha. Based on species-area models, we predict that only 0.7% of all islands now harbor a species-rich vertebrate assemblage consisting of ≥80% of all species. We highlight the colossal erosion in vertebrate diversity driven by a man-made dam and show that the biodiversity impacts of mega dams in lowland tropical forest regions have been severely overlooked. The geopolitical strategy to deploy many more large hydropower infrastructure projects in regions like lowland Amazonia should be urgently reassessed, and we strongly advise that long-term biodiversity impacts should be explicitly included in pre-approval environmental impact assessments

Holocene climate and environmental change in north-eastern Kamchatka (Russian Far East), inferred from a multi-proxy study of lake sediments

© 2015. A sediment record from a small lake in the north-eastern part of the Kamchatka Peninsula has been investigated in a multi-proxy study to gain knowledge of Holocene climatic and environmental change. Pollen, diatoms, chironomids and selected geochemical parameters were analysed and the sediment record was dated with radiocarbon. The study shows Holocene changes in the terrestrial vegetation as well as responses of the lake ecosystem to catchment maturity and multiple stressors, such as climate change and volcanic eruptions. Climate change is the major driving force resulting in the recorded environmental changes in the lake, although recurrent tephra deposition events also contributed. The sediment record has an age at the base of about 10,000. cal. yrs BP, and during the first 400 years the climate was cold and the lake exhibited extensive ice-cover during winter and relatively low primary production. Soils in the catchment were poor with shrub alder and birches dominating the vegetation surrounding the lake. At about 9600-8900. cal. yrs BP the climate was cold and moist, and strong seasonal wind stress resulted in reduced ice-cover and increased primary production. After ca. 8900 cal. yrs BP the forest density increased around the lake, runoff decreased in a generally drier climate resulting in decreased primary production in the lake until ca. 7000 cal. yrs BP. This generally dry climate was interrupted by a brief climatic perturbation, possibly attributed to the 8.2. ka event, indicating increasingly windy conditions with thick snow cover, reduced ice-cover and slightly elevated primary production in the lake. The diatom record shows maximum thermal stratification at ca. 6300-5800. cal. yrs BP and indicates together with the geochemical proxies a dry and slightly warmer climate resulting in a high productive lake. The most remarkably change in the catchment vegetation occurred at ca. 4200 cal. yrs BP in the form of a conspicuous increase in Siberian dwarf pine (Pinus pumila), indicating a shift to a cooler climate with a thicker and more long-lasting snow cover. This vegetational change was accompanied by marked shifts in the diatom and chironomid stratigraphies, which are also indicative of colder climate and more extensive ice-cover

Therapist-Supported Online Remote Behavioural Intervention for Tics (ORBIT) in Children and Adolescents: A Single-Blind Randomised Controlled Trial

Background: Behaviour therapy is an effective treatment in children and adolescents with tic disorders but is rarely available. Online delivery could widen access to therapy. We evaluated the efficacy of internet-delivered, therapist-supported and parent-assisted Exposure and Response Prevention (ERP) for tics. / Methods: Multi-centre, parallel group, single-blind, randomised controlled trial. Eligible participants were aged 9-17 years with Tourette syndrome/chronic tic disorder, who had not received behaviour therapy for tics within 12 months, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of >15, or >10 if motor or vocal tics only. Participants were recruited via 16 patient identification centres, two study sites, or online self-referral, and were randomised (1:1) by blinded outcome-assessors to receive either 10 weeks of ERP or psychoeducation (active control). The primary outcome was YGTSS-TTSS at 3 months’ post-randomisation, analysis was by intention-to-treat. The mean cost per patient for the intervention and health care costs were calculated. Registrations are ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). / Findings: Between 8 th May 2018 and 30 th September 2019, 224 participants were enrolled; 112 to ERP and 112 to psychoeducation. The ERP intervention reduced YGTSS-TTSS by 2 . 29 points (95% CI: ‑3 . 86 to -0 . 71) compared to the psychoeducation group at 3 months, an effect that increased by 6 months post-randomisation (-2 . 64, 95% CI: -4 . 56 to -0 . 73). The average therapist time spent supporting the intervention was 2 . 5 hours. The additional cost per participant of the ERP intervention compared to psychoeducation was £159 (95% CI -£53 to £370). There were two unrelated serious adverse events, both in the psychoeducation group. / Interpretation: Online-delivered, therapist-supported ERP therapy is clinically effective at reducing tics, with minimal therapist contact time. Online delivery could improve access to evidence-based treatment for tics in children and adolescents

Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies

Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment