ORCID Profile
0000-0003-2217-3052
Current Organisations
Memorial Sloan Kettering Cancer Center
,
University of Oxford
,
Big Health
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Publisher: Wiley
Date: 18-08-2020
DOI: 10.1111/JSR.13140
Publisher: Rockefeller University Press
Date: 08-09-2003
Abstract: Bone morphogenetic proteins (BMPs) regulate multiple cellular processes, including cell differentiation and migration. Their signals are transduced by the kinase receptors BMPR-I and BMPR-II, leading to Smad transcription factor activation via BMPR-I. LIM kinase (LIMK) 1 is a key regulator of actin dynamics as it phosphorylates and inactivates cofilin, an actin depolymerizing factor. During a search for LIMK1-interacting proteins, we isolated clones encompassing the tail region of BMPR-II. Although the BMPR-II tail is not involved in BMP signaling via Smad proteins, mutations truncating this domain are present in patients with primary pulmonary hypertension (PPH). Further analysis revealed that the interaction between LIMK1 and BMPR-II inhibited LIMK1's ability to phosphorylate cofilin, which could then be alleviated by addition of BMP4. A BMPR-II mutant containing the smallest COOH-terminal truncation described in PPH failed to bind or inhibit LIMK1. This study identifies the first function of the BMPR-II tail domain and suggests that the deregulation of actin dynamics may contribute to the etiology of PPH.
Publisher: Wiley
Date: 28-02-2020
DOI: 10.1111/JSR.13018
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
DOI: 10.1186/S13063-020-4230-6
Abstract: Generalised anxiety disorder (GAD) is a chronic and disabling condition with considerable personal and economic impact. Cognitive behavioural therapy (CBT) is a recommended psychological therapy for GAD however, there are substantial barriers to accessing treatment. Digital CBT, in particular smartphone-delivered CBT, has the potential to improve accessibility and increase dissemination of CBT. Despite the emerging evidence of smartphone-based psychological interventions for reducing anxiety, effect size scores are typically smaller than in-person interventions, and there is a lack of research assessing the efficacy of smartphone-delivered digital interventions specifically for GAD. In the DeLTA trial (DigitaL Therapy for Anxiety), we plan to conduct a parallel-group superiority randomised controlled trial examining the efficacy of a novel smartphone-based digital CBT intervention for GAD compared to a waitlist control. We aim to recruit 242 adults (aged 18 years or above) with moderate-to-severe symptoms of GAD. This trial will be conducted entirely online and will involve assessments at baseline (week 0 immediately preceding randomisation), mid-intervention (week 3), post-intervention (week 6 primary end point) and follow-up (week 10). The primary objective is to evaluate the efficacy of the intervention on GAD symptom severity compared to a waitlist control at post-intervention. Secondary objectives are to examine between-group effects on GAD at follow-up, and to examine the following secondary outcomes at both post-intervention and follow-up: 1) worry 2) depressive symptoms 3) wellbeing 4) quality of life and 5) sleep difficulty. This trial will report findings on the initial efficacy of a novel digital CBT intervention for GAD. Results have the potential to contribute towards the evidence base for digital CBT for GAD and increase the dissemination of CBT. ISRCTN, ISRCTN12765810 . Registered on 11 January 2019.
Publisher: Oxford University Press (OUP)
Date: 05-11-2020
Abstract: To examine the cost-effectiveness and potential net monetary benefit (NMB) of a fully automated digital cognitive behavioral therapy (CBT) intervention for insomnia compared with no insomnia treatment in the United States (US). Similar relative comparisons were made for pharmacotherapy and clinician-delivered CBT (in idual and group). We simulated a Markov model of 100,000 in iduals using parameters calibrated from the literature including direct (treatment) and indirect costs (e.g. insomnia-related healthcare expenditure and lost workplace productivity). Health utility estimates were converted into quality-adjusted life years (QALYs) and one QALY was worth $50,000. Simulated in iduals were randomized equally to one of five arms (digital CBT, pharmacotherapy, in idual CBT, group CBT, or no insomnia treatment). Sensitivity was assessed by bootstrapping the calibrated parameters. Cost estimates were expressed in 2019 US dollars. Digital CBT was cost beneficial when compared with no insomnia treatment and had a positive NMB of $681.06 (per in idual over 6 months). Bootstrap sensitivity analysis demonstrated that the NMB was positive in 94.7% of simulations. Relative to other insomnia treatments, digital CBT was the most cost-effective treatment because it generated the smallest incremental cost-effectiveness ratio (−$3,124.73). Digital CBT was the most cost-effective insomnia treatment followed by group CBT, pharmacotherapy, and in idual CBT. It is financially prudent and beneficial from a societal perspective to utilize automated digital CBT to treat insomnia at a population scale.
Publisher: Hindawi Limited
Date: 29-07-2020
DOI: 10.1002/DA.23079
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.SMRV.2015.02.003
Abstract: Sleep restriction therapy is a core element of contemporary cognitive-behavioural therapy for insomnia and is also effective as a single-component therapeutic strategy. Since its original description, sleep restriction therapy has been applied in several different ways, potentially limiting understanding of key therapeutic ingredients, mode of action, evidence synthesis, and clinical implementation. We sought to examine the quality of reporting and variability in the application of sleep restriction therapy within the context of insomnia intervention trials. Systematic literature searches revealed 88 trials of cognitive-behavioural therapy/sleep restriction therapy that met pre-defined inclusion/exclusion criteria. All papers were coded in relation to their description of sleep restriction therapy procedures. Findings indicate that a large proportion of papers (39%) do not report any details regarding sleep restriction therapy parameters and, for those papers that do, variability in implementation is present at every level (sleep window generation, minimum time-in-bed, sleep efficiency titration criteria, and positioning of sleep window). Only 7% of papers reported all parameters of sleep restriction treatment. Poor reporting and variability in the application of sleep restriction therapy may hinder progress in relation to evidence synthesis, specification of mechanistic components, and refinement of therapeutic procedures for patient benefit. We set out guidelines for the reporting of sleep restriction therapy as well as a research agenda aimed at advancing understanding of sleep restriction therapy.
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alasdair Henry.