Reversible DNA micro-patterning using the fluorous effect

We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences

Insomnia, depression, and anxiety symptoms interact and individually impact functioning: A network and relative importance analysis in the context of insomnia

STUDY OBJECTIVES: Insomnia, depression, and anxiety show high rates of comorbidity and functional impairment. Transdiagnostic symptom interactions may be implicated in this comorbidity. This network analysis sought to assess how symptoms of insomnia, depression, and anxiety may interact and individually predict impairment across several domains for individuals with insomnia. METHODS: Baseline psychometric data from a randomised controlled trial were analysed (N = 1711). A regularized partial correlation network was estimated from the symptom data. Centrality (symptom connectivity), community structure (symptom clustering), and bridging (inter-community connectivity) were assessed. The replicability of the network model was assessed via confirmatory analyses in a holdout sample. Separately, Shapley values were estimated to determine the relative importance of each symptom in predicting functioning (i.e., psychological wellbeing, psychosocial functioning, and physical health impairment). RESULTS: The most connected nodes were uncontrollable worrying; trouble relaxing; and depressed mood/hopelessness. Five communities were identified with trouble relaxing identified as the bridge symptom between communities. The model showed good fit in the holdout sample. Low energy and depressive affect symptoms (feelings of failure/guilt; depressed mood/hopelessness; anhedonia) were key predictors in the relative importance analysis across multiple domains of impairment. CONCLUSION: Trouble relaxing may be of clinical and transdiagnostic significance in the context of insomnia. In terms of how symptoms relate to functioning, it was clear that, while low energy and feelings of failure/guilt were prominent predictors, a range of symptoms are associated with functional impairment. Consideration of both symptoms and functional impairment across domains may be useful in determining targets for treatment. CLINICAL TRIAL REGISTRATION: This is a secondary analysis of an original clinical trial. TRIAL REGISTRATION NUMBER: ISRCTN60530898. Registry URL: https://www.isrctn.com/ISRCTN60530898

Does treating insomnia with digital cognitive behavioural therapy (Sleepio) mediate improvements in anxiety for those with insomnia and comorbid anxiety?:An analysis using individual participant data from two large randomised controlled trials

Background: Considerable comorbidity exists between insomnia and anxiety, and evidence shows that the benefits of CBT for insomnia extend to anxiety. Using data from two large trials of digital CBT (dCBT) for insomnia, we evaluated whether improving sleep is an effective treatment target to reduce both insomnia and anxiety symptoms in individuals with insomnia and clinically significant anxiety. Methods: This was a controlled sub-analysis combining individual participant data from two previous randomised controlled trials of dCBT for insomnia (Sleepio). Participants (N = 2172) with insomnia disorder and clinically significant anxiety symptoms were included in this sub-analysis and received either dCBT or control (usual care or sleep hygiene education). Assessments were evaluated at baseline, post-intervention (week 8 or 10), and follow-up (week 22 or 24). Mediation was evaluated using structural equation models. Results: dCBT for insomnia was superior to control at reducing both insomnia (Hedges' g range = 0.77–0.81; both p &lt; 0.001) and anxiety symptoms (Hedges' g range = 0.39–0.44; both p &lt; 0.001) at all time points. Baseline insomnia symptoms moderated the effects of dCBT on insomnia, however no variables moderated treatment effects on anxiety. Reductions in anxiety symptoms at follow-up were mediated by improvements in sleep at post-intervention (% mediated = 84 %), suggesting a causal pathway. Limitations: Participants did not have a formal anxiety disorder diagnosis and so the effects of dCBT for insomnia on anxiety may differ by anxiety disorder. Conclusions: Addressing sleep using dCBT for insomnia may serve as a treatment target from which to improve anxiety in individuals with insomnia and clinically significant comorbid anxiety. Clinical trial registrations: Digital Insomnia therapy to Assist your Life as well as your Sleep (DIALS) - ISRCTN60530898 http://www.isrctn.com/ISRCTN60530898. Oxford Access for Students Improving Sleep (OASIS) - ISRCTN61272251 http://www.isrctn.com/ISRCTN61272251.</p

Development of a hybrid sleep and physical activity improvement intervention for adults with osteoarthritis-related pain and sleep disturbance : a focus group study with potential users

Objective: Suboptimal sleep and physical activity are common among people living with osteoarthritis (OA) and simultaneous improvements in both may have a beneficial impact on pain. This study aimed to gather perspectives of people living with OA on important aspects to incorporate in a hybrid sleep and physical activity improvement intervention for OA pain management. Design: Qualitative study using two rounds of two focus groups. Setting and participants: Focus groups were conducted with adults living with OA-related chronic pain and sleep disturbances. Eighteen people attended focus groups in January 2020 and, of these, 16 attended subsequent focus groups in February 2020. Methods: Discussion at the first round of focus groups informed generation of prototype intervention materials that were shared, discussed and refined at the second round of focus groups. Thematic analysis was used to identify themes and sub-themes from the data. Results: Three themes, each with three sub-themes, were identified: facilitators of engagement with the intervention (sub-themes: motivational language, accountability and education); barriers to engagement (sub-themes: suboptimal interaction with healthcare practitioners, recording behaviour as burdensome/disruptive and uncertainty about technique) and characteristics of a physical activity intervention component (sub-themes: tailored, sustainable and supported). Conclusion: We have identified important aspects to incorporate into the design and delivery of a hybrid sleep and physical activity improvement intervention for OA pain management. Insights will be incorporated into intervention materials and protocols, with feasibility and acceptability assessed in a future study

Exploring digital cognitive behavioural therapy for insomnia in an early intervention in psychosis service – a study protocol for an initial feasibility study with process evaluation

Aim: Early psychosis may be a critical time at which clinical trajectories are still evolving, and sleep interventions hold promise to improve outcomes at this stage. Although cognitive behavioural therapy (CBT) for insomnia shows promise in psychosis, there has been limited evaluation of delivery within current care. This study aims to evaluate the feasibility and acceptability of providing fully-automated digital CBT for insomnia (CBT-I) within an early intervention in psychosis service. Methods: We will conduct a single-arm feasibility trial within an early psychosis intervention service, and up to 40 individuals experiencing a first episode of psychosis and with evidence of insomnia can be enrolled (May 2021 – August 2022). Additional service user inclusion criteria are capacity to consent and access to a suitable technological device to access digital CBT. Participants will be offered access to a fully-automated digital CBT-I program (Sleepio) delivered using web and/or mobile app. The study comprises pre- and post- intervention questionnaire assessments and interviews with service users and staff to provide initial outcome signals. Results: Quantitative questionnaire data will be analysed descriptively, alongside rates of eligibility, consent, uptake and completion. Qualitative data will be analysed using thematic analysis. Results will be used to develop a logic model describing feasibility and implementation. Conclusions: From this study, we hope to better understand how to deliver digital CBT for insomnia within an early intervention in psychosis service. This study will help inform further research, including how best to support staff in using Sleepio, and inform the design of subsequent trials in this area

Patient-reported outcome measures in dermatology: a systematic review

By relying on data from existing patient-reported outcome measures of quality of life, the true impact of skin conditions on patients’ lives may be underestimated. This study systematically reviewed all dermatology-specific (used across skin conditions) patient-reported outcome measures and makes evidence-based recommendations for their use. The study protocol is registered on PROSPERO (CRD42018108829). PubMed, PsycInfo and CINAHL were searched from inception to 25 June 2018. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria were used to assess the measurement properties and methodological quality of studies. A total of 12,925 abstracts were identified. Zero patient-reported outcome measures were assigned to category A (ready for use without further validation), 31 to category B (recommended for use, but only with further validation) and 5 to category C (not recommended for use). There is no gold-standard dermatology-specific patient-reported outcome measure that can be recommended or used without caution. A new measure that can comprehensively capture the impact of dermatological conditions on the patient’s life is needed

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context

Background: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. Aims: The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. Method: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. Results: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. Conclusion: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk

HpARI protein secreted by a helminth parasite suppresses interleukin-33

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. Osbourn et al identified HpARI, a protein secreted by a helminth parasite that is capable of suppressing allergic responses. HpARI binds to IL-33 (a critical inducer of allergy) and nuclear DNA, preventing the release of IL-33 from necrotic epithelial cells