Binding of IscU and TusA to different but competing sites of IscS influences the activity of IscS and directs sulfur to the respective biomolecular synthesis pathway.

All sulfur transfer pathways generally have in common an l-cysteine desulfurase as the initial sulfur-mobilizing enzyme, which serves as a sulfur donor for the biosynthesis of numerous sulfur-containing biomolecules in the cell. In Escherichia coli, the housekeeping l-cysteine desulfurase IscS functions as a hub for sulfur transfer through interactions with several partner proteins, which bind at different sites on IscS. So far, the interaction sites of IscU, Fdx, CyaY, and IscX involved in iron sulfur (Fe-S) cluster assembly, TusA, required for molybdenum cofactor biosynthesis and mnm5s2U34 transfer RNA (tRNA) modifications, and ThiI, involved in both the biosynthesis of thiamine and s4U8 tRNA modifications, have been mapped. Previous studies have suggested that IscS partner proteins bind only one at a time, with the exception of Fe-S cluster assembly, which involves the formation of a ternary complex involving IscS, IscU, and one of CyaY, Fdx, or IscX. Here, we show that the affinity of TusA for IscS is similar to but lower than that of IscU and that these proteins compete for binding to IscS. We show that heterocomplexes involving the IscS dimer and single IscU and TusA molecules are readily formed and that binding of both TusA and IscU to IscS affects its l-cysteine desulfurase activity. A model is proposed in which the delivery of sulfur to different sulfur-requiring pathways is controlled by sulfur acceptor protein levels, IscS-binding affinities, and acceptor protein-modulated IscS desulfurase activity.IMPORTANCEIron-sulfur clusters are evolutionarily ancient prosthetic groups. The housekeeping l-cysteine desulfurase IscS functions as a central core for sulfur transfer through interactions with several partner proteins, which bind at different sites on each IscS monomer with different affinities and partially overlapping binding sites. We show that heterocomplexes involving the IscS dimer and single IscU and TusA molecules at each site of the dimer are formed, thereby influencing the activity of IscS.

Mental health clinical pathways for children and young people with long-term health conditions: A systematic review.

RATIONALE: Clinical pathways (CPWs) are structured care plans that set out essential steps in the care of patients with a specific clinical problem. Amidst calls for the prioritisation of integrated mental and physical health care for young people, multidisciplinary CPWs have been proposed as a step towards closer integration. There is very limited evidence around CPWs for young people with mental and physical health needs, necessitating a review of the literature. AIMS AND OBJECTIVES: The aim of this review is to understand how clinical pathways have been used to deliver mental health support to children and young people with long-term physical health conditions and their effectiveness across a range of outcomes. METHODS: The databases MEDLINE, CENTRAL, PsycINFO and CINAHL were searched from inception to 6 September 2023. Keywords linked to children and young people, mental health, long-term physical health conditions and CPWs were used. Studies using either quantitative or qualitative research designs were included. All studies must have evaluated a CPW to provide mental health support to children and young people (up to 25 years old) with long-term health physical conditions. Both mental and physical health outcomes were considered. Pathways were grouped by integration 'model' as described in the wider literature. RESULTS: The initial search returned 4082 studies after deduplication. A total of eight studies detailing six distinct care pathways (232 participants [170 children and young people; 50 caregivers; 12 healthcare professionals]) met eligibility criteria and were included in the analysis. Four pathways were conducted within an 'integrated model'; two were a combination of 'integrated' and 'colocated'; and none within a 'co-ordinated model'. Only pathways within an integrated model reported quantitative health outcomes, with improvements across a range of mental health measures. One negative physical health outcome was reported from an integrated diabetes pathway, but this should be interpreted with caution. CONCLUSION: This review identified a range of CPW designs but most fell under an integrated model. The results suggest that calls for integrated mental health pathways in this population may be appropriate; however, conclusions are limited by a paucity of evidence.

Training and supervision of physical health professionals to implement mental health care in paediatric epilepsy clinics.

BACKGROUND: Children and young people with epilepsy are more likely to experience multiple mental health problems than those without chronic physical health conditions, yet they often do not receive evidence-based (or indeed any) psychological interventions. Integrated healthcare is recommended as a solution to address these inequalities, but remains limited in the United Kingdom. This is partly due to the lack of training and availability of ongoing supervision for clinicians to ensure the safe and effective delivery of treatments. This study aimed to train and provide supervision for health professionals to deliver a modular cognitive-behavioural intervention for common mental health problems, optimised for use in paediatric epilepsy. Specifically, this study aimed to measure therapist competence and evaluate the acceptability of training and supervision. METHODS: Fifteen health professionals working in paediatric epilepsy services were trained over a six-month period. Training included face-to-face training workshops and completing at least one training case of a young person with epilepsy and anxiety, depression and/or behavioural problems under close clinical supervision. Throughout the training, health professionals were offered weekly one-hour supervisions with an experienced Clinical Psychologist. Clinical competence was assessed using a widely used measure of therapist competence in cognitive-behavioural therapy. Rates of attendance at supervision sessions and therapist ratings of satisfaction were recorded. RESULTS: At the end of the six-month training, 14 health professionals reached clinical competence in delivering the mental health intervention. One person left the service and therefore did not complete the training. Overall, health professionals were satisfied with the training and supervision. However, 14 % of supervision sessions were cancelled and a further 11 % were not attended. Supervision sessions were also often shorter than the standard hour used in mental health settings (M = 41.18 min, SD = 10.30). CONCLUSIONS: Our findings suggest that health professionals working in paediatric epilepsy services can be trained to deliver a psychological intervention with proficiency. However, the supervision model typically used in mental health may need adaptation to be sustainable in physical health settings. Future research is needed to evaluate the impact of training and supervision on patient outcomes and to ensure that ethical delivery of psychological interventions by health professionals without a mental health background.

Clinical effectiveness of drop-in mental health services at paediatric hospitals: A non-randomised multi-site study for children and young people and their families - study protocol.

BACKGROUND: Despite the high prevalence of mental health difficulties in children and young people with long-term health conditions (LTCs), these difficulties and experiences are often overlooked and untreated. Previous research demonstrated the effectiveness of psychological support provided via a drop-in mental health centre located in a paediatric hospital. The aim of this prospective non-randomised single-arm multi-centre interventional study is to determine the clinical effectiveness of drop-in mental health services when implemented at paediatric hospitals in England. METHODS: It is hypothesised that families who receive psychological interventions through the drop-in services will show improved emotional and behavioural symptoms. Outcomes will be measured at baseline and at 6-month follow-up. The primary outcome is the difference in the total difficulties score on the Strengths and Difficulties Questionnaire (SDQ) reported by parent or child at 6 months. Secondary outcomes include self and parent reported Paediatric Quality of Life Inventory (PedsQL), self-reported depression (PHQ-9) and anxiety measures (GAD-7) and family satisfaction (CSQ-8). DISCUSSION: This trial aims to determine the clinical effectiveness of providing psychological support in the context of LTCs through drop-in mental health services at paediatric hospitals in England. These findings will contribute to policies and practice addressing mental health needs in children and young people with other long-term health conditions. TRIAL REGISTRATION: ISRCTN15063954, Registered on 9 December 2022.

Guided self-help treatment for children and young people with threshold and subthreshold eating disorders: A pilot study protocol.

BACKGROUND: Prompt access to evidence-based treatment for children and young people with eating disorders is important for outcomes, yet the gap in service provision remains pervasive. Record levels of young people are waiting for eating disorder treatment and access to care is limited. Guided self-help interventions that are brief and require minimal clinician support have the potential to meet the unprecedented demand for treatment quickly and effectively. OBJECTIVE: To examine the feasibility, acceptability and proof of concept of a novel, CBT guided self-help intervention for children and young people with threshold and subthreshold eating disorders. METHODS: A single-arm, proof-of-concept pilot study of the CBT guided self-help intervention will be conducted. Children and young people (aged 11-19) with threshold and subthreshold eating disorders will receive a self-help intervention covering the core components of CBT, supported by 8 weekly guidance sessions delivered remotely. Clinical outcomes (eating-related psychopathology and associated impairment, changes in weight, depression, anxiety, and behavioural difficulties) will be assessed at baseline and post-intervention (12 weeks). Feasibility and acceptability of the intervention will be measured using various outcomes, including adherence to, and engagement with the intervention, rates of recruitment and retention, measure completion and treatment satisfaction. Qualitative data will also be collected for future intervention refinement. DISCUSSION: If the intervention is shown to produce clinical benefits in this pilot study, a fully powered randomised pilot study will be warranted with the ultimate goal of increasing access to psychological treatment for children and young people threshold and subthreshold eating disorders. ADMINISTRATIVE INFORMATION: This study protocol (S1 File) adheres to the guidelines outlined in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist for trial protocols [1, 2] which can be found in S1 Checklist. The numbers in parentheses in this protocol correspond to the item numbers in the SPIRIT checklist. The order of items has been modified to group similar items.

Probing Non-Covalent Interactions through Molecular Balances: A REG-IQA Study.

The interaction energies of two series of molecular balances (1-X with X = H, Me, OMe, NMe2 and 2-Y with Y = H, CN, NO2, OMe, NMe2) designed to probe carbonyl…carbonyl interactions were analysed at the B3LYP/6-311++G(d,p)-D3 level of theory using the energy partitioning method of Interacting Quantum Atoms/Fragments (IQA/IQF). The partitioned energies are analysed by the Relative Energy Gradient (REG) method, which calculates the correlation between these energies and the total energy of a system, thereby explaining the role atoms have in the energetic behaviour of the total system. The traditional "back-of-the-envelope" open and closed conformations of molecular balances do not correspond to those of the lowest energy. Hence, more care needs to be taken when considering which geometries to use for comparison with the experiment. The REG-IQA method shows that the 1-H and 1-OMe balances behave differently to the 1-Me and 1-NMe2 balances because the latter show more prominent electrostatics between carbonyl groups and undergoes a larger dihedral rotation due to the bulkiness of the functional groups. For the 2-Y balance, REG-IQA shows the same behaviour across the series as the 1-H and 1-OMe balances. From an atomistic point of view, the formation of the closed conformer is favoured by polarisation and charge-transfer effects on the amide bond across all balances and is counterbalanced by a de-pyramidalisation of the amide nitrogen. Moreover, focusing on the oxygen of the amide carbonyl and the α-carbon of the remaining carbonyl group, electrostatics have a major role in the formation of the closed conformer, which goes against the well-known n-π* interaction orbital overlap concept. However, REG-IQF shows that exchange-correlation energies overtake electrostatics for all the 2-Y balances when working with fragments around the carbonyl groups, while they act on par with electrostatics for the 1-OMe and 1-NMe2. REG-IQF also shows that exchange-correlation energies in the 2-Y balance are correlated to the inductive electron-donating and -withdrawing trends on aromatic groups. We demonstrate that methods such as REG-IQA/IQF can help with the fine-tuning of molecular balances prior to the experiment and that the energies that govern the probed interactions are highly dependent on the atoms and functional groups involved.

Clinical effectiveness of the psychological therapy Mental Health Intervention for Children with Epilepsy in addition to usual care compared with assessment-enhanced usual care alone: a multicentre, randomised controlled clinical trial in the UK.

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.

Risk of new onset and persistent psychopathology in children with long-term physical health conditions: a population-based cohort study.

Children and young people (CYP) with long-term physical health conditions (pLTCs) have increased risk of psychopathology compared to physically healthier peers. We explored risk factors for new onset and persistent psychiatric disorders in CYP with pLTCs compared to CYP without pLTCs. This 3-year follow-up study involved a UK representative sample of CYP from the British Child and Adolescent Mental Health Surveys (N = 7804). We examined potential baseline predictors of new onset and persistent psychiatric disorders at follow-up in four groups of children based on the presence of any physical and/or any psychiatric conditions at baseline. Psychiatric disorders were assessed using standardised multi-informant diagnostic assessment. Separate multivariable binary logistic regressions were conducted for each group. In CYP with pLTCs, rented housing (aOR = 1.42, 95% CI 1.01 to 1.99), non-traditional family structure (aOR = 2.08, 95% CI 1.42 to 3.05), increased parental distress (aOR = 1.09, 95% CI 1.04 to 1.14), and greater peer relationship difficulties (aOR = 1.29, 95% CI 1.19 to 1.39) predicted future psychiatric disorder. Only peer relationship difficulties predicted persistent disorder (aOR = 1.27, 95% CI 1.17 to 1.38) in this group. A greater number of factors predicted the onset of psychiatric disorder in CYP with pLTCs compared to physically healthier peers and similarly, a higher number of factors predicted persistent disorder in CYP without pLTCs. CYP with pLTCs might comprise a group with different vulnerabilities, some of which are potentially tractable and may be useful indicators of patients who require preventable or management interventions.

Mental health interventions for children and young people with long-term health conditions in Children and Young People's Mental Health Services in England.

BACKGROUND: Almost a quarter of children and young people (CYP) in England have a long-term health condition (LTC), which increases the risk of developing mental health difficulties. There is a lack of understanding regarding the routine provision and efficacy of mental health interventions for CYP with LTCs within Children and Young People's Mental Health Services (CYPMHS). METHODS: This study analysed national service-reported data in England from two secondary datasets. Data were submitted by services between 2011 and 2019. We evaluated data on the presence or absence of a serious physical health or neurological issue, and which interventions were offered. RESULTS: A total of 789 CYP had serious physical health issues and 635 had neurological issues. The most common interventions delivered to CYP in either group have some evidence in the literature. Most CYP showed improvements across a range of outcomes. CONCLUSIONS: This study found that prevalence rates and psychological intervention and outcome data were widely under-reported across both datasets, posing questions about their utility for this population. Such data would benefit from triangulation with data from other sources to understand pathways of care for these young people and the extent to which clinical datasets underreport the number of CYP with LTCs.

Almost a quarter of children and young people (CYP) in England have a long-term health condition (LTC), such as asthma, diabetes, or epilepsy. We know that these young people are at increased risk of developing mental health difficulties. It is important these young people are able to access safe and effective treatments for their mental health. Therefore, they are sometimes referred to Children and Young People's Mental Health Services (CYPMHS) for appropriate treatment. However, at the moment, not much is known about the types of mental health support these services offer to children with co-existing physical health needs, or if this support is effective. The aim of this study was to try and find this out. We used data that had already been collected from mental health services across England. We looked at specific parts of this data that gave us information about the type of mental health treatments delivered to children with a long-term health condition. We separated long-term health conditions into two categories: physical health, such as diabetes or asthma; and neurological, such as epilepsy. In the sample we looked at, a range of mental health treatments were delivered to young people in both groups. Encouragingly, many of the young people's mental health improved. However, a lot of information we would hope to find was not available in the datasets. Also, the number of children with a long-term health condition was much lower than we expected. This might have been for a number of reasons, which we recommend other future research tries to find out. Going forward, it is important to think about how to make sure that accurate information about these children is collected from mental health services. This will help ensure that the right decisions are made for the care of young people with long-term health conditions.

Persistent symptoms are associated with long term effects of COVID-19 among children and young people: Results from a systematic review and meta-analysis of controlled studies.

BACKGROUND: Research on the long-term impact on COVID-19 in children and young people (CYP) has been published at pace. We aimed to update and refine an earlier systematic review and meta-analysis to assess the current evidence for Post-COVID-19 Condition in CYP. METHODS: Studies from the previous systematic review were combined with studies from a systematic search from July 2021 to November 2022 (registration PROSPERO CRD42021233153). Eligible studies included CYP aged ≤19 years with confirmed or probable SARS-CoV-2 infection and symptoms persisting at least 12 weeks. FINDINGS: 55 studies (n = 1,139,299 participants) were included. Over two-hundred symptoms were associated with Post COVID-19 Condition. Gastrointestinal problems, headaches, cough and fever were among the most prevalent symptoms with rates of 50.2%, 35.6%, 34.7% and 25.8% respectively. Twenty-one symptoms from 11 studies were suitable for meta-analysis. There were significantly higher pooled estimates of proportions of symptoms for altered / loss of smell or taste, dyspnoea, fatigue, and myalgia in CYP with confirmed SARS-CoV-2 infection. Heterogeneity was high suggesting substantial variation amongst the included studies. CONCLUSIONS: Many CYP continue to experience symptoms after SARS-CoV-2 infection. Efforts to aid early identification and intervention of those most in need is warranted and the consequences of COVID-19 for CYP call for long-term follow-up.

Online remote behavioural intervention for tics in 9- to 17-year-olds: the ORBIT RCT with embedded process and economic evaluation.

Background: Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective: To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design: Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting: Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants: Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions: Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome: Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results: Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval -0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms: Two serious, unrelated adverse events occurred in the control group. Limitations: We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion: Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work: Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration: This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9­17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy.

Feasibility, acceptability and preliminary effectiveness of a mental health drop-in centre for the siblings of young people attending a paediatric hospital.

Siblings of children with long-term conditions (LTCs) can have significantly elevated mental health needs, but these are often overlooked. A pragmatic single-arm feasibility pilot assessed feasibility, acceptability and preliminary effectiveness of a drop-in centre in a paediatric hospital addressing mental health needs of patients with LTCs, their carers and siblings. The drop-in centre accepted self-referral and supplemented existing provision offering a suite of interventions, including signposting, diagnostic assessments and/or guided self-help. This paper reports on feasibility, acceptability and preliminary outcomes of this centre for siblings. Eighteen siblings aged 2-17 used the centre. Sixteen of their parents completed the Strengths and Difficulties Questionnaires at baseline and 6 months post-baseline, and ten completed parent-reported PedsQL across two time points. Preliminary effectiveness results demonstrated a decrease in mental health symptoms with large effect size (score reduction of 3.44, 95% CI [1.25, 5.63], d = 0.84) and small effect on quality of life, with scores increasing from a median of 69.91, 95% CI [53.57, 91.67], to a median of 80.44, 95% CI [67.39, 89.13], r = 0.11 for these siblings. 88% of parents were satisfied with this provision for their sibling child. This study highlights the feasibility and value of assessing siblings for emotional and behavioural difficulties and providing them with an accessible, effective and acceptable intervention.

Harnessing water fleas for water reclamation: A nature-based tertiary wastewater treatment technology.

Urbanisation, population growth, and climate change have put unprecedented pressure on water resources, leading to a global water crisis and the need for water reuse. However, water reuse is unsafe unless persistent chemical pollutants are removed from reclaimed water. State-of-the-art technologies for the reduction of persistent chemical pollutants in wastewater typically impose high operational and energy costs and potentially generate toxic by-products (e.g., bromate from ozonation). Nature-base solutions are preferred to these technologies for their lower environmental impact. However, so far, bio-based tertiary wastewater treatments have been inefficient for industrial-scale applications. Moreover, they often demand significant financial investment and large infrastructure, undermining sustainability objectives. Here, we present a scalable, low-cost, low-carbon, and retrofittable nature-inspired solution to remove persistent chemical pollutants (pharmaceutical, pesticides and industrial chemicals). We showed Daphnia's removal efficiency of individual chemicals and chemicals from wastewater at laboratory scale ranging between 50 % for PFOS and 90 % for diclofenac. We validated the removal efficiency of diclofenac at prototype scale, showing sustained performance over four weeks in outdoor seminatural conditions. A techno-commercial analysis on the Daphnia-based technology suggested several technical, commercial and sustainability advantages over established and emerging treatments at comparable removal efficiency, benchmarked on available data on individual chemicals. Further testing of the technology is underway in open flow environments holding real wastewater. The technology has the potential to improve the quality of wastewater effluent, meeting requirements to produce water appropriate for reuse in irrigation, industrial application, and household use. By preventing persistent chemicals from entering waterways, this technology has the potential to maximise the shift to clean growth, enabling water reuse, reducing resource depletion and preventing environmental pollution.

Do single-case experimental designs lead to randomised controlled trials of cognitive behavioural therapy interventions for adolescent anxiety and related disorders recommended in the National Institute of Clinical Excellence guidelines? A systematic review.

Background: Although Cognitive Behavioural Therapy (CBT) is effective for 60% of adolescents with anxiety disorders, only 36% are in remission post-intervention. This indicates that more effective treatments are needed which should be reflected in the NICE guidelines. We hypothesised that Single-case experimental designs (SCEDs) may provide a framework for accelerating the development of novel interventions. The primary purpose of this review was to investigate whether SCEDs are currently followed by randomised controlled trials (RCTs) of CBT intervention for adolescent anxiety disorders named in the NICE guidelines. The secondary objective was to investigate whether using SCEDs prior to RCTs could be a helpful approach. Method: For the primary search of SCEDs five databases were used (PsycINFO, PubMed, PsycArticles, Web of Science and ProQuest). Nineteen articles met eligibility criteria including a total of 107 participants. For the secondary search of RCTs named in the NICE guidelines for adolescent anxiety disorders 53 articles met inclusion criteria and were included in the systematic review. Results: The 19 SCED studies included in the review were conducted with participants with a diverse range of anxiety disorders and across a range of CBT formats. Two of the SCEDs were followed by RCTs, but neither of these were named in the NICE guidelines for anxiety disorders. All of the SCEDs identified were rated as low quality with none meeting the criteria for the highest or second highest quality rating. From the secondary searches, none of the RCTs named in the NICE guide were preceded by SCEDs. Conclusions: It was concluded that currently SCEDs were not followed by RCTs of CBT interventions named in the NICE guidelines for adolescent anxiety disorders. However, it was suggested that SCEDs may provide an important framework for the development of more effective interventions for adolescents with anxiety.

The development and preliminary evaluation of Cognitive Behavioural Therapy (CBT) for Chronic Loneliness in Young People.

BACKGROUND: Approximately 10% of young people 'often' feel lonely, with loneliness being predictive of multiple physical and mental health problems. Research has found CBT to be effective for reducing loneliness in adults, but interventions for young people who report loneliness as their primary difficulty are lacking. METHOD: CBT for Chronic Loneliness in Young People was developed as a modular intervention. This was evaluated in a single-case experimental design (SCED) with seven participants aged 11-18 years. The primary outcome was self-reported loneliness on the Three-Item Loneliness Scale. Secondary outcomes were self-reported loneliness on the UCLA-LS-3, and self- and parent-reported RCADS and SDQ impact scores. Feasibility and participant satisfaction were also assessed. RESULTS: At post-intervention, there was a 66.41% reduction in loneliness, with all seven participants reporting a significant reduction on the primary outcome measure (p < .001). There was also a reduction on the UCLA-LS-3 of a large effect (d = 1.53). Reductions of a large effect size were also found for parent-reported total RCADS (d = 2.19) and SDQ impact scores (d = 2.15) and self-reported total RCADS scores (d = 1.81), with a small reduction in self-reported SDQ impact scores (d = 0.41). Participants reported high levels of satisfaction, with the protocol being feasible and acceptable. CONCLUSIONS: We conclude that CBT for Chronic Loneliness in Young People may be an effective intervention for reducing loneliness and co-occurring mental health difficulties in young people. The intervention should now be evaluated further through a randomised controlled trial (RCT).

British Society for Paediatric and Adolescent Dermatology assessment and support of mental health in children and young people with skin conditions: a multidisciplinary expert consensus statement and recommendations.

BACKGROUND: Psychological and mental health difficulties are common in children and young people (CYP) living with skin conditions and can have a profound impact on wellbeing. There is limited guidance on how best to assess and support the mental health of this population, who are at risk of poor health outcomes. OBJECTIVES: To provide consensus-based recommendations on the assessment and monitoring of and support for mental health difficulties in CYP with skin conditions (affecting the skin, hair and nails); to address practical clinical implementation questions relating to consensus guidance; and to provide audit and research recommendations. METHODS: This set of recommendations was developed with reference to the AGREE II instrument. A systematic review and literature appraisal was carried out. A multidisciplinary consensus group was convened, with two virtual panel meetings held: an initial meeting to discuss the scope of the study, to review the current evidence and to identify areas for development; and a second meeting to agree on the content and wording of the recommendations. Recommendations were then circulated to stakeholders, following which amendments were made and agreed by email. RESULTS: The expert panel achieved consensus on 11 recommendations for healthcare workers managing CYP with skin conditions. A new patient-completed history-taking aid ('You and Your Skin') was developed and is being piloted. CONCLUSIONS: The recommendations focus on improved mental health assessments for CYP presenting with a skin condition, with clinical guidance and suggested screening measures included. Information on accessing psychological support for CYP, when required, is given, and recommendations for staff training in mental health and neurodiversity provided. Embedding a psychosocial approach within services treating CYP with skin disease should ensure that CYP with psychological needs are able to be identified, listened to, supported and treated. This is likely to improve health outcomes.

Improving programme-led and focused interventions for eating disorders: An experts' consensus statement-A UK perspective.

OBJECTIVE: Eating disorders are associated with significant illness burden and costs, yet access to evidence-based care is limited. Greater use of programme-led and focused interventions that are less resource-intensive might be part of the solution to this demand-capacity mismatch. METHOD: In October 2022, a group of predominantly UK-based clinical and academic researchers, charity representatives and people with lived experience convened to consider ways to improve access to, and efficacy of, programme-led and focused interventions for eating disorders in an attempt to bridge the demand-capacity gap. RESULTS: Several key recommendations were made across areas of research, policy, and practice. Of particular importance is the view that programme-led and focused interventions are suitable for a range of different eating disorder presentations across all ages, providing medical and psychiatric risk are closely monitored. The terminology used for these interventions should be carefully considered, so as not to imply that the treatment is suboptimal. CONCLUSIONS: Programme-led and focused interventions are a viable option to close the demand-capacity gap for eating disorder treatment and are particularly needed for children and young people. Work is urgently needed across sectors to evaluate and implement such interventions as a clinical and research priority.

Low intensity psychological interventions for the treatment of feeding and eating disorders: a systematic review and meta-analysis.

BACKGROUND: Feeding and eating disorders are associated with significant illness burden and costs, yet access to evidence-based care is limited. Low intensity psychological interventions have the potential to increase such access. METHODS: A systematic review and meta-analysis were conducted on the use of low intensity psychological interventions for the treatment of feeding and eating disorders. Studies comparing low intensity psychological interventions against high intensity therapies and non-eating disorder specific psychological interventions were included, as well as those with waiting list control arms. There were three primary outcomes: eating disorder psychopathology, diagnostic and statistical manual of mental disorders (DSM) severity specifier-related outcomes and rates of remission/recovery. RESULTS: Thirty-three studies met the inclusion criteria, comprising 3665 participants, and 30 studies were included in the meta-analysis. Compared to high intensity therapies, low intensity psychological interventions were equivalent on reducing eating disorder psychopathology (g = - 0.13), more effective at improving DSM severity specifier-related outcomes (g = - 0.15), but less likely to achieve remission/recovery (risk ratio (RR) = 0.70). Low intensity psychological interventions were superior to non-eating disorder specific psychological interventions and waiting list controls across all three primary outcomes. CONCLUSION: Overall, findings suggest that low intensity psychological interventions can successfully treat eating disorder symptoms. Few potential moderators had a statistically significant effect on outcome. The number of studies for many comparisons was low and the methodological quality of the studies was poor, therefore results should be interpreted with caution. More research is needed to establish the effectiveness of low intensity psychological interventions for children and young people, as well as for individuals with anorexia nervosa, avoidant/restrictive food intake disorder, pica and rumination disorder.

Feeding and eating disorders can significantly impair health and psychosocial functioning. However, demand for eating disorder services is greater than services' ability to deliver effective treatment. Low intensity psychological interventions, which are brief in nature and require less therapist input than standard treatments, have the potential to bridge this demand-capacity gap. The current review examined the effectiveness of low intensity psychological interventions for the treatment of feeding and eating disorders. Overall, findings suggest that low intensity psychological interventions can successfully treat eating disorder symptoms, particularly binge eating-related symptoms. Given their relatively low costs and ease of accessibility, such interventions can help people to access treatment at a time when this is so desperately needed. More research is needed to determine the value of low intensity psychological interventions for children and adolescents, and people with feeding and eating disorders that are not characterised by recurrent binge eating, such as anorexia nervosa, ARFID, pica and rumination disorder.

Quantifying the impacts of predation by Great Black-backed Gulls Larus marinus on an Atlantic Puffin Fratercula arctica population: Implications for conservation management and impact assessments.

The management of predator-prey conflicts can be a key aspect of species conservation. For management approaches to be effective, a robust understanding of the predator-prey relationship is needed, particularly when both predator and prey are species of conservation concern. On the Isle of May, Firth of Forth, Scotland, numbers of breeding Great Black-backed Gulls Larus marinus, a generalist predator, have been increasing since the 1980s, which has led to increasing numbers of sympatrically breeding Atlantic Puffins Fratercula arctica being predated during the breeding season. This may have consequences for species management on the Isle of May and impact assessments of offshore windfarms in the wider Firth of Forth area. We used population viability analysis to quantify under what predation pressure the Atlantic Puffin population may decline and become locally extinct over a three-generation period. The predation level empirically estimated in 2017 (1120 Puffins per year) was not sufficient to drive a decline in the Puffin population. Rather, an increase to approximately 3000 Puffins per year would be required to cause a population decline, and >4000 to drive the population to quasi-extinction within 66 years. We discuss the likelihood of such a scenario being reached on the Isle of May, and we recommend that where predator-prey conflicts occur, predation-driven mortality should be regularly quantified to inform conservation management and population viability analyses associated with impact assessments.

The Influence of Comorbidity and Perceived Complexity on Outcomes of Referrals to Children and Young Person Mental Health Services (UK): A Mixed Methods Vignette Study.

Children and young people (CYP) with long-term physical conditions (LTCs) are four times more likely to develop mental health disorders yet many cannot access Children and Young People's Mental Health Services (CYPMHS) or evidence-based interventions. This study aimed to understand the reasons for this; presence of an LTC neurodevelopmental disorder, or service requirements. 79 CYP mental health practitioners were randomly assigned to read vignettes depicting a hypothetical referral letter for a child with a mental health condition alone (n = 27), mental health condition and LTC (n = 25), or mental health condition and neurodevelopmental disorder (Autism Spectrum Disorder-ASD) (n = 27), answering questions about their likelihood of accepting the referral and proposed treatment plan. There were no significant differences between accessing CYPMHS or being offered first line evidence-based interventions in those with a LTC or ASD compared to those without. However, additional perceived complexity was frequently provided as a reason for rejecting referrals and not offering evidence-based intervention, with clinicians' predicted success of intervention significantly lower for these CYP. Clinicians were significantly more likely to suggest adapting the intervention in the LTC and the ASD groups to account for additional perceived complexity. The research suggests a need for additional services for CYP with LTCs and those with neurodevelopmental disorders, as well as training/awareness for clinicians.