Lifetime incidence and healthcare disparities in alopecia areata: A UK population-based cohort study.

BACKGROUND: Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden. OBJECTIVES: We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilisation and work-related outcomes, assessing variation across major sociodemographic subgroups. METHODS: AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009-2018). Lifetime incidence of AA was estimated at age 80 using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation, and geography. Mental health, healthcare utilisation and work-related outcomes were assessed in the two years after AA diagnosis compared to matched unaffected controls, and stratified by the same sociodemographic subgroups . RESULTS: 6,961 people developed AA during the study period. Overall lifetime incidence of AA was 2.11% (95% Confidence Interval [CI] 2.06, 2.16%). Females had a higher lifetime incidence 2.35% (95%CI 2.28, 2.43%) than males 1.88% (95%CI 1.81, 1.94%). Lifetime incidence was higher in those of Asian ethnicity 5.87% (95%CI 5.51, 6.24), other 4.47% (95%CI 3.63, 5.31), mixed 4.44% (95%CI 3.50, 5.37) and black 3.03% (95%CI 2.63, 3.42) ethnicity, compared to white ethnicity 1.74% (95%CI 1.68, 1.80). Lifetime incidence was highest in those with the greatest deprivation; most-deprived quintile 2.92% (95%CI 2.77, 3.07%) compared to least-deprived 1.68% (95%CI 1.59, 1.78%). Across sociodemographic subgroups, people with AA of black ethnicity were most likely to have anxiety (adjusted Odds Ratio versus matched controls 2.92, 95%CI 1.71, 4.91), and had the greatest risk of time off work (adjusted Hazard Ratio versus matched controls 2.54, 95%CI 1.80, 3.56). CONCLUSIONS: AA affects around 1 in 50 people over their lifetime. Incidence and the impact of AA on mental health and work outcomes, is highest in ethnic groups other than white. Clinicians should be aware of the marked heterogeneity in the incidence and impact of AA, and support targeted healthcare to groups at the highest risk of alopecia and its consequences.The study protocol for this retrospective observational study was registered with ClinicalTrials.gov (Identifier: NCT05727306).

Healthcare professionals' views on psychological support for children and families affected by skin conditions in the UK: A qualitative study.

Background: Skin conditions can have a psychological impact on a child and their caregivers, however, support is not equally distributed between geographical regions in the United Kingdom (UK). Objectives: This study aimed to investigate the experience of National Health Service (NHS) healthcare professionals (HCPs) of addressing the psychological needs of children with skin conditions and their families, and gain expert opinion as to how services need to further develop. Design: HCPs were recruited to a qualitative study with an advert posted on social media. Methods: Fifteen HCPs took part in interviews, including dermatologists (n = 4), dermatology nurse consultants/specialists (n = 4), clinical psychologists (n = 4), liaison psychiatrists (n = 2), and a children's psychological well-being practitioner (n = 1). Results: Thematic analysis revealed children often presented with anxiety, depression, self-harm and suicidal ideation. The impact on caregivers was equally profound. There were differences in service provision across the UK and all HCPs recognised the urgent need for psychological support to be integrated into standard care. Participants described how a range of interventions are typically required including cognitive behavioural therapy (CBT), and systemic approaches, as well as mindfulness/third-wave approaches. Barriers to the delivery of psychological services were associated with a lack of funding and training opportunities for core and specialist staff alike. However, in some instances, participants had overcome these challenges to be able to deliver unique services. Conclusions: There exist several barriers to providing paediatric psychological interventions, and many locations across the UK remain vulnerable as a result of continuing lack of national guidelines for the provision of psychological services.

Educational and psychological interventions for managing atopic dermatitis (eczema).

BACKGROUND: Atopic dermatitis (eczema), can have a significant impact on well-being and quality of life for affected people and their families. Standard treatment is avoidance of triggers or irritants and regular application of emollients and topical steroids or calcineurin inhibitors. Thorough physical and psychological assessment is central to good-quality treatment. Overcoming barriers to provision of holistic treatment in dermatological practice is dependent on evaluation of the efficacy and economics of both psychological and educational interventions in this participant group. This review is based on a previous Cochrane review published in 2014, and now includes adults as well as children. OBJECTIVES: To assess the clinical outcomes of educational and psychological interventions in children and adults with atopic dermatitis (eczema) and to summarise the availability and principal findings of relevant economic evaluations. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, APA PsycINFO and two trials registers up to March 2023. We checked the reference lists of included studies and related systematic reviews for further references to relevant randomised controlled trials (RCTs) and contacted experts in the field to identify additional studies. We searched NHS Economic Evaluation Database, MEDLINE and Embase for economic evaluations on 8 June 2022. SELECTION CRITERIA: Randomised, cluster-randomised and cross-over RCTs that assess educational and psychological interventions for treating eczema in children and adults. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, with GRADE to assess the certainty of the evidence for each outcome. Primary outcomes were reduction in disease severity, as measured by clinical signs, patient-reported symptoms and improvement in health-related quality-of-life (HRQoL) measures. Secondary outcomes were improvement in long-term control of symptoms, improvement in psychological well-being, improvement in standard treatment concordance and adverse events. We assessed short- (up to 16 weeks after treatment) and long-term time points (more than 16 weeks). MAIN RESULTS: We included 37 trials (6170 participants). Most trials were conducted in high-income countries (34/37), in outpatient settings (25/37). We judged three trials to be low risk of bias across all domains. Fifteen trials had a high risk of bias in at least one domain, mostly due to bias in measurement of the outcome. Trials assessed interventions compared to standard care. Individual educational interventions may reduce short-term clinical signs (measured by SCORing Atopic Dermatitis (SCORAD); mean difference (MD) -5.70, 95% confidence interval (CI) -9.39 to -2.01; 1 trial, 30 participants; low-certainty evidence) but patient-reported symptoms, HRQoL, long-term eczema control and psychological well-being were not reported. Group education interventions probably reduce clinical signs (SCORAD) both in the short term (MD -9.66, 95% CI -19.04 to -0.29; 3 studies, 731 participants; moderate-certainty evidence) and the long term (MD -7.22, 95% CI -11.01 to -3.43; 3 studies, 1424 participants; moderate-certainty evidence) and probably reduce long-term patient-reported symptoms (SMD -0.47 95% CI -0.60 to -0.33; 2 studies, 908 participants; moderate-certainty evidence). They may slightly improve short-term HRQoL (SMD -0.19, 95% CI -0.36 to -0.01; 4 studies, 746 participants; low-certainty evidence), but may make little or no difference to short-term psychological well-being (Perceived Stress Scale (PSS); MD -2.47, 95% CI -5.16 to 0.22; 1 study, 80 participants; low-certainty evidence). Long-term eczema control was not reported. We don't know whether technology-mediated educational interventions could improve short-term clinical signs (SCORAD; 1 study; 29 participants; very low-certainty evidence). They may have little or no effect on short-term patient-reported symptoms (Patient Oriented Eczema Measure (POEM); MD -0.76, 95% CI -1.84 to 0.33; 2 studies; 195 participants; low-certainty evidence) and probably have little or no effect on short-term HRQoL (MD 0, 95% CI -0.03 to 0.03; 2 studies, 430 participants; moderate-certainty evidence). Technology-mediated education interventions probably slightly improve long-term eczema control (Recap of atopic eczema (RECAP); MD -1.5, 95% CI -3.13 to 0.13; 1 study, 232 participants; moderate-certainty evidence), and may improve short-term psychological well-being (MD -1.78, 95% CI -2.13 to -1.43; 1 study, 24 participants; low-certainty evidence). Habit reversal treatment may reduce short-term clinical signs (SCORAD; MD -6.57, 95% CI -13.04 to -0.1; 1 study, 33 participants; low-certainty evidence) but we are uncertain about any effects on short-term HRQoL (Children's Dermatology Life Quality Index (CDLQI); 1 study, 30 participants; very low-certainty evidence). Patient-reported symptoms, long-term eczema control and psychological well-being were not reported. We are uncertain whether arousal reduction therapy interventions could improve short-term clinical signs (Eczema Area and Severity Index (EASI); 1 study, 24 participants; very low-certainty evidence) or patient-reported symptoms (visual analogue scale (VAS); 1 study, 18 participants; very low-certainty evidence). Arousal reduction therapy may improve short-term HRQoL (Dermatitis Family Impact (DFI); MD -2.1, 95% CI -4.41 to 0.21; 1 study, 91 participants; low-certainty evidence) and psychological well-being (PSS; MD -1.2, 95% CI -3.38 to 0.98; 1 study, 91 participants; low-certainty evidence). Long-term eczema control was not reported. No studies reported standard care compared with self-help psychological interventions, psychological therapies or printed education; or adverse events. We identified two health economic studies. One found that a 12-week, technology-mediated, educational-support programme may be cost neutral. The other found that a nurse practitioner group-education intervention may have lower costs than standard care provided by a dermatologist, with comparable effectiveness. AUTHORS' CONCLUSIONS: In-person, individual education, as an adjunct to conventional topical therapy, may reduce short-term eczema signs compared to standard care, but there is no information on eczema symptoms, quality of life or long-term outcomes. Group education probably reduces eczema signs and symptoms in the long term and may also improve quality of life in the short term. Favourable effects were also reported for technology-mediated education, habit reversal treatment and arousal reduction therapy. All favourable effects are of uncertain clinical significance, since they may not exceed the minimal clinically important difference (MCID) for the outcome measures used (MCID 8.7 points for SCORAD, 3.4 points for POEM). We found no trials of self-help psychological interventions, psychological therapies or printed education. Future trials should include more diverse populations, address shared priorities, evaluate long-term outcomes and ensure patients are involved in trial design.

The experience of living with vitiligo in Nigeria: A participatory Interpretative Phenomenological Analysis.

Vitiligo is a visible depigmenting skin condition, particularly noticeable on Black skin. There is widespread misunderstanding of the condition. Using a participatory form of Interpretative Phenomenological Analysis (IPA), we conducted eight semi-structured interviews with Nigerians living with vitiligo. Participants described their initial attempts to understand the condition, which typically drew on both traditional illness beliefs, religious influences, and the biomedical disease model. All participants reported experiencing marked stigmatization and discrimination. Participants experienced distress associated with thoughts about the personal meaning of the disease including its impact on their appearance and from concerns about anticipated and direct discrimination. Despite the wide-ranging impact, the participants' narratives also contained references to the development of strategies that maintained wellbeing. This study provides valuable insights into the role of faith and traditional beliefs in both the experience and management of vitiligo in Nigeria. These insights can be used to develop individual and community interventions.

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors.

The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction of BRAF dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking BRAF dimerization and conformation, we built an allosteric model of inhibitor-induced dimerization that resolves the allosteric contributions of inhibitor binding to the two active sites of the dimer, revealing key differences between type I and type II RAF inhibitors. For type II inhibitors the allosteric coupling between inhibitor binding and BRAF dimerization is distributed asymmetrically across the two dimer binding sites, with binding to the first site dominating the allostery. This asymmetry results in efficient and selective induction of dimers with one inhibited and one catalytically active subunit. Our allosteric models quantitatively account for paradoxical activation data measured for 11 RAF inhibitors. Unlike type II inhibitors, type I inhibitors lack allosteric asymmetry and do not activate BRAF homodimers. Finally, NMR data reveal that BRAF homodimers are dynamically asymmetric with only one of the subunits locked in the active αC-in state. This provides a structural mechanism for how binding of only a single αC-in inhibitor molecule can induce potent BRAF dimerization and activation.

Memory, mood and associated neuroanatomy in individuals with steroid sulphatase deficiency (X-linked ichthyosis).

Steroid sulphatase (STS) cleaves sulphate groups from steroid hormones, and steroid (sulphate) levels correlate with mood and age-related cognitive decline. In animals, STS inhibition or deletion of the associated gene, enhances memory/neuroprotection and alters hippocampal neurochemistry. Little is known about the consequences of constitutive STS deficiency on memory-related processes in humans. We investigated self-reported memory performance (Multifactorial Memory Questionnaire), word-picture recall and recent mood (Kessler Psychological Distress Scale, K10) in adult males with STS deficiency diagnosed with the dermatological condition X-linked ichthyosis (XLI; n = 41) and in adult female carriers of XLI-associated genetic variants (n = 79); we compared results to those obtained from matched control subjects [diagnosed with ichthyosis vulgaris (IV, n = 98) or recruited from the general population (n = 250)]. Using the UK Biobank, we compared mood/memory-related neuroanatomy in carriers of genetic deletions encompassing STS (n = 28) and non-carriers (n = 34,522). We found poorer word-picture recall and lower perceived memory abilities in males with XLI and female carriers compared with control groups. XLI-associated variant carriers and individuals with IV reported more adverse mood symptoms, reduced memory contentment and greater use of memory aids, compared with general population controls. Mood and memory findings appeared largely independent. Neuroanatomical analysis only indicated a nominally-significantly larger molecular layer in the right hippocampal body of deletion carriers relative to non-carriers. In humans, constitutive STS deficiency appears associated with mood-independent impairments in memory but not with large effects on underlying brain structure; the mediating psychobiological mechanisms might be explored further in individuals with XLI and in new mammalian models lacking STS developmentally.

The experiences of individuals with body dysmorphic disorder: A systematic review and thematic synthesis of qualitative research.

Body Dysmorphic Disorder (BDD) is a distressing psychological condition where an individual is preoccupied by a perceived issue with their appearance. Qualitative studies enable nuanced aspects of BDD phenomenology to be investigated. The current systematic review used thematic synthesis to integrate the findings from the extant qualitative studies. Searches were run on six databases to identify studies that had sought to describe the experience of individuals with BDD. PRISMA guidance was followed and ten articles were identified for inclusion. The quality of each article was appraised and thematic synthesis was conducted to generate novel and summative themes. Three superordinate themes were created: 'self-objectification and the view of self'; 'control and protecting the self'; and 'sociocultural influences and the impact of others in BDD'. Shame and self-disgust emerged as key experiential elements of BDD. The findings of the review suggest that self-objectification theory and possibly models of self-compassion are theoretically relevant to understanding the experience of individuals presenting with BDD. Current interventions may benefit from consideration of these theoretical models when seeking to improve efficacy.

Dynamic Opportunities for Medical Students to Assume the Roles of "Medical Teacher".

The traditional undergraduate medical education curriculum focuses on bolstering knowledge for practice and building clinical skills. However, as future clinicians, medical students will be tasked with teaching throughout their careers, first as residents and then as attendings. Here, we describe teaching opportunities for students that foster their development as future teachers and potential clinician educators. These offerings are diverse in their focus and duration and are offered across various levels of the curriculum - including course-based learning, longitudinal electives, and extra-curricular opportunities for medical students who have a passion for teaching.

Online compassion-based self-help for depression in people with skin conditions: a feasibility study.

BACKGROUND: There is a need to develop psychological interventions for depression in people with skin conditions. This study aimed to investigate the acceptability, feasibility, and effects of an online compassion-based self-help intervention for depression in people with skin conditions. METHODS: Adult participants (n = 34) with skin conditions and mild-moderate depressive symptoms were invited to undertake a six-week, compassion-based online intervention for depression with email support. Engagement with the intervention was monitored, along with time spent facilitating the intervention, and participant feedback was collected each week and post-intervention. Pre-post changes in depression, self-compassion and dermatological quality of life were also assessed. RESULTS: The intervention was started by 25 participants and completed by 13. Feedback scores indicated that the website was evaluated positively and that the sessions had positive impacts on participants. Participants appreciated the skin-specific aspects of the intervention but varied as to which of the compassion-based exercises they found helpful. The online intervention was feasible to provide and facilitate, and treatment completers showed improvements in depression, quality of life and self-compassion. CONCLUSIONS: The online compassion-based intervention holds promise as a treatment for depression in people with skin conditions. Recommendations are made for future research and further development of the intervention. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 21 October 2019, NCT04132973.

How healthcare systems are experienced by autistic adults in the United Kingdom: A meta-ethnography.

LAY ABSTRACT: Autistic adults are more likely to experience mental and physical health difficulties, and yet can find it difficult to get the support that they need. A meta-ethnographic approach was used to review the existing research on autistic adults' experiences of accessing healthcare. Four databases were searched for qualitative and mixed-method studies which looked at the experiences of autistic adults who did not also have a learning disability when using healthcare services in the United Kingdom. Fifteen papers met the criteria to be included, and seven steps were used to analyse the information and develop new themes. Three main themes were identified: Professionals' lack of knowledge can be damaging, Need to reduce processing demands and Adaptation to improve engagement. This review highlights how damaging misdiagnosis, inappropriate treatment, overwhelming environments and systems that are difficult to access can have on the well-being of autistic adults. Limited knowledge and understanding about autism knowledge among healthcare professionals along with autistic adult's own communication and sensory differences indicate that there is a need for improved training developed with autistic adults and adaptations.

Burden of disease and treatment patterns in patients with vitiligo: findings from a national longitudinal retrospective study in the UK.

BACKGROUND: UK studies examining vitiligo burden and vitiligo-related healthcare resource utilization (HCRU) are lacking. OBJECTIVE: To describe the incidence and prevalence of vitiligo, the demographic and clinical characteristics of patients with vitiligo, vitiligo burden, HCRU, incidence of mental health comorbidities and management strategies, including treatment patterns. METHODS: This retrospective study used UK Clinical Practice Research Datalink and Hospital Episode Statistics databases to analyse patients with vitiligo from 1 January 2010 to 31 December 2021. RESULTS: Among 17 239 incident patients, mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years [PY; range 0.10 (2020-COVID-19) to 0.19 (2010/2013/2018)]; among 66 217 prevalent patients, prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%) and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time included depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%) and sleep disturbance (12.7%), and recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5% and 3.9%, respectively. Mental health comorbidities were more common in White (e.g. depression and/or anxiety 29.0%) than in Black (18.8%) and Asian (16.1%) patients. In adolescents, depression and/or anxiety was most commonly diagnosed after a vitiligo diagnosis than before (7.4% vs. 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 PY) and general practitioner consultations (97.9/100 PY). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatment (i.e. topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids or phototherapy), increasing to 82.0% the next year; median time from diagnosis to first treatment was 34.0 months (95% confidence interval 31.6-36.4). Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments. CONCLUSION: Most patients were not on vitiligo-related treatments within a year of diagnosis, with the time to first treatment exceeding 2 years, suggesting that vitiligo may be dismissed as unimportant. New effective treatments, early initiation and psychological intervention and support are needed to reduce the vitiligo burden on patients.

Vitiligo is a chronic disease in which cells that produce the skin pigment called melanin are attacked, resulting in white or pale patches of skin. It is diagnosed in an estimated 0.2­0.8% of people in Europe. This study aimed to describe how many new cases of vitiligo were recorded between 2010 and 2021 in the UK and the overall percentage of people with vitiligo. Linked national general practitioner (GP) and hospital-based records containing information on medical diagnoses, admissions and hospital visits were used. Records of other diseases and conditions, including mental health conditions, in combination with healthcare service use and treatment prescribed to patients with vitiligo, were studied to describe the impact of living with vitiligo. It was found that 0.16 new cases of vitiligo were recorded per 1000 person-years (for example, 0.16 new cases would have been recorded if 1000 people were followed for 1 year or if 100 people were all followed for 10 years) between 2010 and 2021. In 2021, 0.4% of the population studied had vitiligo. In the 5 years after a new diagnosis of vitiligo, the most common other diseases recorded were diabetes (19%), eczema (9%), thyroid disease (8%) and rheumatoid arthritis (7%), and the most common mental health conditions were depression and/or anxiety (25%). In the year after diagnosis, GP and dermatology outpatient visits were the most common type of medical services used. In 2019, 85% of all individuals with vitiligo were not receiving any vitiligo-related treatment (such as creams or phototherapy). It took approximately 34 months from diagnosis of vitiligo to the start of first treatment. The results suggest that new effective treatments and psychological interventions are needed to reduce the burden of vitiligo.

A comparison of two learning approach inventories and their utility in predicting examination performance and study habits.

The revised two-factor Study Process Questionnaire and the Approaches and Study Skills Inventory for Students are two instruments commonly used to measure student learning approach. Although they are designed to measure similar constructs, it is unclear whether the metrics they provide differ in terms of their real-world classification of learning approach. The purpose of this study is to compare outcomes of these two inventories in a study population from an undergraduate (baccalaureate) human anatomy course. The three central goals of this study are to compare the inventories in terms of 1) how students are classified, 2) the relationship between examination performance, time spent studying, and learning approach, and 3) instrument reliability. Results demonstrate that student classifications of corresponding scales of each inventory are significantly correlated, suggesting they measure similar constructs. Although the inventories had similar reliability, neither was consistently strong in predicting examination performance or study habits. Overall, these results suggest that the two inventories are comparable in terms of how they measure learning approach, but the lack of correspondence between learning approach scores and measurement outcomes questions their validity as tools that can be used universally in classrooms.NEW & NOTEWORTHY Although learning approach inventories have been used extensively in education research, there has been no direct comparison of how student classification differs between instruments or how classification influences the interpretation of how learning approach impacts student performance. This is especially relevant in light of recent research questioning the validity of the Study Process Questionnaire (LoGiudice AB, Norman GR, Manzoor S, Monteiro S. Adv Health Sci Educ Theory Pract 28: 47-63, 2023; Johnson SN, Gallagher ED, Vagnozzi AM. PLoS One 16: e0250600, 2021).

A qualitative feasibility and acceptability study of an acceptance and commitment-based bibliotherapy intervention for people with cancer.

Self-directed bibliotherapy interventions can be effective means of psychological support for individuals with cancer, yet mixed findings as to the efficacy of these interventions indicate the need for further research. We investigated the experience of individuals with cancer after using a new self-help book, based on Acceptance and Commitment Therapy (ACT). Ten participants with cancer (nine females and one male, 40-89 years old) were given access to a bibliotherapy self-help ACT-based book and participated in post-intervention semi-structured interviews. Five themes were generated from reflexive thematic analysis: (1) The value of bibliotherapy (2) Timing is important (3) Resonating with cancer experiences (4) Tools of the book (5) ACT in action. The book was found to be acceptable (self-directed, accessible, understandable content, good responsiveness to exercises) and feasible (easy to use, ACT-consistent). Although not explicitly evaluated, participants' reports indicated defusion, present moment awareness, and consideration of values, as the ACT processes that contributed to adjustment, via helping them to regain control over their lives and become more present within the moment. Findings also indicate that the intervention may be best accessed following completion of initial medical treatment.

Anchovy boom and bust linked to trophic shifts in larval diet.

Although massive biomass fluctuations of coastal-pelagic fishes are an iconic example of the impacts of climate variability on marine ecosystems, the mechanisms governing these dynamics are often elusive. We construct a 45-year record of nitrogen stable isotopes measured in larvae of Northern Anchovy (Engraulis mordax) in the California Current Ecosystem to assess patterns in food chain length. Larval trophic efficiency associated with a shortened food chain increased larval survival and produced boom periods of high adult biomass. In contrast, when larval food chain length increased, and energy transfer efficiency decreased, the population crashed. We propose the Trophic Efficiency in Early Life (TEEL) hypothesis, which states that larval fishes must consume prey that confer sufficient energy for survival, to help explain natural boom-bust dynamics of coastal pelagic fishes. Our findings illustrate a potential for trophic indicators to generally inform larval survival and adult population dynamics of coastal-pelagic fishes.

'I'm not just being difficult . . . I'm finding it difficult': A qualitative approach to understanding experiences of autistic parents when interacting with statutory services regarding their autistic child.

LAY ABSTRACT: Becoming a parent is an important part of adult life for many people, including autistic people. Many parents of autistic children can find getting the right support for their children difficult. Knowledge is currently poor about how this is experienced by parents who are also autistic themselves. The main researcher is also an autistic parent to an autistic child and other experts by experience were consulted in the development of the study. Ten autistic mothers with autistic children in mainstream education were interviewed about their experiences of seeking support for their autistic children from services such as healthcare and education. Participants talked about finding the overall system being the main problem, rather than the individuals working in it, and about needing to fight to get the right support for their children. These are points that non-autistic parents have also raised before. Participants also talked about feeling judged and stigmatised for being autistic, and about struggling to manage sensory and communication difficulties, which is something that has not been talked about by non-autistic parents. Improving services to offer better support to autistic families is important and can be achieved through better training. This training should be developed and run by autistic adults and focus on positive aspects of autism, rather than negative.

An ACT self-help intervention for adults with a visible difference in appearance: A pilot feasibility and acceptability randomized controlled study.

Individuals living with a visible difference in appearance experience high levels of social anxiety, yet self-help interventions for this heterogeneous population are not available. We conducted a pilot trial of a novel Acceptance and Commitment Therapy (ACT) based self-help intervention.Individuals with anxiety about having a visible difference in appearance (n = 284) were randomized to an ACT-based four-week intervention (n = 145) or a waitlist control condition (n = 139). We collected pre and follow-up (four-weeks after the completion of the intervention) data. Primary outcomes included social anxiety and impairments in functioning. Psychological flexibility (PF) was also examined. ANCOVAs, controlling for pre scores, indicated significant improvements in functioning by the intervention group. No significant differences were observed for anxiety and PF between conditions at follow-up. Drop out was 68% for the intervention and 41% for the control group, with no differences in the groups in age, origin, gender, or type of visible difference. Participants in the intervention group found the intervention almost equally, useful (77%) and helpful (73%). An ACT-based self-help intervention can alleviate distress related to visible difference in appearance. More sophisticated designs are needed now, to collect idiographic and longitudinal data and examine personalized changes across time in this population.

Drug discovery for heart failure targeting myosin-binding protein C.

Cardiac MyBP-C (cMyBP-C) interacts with actin and myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces the binding of cMyBP-C to actin and myosin, is often decreased in patients with heart failure (HF) and is cardioprotective in model systems of HF. Therefore, cMyBP-C is a potential target for HF drugs that mimic its phosphorylation and/or perturb its interactions with actin or myosin. We labeled actin with fluorescein-5-maleimide (FMAL) and the C0-C2 fragment of cMyBP-C (cC0-C2) with tetramethylrhodamine (TMR). We performed two complementary high-throughput screens (HTS) on an FDA-approved drug library, to discover small molecules that specifically bind to cMyBP-C and affect its interactions with actin or myosin, using fluorescence lifetime (FLT) detection. We first excited FMAL and detected its FLT, to measure changes in fluorescence resonance energy transfer (FRET) from FMAL (donor) to TMR (acceptor), indicating binding. Using the same samples, we then excited TMR directly, using a longer wavelength laser, to detect the effects of compounds on the environmentally sensitive FLT of TMR, to identify compounds that bind directly to cC0-C2. Secondary assays, performed on selected modulators with the most promising effects in the primary HTS assays, characterized the specificity of these compounds for phosphorylated versus unphosphorylated cC0-C2 and for cC0-C2 versus C1-C2 of fast skeletal muscle (fC1-C2). A subset of identified compounds modulated ATPase activity in cardiac and/or skeletal myofibrils. These assays establish the feasibility of the discovery of small-molecule modulators of the cMyBP-C-actin/myosin interaction, with the ultimate goal of developing therapies for HF.