Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting

Faster decline of pitch memory over time in congenital amusia

Congenital amusia (amusia, hereafter) is a developmental disorder that impacts negatively on the perception of music. Psychophysical testing suggests that individuals with amusia have above average thresholds for detection of pitch change and pitch direction discrimination; however, a low-level auditory perceptual problem cannot completely explain the disorder, since discrimination of melodies is also impaired when the constituent intervals are suprathreshold for perception. The aim of the present study was to test pitch memory as a function of (a) time and (b) tonal interference, in order to determine whether pitch traces are inherently weaker in amusic individuals. Memory for the pitch of single tones was compared using two versions of a paradigm developed by Deutsch (1970a). In both tasks, participants compared the pitch of a standard (S) versus a comparison (C) tone. In the time task, the S and C tones were presented, separated in time by 0, 1, 5, 10, and 15 s (blocked presentation). In the interference task, the S and C tones were presented with a fixed time interval (5 s) but with a variable number of irrelevant tones in between: 0, 2, 4, 6, and 8 tones (blocked presentation). In the time task, control performance remained high for all time in tervals, but amusics showed a performance decrement over time. In the interference task, controls and amusics showed a similar performance decrement with increasing number of irrelevant tones. Overall, the results suggest that the pitch representations of amusic individuals are less stable and more prone to decay than those of matched non-amusic individuals

A randomised controlled trial to compare clinical and cost-effectiveness of an online parent-led treatment for child anxiety problems with usual care in the context of COVID-19 delivered in Child and Adolescent Mental Health Services in the UK (Co-CAT): a study protocol for a randomised controlled trial

In the context of COVID-19, NHS Child and Adolescent Mental Health Services (CAMHS) and other children's mental health services have faced major challenges in providing psychological treatments that (i) work when delivered remotely and (ii) can be delivered efficiently to manage increases in referrals as social distancing measures have been relaxed. Anxiety problems are a common reason for referral to CAMHS, children with pre-existing anxiety problems are particularly vulnerable in the context of COVID-19, and there were concerns about increases in childhood anxiety as schools reopened. The proposed research will evaluate the clinical and cost-effectiveness of a brief online parent-led cognitive behavioural treatment (CBT) delivered by the OSI (Online Support and Intervention for child anxiety) platform with remote support from a CAMHS therapist compared to 'COVID-19 treatment as usual' (C-TAU) in CAMHS and other children's mental health services throughout the COVID-19 pandemic. We will conduct a two-arm, multi-site, randomised controlled non-inferiority trial to evaluate the clinical and cost-effectiveness of OSI with therapist support compared to CAMHS and other child mental health services 'COVID-19 treatment as usual' (C-TAU) during the COVID-19 outbreak and to explore parent and therapists' experiences. If non-inferiority is shown, the research will provide (1) a solution for efficient psychological treatment for child anxiety disorders while social distancing (for the COVID-19 context and future pandemics); (2) an efficient means of treatment delivery as 'normal service' resumes to enable CAMHS to cope with the anticipated increase in referrals; and (3) a demonstration of rapid, high-quality evaluation and application of online interventions within NHS CAMHS to drive forward much-needed further digital innovation and evaluation in CAMHS settings. The primary beneficiaries will be children with anxiety disorders and their families, NHS CAMHS teams, and commissioners who will access a potentially effective, cost-effective, and efficient treatment for child anxiety problems. ISRCTN ISRCTN12890382 . Registered prospectively on 23 October 2020. [Abstract copyright: © 2022. The Author(s).

Digitally augmented, parent-led CBT versus treatment as usual for child anxiety problems in child mental health services in England and Northern Ireland: a pragmatic, non-inferiority, clinical effectiveness and cost-effectiveness randomised controlled trial

Anxiety problems are common in children, yet few affected children access evidence-based treatment. Digitally augmented psychological therapies bring potential to increase availability of effective help for children with mental health problems. This study aimed to establish whether therapist-supported, digitally augmented, parent-led cognitive behavioural therapy (CBT) could increase the efficiency of treatment without compromising clinical effectiveness and acceptability. We conducted a pragmatic, unblinded, two-arm, multisite, randomised controlled non-inferiority trial to evaluate the clinical effectiveness and cost-effectiveness of therapist-supported, parent-led CBT using the Online Support and Intervention (OSI) for child anxiety platform compared with treatment as usual for child (aged 5-12 years) anxiety problems in 34 Child and Adolescent Mental Health Services in England and Northern Ireland. We examined acceptability of OSI plus therapist support via qualitative interviews. Participants were randomly assigned (1:1) to OSI plus therapist support or treatment as usual, minimised by child age, gender, service type, and baseline child anxiety interference. Outcomes were assessed at week 14 and week 26 after randomisation. The primary clinical outcome was parent-reported interference caused by child anxiety at week 26 assessment, using the Child Anxiety Impact Scale-parent report (CAIS-P). The primary measure of health economic effect was quality-adjusted life-years (QALYs). Outcome analyses were conducted blind in the intention-to-treat (ITT) population with a standardised non-inferiority margin of 0·33 for clinical analyses. The trial was registered with ISRCTN, 12890382. Between Dec 5, 2020, and Aug 3, 2022, 706 families (706 children and their parents or carers) were referred to the study information. 444 families were enrolled. Parents reported 255 (58%) child participants' gender to be female, 184 (41%) male, three (<1%) other, and one (<1%) preferred not to report their child's gender. 400 (90%) children were White and the mean age was 9·20 years (SD 1·79). 85% of families for whom clinicians provided information in the treatment as usual group received CBT. OSI plus therapist support was non-inferior for parent-reported anxiety interference on the CAIS-P (SMD 0·01, 95% CI -0·15 to 0·17; p<0·0001) and all secondary outcomes. The mean difference in QALYs across trial arms approximated to zero, and OSI plus therapist support was associated with lower costs than treatment as usual. OSI plus therapist support was likely to be cost effective under certain scenarios, but uncertainty was high. OSI plus therapist support acceptability was good. No serious adverse events were reported. Digitally augmented intervention brought promising savings without compromising outcomes and as such presents a valuable tool for increasing access to psychological therapies and meeting the demand for treatment of child anxiety problems

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.</p

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R):protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium

Introduction Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. Methods and analysis This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform (www.yourcovidrecovery.nhs.uk). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. Ethics and dissemination Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Article summary Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priorit

Recurrent Coding Sequence Variation Explains only A Small Fraction of the Genetic Architecture of Colorectal Cancer

Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10-7), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10-7); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10-

Detecting and predicting forest degradation: A comparison of ground surveys and remote sensing in Tanzanian forests

Funder: Critical Ecosystem Partnership Fund; Id: http://dx.doi.org/10.13039/100013724Funder: Global Environment Facility; Id: http://dx.doi.org/10.13039/100011150Funder: Danish International Development Agency; Id: http://dx.doi.org/10.13039/501100011054Funder: Scottish Government’s Rural and Environment Science and Analytical Services DivisionFunder: Finnish International Development AgencyFunder: Leverhulme Trust; Id: http://dx.doi.org/10.13039/501100000275Societal Impact Statement: Large areas of tropical forest are degraded. While global tree cover is being mapped with increasing accuracy from space, much less is known about the quality of that tree cover. Here we present a field protocol for rapid assessments of forest condition. Using extensive field data from Tanzania, we show that a focus on remotely‐sensed deforestation would not detect significant reductions in forest quality. Radar‐based remote sensing of degradation had good agreement with the ground data, but the ground surveys provided more insights into the nature and drivers of degradation. We recommend the combined use of rapid field assessments and remote sensing to provide an early warning, and to allow timely and appropriately targeted conservation and policy responses. Summary: Tropical forest degradation is widely recognised as a driver of biodiversity loss and a major source of carbon emissions. However, in contrast to deforestation, more gradual changes from degradation are challenging to detect, quantify and monitor. Here, we present a field protocol for rapid, area‐standardised quantifications of forest condition, which can also be implemented by non‐specialists. Using the example of threatened high‐biodiversity forests in Tanzania, we analyse and predict degradation based on this method. We also compare the field data to optical and radar remote‐sensing datasets, thereby conducting a large‐scale, independent test of the ability of these products to map degradation in East Africa from space. Our field data consist of 551 ‘degradation’ transects collected between 1996 and 2010, covering >600 ha across 86 forests in the Eastern Arc Mountains and coastal forests. Degradation was widespread, with over one‐third of the study forests—mostly protected areas—having more than 10% of their trees cut. Commonly used optical remote‐sensing maps of complete tree cover loss only detected severe impacts (≥25% of trees cut), that is, a focus on remotely‐sensed deforestation would have significantly underestimated carbon emissions and declines in forest quality. Radar‐based maps detected even low impacts (<5% of trees cut) in ~90% of cases. The field data additionally differentiated types and drivers of harvesting, with spatial patterns suggesting that logging and charcoal production were mainly driven by demand from major cities. Rapid degradation surveys and radar remote sensing can provide an early warning and guide appropriate conservation and policy responses. This is particularly important in areas where forest degradation is more widespread than deforestation, such as in eastern and southern Africa

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (P = 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association