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Abstract Background Despite being preventable, suicide is a leading cause of death and a major global public health problem. For every death by suicide, many more suicide attempts are undertaken, and this presents as a critical risk factor for suicide. Currently, there are limited treatment options with limited underpinning research for those who present to emergency departments with suicidal behaviour. The aim of this study is to assess if adding one of two structured suicide-specific psychological interventions (Attempted Suicide Short Intervention Program [ASSIP] or Brief Cognitive Behavioural Therapy [CBT] for Suicide Prevention) to a standardised clinical care approach (Suicide Prevention Pathway [SPP]) improves the outcomes for consumers presenting to a Mental Health Service with a suicide attempt. Methods This is a randomised controlled trial with blinding of those assessing the outcomes. People who attempt suicide or experience suicidality after a suicide attempt, present to the Gold Coast Mental Health and Specialist Services, are placed on the Suicide Prevention Pathway (SPP), and meet the eligibility criteria, are offered the opportunity to participate. A total of 411 participants will be recruited for the study, with 137 allocated to each cohort (participants are randomised to SPP, ASSIP + SPP, or CBT + SPP). The primary outcomes of this study are re-presentation to hospitals with suicide attempts. Presentations with suicidal ideation will also be examined (in a descriptive analysis) to ascertain whether a rise in suicidal ideation is commensurate with a fall in suicide attempts (which might indicate an increase in help-seeking behaviours). Death by suicide rates will also be examined to ensure that representations with a suicide attempt are not due to participants dying, but due to a potential improvement in mental health. For participants without a subsequent suicide attempt, the total number of days from enrolment to the last assessment (24 months) will be calculated. Self-reported levels of suicidality, depression, anxiety, stress, resilience, problem-solving skills, and self- and therapist-reported level of therapeutic engagement are also being examined. Psychometric data are collected at baseline, end of interventions, and 6,12, and 24 months. Discussion This project will move both ASSIP and Brief CBT from efficacy to effectiveness research, with clear aims of assessing the addition of two structured psychological interventions to treatment as usual, providing a cost-benefit analysis of the interventions, thus delivering outcomes providing a clear pathway for rapid translation of successful interventions. Trials registration ClinicalTrials.gov NCT04072666 . Registered on 28 August 2019

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg2 of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with planck and wmap data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the ΛCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. The new ACTPol data provide information on damping tail parameters. The joint uncertainty on the number of neutrino species and the primordial helium fraction is reduced by 20% when adding ACTPol to Planck temperature data alone.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene (ITGA7) have been reported in children with congenital myopathy. Methods and Results In this study, we described skeletal and cardiac muscle pathology in Itga7−/− mice and 5 patients from 2 unrelated families with ITGA7 mutations. Proband in family 1 presented a homozygous c.806_818del [p.S269fs] variant, and proband in family 2 was identified with 2 intron variants in the ITGA7 gene. The complete absence of the integrin α7 protein in muscle supports the ITGA7 mutations are pathogenic. We performed electrocardiography, echocardiography, or cardiac magnetic resonance imaging, and histological biopsy analyses in patients with ITGA7 deficiency and Itga7−/− mice. The patients exhibited cardiac dysrhythmia and dysfunction from the third decade of life and late‐onset respiratory insufficiency, but with relatively mild limb muscle involvement. Mice demonstrated corresponding abnormalities in cardiac conduction and contraction as well as diaphragm muscle fibrosis. Conclusions Our data suggest that loss of integrin α7 causes a novel form of adult‐onset cardiac dysfunction indicating a critical role for the integrin α7β1 in normal cardiac function and highlights the need for long‐term cardiac monitoring in patients with ITGA7‐related congenital myopathy.

Abstract Background Children with physical disabilities (PD) are less physically active than typically developing peers. The most important contributor to physical activity for primary school-aged children is outside play and therefore this should be part of every child’s life. However, children with PD experience multiple barriers to participation in playgrounds. Despite recent improvements in the accessibility of Dutch playgrounds, the participation of children with PD has not increased. This study aims to explore facilitators, barriers and solutions influencing the participation of children with PD in Dutch outdoor playgrounds, from parents’ and professionals’ perspectives. Methods Twelve semi-structured interviews with parents of children with PD aged 2–12 years and five focus group meetings with professionals working with these children were conducted. To ensure data saturation, we performed three member-check meetings. Two independent researchers analyzed the data using an inductive thematic approach. Results Similar barriers, facilitators and solutions were mentioned by parents and professionals. Three main themes were identified: the emotional barrier versus the physical barrier, play as a part of an inclusive society and the role of professionals in facilitating active inclusive play. The most important personal factors were physical and social problems experienced when children with PD wanted to join outdoor play. Interestingly, parents and professionals believed the social barrier was far more important than the physical one. The most important environmental factor was that the Dutch society is not sufficiently inclusive. Conclusions According to both parents and professionals, the most important barrier to active inclusive outdoor play was social, hindering the participation of children with PD in play with typically developing peers. To overcome such problems, professionals should take an active role in empowering children with PD and their parents. Furthermore, it is important to introduce outdoor active play early, so it becomes part of normal daily life. In addition, a change in the mindset of typically developing children and their parents seems essential to achieve true inclusive active play.

Abstract Background SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness. Methods LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient’s age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed. Discussion Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up. Conclusion Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD. Trial registration This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017–3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).

Background and purpose: Behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), such as mood, psychotic, and autism spectrum disorders, share similar clinical characteristics of behavior and social cognition. Better understanding of clinical progression in bvFTD and PPD is essential for adequate disease monitoring and trial design. Methods: In this longitudinal study (N = 89), patients with bvFTD and PPD with at least one follow‐up assessment were included from the Social Brain Project of the Alzheimer Center Amsterdam. Behavioral change and social cognitive decline were assessed via informant‐rated questionnaires (Cambridge Behavioral Inventory–Revised, Frontal Behavioral Inventory [FBI], Stereotypy Rating Inventory, Frontotemporal Dementia Rating Scale, Revised Self‐Monitoring Scale [RSMS]‐caregiver) and patient assessment (Ekman 60‐Faces Test, RSMS‐patient, Emotional Contagion Scale). Clinical trajectories (median = 1.4 years, interquartile range = 1.0–2.2) were examined using linear mixed models. In a subsample, associations with baseline serum neurofilament light (sNfL) were examined. Results: At baseline, behavioral and social cognitive symptoms were similar between diagnosis groups, except for poorer emotion recognition in bvFTD. Over time, behavioral symptoms worsened in bvFTD, whereas most measures remained stable and the FBI improved in PPD. Regarding social cognition, emotion recognition and caregiver‐reported socioemotional sensitivity worsened in bvFTD and remained stable in PPD. Patient‐reported social cognitive measures did not change over time. Higher sNfL was associated with faster behavioral change. Conclusions: Trajectories of behavior and social cognition differentiate bvFTD from PPD, provided that social cognition is not patient‐reported. Therefore, we stress the need to optimize longitudinal social cognitive assessment in bvFTD. sNfL may be a useful prognostic marker of behavioral progression in neuropsychiatric populations. [ABSTRACT FROM AUTHOR]

Background: To retrospectively assess the added value of an artificial intelligence (AI) algorithm for detecting pulmonary nodules on ultra-low-dose computed tomography (ULDCT) performed at the emergency department (ED). Methods: In the OPTIMACT trial, 870 patients with suspected nontraumatic pulmonary disease underwent ULDCT. The ED radiologist prospectively read the examinations and reported incidental pulmonary nodules requiring follow-up. All ULDCTs were processed post hoc using an AI deep learning software marking pulmonary nodules ≥ 6 mm. Three chest radiologists independently reviewed the subset of ULDCTs with either prospectively detected incidental nodules in 35/870 patients or AI marks in 458/870 patients; findings scored as nodules by at least two chest radiologists were used as true positive reference standard. Proportions of true and false positives were compared. Results: During the OPTIMACT study, 59 incidental pulmonary nodules requiring follow-up were prospectively reported. In the current analysis, 18/59 (30.5%) nodules were scored as true positive while 104/1,862 (5.6%) AI marks in 84/870 patients (9.7%) were scored as true positive. Overall, 5.8 times more (104 versus 18) true positive pulmonary nodules were detected with the use of AI, at the expense of 42.9 times more (1,758 versus 41) false positives. There was a median number of 1 (IQR: 0–2) AI mark per ULDCT. Conclusion: The use of AI on ULDCT in patients suspected of pulmonary disease in an emergency setting results in the detection of many more incidental pulmonary nodules requiring follow-up (5.8×) with a high trade-off in terms of false positives (42.9×). Relevance statement: AI aids in the detection of incidental pulmonary nodules that require follow-up at chest-CT, aiding early pulmonary cancer detection but also results in an increase of false positive results that are mainly clustered in patients with major abnormalities. Trial registration: The OPTIMACT trial was registered on 6 December 2016 in the National Trial Register (number NTR6163) (onderzoekmetmensen.nl). Key Points: An AI deep learning algorithm was tested on 870 ULDCT examinations acquired in the ED. AI detected 5.8 times more pulmonary nodules requiring follow-up (true positives). AI resulted in the detection of 42.9 times more false positive results, clustered in patients with major abnormalities. AI in the ED setting may aid in early pulmonary cancer detection with a high trade-off in terms of false positives. [ABSTRACT FROM AUTHOR]

Noonan syndrome (NS) is an autosomal dominant condition characterized by facial dysmorphism, congenital heart disease, development delay, growth retardation and lymphatic disease. It is caused by germline pathogenic variants in genes encoding proteins in the Ras/mitogen‐activated protein kinase signaling pathway. Nerve enlargement is not generally considered as a feature of NS, although some cases have been reported. High‐resolution nerve ultrasound enables detailed anatomical assessment of peripheral nerves and can show enlarged nerves. This retrospective cohort study aims to describe the sonographic findings of patients with NS performed during a 1‐year time period. Data on the degree of enlargement, the relation to increasing age, pain in extremities, genotype on the gene level and clinical features were collected. Twenty‐nine of 93 patients visiting the NS Center of Expertise of the Radboud University Medical Center Nijmegen underwent high‐resolution ultrasound. In 24 patients (83%) nerve enlargement was found. Most of them experienced pain. We observed a weak correlation with increasing age and the degree of nerve enlargement but no association with pain, genotype at the gene level or clinical features. This study shows that patients with NS have a high predisposition for sonographic nerve enlargement and that the majority experience pain. [ABSTRACT FROM AUTHOR]

Introduction/Aims: One of the most distinct clinical features of facioscapulohumeral muscular dystrophy (FSHD) is facial weakness. It leads to diminished facial expression and functional impairments. Despite its clinical relevance, little else is known about orofacial muscle involvement. We therefore evaluated orofacial muscle involvement in a sizeable cohort of FSHD participants with muscle ultrasound. Methods: Muscle ultrasound images of the following orofacial muscles were scored visually and quantitatively: depressor anguli oris (DAO), orbicularis oris (OO), buccinator, temporalis, masseter, digastric, zygomaticus major and minor bilaterally, and the geniohyoid. Reliability analyses of both visual and quantitative evaluations were performed. Ultrasound results were correlated with other measures: the FSHD clinical score, facial weakness score, and facial function scale. Results: We included 107 FSHD participants (male 54%; age 52 ± 14 years), of whom 92% showed signs of facial weakness. The reliability of visual ultrasound analysis varied widely (κ 0.0–1.0). Quantitative ultrasound reliability was high (intraclass correlation analysis ≥ 0.96). The DAO, buccinator, OO, temporalis, and zygomaticus minor muscles were affected most often (15%–39%). The digastric, geniohyoid, zygomaticus major, and masseter muscles were least often affected (<5%). The ultrasound compound score correlated weakly to moderately with other outcome measures used (ρ = 0.3–0.7). Discussion: This study adds to the understanding of orofacial weakness in FSHD, confirming the involvement of the muscles of facial expression in FSHD using ultrasound. We showed that orofacial muscle ultrasound is feasible and reliable when quantitatively assessed. Future studies should evaluate orofacial muscle ultrasound longitudinally, alongside clinical and patient‐reported facial weakness outcome measures, to assess their potential as outcome measures. [ABSTRACT FROM AUTHOR]