Proprioceptive and Visual Feedback Responses in Macaques Exploit Goal Redundancy.

A common problem in motor control concerns how to generate patterns of muscle activity when there are redundant solutions to attain a behavioral goal. Optimal feedback control is a theory that has guided many behavioral studies exploring how the motor system incorporates task redundancy. This theory predicts that kinematic errors that deviate the limb should not be corrected if one can still attain the behavioral goal. Studies in humans demonstrate that the motor system can flexibly integrate visual and proprioceptive feedback of the limb with goal redundancy within 90 ms and 70 ms, respectively. Here, we show monkeys (Macaca mulatta) demonstrate similar abilities to exploit goal redundancy. We trained four male monkeys to reach for a goal that was either a narrow square or a wide, spatially redundant rectangle. Monkeys exhibited greater trial-by-trial variability when reaching to the wide goal consistent with exploiting goal redundancy. On random trials we jumped the visual feedback of the hand and found monkeys corrected for the jump when reaching to the narrow goal and largely ignored the jump when reaching for the wide goal. In a separate set of experiments, we applied mechanical loads to the arm of the monkey and found similar corrective responses based on goal shape. Muscle activity reflecting these different corrective responses were detected for the visual and mechanical perturbations starting at ∼90 and ∼70 ms, respectively. Thus, rapid motor responses in macaques can exploit goal redundancy similar to humans, creating a paradigm to study the neural basis of goal-directed motor action and motor redundancy.SIGNIFICANCE STATEMENT Moving in the world requires selecting from an infinite set of possible motor commands. Theories predict that motor commands are selected that exploit redundancies. Corrective responses in humans to either visual or proprioceptive disturbances of the limb can rapidly exploit redundant trajectories to a goal in <100 ms after a disturbance. However, uncovering the neural correlates generating these rapid motor corrections has been hampered by the absence of an animal model. We developed a behavioral paradigm in monkeys that incorporates redundancy in the form of the shape of the goal. Critically, monkeys exhibit corrective responses and timings similar to humans performing the same task. Our paradigm provides a model for investigating the neural correlates of sophisticated rapid motor corrections.

Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma.

BACKGROUND & AIMS: There is a knowledge gap in understanding mechanisms of resistance to fibroblast growth factor receptor (FGFR) inhibitors (FGFRi) and a need for novel therapeutic strategies to overcome it. We investigated mechanisms of acquired resistance to FGFRi in patients with FGFR2-fusion-positive cholangiocarcinoma (CCA). METHODS: A retrospective analysis of patients who received FGFRi therapy and underwent tumor and/or cell-free DNA analysis, before and after treatment, was performed. Longitudinal circulating tumor DNA samples from a cohort of patients in the phase I trial of futibatinib (NCT02052778) were assessed. FGFR2-BICC1 fusion cell lines were developed and secondary acquired resistance mutations in the mitogen-activated protein kinase (MAPK) pathway were introduced to assess their effect on sensitivity to FGFRi in vitro. RESULTS: On retrospective analysis of 17 patients with repeat sequencing following FGFRi treatment, new FGFR2 mutations were detected in 11 (64.7%) and new alterations in MAPK pathway genes in nine (52.9%) patients, with seven (41.2%) patients developing new alterations in both the FGFR2 and MAPK pathways. In serially collected plasma samples, a patient treated with an irreversible FGFRi tested positive for previously undetected BRAF V600E, NRAS Q61K, NRAS G12C, NRAS G13D and KRAS G12K mutations upon progression. Introduction of a FGFR2-BICC1 fusion into biliary tract cells in vitro sensitized the cells to FGFRi, while concomitant KRAS G12D or BRAF V600E conferred resistance. MEK inhibition was synergistic with FGFRi in vitro. In an in vivo animal model, the combination had antitumor activity in FGFR2 fusions but was not able to overcome KRAS-mediated FGFRi resistance. CONCLUSIONS: These findings suggest convergent genomic evolution in the MAPK pathway may be a potential mechanism of acquired resistance to FGFRi. CLINICAL TRIAL NUMBER: NCT02052778. IMPACT AND IMPLICATIONS: We evaluated tumors and plasma from patients who previously received inhibitors of fibroblast growth factor receptor (FGFR), an important receptor that plays a role in cancer cell growth, especially in tumors with abnormalities in this gene, such as FGFR fusions, where the FGFR gene is fused to another gene, leading to activation of cancer cell growth. We found that patients treated with FGFR inhibitors may develop mutations in other genes such as KRAS, and this can confer resistance to FGFR inhibitors. These findings have several implications for patients with FGFR2 fusion-positive tumors and provide mechanistic insight into emerging MAPK pathway alterations which may serve as a therapeutic vulnerability in the setting of acquired resistance to FGFRi.

Robotic assessment of sensorimotor and cognitive deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Individuals with temporal lobe epilepsy (TLE) frequently demonstrate impairments in executive function, working memory, and/or declarative memory. It is recommended that screening for cognitive impairment is undertaken in all people newly diagnosed with epilepsy. However, standard neuropsychological assessments are a limited resource and thus not available to all. Our study investigated the use of robotic technology (the Kinarm robot) for cognitive screening. METHODS: 27 participants with TLE (17 left) underwent both a brief neuropsychological screening and a robotic (Kinarm) assessment. The degree of impairments and correlations between standardized scores from both approaches to assessments were analysed across different neurocognitive domains. Performance was compared between people with left and right TLE to look for laterality effects. Finally, the association between the duration of epilepsy and performance was assessed. RESULTS: Across the 6 neurocognitive domains (attention, executive function, language, memory, motor and visuospatial) assessed by our neuropsychological screening, all showed scores that significantly correlated with Kinarm tasks assessing the same cognitive domains except language and memory that were not adequately assessed with Kinarm. Participants with right TLE performed worse on most tasks than those with left TLE, including both visuospatial (typically considered right hemisphere), and verbal memory and language tasks (typically considered left hemisphere). No correlations were found between the duration of epilepsy and either the neuropsychological screening or Kinarm assessment. SIGNIFICANCE: Our findings suggest that Kinarm may be a useful tool in screening for neurocognitive impairment in people with TLE. Further development may facilitate an easier and more rapid screening of cognition in people with epilepsy and distinguishing patterns of cognitive impairment.

Integrating Mental Health Care in Ambulatory Obstetrical Practices: Strategies and Models.

Perinatal mental health is recognized as a priority component of obstetrical care. Perinatal patients often turn to their obstetrician for help with mental health concerns as they view them as their primary health care provider. Unfortunately, obstetricians face challenges in providing adequate support due to time constraints and limited expertise. Integrated behavioral health care offers a collaborative and cost-effective solution to enhance patient care and clinician satisfaction. Integrated behavioral health clinicians possess fundamental skills to care for patients throughout the reproductive lifespan and assist obstetricians in identifying and managing common mood concerns.

Maternal depression, psychosocial stress and race/ethnicity: examining barriers to breastfeeding for young mothers.

BACKGROUND: Breastfeeding has a positive impact on child and maternal health outcomes. Black and Latina women and adolescent mothers have lower rates of breastfeeding initiation and continuance in the U.S. Maternal depression and psychosocial stressors may contribute to reduced rates of breastfeeding. The current study aims to better understand behaviours and associated factors related to breastfeeding in a diverse group of adolescent mothers attending a teen-tot clinic for postpartum and infant well care. METHODS: Participants were 191 mother-infant dyads. Mother's age ranged from 13 to 25, and 54% of mothers identified as Latina, 22% Black, 11% more than one race and 5% white. Demographic information and breastfeeding behaviour were abstracted from the medical record. Rates of postpartum mood/anxiety symptoms and psychosocial stressors were obtained from screening measures completed at medical visits. RESULTS: Analyses revealed that 87% of adolescent mothers in the sample initiated breastfeeding at birth and the racial/ethnic breakdown of those mothers closely mirrored the overall population (58% Hispanic or Latina, 17% Black, 10% more than one race, 5% white). At 2 months postpartum, only 41% of the population was still breastfeeding. Mothers with significant mood/anxiety symptoms at the newborn visit were more likely to be breastfeeding at the 1- and 2-month visits. Mothers with psychosocial stressors at the newborn visit were less likely to be breastfeeding at the 1- and 2-month visits. CONCLUSION: Efforts to promote health equity through breastfeeding for at-risk mothers must occur within the first few weeks postpartum and must consider associated factors including postpartum mood/anxiety symptoms and psychosocial stressors.

Elucidation of dynamic microRNA regulations in cancer progression using integrative machine learning.

MOTIVATION: Empowered by advanced genomics discovery tools, recent biomedical research has produced a massive amount of genomic data on (post-)transcriptional regulations related to transcription factors, microRNAs, long non-coding RNAs, epigenetic modifications and genetic variations. Computational modeling, as an essential research method, has generated promising testable quantitative models that represent complex interplay among different gene regulatory mechanisms based on these data in many biological systems. However, given the dynamic changes of interactome in chaotic systems such as cancers, and the dramatic growth of heterogeneous data on this topic, such promise has encountered unprecedented challenges in terms of model complexity and scalability. In this study, we introduce a new integrative machine learning approach that can infer multifaceted gene regulations in cancers with a particular focus on microRNA regulation. In addition to new strategies for data integration and graphical model fusion, a supervised deep learning model was integrated to identify conditional microRNA-mRNA interactions across different cancer stages. RESULTS: In a case study of human breast cancer, we have identified distinct gene regulatory networks associated with four progressive stages. The subsequent functional analysis focusing on microRNA-mediated dysregulation across stages has revealed significant changes in major cancer hallmarks, as well as novel pathological signaling and metabolic processes, which shed light on microRNAs' regulatory roles in breast cancer progression. We believe this integrative model can be a robust and effective discovery tool to understand key regulatory characteristics in complex biological systems. AVAILABILITY: http://sbbi-panda.unl.edu/pin/.

Opportunistic optimization of inhaler technique in hospitalized adults with asthma: a two-phase educational study.

OBJECTIVE: To investigate effectiveness of two different educational methods to improve inhaler techniques in patients with prior diagnosis of asthma, hospitalized with a non-asthma-related diagnosis. METHODS: We undertook a real-world, opportunistic quality-improvement project. Inhaler technique in hospitalized patients with prior diagnosis of asthma was assessed in two cohorts over two 12-week cycles using a standardized device-specific proforma of seven-step inhaler technique, classed: "good" if 6/7 steps achieved; "fair" if 5/7 compliant; "poor" for others. Baseline data was collected in both cycles. Cycle one involved face-to-face education by a healthcare professional; cycle two involved additional use of an electronic device to show device-specific videos (asthma.org.uk). In both cycles, patients were reassessed within two days for improvements and the two methods compared for effectiveness. RESULTS: During cycle one 32/40 patients were reassessed within 48 h; eight lost to follow-up. During cycle two 38/40 patients were reassessed within 48 h; two lost to follow-up During cycle one, two and 12 had good/fair baseline technique respectively, and 26 poor. Most commonly missed steps were no expiry check/not rinsing mouth after steroid use. On reassessment 17% patients improved from poor to fair/good. During cycle two, initial technique assessment identified: 23 poor; 12 fair; five good. Post-videos, 35% of patients improved from poor to fair/good. Proportion of patients improving from poor to fair, or poor/fair to good increased in cycle two vs one (52.5% vs 33%). CONCLUSION: Visual instruction is associated with improved technique compared to verbal feedback. This is a user-friendly and cost-effective approach to patient education.

Personalised interventions for subgroups of children with conduct problems.

BACKGROUND: Conduct problems are a range of disruptive behaviours in childhood that are associated with long-term adverse outcomes in adolescence and adulthood, including antisocial behaviour, substance misuse, and poor academic achievement. Children with conduct problems can vary according to age of onset, comorbidities, and environmental factors, and it has been suggested that certain groups of children may have different treatment outcomes. Therefore, it is important to assess the extent to which personalised interventions for different groups of children with conduct problems may affect outcomes. To our knowledge, this is the first review to systematically identify and appraise the effectiveness of personalised interventions, adapted, or developed, for prespecified subgroups of children with conduct problems. OBJECTIVES: To assess whether personalised interventions, adapted or developed for subgroups of children with conduct problems are effective in improving outcomes. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 1 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs), in any setting, in children (aged two to 12 years) with conduct problems and within a prespecified subgroup, comparing a personalised intervention with a non-personalised intervention, waitlist control, or treatment as usual. Personalised interventions included adaptations to standard practice, such as parent-training programmes; other recommended interventions for children with conduct problems; or interventions developed specifically to target subgroups of children with conduct problems. We excluded non-personalised and non-psychological interventions (e.g. pharmacological or dietary intervention). Prespecified subgroups of children with conduct problems, however defined, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. child conduct problems or disruptive behaviour and 2. ADVERSE EVENTS: Our secondary outcomes were 3. personalised treatment outcomes relevant to each subgroup, 4. parenting skills and knowledge, 5. family functioning, engagement and decreased dropout, and 6. educational outcomes. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We identified 13 RCTs (858 participants). Seven studies were conducted in the USA, five in Australia, and one in Germany. Eleven studies reported their source of funding, with five studies receiving grants from the National Institute of Mental Health. In total, 15 different funders supported the studies included in the review. We separated subgroups of children with conduct problems into three broad categories: children with co-occurring conditions (e.g. emotional difficulties), parent characteristics (e.g. conflict between parents), or familial/environmental circumstances (e.g. rural families). All studies delivered a personalised intervention that was adapted or developed for a prespecified subgroup of children with conduct problems. We rated all trials at unclear or high risk of bias in most domains. Below, we report the results of improvement in child conduct problems and disruptive behaviour, personalised treatment outcomes, and parenting skills and knowledge for our main comparison: personalised versus non-personalised interventions. Improvement in child conduct problems and disruptive behaviour Compared with a non-personalised intervention, a personalised intervention may result in a slight improvement in child conduct problems or disruptive behaviour measured using the Eyberg Child Behavior Inventory (ECBI) Problem subscale in the short term (mean difference (MD) -3.04, 95% confidence interval (CI) -6.06 to -0.02; 6 studies, 278 participants; P = 0.05), but may have little to no effect on improving child conduct problems or disruptive behaviour measured by the ECBI Intensity subscale (MD -6.25, 95% CI -16.66 to 4.15; 6 studies, 278 participants; P = 0.24), or the Externalising subscale of the Child Behaviour Checklist (CBCL) (MD -2.19, 95% CI -6.97 to 2.59; 3 studies, 189 participants, P = 0.37) in the short term. We graded the certainty of evidence as very low for all three outcomes, meaning any estimate of effect is very uncertain.  Personalised treatment outcomes, relevant to each subgroup Although six studies reported personalised treatment outcomes, relevant to each subgroup, we were unable to pool the data due to differences between the measures used in the studies and the heterogeneity this would produce in analysis. The results for this outcome were inconclusive. Parenting skills and knowledge Although seven studies reported parenting skills and knowledge, we were unable to pool the data due to differences between the measures used in the studies and the heterogeneity this would produce in analysis. The results for this outcome were inconclusive.  Adverse events None of the trials reported monitoring adverse events. Summary of results In summary, there is limited evidence that personalised intervention improves child conduct problems, personalised treatment outcomes, relevant to each subgroup, or parenting skills and knowledge compared with a non-personalised intervention. AUTHORS' CONCLUSIONS: There is limited evidence for the effectiveness of personalised interventions for subgroups of children with conduct problems. The certainty of evidence for all outcomes was very low, meaning that we have very little confidence in the estimated effects and the true effects may be different to our findings, which will limit the relevance of our findings to clinical decisions. To overcome the limitations of the evidence, large-scale RCTs are needed to determine whether personalised interventions, adapted or developed, for subgroups of children with conduct problems are effective in improving outcomes. Consensus on the most appropriate measures to use in these studies is needed in order to facilitate cross-study comparisons. Persistent conduct problems predict a range of adverse long-term outcomes, so future research should investigate the medium- and long-term effects of personalised treatments. Studies are needed in low- and middle-income countries as well as studies recruiting children aged between nine and 12 years, as they were under-represented in the studies.

Informed consent practices in clinical research: present and future.

Clinical research must balance the need for ambitious recruitment with protecting participants' autonomy; a requirement of which is informed consent. Despite efforts to improve the informed consent process, participants are seldom provided sufficient information regarding research, hindering their ability to make informed decisions. These issues are particularly pervasive among patients experiencing acute illness or neurological impairment, both of which may impede their capacity to provide consent. There is a critical need to understand the components, requirements, and methods of obtaining true informed consent to achieve the vast numbers required for meaningful research. This paper provides a comprehensive review of the tenets underlying informed consent in research, including the assessment of capacity to consent, considerations for patients unable to consent, when to seek consent from substitute decision-makers, and consent under special circumstances. Various methods for obtaining informed consent are addressed, along with strategies for balancing recruitment and consent.

Does Social and Economic Disadvantage Predict Lower Engagement with Parenting Interventions? An Integrative Analysis Using Individual Participant Data.

There is a social gradient to the determinants of health; low socioeconomic status (SES) has been linked to reduced educational attainment and employment prospects, which in turn affect physical and mental wellbeing. One goal of preventive interventions, such as parenting programs, is to reduce these health inequalities by supporting families with difficulties that are often patterned by SES. Despite these intentions, a recent individual participant data (IPD) meta-analysis of the Incredible Years (IY) parenting program found no evidence for differential benefit by socioeconomic disadvantage (Gardner et al. in Public Health Resesearch 5, 1-144, 2017). However, it did not examine whether this was influenced by engagement in the intervention. Using intervention arm data from this pooled dataset (13 trials; N = 1078), we examined whether there was an SES gradient to intervention attendance (an indicator of engagement). We ran mixed-effects Poisson regression models to estimate incidence rate ratios (IRRs) for program attendance for each of five (binary) markers of SES: low income; unemployment; low education status; teen parent; and lone parent status. The multilevel structure of the data allowed for comparison of within-trial and between-trial effects, including tests for contextual effects. We found evidence that low SES was associated with reduced attendance at parenting programs-an 8-19% reduction depending on the SES marker. However, there was no evidence that this association is impacted by differences in SES composition between trials or by the attendance levels of higher-SES families. The findings underscore the importance of developing and prioritizing strategies that enable engagement in parenting interventions and encourage program attendance by low-SES families.

The use of machine learning and deep learning techniques to assess proprioceptive impairments of the upper limb after stroke.

BACKGROUND: Robots can generate rich kinematic datasets that have the potential to provide far more insight into impairments than standard clinical ordinal scales. Determining how to define the presence or absence of impairment in individuals using kinematic data, however, can be challenging. Machine learning techniques offer a potential solution to this problem. In the present manuscript we examine proprioception in stroke survivors using a robotic arm position matching task. Proprioception is impaired in 50-60% of stroke survivors and has been associated with poorer motor recovery and longer lengths of hospital stay. We present a simple cut-off score technique for individual kinematic parameters and an overall task score to determine impairment. We then compare the ability of different machine learning (ML) techniques and the above-mentioned task score to correctly classify individuals with or without stroke based on kinematic data. METHODS: Participants performed an Arm Position Matching (APM) task in an exoskeleton robot. The task produced 12 kinematic parameters that quantify multiple attributes of position sense. We first quantified impairment in individual parameters and an overall task score by determining if participants with stroke fell outside of the 95% cut-off score of control (normative) values. Then, we applied five machine learning algorithms (i.e., Logistic Regression, Decision Tree, Random Forest, Random Forest with Hyperparameters Tuning, and Support Vector Machine), and a deep learning algorithm (i.e., Deep Neural Network) to classify individual participants as to whether or not they had a stroke based only on kinematic parameters using a tenfold cross-validation approach. RESULTS: We recruited 429 participants with neuroimaging-confirmed stroke (< 35 days post-stroke) and 465 healthy controls. Depending on the APM parameter, we observed that 10.9-48.4% of stroke participants were impaired, while 44% were impaired based on their overall task score. The mean performance metrics of machine learning and deep learning models were: accuracy 82.4%, precision 85.6%, recall 76.5%, and F1 score 80.6%. All machine learning and deep learning models displayed similar classification accuracy; however, the Random Forest model had the highest numerical accuracy (83%). Our models showed higher sensitivity and specificity (AUC = 0.89) in classifying individual participants than the overall task score (AUC = 0.85) based on their performance in the APM task. We also found that variability was the most important feature in classifying performance in the APM task. CONCLUSION: Our ML models displayed similar classification performance. ML models were able to integrate more kinematic information and relationships between variables into decision making and displayed better classification performance than the overall task score. ML may help to provide insight into individual kinematic features that have previously been overlooked with respect to clinical importance.

A robot-based interception task to quantify upper limb impairments in proprioceptive and visual feedback after stroke.

BACKGROUND: A key motor skill is the ability to rapidly interact with our dynamic environment. Humans can generate goal-directed motor actions in response to sensory stimulus within ~ 60-200ms. This ability can be impaired after stroke, but most clinical tools lack any measures of rapid feedback processing. Reaching tasks have been used as a framework to quantify impairments in generating motor corrections for individuals with stroke. However, reaching may be inadequate as an assessment tool as repeated reaching can be fatiguing for individuals with stroke. Further, reaching requires many trials to be completed including trials with and without disturbances, and thus, exacerbate fatigue. Here, we describe a novel robotic task to quantify rapid feedback processing in healthy controls and compare this performance with individuals with stroke to (more) efficiently identify impairments in rapid feedback processing. METHODS: We assessed a cohort of healthy controls (n = 135) and individuals with stroke (n = 40; Mean 41 days from stroke) in the Fast Feedback Interception Task (FFIT) using the Kinarm Exoskeleton robot. Participants were instructed to intercept a circular white target moving towards them with their hand represented as a virtual paddle. On some trials, the arm could be physically perturbed, the target or paddle could abruptly change location, or the target could change colour requiring the individual to now avoid the target. RESULTS: Most participants with stroke were impaired in reaction time (85%) and end-point accuracy (83%) in at least one of the task conditions, most commonly with target or paddle shifts. Of note, this impairment was also evident in most individuals with stroke when performing the task using their unaffected arm (75%). Comparison with upper limb clinical measures identified moderate correlations with the FFIT. CONCLUSION: The FFIT was able to identify a high proportion of individuals with stroke as impaired in rapid feedback processing using either the affected or unaffected arms. The task allows many different types of feedback responses to be efficiently assessed in a short amount of time.

Impairments of the ipsilesional upper-extremity in the first 6-months post-stroke.

BACKGROUND: Ipsilesional motor impairments of the arm are common after stroke. Previous studies have suggested that severity of contralesional arm impairment and/or hemisphere of lesion may predict the severity of ipsilesional arm impairments. Historically, these impairments have been assessed using clinical scales, which are less sensitive than robot-based measures of sensorimotor performance. Therefore, the objective of this study was to characterize progression of ipsilesional arm motor impairments using a robot-based assessment of motor function over the first 6-months post-stroke and quantify their relationship to (1) contralesional arm impairment severity and (2) stroke-lesioned hemisphere. METHODS: A total of 106 participants with first-time, unilateral stroke completed a unilateral assessment of arm motor impairment (visually guided reaching task) using the Kinarm Exoskeleton. Participants completed the assessment along with a battery of clinical measures with both ipsilesional and contralesional arms at 1-, 6-, 12-, and 26-weeks post-stroke. RESULTS: Robotic assessment of arm motor function revealed a higher incidence of ipsilesional arm impairment than clinical measures immediately post-stroke. The incidence of ipsilesional arm impairments decreased from 47 to 14% across the study period. Kolmogorov-Smirnov tests revealed that ipsilesional arm impairment severity, as measured by our task, was not related to which hemisphere was lesioned. The severity of ipsilesional arm impairments was variable but displayed moderate significant relationships to contralesional arm impairment severity with some robot-based parameters. CONCLUSIONS: Ipsilesional arm impairments were variable. They displayed relationships of varying strength with contralesional impairments and were not well predicted by lesioned hemisphere. With standard clinical care, 86% of ipsilesional impairments recovered by 6-months post-stroke.

I Know What to Do; I Can Do It; It Will Work: The Brief Parental Self Efficacy Scale (BPSES) for Parenting Interventions.

Parental self-efficacy predicts outcomes for parenting interventions for child behaviour problems, but there is a need for a brief measure that can be repeated over treatment and applies to a wide age range. The present study describes the development of such a measure, the Brief Parental Self-Efficacy Scale (BPSES). The psychometrics of the BPSES is presented across a wide age range from preschool to late adolescent in a sample comprised of four different intervention contexts. Evidence for structural validity, internal consistency, content validity, configural measurement invariance (equivalent factor structure) and test-retest reliability is presented alongside convergent validity against measures of parental self-efficacy, child behaviour problems, as well as self-report and observed parenting styles. Finally, lower levels of BPSES at baseline predicted increased disengagement from an intensive, individualised family therapy intervention for antisocial youth, while higher baseline levels predicted increased response to a group parenting programme for primary school aged children. The BPSES shows promise as a measure that can be used across a wide age-range, for a variety of parenting interventions for disruptive behaviour problems and which is sufficiently brief to be used as a routine outcome measurement during treatment.

Global Workforce Development in Father Engagement Competencies for Family-Based Interventions Using an Online Training Program: A Mixed-Method Feasibility Study.

Global access to practitioner training in the clinical engagement of fathers in family-based interventions is limited. The current study evaluated the feasibility of training practitioners in Canada and UK using online training developed in Australia by examining improvements in practitioner confidence and competence in father engagement, training satisfaction, qualitative feedback, and benchmarking results to those from an Australian sample. Practitioners were recruited to participate in a 2-h online training program through health services and charity organisations. The online program required practitioners to watch a video and complete self-reflection exercises in a digital workbook. Pre- and post-training measures were collected immediately before and after the online training program. The results indicated significantly large improvements in self-reported confidence and competence in engaging fathers following training, with levels of improvement similar to those found in Australia. Training satisfaction was high and qualitative feedback suggested providing local resources and increasing representation of social diversity could improve training relevance in local contexts. The findings suggest online training in father engagement can contribute to global workforce development in improving practitioners' skills in engaging fathers in family-based interventions.

Impact of counselling provision in primary schools on child and adolescent mental health service referral rates: a longitudinal observational cohort study.

BACKGROUND: In the United Kingdom, schools play an increasingly important role in supporting young peoples' mental health. While there is a growing evidence base to support the effectiveness of school-based interventions, less is known about how these provisions impact on local Child and Adolescent Mental Health Service (CAMHS) referral rates. There is a concern that an increase in school-based provision might lead to an increase in CAMHS referrals and overwhelm services. We aimed to examine the longitudinal association between Place2Be counselling provision in primary schools on CAMHS referral rates in South London. METHOD: This was a retrospective cohort study using linked data from the National Pupil Database (NPD) and CAMHS referrals to the South London and Maudsley's NHS Foundation Trust (SLaM) identified through the Clinical Record Interactive Search (CRIS) tool. The cohort included a total of 285 state-maintained primary schools in four London boroughs for the academic years of 2007-2012. During the study period, 23 of these schools received school-based mental health provision from Place2Be. The primary outcome was the incident rate ratio (IRR) of school-level accepted CAMHS referrals in 2012/13 in schools with, or without, Place2Be provision. RESULTS: There was no significant association between elevated rates of CAMHS referral and Place2Be provision, even after comprehensive adjustment for school-level and pupil characteristics (IRR 0.91 (0.67-1.23)). School-level characteristics, including higher proportion of white-British pupils (IRR 1.009 (1.002-1.02)), medical staff ratio (IRR 6.49 (2.05-20.6)) and poorer Ofsted school inspection ratings (e.g. IRR 1.58 (1.06-2.34) for 'Requires Improvement' vs. 'Outstanding') were associated with increased CAMHS referral rates. CONCLUSIONS: Place2Be provision did not result in increased specialist mental health referrals; however, other school-level characteristics did. Future research should investigate pupils' Place2Be clinical outcomes, as well the outcomes of individuals referred to CAMHS to better understand which needs are being met by which services.

Integration of proprioceptive and visual feedback during online control of reaching.

Visual and proprioceptive feedback both contribute to perceptual decisions, but it remains unknown how these feedback signals are integrated together or consider factors such as delays and variance during online control. We investigated this question by having participants reach to a target with randomly applied mechanical and/or visual disturbances. We observed that the presence of visual feedback during a mechanical disturbance did not increase the size of the muscle response significantly but did decrease variance, consistent with a dynamic Bayesian integration model. In a control experiment, we verified that vision had a potent influence when mechanical and visual disturbances were both present but opposite in sign. These results highlight a complex process for multisensory integration, where visual feedback has a relatively modest influence when the limb is mechanically disturbed, but a substantial influence when visual feedback becomes misaligned with the limb.NEW & NOTEWORTHY Visual feedback is more accurate, but proprioceptive feedback is faster. How should you integrate these sources of feedback to guide limb movement? As predicted by dynamic Bayesian models, the size of the muscle response to a mechanical disturbance was essentially the same whether visual feedback was present or not. Only under artificial conditions, such as when shifting the position of a cursor representing hand position, can one observe a muscle response from visual feedback.

Editorial: 'The giant's shoulders': understanding Michael Rutter's impact on science and society.

The recent death of our colleague and friend Professor Sir Michael Rutter has quite rightly been greeted by an outpouring of gratitude and respect from distinguished commentators across the globe working in diverse fields of the basic, social and clinical sciences as well as from clinicians and policy makers. These have without exception highlighted his seminal role as a pioneer, perhaps The Pioneer, of the application of the scientific method to the study of child and adolescent mental health and disorder - the father of evidence-based Child Psychiatry and the most influential voice in the new field of Developmental Psychopathology (Stevenson, 2022). In this editorial, we will attempt to build on these commentaries. We will parse Mike's scientific contributions to our field, in order to identify the personal characteristics and intellectual modus operandi that made him such a uniquely important figure, whose influence will resonate through the many fields he influenced for decades to come. We will also attempt something of a reframing of that contribution. Our thesis being that, although he never agitated for it politically or even stated it as a goal explicitly, Mike's work was motivated by a desire for social reform and created the scientific catalyst for such reform to occur.

A good investment: longer-term cost savings of sensitive parenting in childhood.

BACKGROUND: Good quality parenting in early childhood is reliably associated with positive mental and physical health over the lifespan. The hypothesis that early parenting quality has significant long-term financial benefits has not been previously tested. METHODS: Design: Longitudinal study with follow-up from 2012 to 2016. SETTING: UK multicentre study cohort (London, South-East England). PARTICIPANTS: 174 young people drawn from 2 samples, one at moderate risk of poor outcomes and one at high risk, assessed aged 4-6 years then followed up in early adolescence (mean age 12.1 years). MEASURES: The primary outcome was total costs: health, social care, extra school support, out-of-home placements and family-born expenditure, determined through semistructured economic interviews. Early parenting quality was independently assessed through direct observation of parent-child interaction. RESULTS: Costs were lower for youths exposed to more sensitive parenting (most sensitive quartile mean £1,619, least sensitive quartile mean £21,763; p < .001). Costs were spread across personal family expenditure and education, health, social and justice services. The cost difference remained significant after controlling for several potential confounders. These included demographic variables (family poverty, parental education); exposure to child abuse; and child/young person variables including level of antisocial behaviour in both childhood and adolescence, IQ and attachment security. CONCLUSIONS: This study is the first showing that more sensitive early parental care predicts lower costs to society many years later, independent of poverty, child and youth antisocial behaviour levels and IQ. Savings are likely to increase as individuals grow older since early parenting quality predicts health, behavioural and occupational outcomes in adulthood. The findings provide novel evidence for the public health impact of early caregiving quality and likely financial benefits of improving it.

Acute kidney injury is associated with subtle but quantifiable neurocognitive impairments.

BACKGROUND: Acute kidney injury (AKI) is associated with long-term morbidity and mortality. The effects of AKI on neurocognitive functioning remain unknown. Our objective was to quantify neurocognitive impairment after an episode of AKI. METHODS: Survivors of AKI were compared with age-matched controls, as well as a convenience sample of patients matched for cardiovascular risk factors with normal kidney function (active control group). Patients with AKI completed two assessments, while the active control group completed one assessment. The assessment included a standardized test: the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and a robotic assessment: Kinarm. RESULTS: The cohort consisted of 21 patients with AKI, 16 of whom completed both assessments, and 21 active control patients. The majority of patients with AKI had Kidney Disease: Improving Global Outcomes Stage 3 AKI (86%), 57% received dialysis and 43% recovered to ≤25% of their baseline serum creatinine by their first assessment. Compared with the RBANS, which detected little impairment, the Kinarm categorized patients as impaired in visuomotor (10/21, 48%), attention (10/20, 50%) and executive tasks (11/21, 52%) compared with healthy controls. Additionally, patients with AKI performed significantly worse in attention and visuomotor domains when compared with the active controls. Neurocognitive performance was generally not impacted by the need for dialysis or whether kidney function recovered. CONCLUSIONS: Robotic technology identified quantifiable neurocognitive impairment in survivors of AKI. Deficits were noted particularly in attention, visuomotor and executive domains. Further investigation into the downstream health consequences of these neurocognitive impairments is warranted.