Perisylvian and Hippocampal Anomalies in Individuals With Pathogenic GRIN2A Variants.

Background and Objectives: Pathogenic variants in GRIN2A are associated with a spectrum of epilepsy-aphasia syndromes (EASs). Seizures as well as speech and language disorders occur frequently but vary widely in severity, both between individuals and across the life span. The link between this phenotypic spectrum and brain characteristics is unknown. Specifically, altered brain networks at the root of speech and language deficits remain to be identified. Patients with pathogenic variants in GRIN2A offer an opportunity to interrogate the impact of glutamate receptor dysfunction on brain development. Methods: We characterized brain anomalies in individuals with pathogenic GRIN2A variants and EASs, hypothesizing alterations in perisylvian speech-language regions and the striatum. We compared structural MRI data from 10 individuals (3 children and 7 adults, 3 female) with pathogenic GRIN2A variants with data from age-matched controls (N = 51 and N = 203 in a secondary analysis). We examined cortical thickness and volume in 4 a priori hypothesized speech and language regions (inferior frontal, precentral, supramarginal, and superior temporal) and across the whole brain. Subcortical structures (hippocampus, basal ganglia, thalamus) and the corpus callosum were also compared. Results: Individuals with pathogenic GRIN2A variants showed increased thickness and volume in the posterior part of Broca's area (inferior frontal gyrus, pars opercularis). For thickness, the effects were bilateral but more pronounced in the left (large effect size, η2 = 0.37) than the right (η2 = 0.12) hemisphere. Both volume and thickness were also higher in the bilateral superior temporal region while the supramarginal region showed increased thickness only. Whole-brain analyses confirmed left-sided thickness increases in Broca's area, with additional increases in the occipital and superior frontal cortices bilaterally. Hippocampal volume was reduced in the left hemisphere. There were no age-dependent effects or corpus callosum group differences. Discussion: Anomalies in perisylvian regions, with largest differences in Broca's area, suggest an altered development of classical speech-language networks in GRIN2A-related EAS. Left hippocampal reduction suggests a role for this structure in early speech and language development and is consistent with GRIN2A gene expression in that region. Overall, elucidating the neural correlates of EAS provides insights into the impact of GRIN2A dysfunction, opening avenues for targeted intervention in developmental syndromes with compromised speech-language development.

Nurses' use of 'wellness' supplements during the COVID-19 pandemic in the United States.

AIM: Quantify disparities and identify correlates and predictors of 'wellness' supplement use among nurses during the first year of the pandemic. DESIGN: Longitudinal secondary analysis of Nurses' Health Studies 2 and 3 and Growing Up Today Study data. METHODS: Sample included 36,518 total participants, 12,044 of which were nurses, who completed surveys during the first year of the COVID-19 pandemic (April 2020 to April 2021). Analyses were conducted in March 2023. Modified Poisson models were used to estimate disparities in 'wellness' supplement use between nurses and non-healthcare workers and, among nurses only, to quantify associations with workplace-related predictors (occupational discrimination, PPE access, workplace setting) and psychosocial predictors (depression/anxiety, county-level COVID-19 mortality). Models included race/ethnicity, gender identity, age and cohort as covariates. RESULTS: Nurses were significantly more likely to use all types of supplements than non-healthcare workers. Lacking personal protective equipment and experiencing occupational discrimination were significantly associated with new immune supplement use. Depression increased the risk of using weight loss, energy and immune supplements. CONCLUSION: Nurses' disproportionate use of 'wellness' supplements during the COVID-19 pandemic may be related to workplace and psychosocial stressors. Given well-documented risks of harm from the use of 'wellness' supplements, the use of these products by nurses is of concern. IMPACT: 'Wellness' supplements promoting weight loss, increased energy, boosted immunity and cleansing of organs are omnipresent in today's health-focused culture, though their use has been associated with harm. This is of added concern among nurses given their risk of COVID-19 infection at work. Our study highlighted the risk factors associated with use of these products (lacking PPE and experiencing occupational discrimination). Findings support prior research suggesting a need for greater public health policy and education around the use of 'wellness' supplements. REPORTING METHOD: STROBE guidelines were followed throughout manuscript. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was involved.

Does vaping affect the taste and smell perception? An exploratory study with New Zealand young adults.

OBJECTIVE: The study aimed to assess potential effects of vaping on individual taste and smell perception in a sample of young adult New Zealanders. DESIGN: This cross-sectional study measured taste and smell perception using intensity and hedonic ratings to two olfactory (i.e., vanillin, methional) and two gustatory stimuli (i.e., sucrose, monosodium glutamate), representing sweet and savoury flavours. Detection sensitivities to sucrose and vanillin were also assessed using a forced choice detection paradigm aligned with the signal detection framework. MANCOVAs were employed to compare sensory perception between groups based on vaping use frequency. Additional regression analyses were conducted to identify potential predictors of intensity and hedonic sensory ratings. SETTING: Participants were recruited from the University of Otago student population and surrounding neighbourhoods of Dunedin, New Zealand in 2023. PARTICIPANTS: The study included 213 university students (98 vapers and 115 non-vapers) RESULTS: We found a significant difference in hedonic ratings for vanillin, indicating a stronger preference among non-vapers. However, no other differences between the two groups were significant. Notably, the use of tobacco and mint flavours were emerged as significant predictors for hedonic responses to the savoury smell and sweet taste stimulus, respectively. No significant differences were observed between groups in the ability to detect weak stimuli. CONCLUSIONS: Our findings suggest that vape use, particularly with specific flavours, may be associated with alterations in hedonic responses to smells. This finding may have potential implications for how vaping affects on food preferences and dietary choices.

Pediatric healthcare professionals' attitudes and beliefs about weight stigma: A descriptive study.

PURPOSE: Children face weight-based stigma from their healthcare providers at a disconcerting rate, and efforts to mitigate this have been scant. This study aimed to quantify pediatric healthcare professionals' attitudes and beliefs about weight stigma and to determine stigma reduction interventions that are most supported by pediatric healthcare providers. DESIGN AND METHODS: Participants completed two validated instruments which measured implicit and explicit weight bias, respectively. They then completed a researcher-designed questionnaire to assess their attitudes and beliefs about weight stigma, and demographic questions. ANOVA models were used to examine associations between bias measures and participant characteristics, chi-square analyses were used to examine associations between questionnaire responses and participant characteristics, and Spearman's rank was used to determine correlations between weight bias and questionnaire responses. RESULTS: Participants exhibited moderate-to-high levels of implicit and explicit weight bias (mean Implicit Association Test score = 0.59, mean Crandall Anti-Fat Attitudes Score = 38.95). Associations were noted between implicit bias and years in practice (p < 0.05), and implicit bias and occupation (p < 0.05). There was a significant correlation between explicit bias and multiple questionnaire items, suggesting that healthcare providers with greater weight bias are aware of those biases and are ready to take action to address them. CONCLUSION: Though pediatric healthcare exhibit weight-based biases, they are invested in taking steps to mitigate these biases and their impact on patients. PRACTICE IMPLICATIONS: The results of this study can inform the design of future interventions that aim to reduce healthcare-based weight bias, thus improving the quality of pediatric healthcare.

Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40.

Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members.

Population-level policy recommendations for the prevention of disordered weight control behaviors: A scoping review.

OBJECTIVE: The aim of this scoping review was to identify recommendations and gaps in knowledge surrounding the prevention of disordered weight control behaviors (DWCBs) through policy. METHOD: A search was conducted in several databases to identify English language articles that described an active policy, recommendation, guideline, or educational curriculum that could be implemented by governments or regulatory bodies to prevent DWCBs or related constructs (e.g., weight stigma, body dissatisfaction). Two researchers independently screened articles with oversight from a third researcher. Data were extracted from the final sample (n = 65) and analyzed qualitatively across all articles and within the domains of education, public policy, public health, industry regulation, and media. RESULTS: Only a single empirical evaluation of an implemented policy to reduce DWCBs was identified. Over one-third of articles proposed recommendations relating to industry regulation and media (n = 24, 36.9%), followed by education (n = 21, 32.3%), public policy (n = 19, 29.2%), and public health (n = 10, 15.4%). Recommendations included school-based changes to curricula, staff training, and anti-bullying policies; legislation to ban weight discrimination; policies informed by strategic science; collaboration with researchers from other fields; de-emphasizing weight in health communications; diversifying body sizes and limiting modified images in media; and restricting the sale of weight-loss supplements. DISCUSSION: The findings of this review highlight gaps in empirically evaluated policies to reduce DWCBs but also promising policy recommendations across several domains. Although some policy recommendations were supported by empirical evidence, others were primarily based on experts' knowledge, highlighting the need for greater research on population-level DWCBs prevention through policy. PUBLIC SIGNIFICANCE: Our scoping review of the evidence on policies for the prevention of disordered weight control behaviors identified several recommendations across the domains of education, public policy, public health, and industry regulation and media. Although few empirical investigations of implemented policies have been conducted, expert recommendations for policies to prevent disordered weight control behaviors among populations are plentiful and warrant future consideration by researchers and policymakers alike.

OBJETIVO: El objetivo de esta revisión sistemática exploratoria fue identificar recomendaciones y lagunas en el conocimiento sobre la prevención de comportamientos disfuncionales de control de peso (DWCB) a través de políticas. MÉTODO: Se realizó una búsqueda en varias bases de datos para identificar artículos en ingel resumenlés que describieran una política activa, recomendación, directriz o currículo educativo que pudieran implementar los gobiernos u organismos reguladores para prevenir DWCB o constructos relacionados (por ejemplo, estigma de peso, insatisfacción corporal). Dos investigadores examinaron de forma independiente los artículos con la supervisión de un tercer investigador. Los datos se extrajeron de la muestra final (n = 65) y se analizaron cualitativamente en todos los artículos y dentro de los dominios de educación, políticas públicas, salud pública, regulación de la industria y medios de comunicación. RESULTADOS: Solo se identificó una evaluación empírica única de una política implementada para reducir los DWCB. Más de un tercio de los artículos propusieron recomendaciones relacionadas con la regulación de la industria y los medios de comunicación (n = 24, 36.9%), seguido de educación (n = 21, 32.3%), políticas públicas (n = 19, 29.2%) y salud pública (n = 10, 15.4%). Las recomendaciones incluyeron cambios en los planes de estudio, capacitación del personal y políticas contra el acoso (bullying); legislación para prohibir la discriminación por peso; políticas basadas en la ciencia estratégica; colaboración con investigadores de otros campos; restar importancia al peso en las comunicaciones sanitarias; diversificar los tamaños corporales y limitar las imágenes modificadas en los medios; y restringir la venta de suplementos para bajar de peso. DISCUSIÓN: Los hallazgos de esta revisión destacan las brechas en las políticas evaluadas empíricamente para reducir los DWCB, pero también las recomendaciones de políticas prometedoras en varios dominios. Aunque algunas recomendaciones de políticas estaban respaldadas por evidencia empírica, otras se basaban principalmente en el conocimiento de expertos, destacando la necesidad de una mayor investigación sobre la prevención de DWCB a nivel poblacional a través de políticas.

In-depth characterisation of a cohort of individuals with missense and loss-of-function variants disrupting FOXP2.

BACKGROUND: Heterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition. METHODS: Here we phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German. RESULTS: Speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations across English and German. Speech was still impaired in adulthood, and some speech sounds (eg, 'th', 'r', 'ch', 'j') were never acquired. Language impairments (21/25, 84%) ranged from mild to severe. Comorbidities included feeding difficulties in infancy (10/26, 38%), fine (13/26, 50%) and gross (13/26, 50%) motor impairment, anxiety (5/27, 19%), depression (6/27, 22%) and sleep disturbance (10/24, 42%). Physical features were common (22/27, 81%) but with no consistent pattern. Cognition ranged from average to mildly impaired and was incongruent with language ability; for example, seven participants with severe language disorder had average non-verbal cognition. CONCLUSIONS: Although we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences of FOXP2 dysfunction remain relatively specific to speech disorder, as compared with other recently identified monogenic conditions associated with CAS. Thus, our findings reinforce that FOXP2 provides a valuable entry point for examining the neurobiological bases of speech disorder.

Atypical development of Broca's area in a large family with inherited stuttering.

Developmental stuttering is a condition of speech dysfluency, characterized by pauses, blocks, prolongations and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene-brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering. We studied a four-generation family, 16 family members were included in genotyping analysis. T1-weighted and diffusion-weighted MRI scans were conducted on seven family members (six male; aged 9-63 years) with two age and sex matched controls without stuttering (n = 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography. We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca's area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold of P < 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (left P = 0.017; right P = 0.037), and a larger right globus pallidus was associated with more severe stuttering (rho = 0.86, P = 0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype. Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca's area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering.

Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions.

INTRODUCTION: The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions. METHODS AND ANALYSIS: Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection. ETHICS AND DISSEMINATION: The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.

Speech in children with cerebral palsy.

AIM: To examine the frequency, characteristics, and factors associated with speech delay and disorder in a community sample of children with cerebral palsy (CP). METHOD: Participants were 84 children (37 females, 47 males; aged between 4y 11mo-6y 6mo) with CP identified through a population-based registry. Speech and oromotor function were systematically evaluated to provide a differential diagnosis of articulation, phonological, and motor speech disorders. RESULTS: In total, 82% (69/84) of participants had delayed or disordered speech production, including minimally verbal presentations (n=20). Verbal participants (n=64) presented with dysarthria (78%), articulation delay or disorder (54%), phonological delay or disorder (43%), features of childhood apraxia of speech (CAS) (17%), or mixed presentations across these conditions. Speech intelligibility was poorest in those with dysarthria and features of CAS. Speech delay or disorder in verbal participants was associated with language impairment (p=0.002) and reduced health-related quality of life (p=0.04) (Fisher's exact test). Poorer speech accuracy (i.e. lower percentage consonants correct) correlated with greater impairments in both language (p<0.001) and oromotor function (p<0.001) (Spearman's test). INTERPRETATION: The speech profile of children with CP is characterized by impairment at multiple levels of speech production (phonetic, cognitive-linguistic, neuromuscular execution, and high-level planning/programming), highlighting the importance of a personalized differential diagnosis informing targeted treatment.

Severe childhood speech disorder: Gene discovery highlights transcriptional dysregulation.

OBJECTIVE: Determining the genetic basis of speech disorders provides insight into the neurobiology of human communication. Despite intensive investigation over the past 2 decades, the etiology of most speech disorders in children remains unexplained. To test the hypothesis that speech disorders have a genetic etiology, we performed genetic analysis of children with severe speech disorder, specifically childhood apraxia of speech (CAS). METHODS: Precise phenotyping together with research genome or exome analysis were performed on children referred with a primary diagnosis of CAS. Gene coexpression and gene set enrichment analyses were conducted on high-confidence gene candidates. RESULTS: Thirty-four probands ascertained for CAS were studied. In 11/34 (32%) probands, we identified highly plausible pathogenic single nucleotide (n = 10; CDK13, EBF3, GNAO1, GNB1, DDX3X, MEIS2, POGZ, SETBP1, UPF2, ZNF142) or copy number (n = 1; 5q14.3q21.1 locus) variants in novel genes or loci for CAS. Testing of parental DNA was available for 9 probands and confirmed that the variants had arisen de novo. Eight genes encode proteins critical for regulation of gene transcription, and analyses of transcriptomic data found CAS-implicated genes were highly coexpressed in the developing human brain. CONCLUSION: We identify the likely genetic etiology in 11 patients with CAS and implicate 9 genes for the first time. We find that CAS is often a sporadic monogenic disorder, and highly genetically heterogeneous. Highly penetrant variants implicate shared pathways in broad transcriptional regulation, highlighting the key role of transcriptional regulation in normal speech development. CAS is a distinctive, socially debilitating clinical disorder, and understanding its molecular basis is the first step towards identifying precision medicine approaches.

Self-harm presentation across healthcare settings by sex in young people: an e-cohort study using routinely collected linked healthcare data in Wales, UK.

BACKGROUND: This study used individual-level linked data across general practice, emergency departments (EDs), outpatients and hospital admissions to examine contacts across settings and time by sex for self-harm in individuals aged 10-24 years old in Wales, UK. METHODS: A whole population-based e-cohort study of routinely collected healthcare data was conducted. Rates of self-harm across settings over time by sex were examined. Individuals were categorised based on the service(s) to which they presented. RESULTS: A total of 937 697 individuals aged 10-24 years contributed 5 369 794 person years of data from 1 January 2003 to 30 September 2015. Self-harm incidence was highest in primary care but remained stable over time (incident rate ratio (IRR)=1.0; 95% CI 0.9 to 1.1). Incidence of ED attendance increased over time (IRR=1.3; 95% CI 1.2 to 1.5) as did hospital admissions (IRR=1.4; 95% CI 1.1 to 1.6). Incidence in the 15-19 years age group was the highest across all settings. The largest increases were seen in the youngest age group. There were increases in ED attendances for both sexes; however, females are more likely than males to be admitted following this. This was most evident in individuals 10-15 years old, where 76% of females were admitted compared with just 49% of males. The majority of associated outpatient appointments were under a mental health specialty. CONCLUSIONS: This is the first study to compare self-harm in people aged 10-24 years across primary care, EDs and hospital settings in the UK. The high rates of self-harm in primary care and for young men in EDs highlight these as important settings for intervention.

Breastfeeding and the Development of Socio-Emotional Competencies: A Systematic Review.

Aim: To assess the current scientific evidence about the relationship between breastfeeding and the development of infant's socio-emotional competencies. Materials and Methods: A systematic review of literature was conducted through PubMed, LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), and PsycINFO of population-based cohorts. Records were screened, data extracted, and a quality assessment performed by two authors independently. Results: Thirteen studies were included in the review with six finding a statistically significant association between breastfeeding and the development of socio-emotional competencies such as problem solving, agreeableness, and optimism. In five studies, no statistically significant association was found, and in three, a negative association existed. Regarding quality assessment, four studies had a strong global rating, four had a moderate rating, and five had a weak global rating. Conclusion: Almost half (6/13) of the studies found a positive association between breastfeeding and the development of social-emotional competencies in infants; however, a great heterogeneity was present in the quality of the included studies. There is a need for further and higher quality research into this field of study.

Looking to the Future: Speech, Language, and Academic Outcomes in an Adolescent with Childhood Apraxia of Speech.

OBJECTIVE: The clinical course of childhood apraxia of speech (CAS) is poorly understood. Of the few longitudinal studies in the field, only one has examined adolescent outcomes in speech, language, and literacy. This study is the first to report long-term speech, language, and academic outcomes in an adolescent, Liam, with CAS. METHODS: Speech, language, literacy, and academic outcome data were collected, including 3 research-based assessments. Overall, data were available at 17 time points from 3;10 to 15 years. RESULTS: Liam had moderate-to-severe expressive language impairment and poor reading, writing, and spelling up to 10 years. His numeracy was at or above the national average from 8 to 14 years. He made gains in preadolescence, with average expressive language at 11 years and above average reading and writing at 14 years. Nonword reading, reading comprehension, and spelling remained areas of weakness. Receptive language impairment was evident at 13 years, which was an unexpected finding. CONCLUSION: Findings from single cases can be hypothesis generating but require verification in larger cohorts. This case shows that at least some children with CAS may gain ground in adolescence, relative to same age peers, in expressive language and academic areas such as reading and writing.

Dorsal language stream anomalies in an inherited speech disorder.

Speech disorders are highly prevalent in the preschool years, but frequently resolve. The neurobiological basis of the most persistent and severe form, apraxia of speech, remains elusive. Current neuroanatomical models of speech processing in adults propose two parallel streams. The dorsal stream is involved in sound to motor speech transformations, while the ventral stream supports sound/letter to meaning. Data-driven theories on the role of these streams during atypical speech and language development are lacking. Here we provide comprehensive behavioural and neuroimaging data on a large novel family where one parent and 11 children presented with features of childhood apraxia of speech (the same speech disorder associated with FOXP2 variants). The genetic cause of the disorder in this family remains to be identified. Importantly, in this family the speech disorder is not systematically associated with language or literacy impairment. Brain MRI scanning in seven children revealed large grey matter reductions over the left temporoparietal region, but not in the basal ganglia, relative to typically-developing matched peers. In addition, we detected white matter reductions in the arcuate fasciculus (dorsal language stream) bilaterally, but not in the inferior fronto-occipital fasciculus (ventral language stream) nor in primary motor pathways. Our findings identify disruption of the dorsal language stream as a novel neural phenotype of developmental speech disorders, distinct from that reported in speech disorders associated with FOXP2 variants. Overall, our data confirm the early role of this stream in auditory-to-articulation transformations. 10.1093/brain/awz018_video1 awz018media1 6018582401001.

"To survey or to register" is that the question for estimating population incidence of injuries?

BACKGROUND: Measuring the true incidence of injury or medically attended injury is challenging. Population surveys, despite problems with recall and selection bias, remain the only source of information for injury incidence calculation in many countries. Emergency department (ED) registry based data provide an alternative source.The aim of this study is to compare the yearly incidence of hospital treated Home and Leisure Injuries (HLI), and Road Traffic Injuries (RTI) estimated by survey-based and register-based methods and combine information from both sources in to a comprehensive injury burden pyramide. METHODS: Data from Luxemburg's European Health Examination Survey (EHES-LUX), European Health Interview Survey (EHIS) and ED surveillance system Injury Data Base (IDB) collected in 2013, were used. EHES-LUX data on 1529 residents 25-64 years old, were collected between February 2013-January 2015. EHIS data on 4004 other residents aged 15+ years old, were collected between February and December 2014. Participants reported last year's injuries at home, leisure and traffic and treatment received. Two-sided exact binomial tests were used to compare incidences from registry with the incidences of each survey by age group and prevention domain. Data from surveys and register were combined to build an RTI and HLI burden pyramide for the 25-64 years old. This project was part of the European Union project BRIDGE-Health (BRidging Information and Data Generation for Evidence-based Health Policy and Research). RESULTS: Among 25-64 years old the incidence of hospital treated injuries per thousand population was 60.1 (95% CI: 59.2-60.9) according to IDB, 62.1 (95% CI: 50.6-75.4) according to EHES-LUX and 53.2 (95% CI: 45.0-62.4) according to EHIS. The incidence of hospital admissions was 3.7 (95% CI: 3.5-4.0) per thousand population from IDB-Luxembourg, 12.4 (95% CI: 7.5-19.3) from EHES-LUX and 18.0 (95% CI: 13.3-23.8) from EHIS. For 15+ years-old incidence of hospital treated HLI was 62.8 (95% CI: 62.1-63.5) per thousand population according to IDB whereas the corresponding EHIS estimate was lower at 46.9 (95% CI: 40.4-54.0). About half of HLI and RTI of the 25-64 years old were treated in hospital. CONCLUSION: The overall incidence estimate of hospital treated injuries from both methods does not differ for the 25-64 years old. Surveys overestimate the number of hospital admissions, probably due to memory bias. For people aged 15+ years, the survey estimate is lower than the register estimate for hospital treated HLI injuries, probably due to selection and recall biases. ED based registry data is to be preferred as single source for estimating the incidence of hospital treated injuries in all age groups.

Comparison of Psychological Response between Concussion and Musculoskeletal Injury in Collegiate Athletes.

The psychological response to musculoskeletal injuries has been well documented, however, research on the psychological response to concussion is limited. The Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI) have recently been used to assess the psychological recovery of concussions. Although some studies indicate that psychological response is different for musculoskeletal injuries and concussion, there is currently not enough information to indicate this difference occurs at specific clinical milestones. The purpose of this study was to compare the psychological responses of student-athletes who have been diagnosed with a concussion to those of athletes diagnosed with musculoskeletal injuries with similar recovery duration. Fifteen collegiate athletes who sustained a musculoskeletal injury were recruited and matched with 15 previously collected concussion participants. The main outcome measures were the scores of POMS constructs: tension-anxiety, anger-hostility, fatigue-inertia, depression-dejection, vigor-activity, confusion-bewilderment, and total mood disturbance and STAI (state anxiety only). Two-way MANOVAs was run to determine the effects of group and time on POMS and STAI constructs. There were no significant interactions identified, but follow-up ANOVAs identified a main effect for time for most POMS subscales, with POMS scores improving over time in both groups. Analyses also revealed that tension-anxiety, vigor-activity and the STAI were not affected by time or group. The findings of this study, that both groups' psychological response to injury improves over time and at similar clinical milestones suggests reduction in sports and team related activities may play a substantial role in the psychological response to either concussion or musculoskeletal injury.

Familial epilepsy with anterior polymicrogyria as a presentation of COL18A1 mutations.

Knobloch syndrome [OMIM: (KNO1) #267750] is a rare and clinically heterogeneous autosomal recessive disorder caused by mutations in COL18A1. Knobloch syndrome is characterised by abnormalities of the eye and occipital skull defects however the full phenotypic spectrum is yet to be defined. This report describes a family of four affected sisters with polymicrogyria, refractory seizures, and intellectual impairment of varying severity with a Lennox-Gastaut phenotype, and complex eye abnormalities where a syndromic diagnosis was not initially made. Whole exome sequencing of two affected sisters followed by filtering for rare and potentially disease causing variants in all genes identified compound heterozygous variants in NM_030582.3 (COL18A1): c.3690G > A: p.(Trp1230*) and NM_030582.3 (COL18A1): c.4063_4064delCT: p.(Leu1355Valfs*72). The two variants co-segregated with the affected individuals in the family. Identification of COL18A1 mutations in individuals with a Lennox-Gastaut phenotype and anterior polymicrogyria but lacking the classical occipital encephalocele expands the COL18A1 clinical spectrum.

Dysarthria and broader motor speech deficits in Dravet syndrome.

OBJECTIVE: To analyze the oral motor, speech, and language phenotype in 20 children and adults with Dravet syndrome (DS) associated with mutations in SCN1A. METHODS: Fifteen verbal and 5 minimally verbal DS patients with SCN1A mutations (aged 15 months-28 years) underwent a tailored assessment battery. RESULTS: Speech was characterized by imprecise articulation, abnormal nasal resonance, voice, and pitch, and prosody errors. Half of verbal patients had moderate to severely impaired conversational speech intelligibility. Oral motor impairment, motor planning/programming difficulties, and poor postural control were typical. Nonverbal individuals had intentional communication. Cognitive skills varied markedly, with intellectual functioning ranging from the low average range to severe intellectual disability. Language impairment was congruent with cognition. CONCLUSIONS: We describe a distinctive speech, language, and oral motor phenotype in children and adults with DS associated with mutations in SCN1A. Recognizing this phenotype will guide therapeutic intervention in patients with DS.

Risk factors associated with unintentional house fire incidents, injuries and deaths in high-income countries: a systematic review.

OBJECTIVE: To identify the distinguishing risk factors associated with unintentional house fire incidents, injuries and deaths. STUDY DESIGN: Systematic review. METHODS: A range of bibliographical databases and grey literature were searched from their earliest records to January 2016. To ensure the magnitude of risk could be quantified, only those study types which contained a control group, and undertook appropriate statistical analyses were included. A best evidence synthesis was conducted instead of a meta-analysis due to study heterogeneity. RESULTS: Eleven studies investigating a variety of risk factors and outcomes were identified. Studies ranged from medium to low quality with no high quality studies identified. Characteristics commonly associated with increased risk of house fire incidents, injuries and fatalities included: higher numbers of residents, male, children under the age of 5 years, non-working households, smoking, low income, non-privately owned properties, apartments and buildings in poor condition. Several risk factors were only associated with one outcome (eg, living alone was only associated with increased risk of injurious fires), and households with older residents were at increased risk of injurious fires, but significantly less likely to experience a house fire in the first place. CONCLUSIONS: This best evidence synthesis indicates that several resident and property characteristics are associated with risk of experiencing house fire incidents, injuries or death. These findings should be considered by the Fire and Rescue Services and others with a role in fire prevention. Future research should adopt robust, standardised study designs to permit meta-analyses and enable stronger conclusions to be drawn.