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A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties.
A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02–17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).
Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55–0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9–16% of the variance, depending on DBC subdomain.
Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.
This article examines provincial policy influence on long-term care (LTC) professionals’ advice-seeking networks in Canada’s Maritime provinces. The effects of facility ownership, geography, and region-specific political landscapes on LTC best-practice dissemination are examined. We used sociometric statistics and network sociograms, calculated from surveys with 169 senior leaders in LTC facilities, to identify advice-seeking network structures and to select 11 follow-up interview participants. Network structures were distinguished by density, sub-group number, opinion leader, and boundary spanner distribution. Network structure was affected by ownership model in Nova Scotia and Prince Edward Island, and by regional geography in New Brunswick. Political instability within each province’s LTC system negatively affected network actors’ capabilities to enact innovation. Moreover, provincial policy variations influence advice-seeking network structures, facilitating and constraining relationship development and networking. Consequently, local policy context is essential to informing dissemination strategy design or implementation.
Although lignin has been negatively correlated with neutral-detergent fibre (NDF) digestibility (NDFD) in ruminants and used to predict potential extent of NDF digestion of forages, selection of an analysis, Klason lignin (KL) or acid-detergent lignin (ADL), to describe that the nutritionally relevant lignin has not been resolved. Dismissed as an artifact is the difference between KL and ADL (ΔL). A question is whether ΔL influences NDFD. We evaluated the relationships of ΔL, KL and ADL with NDFD in order to determine the nutritionally homogeneous or heterogeneous nature of KL. Data sets from two laboratories (DS1 and DS2) were used that included ADL, KL and in vitro NDFD at 48 h (NDFD48). DS1 contained seven C3 grasses, seventeen C4 maize forages and nineteen alfalfas, and DS2 had fifteen C3 grasses, eight C4 forages and six alfalfas. Mean ΔL was greater than ADL in C3 and C4 samples and less in alfalfas. Within forage type and laboratory, ΔL was not correlated with NDFD48 (r −0·34–0·49; all P > 0·17). ADL was more consistently correlated with NDFD48 (r −0·47–−0·95; P < 0·01–0·21) than with KL (r 0·03–−0·91; P < 0·01–0·94). ΔL as a proportion of KL was correlated with NDFD48 in C3 and C4 samples (r 0·44–0·76; P < 0·01–0·08). The differing behaviours of ΔL and ADL relative to NDFD48 indicate that KL is a nutritionally heterogeneous fraction, the behaviour of which may vary by forage type and ratios of ADL and ΔL present.
Innovation Concept: EM Sim Cases is an innovative, open-access website that was created in 2015 to publish medical simulation resources including standardized, peer-reviewed simulation cases. Herein we describe our interim analysis. Methods: We performed a massive online needs assessment using a methodology previously described by Chan et. al. to determine how we can shape EM Sim Cases to meet the needs of learners and educators who use it. We engaged with simulation experts from the Emergency Medicine Simulation Education Research Collaborative to design a Google Forms survey using best practices in survey design. We distributed the survey to our target community of practice via Twitter, email, and a blog post published on emsimcases.com. Curriculum, Tool, or Material: We received 81 responses from simulation educators representing 8 medical specialties and 13 countries. Most survey respondents identified themselves as staff physicians (n = 44) and specialized in emergency medicine (n = 39). They had 0-21+ years of experience. 37% of respondents (n = 30) stated that material from EM Sim Cases makes up 25% or more of their simulation curriculum. Several respondents noted that using this content made them feel more confident and more current. Respondents praised EM Sim Cases for a well-organized case format, the proper level of detail, consistency between case designs, and the wide variety of cases. Suggested improvements included an opportunity to directly comment on cases and more cases in pediatric, rural, and advanced airway management situations. Suggestions were made to improve the navigability of the website. Respondents wanted to see additional blog content on debriefing strategies and self-made task/skill trainers. Conclusion: EM Sim Cases is a novel, free open-access simulation resource. Using a massive online needs assessment we were able to determine future directions including case topics, website reorganization, and educational material. We were also able to capture how impactful a resource like this can be to clinical and educational practice outside of the simulation setting.
Introduction: In 2018, Canadian postgraduate specialist Emergency Medicine (EM) programs began implementing a competency-based medical education (CBME) assessment system. To support improvement of this assessment program, we sought to evaluate its short-term educational outcomes nationally and within individual programs. Methods: Program-level data from the 2018 resident cohort were amalgamated and analyzed. The number of Entrustable Professional Activity (EPA) assessments (overall and for each EPA) and the timing of resident promotion through program stages was compared between programs and to the guidelines provided by the national EM specialty committee. Total EPA observations from each program were correlated with the number of EM and pediatric EM rotations. Results: Data from 15 of 17 (88.2%) EM programs containing 9,842 EPA observations from 68 of the 77 (88.3%) Canadian EM specialist residents in the 2018 cohort were analyzed. The average number of EPAs observed per resident in each program varied from 92.5 to 229.6 and correlated strongly with the number of blocks spent on EM and pediatric EM (r = 0.83, p < 0.001). Relative to the guidelines outlined by the specialty committee, residents were promoted later than expected and with fewer EPA observations than suggested. Conclusion: We present a new approach to the amalgamation of national and program-level assessment data. There was demonstrable variation in both EPA-based assessment numbers and promotion timelines between programs and with national guidelines. This evaluation data will inform the revision of local programs and national guidelines and serve as a starting point for further reaching outcome evaluation. This process could be replicated by other national assessment programs.
Innovation Concept: A major barrier to the development of a national simulation case repository and multi-site simulation research is the lack of a standardized national case template. This issue was recently identified as a priority research topic for Canadian simulation based education (SBE) research in emergency medicine (EM). We partnered with the EM Simulation Education Researchers Collaborative (EM-SERC) to develop a national simulation template. Methods: The EM Sim Cases template was chosen as a starting point for the consensus process. We generated feedback on the template using a three-phase modified nominal group technique. Members of the EM-SERC mailing list were consulted, which included 20 EM simulation educators from every Canadian medical school except Northern Ontario School of Medicine and Memorial University. When comments conflicted, the sentiment with more comments in favour was incorporated. Curriculum, Tool or Material: In phase one we sought free-text feedback on the EM Sim Cases template via email. We received 65 comments from 11 respondents. An inductive thematic analysis identified four major themes (formatting, objectives, debriefing, and assessment tools). In phase two we sought free-text feedback on the revised template via email. A second thematic analysis on 40 comments from 12 respondents identified three broad themes (formatting, objectives, and debriefing). In phase three we sought feedback on the penultimate template via focus groups with simulation educators and technologists at multiple Canadian universities. This phase generated 98 specific comments which were grouped according to the section of the template being discussed and used to develop the final template (posted on emsimcases.com). Conclusion: We describe a national consensus-building process which resulted in a simulation case template endorsed by simulation educators from across Canada. This template has the potential to: 1. Reduce the replication of effort across sites by facilitating the sharing of simulation cases. 2. Enable national collaboration on the development of both simulation cases and curricula. 3. Facilitate multi centre simulation-based research by removing confounders related to the local adoption of an unfamiliar case template. This could improve the rigour and validity of these studies by reducing inter-site variability. 4. Increase the validity of any simulation scenarios developed for use in national high-stakes assessment.
To investigate associations between schizophrenia candidate gene polymorphisms and regional cortical thickness and volume in patients with schizophrenia and healthy control subjects.
Genotyping was performed using PCR and pyrosequencing techniques. Cortical morphology was analyzed by processing magnetic resonance brain images with the FreeSurfer software package. General linear model analysis was used to study associations between gene variants and cortical thickness in patients and controls, respectively. Regional cortical volumes were defined from automatic cortical parcellations. Our first studies from 96 patients with schizophrenia and 104 healthy control subjects demonstrate that polymorphisms in the brain derived neurotrophic factor (BDNF) gene may be associated with variation in frontal lobe morphology. Associations seem to be stronger in patients with schizophrenia than in healthy controls.
Quality improvement and patient safety (QIPS) competencies are increasingly important in emergency medicine (EM) and are now included in the CanMEDS framework. We conducted a survey aimed at determining the Canadian EM residents’ perspectives on the level of QIPS education and support available to them.
An electronic survey was distributed to all Canadian EM residents from the Royal College and Family Medicine training streams. The survey consisted of multiple-choice, Likert, and free-text entry questions aimed at understanding familiarity with QIPS, local opportunities for QIPS projects and mentorship, and the desire for further QIPS education and involvement.
Of 535 EM residents, 189 (35.3%) completed the survey, representing all 17 medical schools; 77.2% of respondents were from the Royal College stream; 17.5% of respondents reported that QIPS methodologies were formally taught in their residency program; 54.7% of respondents reported being “somewhat” or “very” familiar with QIPS; 47.2% and 51.5% of respondents reported either “not knowing” or “not having readily available” opportunities for QIPS projects and QIPS mentorship, respectively; 66.9% of respondents indicated a desire for increased QIPS teaching; and 70.4% were interested in becoming involved with QIPS training and initiatives.
Many Canadian EM residents perceive a lack of QIPS educational opportunities and support in their local setting. They are interested in receiving more QIPS education, as well as project and mentorship opportunities. Supporting residents with a robust QIPS educational and mentorship framework may build a cohort of providers who can enhance the local delivery of care.
The RemoveDEBRIS mission has been the first mission to successfully demonstrate, in-orbit, a series of technologies that can be used for the active removal of space debris. The mission started late in 2014 and was sponsored by a grant from the EC that saw a consortium led by the Surrey Space Centre to develop the mission, from concept to in-orbit demonstrations, that terminated in March 2019. Technologies for the capture of large space debris, like a net and a harpoon, have been successfully tested together with hardware and software to retrieve data on non-cooperative target debris kinematics from observations carried out with on board cameras. The final demonstration consisted of the deployment of a drag-sail to increase the drag of the satellite to accelerate its demise.
At its late Pleistocene maximum, the Laurentide Ice Sheet was the largest ice mass on Earth and a key player in the modulation of global climate and sea level. At the same time, this temperate ice sheet was itself sensitive to climate, and high-magnitude fluctuations in ice extent, reconstructed from relict glacial deposits, reflect past changes in atmospheric temperature. Here, we present a cosmogenic 10Be surface-exposure chronology for the Berlin moraines in the White Mountains of northern New Hampshire, USA, which supports the model that deglaciation of New England was interrupted by a pronounced advance of ice during the Bølling-Allerød. Together with recalculated 10Be ages from the southern New England coast, the expanded White Mountains moraine chronology also brackets the timing of ice sheet retreat in this sector of the Laurentide. In conjunction with existing chronological data, the moraine ages presented here suggest that deglaciation was widespread during Heinrich Stadial 1 event (~18–14.7 ka) despite apparently cold marine conditions in the adjacent North Atlantic. As part of the White Mountains moraine system, the Berlin chronology also places a new terrestrial constraint on the former glacial configuration during the marine incursion of the St. Lawrence River valley north of the White Mountains.
The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology.
169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02–14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89–14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ.
The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (β = −0.18, p = 0.021) and autism spectrum disorder trait (β = −0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (β = −0.20, p = 0.015) and verbal IQ (β = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores.
The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.
Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.
Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).
Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.
How did personal wealth and slaveownership affect the likelihood Southerners fought for the Confederate Army in the American Civil War? On the one hand, wealthy Southerners had incentives to free-ride on poorer Southerners and avoid fighting; on the other hand, wealthy Southerners were disproportionately slaveowners, and thus had more at stake in the outcome of the war. We assemble a dataset on roughly 3.9 million free citizens in the Confederacy and show that slaveowners were more likely to fight than non-slaveowners. We then exploit a randomized land lottery held in 1832 in Georgia. Households of lottery winners owned more slaves in 1850 and were more likely to have sons who fought in the Confederate Army. We conclude that slaveownership, in contrast to some other kinds of wealth, compelled Southerners to fight despite free-rider incentives because it raised their stakes in the war’s outcome.
Introduction: Clinicians treating children in the emergency department (ED) are especially concerned with the efficacy and safety of imaging. Interventions to limit imaging have been proposed to maximize benefits and avoid risks; however, the types and effectiveness of interventions employed in pediatric EDs have not been examined in detail. Methods: Electronic databases and grey literature were systematically searched by a medical librarian. Comparative studies of ED-based interventions reporting computed tomography (CT), radiography (XR), or ultrasound (US) outcomes were included. Interventions introducing new imaging equipment or personnel to the ED, ED diversion strategies, and pre-admission protocols were excluded. At least two independent reviewers assessed each study for inclusion based on pre-defined criteria and extracted data. Disagreements were resolved through consensus. Descriptive results are reported. Results: Overall, 38 pediatric studies were included. Most (66%) interventions implemented two or more components; the most common intervention components were clinical guidelines or pathways (87%) and education or information (66%). Studies were categorized by presentation type: traumatic (n = 27); non-traumatic (n = 19), or combined ‘all-comers’ (n = 2). Included studies reported 62 imaging outcomes (CT = 29; XR = 20; US = 13). Among traumatic studies, 26 imaging outcomes were reported; CT was the most commonly reported outcome (CT = 15; XR = 9; US = 1). Of the CT outcomes, 33% reported significant decreases and five decreased but were either not significant or did not report significance. XR significantly decreased in 44% (4/9). In the non-traumatic studies, the most common imaging outcome remained CT (12 outcomes); 58% of which reported significant decreases. XR was the second most frequent outcome, with 63% reporting significant reductions. Combined success of the interventions to reduce CT and XR was 60%. Reported changes in ordering were less consistent in US. Conclusion: Multifaceted passive interventions have been implemented to reduce imaging in pediatric EDs. Most reported some success changing ordering practices, specifically among patients with non-trauma presentations. Future research exploring relationships between intervention content, effectiveness, and fidelity may provide insight into how to develop more effective interventions to change image ordering in the ED and guide which presentations to target.