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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.
Coronavirus disease 2019, a highly transmissible respiratory infection, has created a public health crisis of global magnitude. The mainstay of diagnostic testing for coronavirus disease 2019 is molecular polymerase chain reaction testing of a respiratory specimen, obtained with a viral swab. As the incidence of new cases of coronavirus disease 2019 increases exponentially, the use of viral swabs to collect nasopharyngeal specimens is anticipated to increase drastically.
This paper draws attention to a complication of viral swab testing in the nasopharynx and describes the premature engagement of a viral swab breakpoint, resulting in impaction in the nasal cavity.
This case highlights a possible design flaw of the viral swab when used to collect nasopharyngeal specimens, which then requires an aerosol-generating procedure in a high-risk patient to be performed. The paper outlines a safe technique of nasal foreign body removal in a suspected coronavirus disease 2019 patient and suggests alternative testing materials.
Feeding cattle with on-pasture supplementation or feedlot diets can increase animal efficiency and system profitability while minimizing environmental impacts. However, cattle system profit margins are relatively small and nutrient supply accounts for most of the costs. This paper introduces a nonlinear profit-maximizing diet formulation problem for beef cattle based on well-established predictive equations. Nonlinearity in predictive equations for nutrient requirements poses methodological challenges in the application of optimization techniques. In contrast to other widely used diet formulation methods, we develop a mathematical model that guarantees an exact solution for maximum profit diet formulations. Our method can efficiently solve an often-impractical nonlinear problem by solving a finite number of linear problems, that is, linear time complexity is achieved through parametric linear programming. Results show the impacts of choosing different objective functions (minimizing cost, maximizing profit and maximizing profit per daily weight gain) and how this may lead to different optimal solutions. In targeting improved ration formulation on feedlot systems, this paper demonstrates how profitability and nutritional constraints can be met as an important part of a sustainable intensification production strategy.
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: A critical component for successful implementation of any innovation is an organization's readiness for change. Competence by Design (CBD) is the Royal College's major change initiative to reform the training of medical specialists in Canada. The purpose of this study was to measure readiness to implement CBD among the 2019 launch disciplines. Methods: An online survey was distributed to program directors of the 2019 CBD launch disciplines one month prior to implementation. Questions were developed based on the R = MC2 framework for organizational readiness. They addressed program motivation to implement CBD, general capacity for change, and innovation-specific capacity. Questions related to motivation and general capacity were scored using a 5-point scale of agreement. Innovation-specific capacity was measured by asking participants whether they had completed 33 key pre-implementation tasks (yes/no) in preparation for CBD. Bivariate correlations were conducted to examine the relationship between motivation, general capacity and innovation specific capacity. Results: Survey response rate was 42% (n = 79). A positive correlation was found between all three domains of readiness (motivation and general capacity, r = 0.73, p < 0.01; motivation and innovation specific capacity, r = 0.52, p < 0.01; general capacity and innovation specific capacity, r = 0.47, p < 0.01). Most respondents agreed that successful launch of CBD was a priority (74%). Fewer felt that CBD was a move in the right direction (58%) and that implementation was a manageable change (53%). While most programs indicated that their leadership (94%) and faculty and residents (87%) were supportive of change, 42% did not have experience implementing large-scale innovation and 43% indicated concerns about adequate support staff. Programs had completed an average of 72% of pre-implementation tasks. No difference was found between disciplines (p = 0.11). Activities related to curriculum mapping, competence committees and programmatic assessment had been completed by >90% of programs, while <50% of programs had engaged off-service rotations. Conclusion: Measuring readiness for change aids in the identification of factors that promote or inhibit successful implementation. These results highlight several areas where programs struggle in preparation for CBD launch. Emergency medicine training programs can use this data to target additional implementation support and ongoing faculty development initiatives.
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.
The anchoritic life was first attested among women in England in the early twelfth century and became an increasingly popular choice that continued up to the Reformation. In the thirteenth century, the time period under consideration here, the anchoritic life was flourishing, particularly for aristocratic women. The Ancrene Wisse, or Ancrene Riwle as it is alternatively known, was written in the West Midlands of England in the early thirteenth century as a handbook for such solitary women who sought physical enclosure, away from the world, in order to pursue a higher spiritual calling. The AW author's autograph text does not survive, but the unrevised version does, at one or two removes from the original, in the Nero manuscript (London, British Library, Cotton MS Nero A.xiv, henceforth “Nero”), dedicated to three aristocratic sisters who took up the anchoritic life and for whom the text was composed. The text was revised, possibly by the author himself, for a wider group of anchoresses, and this revised version is preserved in the Corpus, Cleopatra, Titus, Vitellius, and Vernon manuscripts. These, with the exception of Vitellius, make up the early manuscripts of the AW.
Particularly in the past thirty years, though studies of the readership of the AW have grown, few have probed more than superficially the relationship between the text and its thirteenth-century women readers. Even these studies typically consider English and French devotional literacy; questions of Latin literacy among this readership are often dealt with briefly and then set aside on the grounds that Latin literacy among thirteenth-century laywomen readers was exceptional, and the Latin that appears in the AW was not in the main directed at the women readers but at their supervisors. The predominant language of literacy was shifting; this shift is highlighted by the composition of the AW in English rather than in the Latin of Aelred of Rievaulx's anchoritic guidebook De institutione inclusarum only sixty or so years earlier. Also, the remarkable texts of the contemporary Katherine Group (KG) and the Wooing Group (WG) have often been taken as evidence that vernacular literacy among their women readers was supreme.
Depression and mortality have been studied separately in patients with coronary heart disease (CHD) and in populations healthy at study inception. This does not allow comparisons across risk-factor groups based on the cross-classification of depression and CHD status. We prospectively examined the effects of depressive symptoms, assessed in 2002-2004, on all-cause and cardiovascular -mortality in a large sample of 5936 middle-aged participants, with and without established CHD, followed over 5.6 years
We created 4-risk-factor groups based on the cross classification of depressive symptoms and CHD status. The age-and-sex-adjusted hazard ratios for all causes death were 1.67-fold (p< 0.05) higher for participants with only CHD, 2.10-fold (p< 0.001) higher for those with only depressive symptoms and 4.99-fold (p< 0.001) higher for those with both CHD and depressive symptoms when compared to participants without either condition. The two latter risk-factor groups remained at increased risk after adjustments for relevant confounders. Further comparisons indicated that the risks of all-cause death were also higher, but to a lesser extent, for participants with both depressive-symptoms and CHD when compared to those with only one of these conditions. These associations were also observed for cardiovascular mortality
This study provides evidence that depressive symptoms are associated with an increased risk of all-cause and CVD death and that this risk is particularly marked in depressive participants with co-morbid CHD. Several clinical guidelines have recommended screening, referral, and treatment of depression in primary and cardiovascular care units. These findings suggest that these recommendations need further consideration.
Structural brain abnormalities of the medial temporal lobe have been found in people with bipolar disorder (BPD). It is not known whether these abnormalities progress over the course of the illness.
We conducted a prospective cohort study of 20 patients with bipolar disorder and 21 control subjects recruited from the community. Participants were group matched for age, sex and premorbid IQ. Longitudinal change in grey matter density was evaluated using the technique of tensor based morphometry (TBM) in SPM2.Changes in grey and white matter density were estimated and compared to changes in cognitive function and clinical outcome.
Patients with bipolar disorder showed a larger decline in hippocampal, fusiform and cerebellar grey matter density over 4 years than controls. No significant changes in white matter density were found. Reductions in temporal lobe grey matter correlated with decline in intellectual function and with global assessment of functioning. No associations were found with medication.
Patients with bipolar disorder lose hippocampal, fusiform and cerebellar grey matter at an accelerated rate compared to healthy controls. This tissue loss is associated with a corresponding deterioration in cognitive function.
Abnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis.
Hundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects.
We refined Chiavaras’ classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor.
Our results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.
There is strong qualitative and quantitative evidence of white matter abnormalities in schizophrenia and bipolar disorder from structural magnetic resonance imaging (MRI). There is also good evidence of altered connectivity in schizophrenia using diffusion tensor magnetic resonance imaging, but no study has yet addressed the diagnostic specificity of these findings or whether they are related to specific susceptibility genes.
Diffusion tensor MRI was used to assess white matter integrity in patients with bipolar I disorder (BD) (n=42), schizophrenia (n=28) and healthy controls (n=38). Clinically stable patients with one other close family member with the same diagnosis were selected. In a second study, we examined white matter associations with Neuregulin I in a sample of healthy controls. Fractional anisotropy (FA) was compared between the groups using voxel-based morphometry, automated region of interest analysis and probabilistic tractography. Results : Patients with BD and those with schizophrenia showed reduced FA in the anterior limb of the internal capsule, anterior thalamic radiation and uncinate fasciculus compared with controls. Results from the second study showed reductions in those carrying a Neuregulin 1 variant previously associated with psychotic symptoms.
Reduced white matter density and integrity is common to both schizophrenia and BD. It is likely that this shared white matter disruption is determined in part by shared genetic risk factors.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
[Improvement in daily accessible risk assessments]
We show enhanced patient safety through a quality improvement methodology project in an intensive psychiatric care unit of a psychiatric hospital in southwest of Scotland. This is a project as part of the national patient safety programme in mental health. The Scottish Patient Safety Programme for Mental Health aims to systematically reduce harm experienced by people using mental health services in Scotland, by supporting frontline staff to test, gather real-time data and reliably implement interventions, before spreading across their catchment area.
Multidisciplinary staff worked together in improving recording of daily electronic and paper based risk assessments from a baseline of 20% to nearly 100% over a sixth month period. We expect better quality risk management by readily accessible risk assessments and safe practise through enhanced safety perception by the patients as well as staff. Patient and staff safety perception tools were designed to measure impact of improvement in risk management. We have seen drop in the number of critical incidents and challenging situations requiring restraint following coordinated approach to risk assessment and easy access to key information. We have been successful as the frontline staff became part of the process of change and this has enabled sustained improvement.
The biosocial developmental model of Borderline Personality Disorder (BPD) proposes that early vulnerability, indicated by behavioral and emotional dysregulation, is potentiated across development by environmental risk factors, culminating in BPD. However, empirical research pertaining to this hypothesis is lacking. The aim of this prospective cohort study was to determine whether dysregulated behavior in childhood is predictive of BPD symptoms in early adolescence; and whether this association is potentiated by negative parent or peer interactions.
The prospective sample consisted of 5711 children in the UK (ALSPAC). Dysregulated behaviour and emotions during the first 7 years of life were assessed and peer victimisation and parenting between 8 and 10 years of age. BPD was assessed at 11–12 years with the UK Childhood Interview for DSM-IV Borderline Personality Disorder (UK-CI-BPD); based on the borderline module of the Diagnostic Interview for DSM-IV Personality Disorders. Five or more BPD probable/definite symptoms were present in 7.3% of the population.
Stable dysregulated behavior, experience of harsh parenting and peer victimization during childhood predicted BPD symptoms at 11 years. However, the association between dysregulated behavior and BPD was entirely dependent on whether the child had experienced peer victimization but not on harsh parenting. Children who were highly dysregulated in their behavior, and victimized, experienced the highest levels of BPD symptoms.
Consistent with the biosocial developmental theory, trait dysregulation is potentiated across development by exposure to environmental risk: Peer victimization. Interventions targeting early dysregulated behavior or peer victimisation may reduce the development of BPD symptoms.
Psychiatric comorbidities and alcohol craving are known contributors to differences in alcohol consumption patterns.
Univariate and multivariable linear regression models were used to examine the association and interactions between the Inventory of Drug Taking Situations (IDTS) negative, positive and temptation sub-scale scores, sex, as well as co-morbid depression and anxiety determined by Psychiatric Research Interview of Substance and Mood Disorders (PRISM) with alcohol consumption measured by Time Line Follow Back (TLFB) during preceding 90 days in 287 males and 156 females meeting DSM-IV criteria for alcohol dependence.
IDTS positive, negative and temptation scores were strongly associated with increased alcohol consumption measures including the number of drinks per day and number of drinking days per week (P < 0.0001). Male sex was associated with higher amount of alcohol consumption per drinking day (P < 0.001), but not with the number of drinking days per week (P > 0.05). In men, lifetime history of depression was associated with fewer drinking days (P = 0.0084) and fewer hazardous drinking days (P = 0.0214) but not with differences in daily alcohol consumption. In women, depression history was not significantly associated with alcohol consumption measures. Post-hoc sex-stratified analyses suggested that the association of the negative IDTS score with total amount of alcohol consumed by men may be modified (decreased) by lifetime depression history. We found no associations of alcohol consumption measures with anxiety or substance-induced depression.
Decreased frequency of drinking in male alcoholics with lifetime depression history is unexpected. This finding emphasizes the complex relationships between alcoholism and depression, which require further investigation.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
On 30 January 2020, WHO declared coronavirus (COVID-19) a global public health emergency. As of 12 March 2020, 125 048 confirmed COVID-19 cases in 118 countries had been reported. On 12 March 2020, the first case in the Pacific islands was reported in French Polynesia; no other Pacific island country or territory has reported cases. The purpose of our analysis is to show how travellers may introduce COVID-19 into the Pacific islands and discuss the role robust health systems play in protecting health and reducing transmission risk. We analyse travel and Global Health Security Index data using a scoring tool to produce quantitative estimates of COVID-19 importation risk, by departing and arriving country. Our analysis indicates that, as of 12 March 2020, the highest risk air routes by which COVID-19 may be imported into the Pacific islands are from east Asian countries (specifically, China, Korea and Japan) to north Pacific airports (likely Guam, Commonwealth of the Northern Mariana Islands or, to a less extent, Palau); or from China, Japan, Singapore, the United States of America or France to south Pacific ports (likely, Fiji, Papua New Guinea, French Polynesia or New Caledonia). Other importation routes include from other east Asian countries to Guam, and from Australia, New Zealand and other European countries to the south Pacific. The tool provides a useful method for assessing COVID-19 importation risk and may be useful in other settings.
The national implementation of competency-based medical education (CBME) has prompted an increased interest in identifying and tracking clinical and educational outcomes for emergency medicine training programs. For the 2019 Canadian Association of Emergency Physicians (CAEP) Academic Symposium, we developed recommendations for measuring outcomes in emergency medicine training in the context of CBME to assist educational leaders and systems designers in program evaluation.
We conducted a three-phase study to generate educational and clinical outcomes for emergency medicine (EM) education in Canada. First, we elicited expert and community perspectives on the best educational and clinical outcomes through a structured consultation process using a targeted online survey. We then qualitatively analyzed these responses to generate a list of suggested outcomes. Last, we presented these outcomes to a diverse assembly of educators, trainees, and clinicians at the CAEP Academic Symposium for feedback and endorsement through a voting process.
Academic Symposium attendees endorsed the measurement and linkage of CBME educational and clinical outcomes. Twenty-five outcomes (15 educational, 10 clinical) were derived from the qualitative analysis of the survey results and the most important short- and long-term outcomes (both educational and clinical) were identified. These outcomes can be used to help measure the impact of CBME on the practice of Emergency Medicine in Canada to ensure that it meets both trainee and patient needs.