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Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic–pituitary–adrenal axis function should be a focus of continued research.
Introduction: September 2017 saw the launch of the British Columbia (BC) Emergency Medicine Network (EM Network), an innovative clinical network established to improve emergency care across the province. The intent of the EM Network is to support the delivery of evidence-informed, patient-centered care in all 108 Emergency Departments and Diagnostic & Treatment Centres in BC. After one year, the Network undertook a formative evaluation to guide its growth. Our objective is to describe the evaluation approach and early findings. Methods: The EM Network was evaluated on three levels: member demographics, online engagement and member perceptions of value and progress. For member demographics and online engagement, data were captured from member registration information on the Network's website, Google Analytics and Twitter Analytics. Membership feedback was sought through an online survey using a social network analysis tool, PARTNER (Program to Analyze, Record, and Track Networks to Enhance Relationships), and semi-structured individual interviews. This framework was developed based on literature recommendations in collaboration with Network members, including patient representatives. Results: There are currently 622 EM Network members from an eligible denominator of approximately 1400 physicians (44%). Seventy-three percent of the Emergency Departments and Diagnostic and Treatment Centres in BC currently have Network members, and since launch, the EM Network website has been accessed by 11,154 unique IP addresses. Online discussion forum use is low but growing, and Twitter following is high. There are currently 550 Twitter followers and an average of 27 ‘mentions’ of the Network by Twitter users per month. Member feedback through the survey and individual interviews indicates that the Network is respected and credible, but many remain unaware of its purpose and offerings. Conclusion: Our findings underscore that early evaluation is useful to identify development needs, and for the Network this includes increasing awareness and online dialogue. However, our results must be interpreted cautiously in such a young Network, and thus, we intend to re-evaluate regularly. Specific action recommendations from this baseline evaluation include: increasing face-to-face visits of targeted communities; maintaining or accelerating communication strategies to increase engagement; and providing new techniques that encourage member contributions in order to grow and improve content.
Introduction: Opioid overdoses (OODs) have become a public health emergency, yet little is known about their long-term outcomes following an OD. We determined the one-year all-cause mortality and associated risk factors in a cohort of patients treated in an urban emergency department (ED) for an OOD. Methods: We reviewed records of all patients who visited St. Paul's Hospital ED from January 2013 to August 2017 and had a discharge diagnosis of OOD or had received naloxone in the ED as per pharmacy records. Patients with a suspected OOD were identified on structured chart review. A patient's first visit for an OOD during the study period was used as the index visit, with subsequent visits excluded. The primary outcome was mortality during the year after the index visit. Mortality was assessed by linking patient electronic medical records with Vital Statistics data. Deaths that occurred in the ED on the index visit were excluded. Patients admitted to hospital following ED treatment were included in this study. We described patient characteristics, calculated mortality rates, and used Cox regression to identify risk factors. Results: A total of 2239 patients visited the ED for an OOD during the study period, with a median patient age of 37 years (IQR 29, 49). Males comprised 73% of patients, while 28% had no fixed address, and 21% received take-home naloxone at the index visit. In total, 137 patients (6.1%) died within 1 year of the index visit. Eighty-one deaths (3.6%) occurred within 6 months, including 24 deaths (1.1%) that occurred within 1 month. The highest mortality rate occurred in 2017, with 8.0% of patients entering the cohort that year dying within 1 year. Gender did not significantly impact mortality risk. A Cox regression analysis controlled for gender, housing status, and whether take-home naloxone was provided at the index visit indicated that advancing age (adjusted hazards ratio [AHR] 1.03; 95%CI: 1.01-1.04 for each year increase in age) and the index visit calendar year (AHR 1.30; 95%CI: 1.10-1.54 for each yearly increase in the study period) were significant factors for mortality within 1 year. Conclusion: The mortality rate following an opioid OD treated in the ED is high, with over 6% of patients in our study dying within 1 year. The rising mortality risk with increasing calendar year may reflect the growing harms of fentanyl-related OODs. Patients visiting the ED for an OOD should be considered high risk and offered preventative treatment and referrals prior to discharge.
While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline.
In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7–16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome.
Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31.
Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.
Introduction: Patients with Heart failure (HF) experience frequent decompensation necessitating multiple emergency department (ED) visits and hospitalizations. If patients are able to receive timely interventions and optimize self-management, recurrent ED visits may be reduced. In this feasibility study, we piloted the application of home telemonitoring to support the discharge of HF patients from hospital to home. We hypothesized that TEC4Home would decrease ED revisits and hospital admissions and improve patient health outcomes. Methods: Upon discharge from the ED or hospital, patients with HF received a blood pressure cuff, weight scale, pulse oximeter, and a touchscreen tablet. Participants submitted measurements and answered questions on the tablet about their HF symptoms daily for 60 days. Data were reviewed by a monitoring nurse. From November 2016 to July 2017, 69 participants were recruited from Vancouver General Hospital (VGH), St. Pauls Hospital (SPH) and Kelowna General Hospital (KGH). Participants completed pre-surveys at enrollement and post-surveys 30 days after monitoring finished. Administrative data related to ED visits and hospital admissions were reviewed. Interviews were conducted with the monitoring nurses to assess the impact of monitoring on patient health outcomes. Results: A preliminary analysis was conducted on a subsample of participants (n=22) enrolled across all 3 sites by March 31, 2017. At VGH and SPH (n=14), 25% fewer patients required an ED visit in the post-survey reporting compared to pre-survey. During the monitoring period, the monitoring nurse observed seven likely avoided ED admissions due to early intervention. In total, admissions were reduced by 20% and total hospital length of stay reduced by 69%. At KGH (n=8), 43% fewer patients required an ED visit in the post-survey reporting compared to the pre-survey. Hospital admissions were reduced by 20% and total hospital length of stay reduced by 50%. Overall, TEC4Home participants from all sites showed a significant improvement in health-related quality of life and in self-care behaviour pre- to 90 days post-monitoring. A full analysis of the 69 patients will be complete in February 2018. Conclusion: Preliminary findings indicate that home telemonitoring for HF patients can decrease ED revisits and improve patient experience. The length of stay data may also suggest the potential for early discharge of ED patients with home telemonitoring to avoid or reduce hospitalization. A stepped-wedge randomized controlled trial of TEC4Home in 22 BC communities will be conducted in 2018 to generate evidence and scale up the service in urban, regional and rural communities. This work is submitted on behalf of the TEC4Home Healthcare Innovation Community.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9–13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.
Neuroticism, a ‘Big Five’ personality trait, has been associated with sub-clinical traits of both autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The objective of the current study was to examine whether causal overlap between ASD and ADHD traits can be accounted for by genetic and environmental risk factors that are shared with neuroticism. We performed twin-based structural equation modeling using self-report data from 12 items of the Neo Five-Factor Inventory Neuroticism domain, 11 Social Responsiveness Scale items, and 12 Adult ADHD Self-Report Scale items obtained from 3,170 young adult Australian individual twins (1,081 complete pairs). Univariate analysis for neuroticism, ASD, and ADHD traits suggested that the most parsimonious models were those with additive genetic and unique environmental components, without sex limitation effects. Heritability of neuroticism, ASD, and ADHD traits, as measured by these methods, was moderate (between 40% and 45% for each respective trait). In a trivariate model, we observed moderate phenotypic (between 0.45 and 0.62), genetic (between 0.56 and 0.71), and unique environmental correlations (between 0.37and 0.55) among neuroticism, ASD, and ADHD traits, with the highest value for the shared genetic influence between neuroticism and self-reported ASD traits (rg = 0.71). Together, our results suggest that in young adults, genetic, and unique environmental risk factors indexed by neuroticism overlap with those that are shared by ASD and ADHD.
Introduction: The following adverse outcomes have been described in patients treated in hospital for opioid overdose: pulmonary edema, cardiac dysrhythmias, neurologic injury secondary to hypoxia, prolonged opioid toxicity, recurrent opioid toxicity. In addition, patients who take an overdose of fentanyl may develop fentanyl induced chest rigidity, a life-threatening complication that appears to be uniquely related to fentanyl. The prevalence of adverse outcomes and the clinical course of patients that develop these complications have been described in patients who have taken an overdose of heroin. However, in British Columbia there has been a dramatic increase in the number of patients who overdose on fentanyl and other ultrapotent opioids. The proportion of illicit drug overdose deaths in British Columbia for which fentanyl was detected was only 5% in 2012 but, by 2016, this proportion had increased to 62%. It is very important to know the prevalence of adverse outcomes and the clinical course of patients that develop these adverse outcomes in patients with an overdose of fentanyl or another ultrapotent opioid. Methods: We are completing a retrospective cohort study to evaluate the prevalence of the following adverse outcomes for patients treated in hospital for an opioid overdose: i) pulmonary edema, ii) cardiac dysrhythmias, iii) fentanyl induced chest rigidity, iv) neurologic injury secondary to hypoxia, v) prolonged opioid toxicity, vi) recurrent opioid toxicity. Health records of patients treated for opioid overdose in the emergency departments of six greater Vancouver hospitals from Jan 1, 2014 to Dec 31, 2016 are being reviewed. Results: All Institutional approvals have been obtained. The dataset of 3600 ED visits for opioid overdose has been obtained and 160 health records have now been reviewed as of January 8, 2017. We will describe the type and prevalence (with 95% confidence intervals) of complications sustained by these patients. Conclusion: The results of this study will guide management of opioid overdose in a setting were ultrapotent opioids are commonly ingested. All health records will have been reviewed and the data analysis completed by May 2017.
Experiments on the National Ignition Facility show that multi-dimensional effects currently dominate the implosion performance. Low mode implosion symmetry and hydrodynamic instabilities seeded by capsule mounting features appear to be two key limiting factors for implosion performance. One reason these factors have a large impact on the performance of inertial confinement fusion implosions is the high convergence required to achieve high fusion gains. To tackle these problems, a predictable implosion platform is needed meaning experiments must trade-off high gain for performance. LANL has adopted three main approaches to develop a one-dimensional (1D) implosion platform where 1D means measured yield over the 1D clean calculation. A high adiabat, low convergence platform is being developed using beryllium capsules enabling larger case-to-capsule ratios to improve symmetry. The second approach is liquid fuel layers using wetted foam targets. With liquid fuel layers, the implosion convergence can be controlled via the initial vapor pressure set by the target fielding temperature. The last method is double shell targets. For double shells, the smaller inner shell houses the DT fuel and the convergence of this cavity is relatively small compared to hot spot ignition. However, double shell targets have a different set of trade-off versus advantages. Details for each of these approaches are described.
VLA observations in the (J, K)=(3,3) line of ammonia reveal new structures in the Galactic center region. An approximate ring of emission is centered on the central ionized streamers. This ring, seen previously in millimeter-wave interferometer maps, is very clumpy in the ammonia emission, with size scales ≲10″ (0.4 pc). The clumps show good spatial and velocity agreement with the ionized gas, and are warm with brightness temperatures exceeding 30 K. A comparison of the (3,3) to (1,1) ratio indicates considerably higher gas temperatures. This circumnuclear ring may not be the dominant feature in the mass distribution of the circumnuclear gas. A streamer, immediately to the south of the Galactic center, connects the gas complex at lII= −4′ (~10 pc) directly to the Galactic center. This streamer may define the path for gas flow into the nuclear region.