To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother–infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.
Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and >18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.
Landforms and sediments on the palaeo–ice stream beds of central Alberta record glacitectonic raft production and subsequent progressive disaggregation and moulding, associated substrate ploughing, and grooving. We identify a subglacial temporal or developmental hierarchy that begins with incipient rafts, including en échelon hill-hole complexes, hill-hole pairs, and strike-slip raft complexes, all of which display patterns typical of transcurrent fault activation and pull apart. Many display jigsaw puzzle–style fragmentation, indicative of substrate displacement along shallow décollement zones and potentially related to patchy ice stream freeze-on. Their gradual fragmentation and smoothing produces ice flow-transverse ridges (ribbed moraine), hill-groove pairs, and paraxial ridge and groove associations. Initiator scarp and megafluting associations are indicative of raft dislodgement and groove ploughing, leading to the formation of murdlins, crag-and-tails, stoss-and-lee type flutings and drumlins, and Type 1 hogsback flutings. Downflow modification of rafts creates linear block trains (rubble stripes), stoss-and-lee type megaflutings, horned crag-and-tails, rubble drumlinoids, and murdlins, diagnostic of an immature palaeo–ice stream footprint. Lateral ice stream margin migration ingests disaggregated thrust masses to form ridged spindles, ladder-type morphologies, and narrow zones of ribbed terrain and Type 2 hogsback flutings, an assemblage diagnostic of ice stream shear margin moraine formation.
Background: Negative body image predicts many adverse outcomes. The current study prospectively examined patterns of body esteem development in early adolescence and identified predictors of developmental subtypes. Methods: 328 girls and 429 boys reported annually across a 4-year period (Mage at baseline = 11.14, SD = 0.35) on body esteem, appearance ideal internalization, perceived sociocultural pressures, appearance comparisons, appearance-related teasing, self-esteem, positive and negative affect, and dietary restraint. We performed latent class growth analyses to identify the most common trajectories of body esteem development and examine risk and protective factors for body image development. Results: Three developmental subgroups were identified: (a) high body esteem (39.1%); (b) moderate body esteem (46.1%); and (c) low body esteem (14.8%). Body esteem was stable within the low trajectory and there were minor fluctuations in the high and moderate trajectories. Greater appearance-related teasing, lower self-esteem, less positive affect, and higher dietary restraint predicted the low trajectory, whereas higher self-esteem and lower dietary restraint best predicted the high trajectory. Conclusions: Low body esteem appears to be largely stable from age 11 years. Prevention programming may be enhanced by incorporating components to address transdiagnostic resilience factors such as self-esteem and positive affect.
Introduction: The New Brunswick Trauma Registry is a database of injury admissions from eight hospitals throughout the province. Data tracks individuals in-hospital. By linking this information with vital statistics, we are able to observe outcomes post-discharge and can model health outcomes for participants. We want to know how outcomes for trauma patients compare with the general population post discharge. Methods: Using data from 2014-15, we followed over 2100 trauma registry observations for one year and tracked mortality rate per 1,000 people by age-group. We also compared the outcomes of this group to all Discharge Abstract Database (DAD) entries in the province (circa. 7500 total). We tracked mortality in-hospital, at six months, and one year after discharge. We truncated age into groups aged 40-64, 65-84, and 85 or older. Results: In-hospital mortality among those in the trauma registry is approximately 20 per 1,000 people for those age 40-64, 50 per 1,000 people for those aged 65-84, and 150 per 1,000 people aged 85 or older. For the oldest age group this is in line with the expected population mortality rate, for the younger two groups these estimates are approximately 2-4 times higher than expected mortality. The mortality at six-month follow-up for both of the younger groups remains higher than expected. At one-year follow-up, the mortality for the 65-84 age group returns to the expected population baseline, but is higher for those age 40-64. Causes of death for those who die in hospital are injury for nearly 50% of observations. After discharge, neoplasms and heart disease are the most common causes of death. Trends from the DAD are similar, with lower mortality overall. Of note, cardiac causes of death account for nearly as many deaths in the 6 months after the injury in the 40 -64 age group as the injury itself. Conclusion: Mortality rates remain high upon discharge for up to a year later for some age groups. Causes of death are not injury-related. Some evidence suggests that the injury could have been related to the eventual cause of death (e.g., dementia), but questions remain about the possibility for trauma-mitigating care increasing the risk of mortality from comorbidities. For example, cardiac death, which is largely preventable, is a significant cause of death in the 40-64 age group after discharge. Including an assessment of Framingham risk factors as part of the patients rehabilitation prescription may reduce mortality.
Introduction: Electronic medical records (EMR) have placed increasing demand on emergency physicians and may contribute to physician burnout and stress. The use of scribes to reduce workload and increase productivity in emergency departments (ED) has been reported. This objective of this study was to evaluate the educational and experiential value of scribing among medical and undergraduate students. We asked: “Will undergraduates be willing to scribe in exchange for clinical exposure and experience?”; and, “Should scribing be integrated into the medical school curriculum?” Methods: A mixed-methods model was employed. The study population included 5 undergraduate, and 5 medical students. Scribes received technical training on how to take physician notes. Undergraduate students were provided with optional resources to familiarize themselves with common medical terminology. Scribes were assigned to physicians based on availability. An exit interview and semi-structured interviews were conducted at the conclusion of the study. Interviews were transcribed and coded into thematic coding trees. A constructivist grounded theory approach was used to analyze the results. Themes were reviewed and verified by two members of the research team. Results: Undergraduate students preferred volunteering in the ED over other volunteer experiences (5/5); citing direct access to the medical field (5/5), demystification of the medical profession (4/5), resume building (5/5), and perceived value added to the health care team (5/5) as main motivators to continue scribing. Medical students felt scribing should be integrated into their curriculum (4/5) because it complemented their shadowing experience by providing unique value that shadowing did not. Based on survey results, five undergraduate students would be required to cover 40 volunteer hours per week. Conclusion: A student volunteer model of scribing is worthwhile to students and may be feasible; however, scribe availability, potentially high scribe turnover, and limited time to develop a rapport with their physician may impact any efficiency benefit scribes might provide. Importantly, scribing may be an invaluable experience for directing career goals and ensuring that students intrinsically interested in medicine pursue the profession. Medical students suggested that scribing could be added to the year one curriculum to help them develop a framework for how to take histories and manage patients.
Introduction: Buprenorphine/naloxone (buprenorphine) has proven to be a life-saving intervention amidst the ongoing opioid epidemic in Canada. Research has shown benefits to initiating buprenorphine from the emergency department (ED) including improved treatment retention, systemic health care savings and fewer drug-related visits to the ED. Despite this, there has been little to no uptake of this evidence-based practice in our department. This qualitative study aimed to determine the local barriers and potential solutions to initiating buprenorphine in the ED and gain an understanding of physician attitudes and behaviours regarding harm reduction care and opioid use disorder management. Methods: ED physicians at a midsize Atlantic hospital were recruited by convenience sampling to participate in semi-structured privately conducted interviews. Audio recordings were transcribed verbatim and de-identified transcripts were uploaded to NVivo 12 plus for concept driven and inductive coding and a hierarchy of open, axial and selective coding was employed. Transcripts were independently reviewed by a local qualitative research expert and themes were compared for similarity to limit bias. Interview saturation was reached after 7 interviews. Results: Emergent themes included a narrow scope of harm reduction care that primarily focused on abstinence-based therapies and a multitude of biases including feelings of deception, fear of diversion, feeling buprenorphine induction was too time consuming for the ED and differentiating patients with opioid use disorder from ‘medically ill’ patients. Several barriers and proposed solutions to initiating buprenorphine from the ED were elicited including lack of training and need for formal education, poor familiarity with buprenorphine, the need for an algorithm and community bridge program and formal supports such as an addictions consult team for the ED. Conclusion: This study elicited several opportunities for improved care for patients with addictions presenting to our ED. Future education will focus on harm reduction care, specifically strategies for managing patients desiring to continue to use substances. Education will focus on addressing the multitude of biases elicited and dispelling common myths. A locally informed buprenorphine pathway will be developed. In future, this study may be used to advocate for improved formal supports for our department including an addictions consult team.
Introduction: Vaginal bleeding in early pregnancy is a common emergency department (ED) presentation, with many of these episodes resulting in poor obstetrical outcome. These outcomes have been extensively studied, but there have been few evaluations of what variables are associated predictors. This study aimed to identify predictors of less than optimal obstetrical outcomes for women who present to the ED with early pregnancy bleeding. Methods: A regional centre health records review included pregnant females who presented to the ED with vaginal bleeding at <20 weeks gestation. This study investigated differences in presenting features between groups with subsequent optimal outcomes (OO; defined as a full-term live birth >37 weeks) and less than optimal outcomes (LOO; defined as a miscarriage, stillbirth or pre-term live birth). Predictor variables included: maternal age, gestational age at presentation, number of return ED visits, socioeconomic status (SES), gravida-para-abortus status, Rh status, Hgb level and presence of cramping. Rates and results of point of care ultrasound (PoCUS) and ultrasound (US) by radiology were also considered. Results: Records for 422 patients from Jan 2017 to Nov 2018 were screened and 180 patients were included. Overall, 58.3% of study participants had a LOO. The only strong predictor of outcome was seeing an Intra-Uterine Pregnancy (IUP) with Fetal Heart Beat (FHB) on US; OO rate 74.3% (95% CI 59.8-88.7; p < 0.01). Cramping (with bleeding) trended towards a higher rate of LOO (62.7%, 95% CI 54.2-71.1; p = 0.07). SES was not a reliable predictor of LOO, with similar clinical outcome rates above and below the poverty line (57.5% [95% CI 46.7-68.3] vs 59% [95% CI 49.3-68.6] LOO). For anemic patients, the non-live birth rate was 100%, but the number with this variable was small (n = 5). Return visits (58.3%, 95% CI 42.2-74.4), previous abortion (58.8%, 95% CI 49.7-67.8), no living children (60.2%, 95% CI 50.7-69.6) and past pregnancy (55.9%, 95% CI 46.6-65.1) were not associated with higher rates of LOO. Conclusion: Identification of a live IUP, anemia, and cramping have potential as predictors of obstetrical outcome in early pregnancy bleeding. This information may provide better guidance for clinical practice and investigations in the emergency department and the predictive value of these variables support more appropriate counseling to this patient population.
Introduction: Distal radial fractures (DRF) remain the most commonly encountered fracture in the Emergency Department (ED). The initial management of displaced DRFs by Emergency Physicians (EP) poses considerable resource allocation. We wished to determine the adequacy of reduction, both initially and at follow up. This data updates previously presented high level findings. Methods: We performed a mixed-methods study including patients who underwent procedural sedation and manipulation by an EP for a DRF. Radiological images performed at initial assessment, post-reduction, and clinic follow up were reviewed by a panel of orthopedic surgeons and radiologists blinded to outcomes, and assessed for evidence of displacement. Demographic data were pooled from patient records and included in statistical analysis. Results: Seventy patients were included and had follow-up completed. Initial reduction was deemed to be adequate in 37 patients (53%; 95% CI 41.32 to 64.10%). At clinic follow-up assessment, 26 reductions remained adequate; a slippage rate of 30% (95% CI of 17.37 to 45.90). Overall 7 patients (10%; 95% CI 4.65 to 19.51%) required revision of the initial reduction in the operating room. Agreement on adequacy of reduction on post-reduction radiographs between radiologists and orthopedic surgeons was 38.6% (95% CI -38.3 to -7.4, Kappa -0.229). The statistical strength of this agreement is worse than what would be expected by chance alone. There was no association found between age, sex, or of time of initial presentation and final outcomes. Conclusion: Although blinded review by specialists determined only half of initial EP DRF reductions to be radiographically adequate, only 10 percent actually required further intervention. Agreement between specialists on adequacy was poor. The majority of DRFs reduced by EPs do not require further surgical intervention.
Introduction: Determining fluid status prior to resuscitation provides a more accurate guide for appropriate fluid administration in the setting of undifferentiated hypotension. Emergency Department (ED) point of care ultrasound (PoCUS) has been proposed as a potential non-invasive, rapid, repeatable investigation to ascertain inferior vena cava (IVC) characteristics. Our goal was to determine the feasibility of using PoCUS to measure IVC size and collapsibility. Methods: This was a planned secondary analysis of data from a prospective multicentre international study investigating PoCUS in ED patients with undifferentiated hypotension. We prospectively collected data on IVC size and collapsibility using a standard data collection form in 6 centres. The primary outcome was the proportion of patients with a clinically useful (determinate) scan defined as a clearly visible intrahepatic IVC, measurable for size and collapse. Descriptive statistics are provided. Results: A total of 138 scans were attempted on 138 patients; 45.7% were women and the median age was 58 years old. Overall, one hundred twenty-nine scans (93.5%; 95% CI 87.9 to 96.7%) were determinate. 131 (94.9%; 89.7 to 97.7%) were determinate for IVC size, and 131 (94.9%; 89.7 to 97.7%) were determinate for collapsibility. Conclusion: In this analysis of 138 ED patients with undifferentiated hypotension, the vast majority of PoCUS scans to investigate IVC characteristics were determinate. Future work should include analysis of the value of IVC size and collapsibility in determining fluid status in this group.
Introduction: Crowding is associated with poor patient outcomes in emergency departments (ED). Measures of crowding are often complex and resource-intensive to score and use in real-time. We evaluated single easily obtained variables to establish the presence of crowding compared to more complex crowding scores. Methods: Serial observations of patient flow were recorded in a tertiary Canadian ED. Single variables were evaluated including total number of patients in the ED (census), in beds, in the waiting room, in the treatment area waiting to be assessed, and total inpatient admissions. These were compared with Crowding scores (NEDOCS, EDWIN, ICMED, three regional hospital modifications of NEDOCS) as predictors of crowding. Predictive validity was compared to the reference standard of physician perception of crowding, using receiver operator curve analysis. Results: 144 of 169 potential events were recorded over 2 weeks. Crowding was present in 63.9% of the events. ED census (total number of patients in the ED) was strongly correlated with crowding (AUC = 0.82 with 95% CI = 0.76 - 0.89) and its performance was similar to that of NEDOCS (AUC = 0.80 with 95% CI = 0.76 - 0.90) and a more complex local modification of NEDOCS, the S-SAT (AUC = 0.83, 95% CI = 0.74 - 0.89). Conclusion: The single indicator, ED census was as predictive for the presence of crowding as more complex crowding scores. A two-stage approach to crowding intervention is proposed that first identifies crowding with a real-time ED census statistic followed by investigation of precipitating and modifiable factors. Real time signalling may permit more standardized and effective approaches to manage ED flow.
Introduction: Patients presenting to the emergency department (ED) with hypotension have a high mortality rate and require careful yet rapid resuscitation. The use of cardiac point of care ultrasound (PoCUS) in the ED has progressed beyond the basic indications of detecting pericardial fluid and activity in cardiac arrest. We examine if finding left ventricular dysfunction (LVD) on emergency physician performed PoCUS reliably predicts the presence of cardiogenic shock in hypotensive ED patients. Methods: We prospectively collected PoCUS findings performed in 135 ED patients with undifferentiated hypotension as part of an international study. Patients with clearly identified etiologies for hypotension were excluded, along with other specific presumptive diagnoses. LVD was defined as identification of a generally hypodynamic LV in the setting of shock. PoCUS findings were collected using a standardized protocol and data collection form. All scans were performed by PoCUS-trained emergency physicians. Final shock type was defined as cardiogenic or non-cardiogenic by independent specialist blinded chart review. Results: All 135 patients had complete follow up. Median age was 56 years, 53% of patients were male. Disease prevalence for cardiogenic shock was 12% and the mortality rate was 24%. The presence of LVD on PoCUS had a sensitivity of 62.50% (95%CI 35.43% to 84.80%), specificity of 94.12% (88.26% to 97.60%), positive-LR 10.62 (4.71 to 23.95), negative-LR 0.40 (0.21 to 0.75) and accuracy of 90.37% (84.10% to 94.77%) for detecting cardiogenic shock. Conclusion: Detecting left ventricular dysfunction on PoCUS in the ED may be useful in confirming the underlying shock type as cardiogenic in otherwise undifferentiated hypotensive patients.
Aripiprazole is a dopamine partial agonist with a low risk of movement disorder and metabolic adverse effects.
We identified 228 patients consecutively prescribed aripiprazole in our unit and established outcome (continuation with treatment) six months after initiation.
The study cohort consisted of subjects of mean age 36.2 years (17-86) of whom 53.1% were male. Two thirds had a diagnosis of schizophrenia. Overall, 112 (49%) patients completed 6 months' treatment. Reasons for discontinuation were adverse events (n = 61, 53% of those who stopped), lack of effectiveness (n = 45, 39%) and a variety of unconnected reasons (n = 10, 9%). The majority of discontinuations (n = 76, 66%) occurred in the first 60 days of treatment, largely because of adverse effects. Most common adverse events reported were anxiety/agitation (n = 57, 25% of total cohort), insomnia (n = 43, 19%) and movement disorder (n = 24, 11%).
Treatment discontinuation was more likely for in-patients than out-patients (61% vs 42%, p = 0.005) and in those previously prescribed clozapine (p = 0.01). Modal initiation dose was 15mg for patients starting in the first year of the study and 10mg for those starting later. Initiation dose was not associated with outcome.
Aripiprazole showed a degree of effectiveness similar to that shown by other antipsychotics. Early-appearing, trivial adverse events are a major factor in treatment discontinuation. Outcome is best in out-patients and those not formerly treated with clozapine.
There is considerable variation in the prevalence of breastfeeding, which allows for investigation of factors that influence the initiation and duration of breastfeeding and its association with well being of the mother infant dyad.
To better understand factors that influence (1) maternal breastfeeding status and (2) the “effects” of breastfeeding on mothers and infants.
Participants (n = 170) derive from a longitudinal Canadian study “Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN)”, a project designed to understand the pre- and postnatal influences on maternal health and child social-emotional development. Mothers provided data on breastfeeding status, early life adversity, oxytocin gene and oxytocin gene receptor polymorphisms, depression/anxiety, infant temperament and maternal sensitivity.
Early life adversity associated with a shorter breastfeeding duration and higher maternal depression levels. The relation between mothers’ early adversity and the duration of breastfeeding was mediated by mothers’ depression level, but only in women carrying one variant of the oxytocin rs2740210 gene marker (CC genotype). Mothers who breastfeed at 3 months acted more sensitively towards their infants when they were 6 months old and they in turn had infants who at 18 months showed reduced negative affectivity.
Women who have been exposed to early adversity are “living with the past” and they are, to certain extent, protected or more vulnerable to depression, depending on their genotype. Breastfeeding associated with higher maternal sensitivity, which associated with decreased negative emotionality in the infant at 18 months. Our results help to clarify associations between early life experiences, breastfeeding, and the mother-infant relationship.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Maternal mental well being influences offspring development. Research suggests that an interplay between genetic and environmental factors underlies this familial transmission of mental disorders.
To explore an interaction between genetic and environmental factors to predict trajectories of maternal mental well being, and to examine whether these trajectories are associated with epigenetic modifications in mothers and their offspring.
We assessed maternal childhood trauma and rearing experiences, prenatal and postnatal symptoms of depression and stress experience from 6 to 72 months postpartum, and genetic and epigenetic variation in a longitudinal birth-cohort study (n = 262) (Maternal adversity, vulnerability and neurodevelopment project). We used latent class modeling to describe trajectories in maternal depressive symptoms, parenting stress, marital stress and general stress, taking polygenetic risk for major depressive disorder (MDD), a composite score for maternal early life adversities, and prenatal depressive symptoms into account.
Genetic risk for MDD associated with trajectories of maternal well being in the postpartum, conditional on the experience of early life adversities and prenatal symptoms of depression. We will explore whether these trajectories are also linked to DNA methylation patterns in mothers and their offspring. Preliminary analyses suggest that maternal early life adversities associate with offspring DNA methylation age estimates, which is mediated through maternal mental well being and maternal DNA methylation age estimates.
We found relevant gene-environment interactions associated with trajectories of maternal well being. Our findings inform research on mechanisms underlying familial transmission of vulnerability for psychopathology and might thus be relevant to prevention and early intervention programs.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We consider the life cycle of an axisymmetric laminar thermal starting from the initial condition of a Gaussian buoyant blob. We find that, as time progresses, the thermal transitions through a number of distinct stages, undergoing several morphological changes before ending up as a vortex ring. Whilst each stage is interesting in its own right, one objective of this study is to set out a consistent mathematical framework under which the entire life cycle can be studied. This allows examination of the transition between the different stages, as well as shedding light on some unsolved questions from previous works. We find that the early stages of formation are key in determining the properties of the final buoyant vortex ring and that, since they occur on a time scale where viscosity has little effect, the final properties of the ring display an independence above a critical Reynolds number. We also find that rings consistently contain the same proportion of the initial heat and have a consistent vorticity flux. By considering the effect of Prandtl number, we show that thermal diffusion can have a significant impact on development, smoothing out the temperature field and inhibiting the generation of vorticity. Finally, by considering the wake left behind as well as the vortex ring that is generated, we observe that the wake can itself roll up to form a second mushroom cap and subsequently a secondary vortex ring that follows the first.
We examined maternal depression and maternal sensitivity as mediators of the association between maternal childhood adversity and her child's temperament in 239 mother–child dyads from a longitudinal, birth cohort study. We used an integrated measure of maternal childhood adversity that included the Childhood Trauma Questionnaire and the Parental Bonding Index. Maternal depression was assessed with the Edinburgh Postnatal Depression Scale at 6 months postpartum. Maternal sensitivity was assessed with the Ainsworth maternal sensitivity scales at 6 months. A measure of “negative emotionality/behavioral dysregulation” was derived from the Early Childhood Behaviour Questionnaire administered at 36 months. Bootstrapping-based mediation analyses revealed that maternal depression mediated the effect of maternal childhood adversity on offspring negative emotionality/behavioral dysregulation (95% confidence interval [0.026, 0.144]). We also found a serial, indirect effect of maternal childhood adversity on child negative emotionality/behavioral mediated first by maternal depression and then by maternal sensitivity (95% confidence interval [0.031, 0.156]). Results suggest the intergenerational transmission of the effects of maternal childhood adversity to the offspring occurs through a two-step, serial pathway, involving maternal depression and maternal sensitivity.
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.