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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.
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.
We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.
Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113
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.
Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.
Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance.
Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM.
The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients.
The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism–schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.
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.
To search for studies on tongue–lip adhesion and tongue repositioning used as isolated treatments for obstructive sleep apnoea in children with Pierre Robin sequence.
A systematic literature search of PubMed/Medline and three additional databases, from inception through to 8 July 2016, was performed by two authors.
Seven studies with 90 patients (59 tongue–lip adhesion and 31 tongue repositioning patients) met the inclusion criteria. Tongue–lip adhesion reduced the mean (± standard deviation) apnoea/hypopnoea index from 30.8 ± 22.3 to 15.4 ± 18.9 events per hour (50 per cent reduction). The apnoea/hypopnoea index mean difference for tongue–lip adhesion was −15.28 events per hour (95 per cent confidence interval = −30.70 to 0.15; p = 0.05). Tongue–lip adhesion improved the lowest oxygen saturation from 75.8 ± 6.8 to 84.4 ± 7.3 per cent. Tongue repositioning reduced the apnoea/hypopnoea index from 46.5 to 17.4 events per hour (62.6 per cent reduction). Tongue repositioning improved the mean oxygen saturation from 90.8 ± 1.2 to 95.0 ± 0.5 per cent.
Tongue–lip adhesion and tongue repositioning can improve apnoea/hypopnoea index and oxygenation parameters in children with Pierre Robin sequence and obstructive sleep apnoea.
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.
The inner few hundred parsecs of the Milky Way, the Central Molecular Zone (CMZ), is our closest laboratory for understanding star formation in the extreme environments (hot, dense, turbulent gas) that once dominated the universe. We present an update on the first large-area survey to expose the sites of star formation across the CMZ at high-resolution in submillimeter wavelengths: the CMZoom survey with the Submillimeter Array (SMA). We identify the locations of dense cores and search for signatures of embedded star formation. CMZoom is a three-year survey in its final year and is mapping out the highest column density regions of the CMZ in dust continuum and a variety of spectral lines around 1.3 mm. CMZoom combines SMA compact and subcompact configurations with single-dish data from BGPS and the APEX telescope, achieving an angular resolution of about 4″ (0.2 pc) and good image fidelity up to large spatial scales.
Sensorineural hearing loss is a recognised complication of cryptococcal meningitis. The mechanism of hearing loss in patients with cryptococcal meningitis is different from that in bacterial meningitis.
An immune-competent man with cryptococcal meningitis presented with sudden onset, bilateral, severe to profound sensorineural hearing loss and vestibular dysfunction. He was initially evaluated for cochlear implantation. However, he had a significant recovery; he no longer required surgery and was able to cope without a hearing aid.
Typically, cochlear implantation is performed with some urgency in patients with hearing loss post-bacterial meningitis, because of the risk of labyrinthitis ossificans. However, this process has not been described in patients with cryptococcal meningitis. Furthermore, patients with hearing loss associated with cryptococcal meningitis have shown varying degrees of reversibility. In this case report, hearing loss from cryptococcal meningitis is compared with that from bacterial meningitis, and the need for cochlear implantation in patients with cryptococcal meningitis is discussed.
At Los Alamos National Laboratory we are developing a new imaging sensor which combines high spatial and high temporal resolution over a large area format, while maintaining single-photon counting sensitivity and sustaining a high count rate. The detector is called a microchannel plate with crossed delay line readout, or MCP/CDL. This detector is ideally suited to the observation of weak transient events, such as stellar flares from red dwarf flare stars in our Galaxy. At present we are initiating an experiment with the MCP/CDL detector which will utilize a 30-cm aperture f/7 telescope to characterize U-band, B-band, and V-band emission from such low-luminosity flare stars, and to search for weak optical transients associated with other astrophysical sources.
We present near-infrared spectra of young radio quasars selected by cross-correlating the Wide-field Infrared Survey Explorer (WISE) all-sky survey catalog with the radio catalog [Faint Images of the Radio Sky at Twenty cm (FIRST) and NRAO VLA Sky Survey (NVSS)]. The objects have typical redshifts of z ≈ 2 and [O III] luminosities of 107 erg s−1 comparable to those of luminous quasars. The observed flux ratios of narrow emission lines indicate that these objects appear to be powered by active galactic nuclei. The [O III] line is broad, with full width at half maximum ~1300 to 2100 km s−1, significantly larger than that of ordinary quasars. These large line widths might be explained by jet-induced outflows.
Atherosclerosis is the underlying cause of cardiovascular disease and stroke. Endothelial cell dysfunctions are early events in atherosclerosis, resulting in the recruitment of circulating monocytes. The immune system can elicit an inflammatory response toward the atherosclerotic lesion, thereby accelerating lesion growth. Risk factors for atherosclerosis include hypertension, smoking, stress perception or low birth weight. As prenatal stress challenge decreases the birth weight and affects the offspring's postnatal immune response, we aimed to investigate whether prenatal stress contributes to the development of atherosclerosis in mice. Syngenic pregnant apolipoprotein E-deficient (apoE−/−) dams were exposed to sound stress on gestation days 12.5 and 14.5. The presence and size of atherosclerotic plaques in the offspring at the age of 15 weeks was evaluated by histomorphology, accompanied by flow cytometric analysis of the frequency and phenotype of monocytes/macrophages and regulatory T (Treg) cells in the blood. Further, cytokine secretion of peripheral blood lymphocytes was analyzed. In response to prenatal stress challenge, an increased frequency of large atherosclerotic plaques was detectable in apoE−/− offspring, which was particularly profound in females. Prenatal stress also resulted in alterations of the offspring's immune response, such as a decreased frequency of Treg cells in blood, alterations of macrophage populations in blood and an increased secretion of inflammatory cytokines. We provide novel evidence that prenatally stressed adult offspring show an increased severity of atherosclerosis. As Treg cells are key players in dampening inflammation, the observed increase in atherosclerosis may be due to the lack of Treg cell frequency. Future interdisciplinary research is urgently required to understand the developmental origin of prenatal stress-induced atherosclerosis. The availability of our model may facilitate and foster such research endeavors.
Critically significant parental effects in behavioral genetics may be partly understood as a consequence of maternal brain structure and function of caregiving systems recently studied in humans as well as rodents. Key parental brain areas regulate emotions, motivation/reward, and decision making, as well as more complex social-cognitive circuits. Additional key environmental factors must include socioeconomic status and paternal brain physiology. These have implications for developmental and evolutionary biology as well as public policy.
Adolescent marijuana use is associated with increased risk for schizophrenia. We previously reported that marijuana misuse in conjunction with specific cannabinoid receptor 1 (CNR1) genetic variants (rs12720071-G-allele carriers) contributed to white-matter (WM) brain volume deficits in schizophrenia patients. In this study, we assessed the influence of another cannabinoid-related gene, mitogen-activated protein kinase 14 (MAPK14), and potential MAPK14–CNR1 gene–gene interactions in conferring brain volume abnormalities among schizophrenia patients with marijuana abuse/dependence. MAPK14 encodes a member of the MAPK family involved in diverse cellular processes, including CNR1-induced apoptosis.
We genotyped 235 schizophrenia patients on nine MAPK14 tag single nucleotide polymorphisms (tSNPs). Approximately one quarter of the sample had marijuana abuse or dependence. Differential effects of MAPK14 tSNPs on brain volumes across patients with versus without marijuana abuse/dependence were examined using ANCOVA.
Of the MAPK14 tSNPs, only rs12199654 had significant genotype effects and genotype × marijuana misuse interaction effects on WM volumes. rs12199654-A homozygotes with marijuana abuse/dependence had significantly smaller total cerebral and lobar WM volumes. The effects of MAPK14 rs12199654 on WM volume deficits remained significant even after controlling for the CNR1 rs12720071 genotype. There were significant main effects of the MAPK14 CNR1 diplotype and diplotype × marijuana interaction on WM brain volumes, with both genetic variants having additive contributions to WM volume deficits only in patients with marijuana misuse.
Given that CNR1-induced apoptosis is preceded by increased MAPK phosphorylation, our study suggests that potential MAPK14–CNR1 gene–gene interactions may mediate brain morphometric features in schizophrenia patients with heavy marijuana use.
To determine the implications of a functional approach to vestibular schwannoma surgery, with facial nerve function prioritised higher than total tumour excision.
A case–control study in a tertiary referral neurotology clinic.
A ‘functional’ surgical group treated after April 2007 (n = 44, mean cerebellopontine angle dimension 27 mm), and an ‘excisional’ surgical group matched for tumour size, treated from 1997 to April 2007 (n = 115).
Facial nerve preservation: 77 per cent House–Brackmann grade I–II in functional group at 12 months, versus 57 per cent grade I–II in excisional group (p = 0.027). Tumour recurrence: 1 per cent in total excision group, 2 per cent in near-total group and 40 per cent in sub-total group.
A functional approach to vestibular schwannoma surgery improves facial nerve preservation outcomes and reduces the requirement for facial nerve rehabilitative interventions. Tumour recurrence rates are low in near-totally excised lesions but significant if only sub-total excision is achieved.