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Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.
Innovation Concept: The outcome of emergency medicine training is to produce physicians who can competently run an emergency department (ED) shift. While many workplace-based ED assessments focus on discrete tasks of the discipline, others emphasize assessment of performance across the entire shift. However, the quality of assessments is generally poor and these tools often lack validity evidence. The use of entrustment scale anchors may help to address these psychometric issues. The aim of this study was to develop and gather validity evidence for a novel tool to assess a resident's ability to independently run an ED shift. Methods: Through a nominal group technique, local and national stakeholders identified dimensions of performance reflective of a competent ED physician. These dimensions were included in a new tool that was piloted in the Department of Emergency Medicine at the University of Ottawa during a 4-month period. Psychometric characteristics of the items were calculated, and a generalizability analysis used to determine the reliability of scores. An ANOVA was conducted to determine whether scores increased as a function of training level (junior = PGY1-2, intermediate = PGY3, senior = PGY4-5), and varied by ED treatment area. Safety for independent practice was analyzed with a dichotomous score. Curriculum, Tool or Material: The developed Ottawa Emergency Department Shift Observation Tool (O-EDShOT) includes 12-items rated on a 5-point entrustment scale with a global assessment item and 2 short-answer questions. Eight hundred and thirty-three assessment were completed by 78 physicians for 45 residents. Mean scores differed significantly by training level (p < .001) with junior residents receiving lower ratings (3.48 ± 0.69) than intermediate residents who received lower ratings (3.98 ± 0.48) than senior residents (4.54 ± 0.42). Scores did not vary by ED treatment area (p > .05). Residents judged to be safe to independently run the shift had significantly higher mean scores than those judged not to be safe (4.74 ± 0.31 vs 3.75 ± 0.66; p < .001). Fourteen observations per resident, the typical number recorded during a 1-month rotation, were required to achieve a reliability of 0.80. Conclusion: The O-EDShOT successfully discriminated between junior, intermediate and senior-level residents regardless of ED treatment area. Multiple sources of evidence support the O-EDShOT producing valid scores for assessing a resident's ability to independently run an ED shift.
Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
Psychosocial disability affects a number of individuals with psychosis and often begins years before the formal onset of disorder. This suggests that for many, their psychosocial disability is enduring, and targeted interventions are therefore needed earlier in their developmental trajectories to ensure that psychosocial disability does not become entrenched. Poor psychosocial functioning also affects individuals with a range of different emerging mental health problems, putting these young people at risk of long-term social marginalisation and economic disadvantage; all of which are known risk factors for the development of psychosis. Identification of the markers of poor psychosocial functioning will help to inform effective treatments. This editorial will discern the early trajectories and markers of poor psychosocial outcome in psychosis, and highlight which individuals are most at risk of having a poor outcome. This editorial will also discuss whether early interventions are currently being targeted appropriately and will propose how intervention and preventative strategies can be implemented, to restore psychosocial trajectories in a way that enables young people to maximise their life chances.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.
Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.
In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.
Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.
Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
Robust time-averaged molecular dynamics has been developed to calculate finite-temperature elastic constants of a single crystal. We find that when the averaging time exceeds a certain threshold, the statistical errors in the calculated elastic constants become very small. We applied this method to compare the elastic constants of Pd and PdH0.6 at representative low (10 K) and high (500 K) temperatures. The values predicted for Pd match reasonably well with ultrasonic experimental data at both temperatures. In contrast, the predicted elastic constants for PdH0.6 only match well with ultrasonic data at 10 K; whereas, at 500 K, the predicted values are significantly lower. We hypothesize that at 500 K, the facile hydrogen diffusion in PdH0.6 alters the speed of sound, resulting in significantly reduced values of predicted elastic constants as compared to the ultrasonic experimental data. Literature mechanical testing experiments seem to support this hypothesis.
Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).
Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).
A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.
Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
The cat flea, Ctenocephalides felis, is a major pest species on companion animals thus of significant importance to the animal health industry. The aim of this study was to develop sampling and storage protocols and identify stable reference genes for gene expression studies to fully utilize the growing body of molecular knowledge of C. felis. RNA integrity was assessed in adult and larvae samples, which were either pierced or not pierced and stored in RNAlater at ambient temperature. RNA quality was maintained best in pierced samples, with negligible degradation evident after 10 days. RNA quality from non-pierced samples was poor within 3 days. Ten candidate reference genes were evaluated for their stability across four group comparisons (developmental stages, genders, feeding statuses and insecticide-treatment statuses). Glyceraldehyde 3 phosphate dehydrogenase (GAPDH), 60S ribosomal protein L19 (RPL19) and elongation factor-1α (Ef) were ranked highly in all stability comparisons, thus are recommended as reference genes under similar conditions. Employing just two of these three stable reference genes was sufficient for accurate normalization. Our results make a significant contribution to the future of gene expression studies in C. felis, describing validated sample preparation procedures and reference genes for use in this common pest.
Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention.
ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression.
This paper presents the rationale for the study and presents a summary of the study design.
ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
Introduction: The anticoagulated trauma patient is a particularly vulnerable population. Our current practice is guided by experience with patients taking vitamin K dependent antagonists (VKA, like warfarin). It is currently unknown how the increasing use of direct oral anticoagulants (DOACs) will change our trauma population. We collected data about this new subset of patients to compare their clinical characteristics to patients on pre-injury VKA therapy. Methods: Retrospective review of anticoagulated trauma patients presenting to Toronto’s two adult trauma centres, Saint Michael’s Hospital and Sunnybrook Health Sciences Centre, from June 2014-June 2015 was undertaken. Patients were recruited through the institutions’ trauma registries and were eligible if they suffered a traumatic injury and taking an oral anticoagulant pre-injury. Clinical and demographic data were extracted by a trained reviewer and analysed with descriptive statistics. Results: Our study recruited 85 patients, 33% were taking DOACs and 67% VKAs. Trauma patients on DOACs & VKAs respectively had similar baseline characteristics such as age (75.9 vs 77.4), initial injury severity score (ISS (16.9 vs 20.6)) and concomitant antiplatelet use (7.1% vs 5.4%). Both groups’ most common mechanism for injury was falls and the most common indication for anticoagulation was atrial fibrillation. Patients on DOACs tended to have lower average INR (1.25 vs 2.3) and serum creatinine (94.9 vs 127.4). Conclusion: Patients on DOACs pre-injury now account for a significant proportion of orally anticoagulated trauma patients. Patients on DOACs tended to have less derangement of basic hematological parameters complicating diagnosis and management of coagulopathy.
Many of the important events in the life of a star occur, or are thought to occur, during the red giant or supergiant phase of evolution. For example, in heavy and intermediate mass stars supernova explosions terminate normal evolutionary processes while in lower mass stars the stellar envelope is entirely removed giving rise to planetary nebulae and, subsequently, white dwarfs. Theoretical calculations suggest that before the onset of these rather drastic events, a significant amount of nucleosynthesis occurs, giving rise to enhanced surface abundances of He, C, N and s-process elements (e.g., Iben and Truran 1978; Renzini and Voli 1981); loss of the envelope material by stellar winds, planetary nebula ejection and supernova explosions produce overall galactic enrichment in these elements.
A photometric survey of a central region of the LMC has been undertaken to obtain a magnitude and colour limited sample of bright asymptotic giant branch (AGB) stars; the stars were selected from V and Ic plates taken by the UK Schmidt Telescope Unit (UKSTU) at Coonabarabran. Infrared JHK photometry has been obtained for all the stars in the sample in order to determine bolometric magnitudes, and spectra have been obtained for most of the stars to obtain spectral types. Stars in the sample have bolometric magnitudes up to the AGB limit of Mbol ∼ – 7.1, and many of the stars show evidence for dredge-up of carbon and s-process elements during helium shell flashes. A bolometric luminosity function has been constructed and its behaviour is discussed in terms of possible mass loss scenarios.
Angular diameters of Magellanic Cloud planetary nebulae obtained using speckle interferometry on the AAT are presented. The mass of ionized gas in each nebula is derived from the angular diameter and published Hβ line fluxes; the derived masses range from 0.005M⊙ to 0.19M⊙, with a mean value of 0.08M⊙. All the planetary nebulae observed are relatively small (diameter ≲0.13pc), young (age ≲ 2500 years), bright and dense. They are therefore almost certainly only partially ionized, so that the masses derived for the ionized parts of the nebula are lower limits to the total nebula mass.