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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Here we present stringent low-frequency (185 MHz) limits on coherent radio emission associated with a short-duration gamma-ray burst (SGRB). Our observations of the short gamma-ray burst (GRB) 180805A were taken with the upgraded Murchison Widefield Array (MWA) rapid-response system, which triggered within 20s of receiving the transient alert from the Swift Burst Alert Telescope, corresponding to 83.7 s post-burst. The SGRB was observed for a total of 30 min, resulting in a
persistent flux density upper limit of 40.2 mJy beam–1. Transient searches were conducted at the Swift position of this GRB on 0.5 s, 5 s, 30 s and 2 min timescales, resulting in
limits of 570–1 830, 270–630, 200–420, and 100–200 mJy beam–1, respectively. We also performed a dedispersion search for prompt signals at the position of the SGRB with a temporal and spectral resolution of 0.5 s and 1.28 MHz, respectively, resulting in a
fluence upper-limit range from 570 Jy ms at DM
pc cm–3 (
) to 1 750 Jy ms at DM
pc cm–3 (
, corresponding to the known redshift range of SGRBs. We compare the fluence prompt emission limit and the persistent upper limit to SGRB coherent emission models assuming the merger resulted in a stable magnetar remnant. Our observations were not sensitive enough to detect prompt emission associated with the alignment of magnetic fields of a binary neutron star just prior to the merger, from the interaction between the relativistic jet and the interstellar medium (ISM) or persistent pulsar-like emission from the spin-down of the magnetar. However, in the case of a more powerful SGRB (a gamma-ray fluence an order of magnitude higher than GRB 180805A and/or a brighter X-ray counterpart), our MWA observations may be sensitive enough to detect coherent radio emission from the jet-ISM interaction and/or the magnetar remnant. Finally, we demonstrate that of all current low- frequency radio telescopes, only the MWA has the sensitivity and response times capable of probing prompt emission models associated with the initial SGRB merger event.
We present 63 new multi-site radial velocity (RV) measurements of the K1III giant HD 76920, which was recently reported to host the most eccentric planet known to orbit an evolved star. We focused our observational efforts on the time around the predicted periastron passage and achieved near-continuous phase coverage of the corresponding RV peak. By combining our RV measurements from four different instruments with previously published ones, we confirm the highly eccentric nature of the system and find an even higher eccentricity of
$e=0.8782 \pm 0.0025$
, an orbital period of
, and a minimum mass of
for the planet. The uncertainties in the orbital elements are greatly reduced, especially for the period and eccentricity. We also performed a detailed spectroscopic analysis to derive atmospheric stellar parameters, and thus the fundamental stellar parameters (
$M_*, R_*, L_*$
), taking into account the parallax from Gaia DR2, and independently determined the stellar mass and radius using asteroseismology. Intriguingly, at periastron, the planet comes to within 2.4 stellar radii of its host star’s surface. However, we find that the planet is not currently experiencing any significant orbital decay and will not be engulfed by the stellar envelope for at least another 50–80 Myr. Finally, while we calculate a relatively high transit probability of 16%, we did not detect a transit in the TESS photometry.
In a multicenter cohort of 963 adults hospitalized due to coronavirus disease 2019 (COVID-19), 5% had a proven hospital-acquired infection (HAI) and 21% had a proven, probable, or possible HAI. Risk factors for proven or probable HAIs included intensive care unit admission, dexamethasone use, severe COVID-19, heart failure, and antibiotic exposure upon admission.
The Scaling-up Health-Arts Programme: Implementation and Effectiveness Research (SHAPER) project is the world's largest hybrid study on the impact of the arts on mental health embedded into a national healthcare system. This programme, funded by the Wellcome Trust, aims to study the impact and the scalability of the arts as an intervention for mental health. The programme will be delivered by a team of clinicians, research scientists, charities, artists, patients and healthcare professionals in the UK's National Health Service (NHS) and the community, spanning academia, the NHS and the charity sector. SHAPER consists of three studies – Melodies for Mums, Dance for Parkinson's, and Stroke Odysseys – which will recruit over 800 participants, deliver the interventions and draw conclusions on their clinical impact, implementation effectiveness and cost-effectiveness. We hope that this work will inspire organisations and commissioners in the NHS and around the world to expand the remit of social prescribing to include evidence-based arts interventions.
Toxoplasma gondii (T. gondii) is an important human disease-causing parasite. In the USA, T. gondii infects >10% of the population, accrues economic losses of US$3.6 billion/year, and ranks as the second leading culprit of foodborne illness-related fatalities. We assessed toxoplasmosis risk among the Old Order Amish, a mostly homogenous population with a high prevalence of T. gondii seropositivity, using a questionnaire focusing on food consumption/preparation behaviours and environmental risk factors. Analyses were conducted using multiple logistic regression. Consuming raw meat, rare meat, or unpasteurised cow or goat milk products was associated with increased odds of seropositivity (unadjusted Odds Ratios: 2.192, 1.613, and 1.718 , respectively). In separate models by sex, consuming raw meat, or consuming unpasteurised cow or goat milk products, was associated with increased odds of seropositivity among women; washing hands after touching meat with decreased odds of seropositivity among women (adjusted OR (AOR): 0.462); and cleaning cat litterbox with increased odds of seropositivity among men (AOR: 5.241). This is the first study to assess associations between behavioural and environmental risk factors and T. gondii seropositivity in a US population with high seroprevalence for T. gondii. Our study emphasises the importance of proper food safety behaviours to avoid the risk of infection.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Finite-amplitude hydromagnetic Rossby waves in the magnetostrophic regime are studied. We consider the slow mode, which travels in the opposite direction to the hydrodynamic or fast mode, in the presence of a toroidal magnetic field and zonal flow by means of quasi-geostrophic models for thick spherical shells. The weakly nonlinear long waves are derived asymptotically using a reductive perturbation method. The problem at the first order is found to obey a second-order ordinary differential equation, leading to a hypergeometric equation for a Malkus field and a confluent Heun equation for an electrical wire field, and is non-singular when the wave speed approaches the mean flow. Investigating its neutral non-singular eigensolutions for different basic states, we find the evolution is described by the Korteweg–de Vries equation. This implies that the nonlinear slow wave forms solitons and solitary waves. These may take the form of a coherent eddy, such as a single anticyclone. We speculate on the relation of the anticyclone to the asymmetric gyre seen in the Earth's fluid core, and in state-of-the-art dynamo direct numerical simulations.
With human influences driving populations of apex predators into decline, more information is required on how factors affect species at national and global scales. However, camera-trap studies are seldom executed at a broad spatial scale. We demonstrate how uniting fine-scale studies and utilizing camera-trap data of non-target species is an effective approach for broadscale assessments through a case study of the brown hyaena Parahyaena brunnea. We collated camera-trap data from 25 protected and unprotected sites across South Africa into the largest detection/non-detection dataset collected on the brown hyaena, and investigated the influence of biological and anthropogenic factors on brown hyaena occupancy. Spatial autocorrelation had a significant effect on the data, and was corrected using a Bayesian Gibbs sampler. We show that brown hyaena occupancy is driven by specific co-occurring apex predator species and human disturbance. The relative abundance of spotted hyaenas Crocuta crocuta and people on foot had a negative effect on brown hyaena occupancy, whereas the relative abundance of leopards Panthera pardus and vehicles had a positive influence. We estimated that brown hyaenas occur across 66% of the surveyed camera-trap station sites. Occupancy varied geographically, with lower estimates in eastern and southern South Africa. Our findings suggest that brown hyaena conservation is dependent upon a multi-species approach focussed on implementing conservation policies that better facilitate coexistence between people and hyaenas. We also validate the conservation value of pooling fine-scale datasets and utilizing bycatch data to examine species trends at broad spatial scales.
A new high time resolution observing mode for the Murchison Widefield Array (MWA) is described, enabling full polarimetric observations with up to
MHz of bandwidth and a time resolution of
s. This mode makes use of a polyphase synthesis filter to ‘undo’ the polyphase analysis filter stage of the standard MWA’s Voltage Capture System observing mode. Sources of potential error in the reconstruction of the high time resolution data are identified and quantified, with the
loss induced by the back-to-back system not exceeding
dB for typical noise-dominated samples. The system is further verified by observing three pulsars with known structure on microsecond timescales.
The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.
A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.
Navajo Nation, USA.
Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles.
The Navajo Fruit and Vegetable Prescription (FVRx) Programme.
A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Among the 10 categories of personality disorders (PDs), interventions for antisocial and borderline personality disorder are best studied. However, the remaining PDs also pose major problems in everyday health care settings. People affected often additionally present with Axis-I disorders such as substance-related, mood or anxiety disorders, and are among those most difficult to treat. Cluster A PDs (paranoid, schizoid, schizotypal) are of particular significance as some authors argue that they may be part of a continuum of mental disorders and be considered as sub-syndrome of schizophrenia
In the context of Cochrane Collaboration reviews for Cluster A, B and C PDs, exhaustive literature searches were completed to identify the current RCT evidence for PD treatments. Retrievals were assessed and evaluated by two reviewers independently and trials for Cluster A PD were identified.
Only very few (under five) RCTs specifically for Cluster A PDs were identified. Some studies reported on mixed PD samples but it was not always possible to extract data specifically for Cluster A disorders. Participants mostly also suffered from Axis-I disorders. Reported outcomes also focus on Axis-I disorder outcomes or general measures such as overall functioning rather than specific PD symptoms.
The current evidence for psychpathological treatment of Cluster A PD is sparse and does not allow for distinct treatment recommendations. Symptom-driven treatment regimes as suggested by several guidelines are not supported by current evidence.
Limited to no literature exists on the association among sleep quality, obesity and depression in pediatric populations. This study aims to explore this association by examining the sleep quality of children and adolescents before and after a twelve-week comprehensive multidisciplinary pediatric obesity program.
Archival data from the pediatric obesity program included 71 children ages 6-17 (M=10.24, SD=2.74 ) who had been assessed pre and post intervention using the Children's Depression Inventory (CDI), a Sleep Questionnaire, and physician derived Body Mass Index (BMI). On all measures, higher scores indicate presence of symptoms of depression, sleep difficulties, or obesity.
High scores on the CDI proved to predict poor sleep quality both at intake and exit. Hierarchical regression exhibited change in BMI from intake to exit and predicted sleep quality. As BMI decreased from intake to exit, sleep quality increased.
The current study suggests that sleep quality is influenced by the level of depression in children and adolescents both at pre and post intervention measures. Both depression and BMI influenced sleep quality. When the effect of BMI was accounted for, depression significantly predicted sleep quality. The more depressed children/adolescents reported to be, the lower their quality of sleep. Thus, this study suggests the importance of sleep and depression in the treatment of pediatric obesity. This research supports the importance of a multidisciplinary approach to addressing pediatric obesity.
Cannabis is a widely used drug, which effects on human health remain controversial. Recent studies have found correlations between cannabis use and brain structural changes that may be related to ageing processes. Eotaxin-1 is a chemokine described as a marker of ageing, which also appear to increase with cognitive deficits and neurogenesis. Here, we aimed at characterising the effect of cannabis in accelerating normal ageing processes, by studying eotaxin-1 plasma levels in people who currently use cannabis, have used cannabis in the past, or have never used cannabis.
A total of 87 healthy volunteers participated in the study. Participants completed the Cannabis Experience Questionnaire, the General Practice Physical Activity Questionnaire, the Sociodemographic, Morphometric, Alcohol and Tobacco Questionnaire, and provided a blood sample. Eotaxin-1 was assessed by ELISA. The three groups were compared using one-way ANOVA to assess levels of eotaxin-1, and nonpaired Student t-tests to assess other factors effects.
Current users of cannabis (n=18) had significantly higher eotaxin-1 plasma levels compared to past users of cannabis (n=33) and individuals who never used cannabis (n=36). The latter two groups had similar eotaxin-1 levels. Higher eotaxin-1 plasma levels were not attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs.
These results suggest that cannabis use increases eotaxin-1 plasma levels and could result in accelerated brain ageing. However, the effects appear to be reversible when cannabis use ceases. These findings have important implications for treatment and care of mental health disorders, such as schizophrenia.
There are limited amount of studies comparing time trends of incidence and risk factors of psychosis.
To compare time trends of incidence of psychosis in two population samples.
To study 1) onset age and cumulative incidence of psychoses in two Northern Finland Birth Cohorts (NFBC), 2) changes in type of diagnosis and risk factors.
The NFBC 1966 (N=12,058) and NFBC 1986 (N=9,432) are prospective cohorts of the two provinces of Finland with the live born children followed since pregnancy. The data for psychosis and risk factors were collected from variety of nationwide registers and earlier collected data of the NFBCs. The follow-up time was in both cohorts in average 26.5 years.
Proportion of all psychoses was higher in NFBC 1986 than in the NFBC 1966 (1.81% vs 1.0%). There were more affective psychoses in NFBC 1986 (0.5% vs 0.1%), but incidence of schizophrenia was the same (0.4%) in both cohorts. The age of onset was lower in NFBC 1986 than in NFBC 1966 and majority of this cases were females. Only parental psychosis was a significant risk factor predicting psychosis (Hazard Ratios >3.0) in both cohorts.
In conclusion, two birth cohorts within 20 years covering altogether about 40 years showed changes in terms of incidence, age of onset, and type of psychosis.
Our aim was to investigate how age of achieving early motor developmental milestones differ among subjects with and without a history of parental psychosis and whether parental psychosis may alter the effects of the age of achievement on the risk of schizophrenia.
The study sample comprised 10,307 individuals from the prospective Northern Finland Birth Cohort 1966. A total of 139 (1.3%) cohort members suffered from schizophrenia by the age of 46 years. Out of them 19 (13.7%) had a parent with a history of psychosis, while among the non-psychotic cohort members this figure was 524 (5.2%).
Out of eight different motor milestones investigated, parental psychosis associated (p>0.05) with later learning of holding head up, grabbing object, and walking without support. In the parental psychosis group, significant risk factors for schizophrenia included later learning of holding head up and touching thumb with index finger. In the non-parental psychosis group risk estimates were lower and statistical significant milestones were different i.e. turning over, sitting without support, standing up, standing and walking without support. Interactions between parental psychosis and touching thumb with index finger and walking without support was found.
Although parental psychosis associated with delays in motor milestones in the first year of life, it does not explain the association between late achievement of motor milestones and later risk for schizophrenia