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In Einstein’s special theory of relativity, all observers measure the speed of light, c, to be the same. However, this refers to the round-trip speed, where a clock at the origin times the outward and return trip of light reflecting off a distant mirror. Measuring the one-way speed of light is fraught with issues of clock synchronisation, and, as long as the average speed of light remains c, the speeds on the outward and return legs could be different. One objection to this anisotropic speed of light is that views of the distant universe would be different in different directions, especially with regard to the ages of observed objects and the smoothness of the Cosmic Microwave Background. In this paper, we explore this in the Milne universe, the limiting case of a Friedmann–Robertson–Walker universe containing no matter, radiation, or dark energy. Given that this universe is empty, it can be mapped onto flat Minkowski space-time and so can be explored in terms of the one-way speed of light. The conclusion is that the presence of an anisotropic speed of light leads to anisotropic time dilation effects, and hence observers in the Milne universe would be presented with an isotropic view of the distant cosmos.
The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders.
To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD).
In participants who did not complete the MHQ, we calculated the number of other depression measures endorsed, for example from hospital episode statistics and interview data. We compared cases defined this way with CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium MDD genome-wide association study.
The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those who endorsed four or five measures of depression. The strength of the genetic contribution to cases defined by at least two measures approximated that for CIDI-defined cases. Most genetic correlations between UK Biobank and the Psychiatric Genomics Consortium MDD study exceeded 0.7, but there was variability between pairwise comparisons.
Multiple measures of depression can serve as a reliable approximation for case status where the CIDI measure is not available, indicating sample size can be optimised using the entire suite of UK Biobank data.
Sedentary behaviour is potentially a modifiable risk factor for anxiety disorders, a major source of global disability that typically starts during adolescence. This is the first prospective study of associations between repeated, device-based measures of sedentary behaviour and anxiety symptoms in adolescents.
A UK cohort with 4257 adolescents aged 12 at baseline (56% female). Main exposures were sedentary behaviour and physical activity measured using accelerometers for 7-days at ages 12, 14, and 16. Primary outcome was anxiety symptom scores at age 18 from a Clinical Interview Schedule-Revised. We used adjusted negative binomial regression and iso-temporal substitution methods to analyse the data.
We found a positive association between sedentary behaviour at ages 12, 14, and 16, with anxiety symptoms at age 18, independent of total physical activity volume. Theoretically replacing an hour of daily sedentary behaviour for light activity at ages 12, 14, and 16, was associated with lower anxiety symptoms by age 18 by 15.9% (95% CI 8.7–22.4), 12.1% (95% CI 3.4–20.1), and 14.7% (95% CI 4–24.2), respectively. Whereas, theoretically replacing an hour of sedentary behaviour with moderate-to-vigorous physical activity was not associated with differences in anxiety symptoms. These results were robust to a series of sensitivity analyses.
Sedentary behaviour is a possible risk factor for increasing anxiety symptoms during adolescence, independent of total physical activity volume. Instead of focusing on moderate-to-vigorous activity, replacing daily sedentary behaviour with light activity during adolescence could be a more suitable method of reducing future anxiety symptoms.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
made over a 288-MHz band centred at 887.5 MHz.
During the past decade, genetics research has allowed scientists and clinicians to explore the human genome in detail and reveal many thousands of common genetic variants associated with disease. Genetic risk scores, known as polygenic risk scores (PRSs), aggregate risk information from the most important genetic variants into a single score that describes an individual’s genetic predisposition to a given disease. This article reviews recent developments in the predictive utility of PRSs in relation to a person’s susceptibility to breast cancer and coronary artery disease. Prognostic models for these disorders are built using data from the UK Biobank, controlling for typical clinical and underwriting risk factors. Furthermore, we explore the possibility of adverse selection where genetic information about multifactorial disorders is available for insurance purchasers but not for underwriters. We demonstrate that prediction of multifactorial diseases, using PRSs, provides population risk information additional to that captured by normal underwriting risk factors. This research using the UK Biobank is in the public interest as it contributes to our understanding of predicting risk of disease in the population. Further research is imperative to understand how PRSs could cause adverse selection if consumers use this information to alter their insurance purchasing behaviour.
The development of childhood anxiety disorders (CADs) is likely to depend on pathways that can be programmed by early-life risk factors. We test the hypothesis that early-life maternal factors can predict this programming effect on CAD.
Data were obtained from 198 women and children from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a cohort study with data collected across pregnancy, postpartum and until 4 years of age. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV), together with antenatal hair cortisol concentrations, maternal childhood trauma and parenting stress at 6 months postpartum. CAD was assessed with the Preschool Age Psychiatric Assessment and the Child Behaviour Checklist.
Antenatal depression, a history of maternal childhood trauma and lower gestational age at birth were each associated with anxiety disorders at 4 years of age in their children. A multivariate binary logistic model with these early predictors explained approximately 9% of variance in CAD outcome at 4 years of age; however, only maternal trauma and gestational age were significant predictors in the model. The effect of early parenting stress on CAD was found to vary by the concentration of maternal antenatal hair cortisol, whereby postpartum parenting stress was associated with CAD only when there were higher maternal antenatal cortisol levels.
This study suggests the importance of maternal factors pre-conception, pregnancy and in the postnatal period, which predict CADs and this is consistent with a developmental programming hypothesis for CAD.
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.
Research on at-risk states of psychosis has mainly aimed to predict conversion. Yet as a considerable number of patients does not to progress to this outcome during the investigated observation periods, the course of these non-converters (NC) is of major interest, particularly with regard to preventive interventions and treatment.
To analyze the psychopathological and functional in 18-month non-converters.
Data were derived from the prospective multicenter European Prediction of Psychosis Study with an 18-month follow-up period. Participants had to fulfill ultra-high risk criteria and/or the COGDIS criterion, which is based on a set of cognitive basic symptoms. Psychopathology was assessed with the Structure Interview for Prodromal Syndromes (SIPS), including the Global Assessment of Functioning Scale (GAF) and a short version of the Schizophrenia Proneness Instrument (SPI-A).
All total and subscale scores improved significantly during follow-up. However, a more detailed analysis revealed that a considerable part of the patients showed no improvement or even a worsening of psychopathology and function.
Our first analysis of course on non-converters shows that a high proportion of patients improved. In the light of results from retrospective studies, however, this improvement has to be interpreted with caution, as the observation period does not allow to determine the proportion of outpost syndromes, i.e. precursors of a later prodrome. Furthermore, a considerable portion of our sample worsened functionally and/or symptomatically. With regard to retrospective schizophrenia related results, very long observation periods may be needed to characterize the patterns of course in subpsychotic syndromes.
A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.
In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).
246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.
The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.
Ultra-high risk (UHR) criteria are defined by attenuated and/or transient full-blown psychotic symptoms and/or a combination of genetic risk factor and deterioration of functioning. To achieve a higher predictive specificity and a clear threshold of clinical importance, functional impairment has been considered as an obligate part of all UHR criteria.
In the European Prediction of Psychosis Study (EPOS)N = 37 participants converted to psychosis, n = 146 completed the whole 18-month follow-up period without conversion. Assessed by the Global Assessment of Functioning Scale, modified version (GAF-M), the following functional states were considered: Considered GAF-M: ≤30%/≤10% reduction of baseline scores related to highest scores in the previous year; scores ≤70/≤60.
The GAF reduction criteria led to a very unfavorable loss of sensitivity, even, if only 10% were demanded. This was accompanied by correspondingly unfavorable accuracy measures. Introducing functional impairment criteria defined by the current state reported to be predictive for psychiatric caseness (score ≤ 70) or to define serious impairment (score ≤ 60) (Kessler et al., 2002, 2003) kept sensitivity at a perfectly high level, yet did not produce any gain of specificity.
These results were certainly be caused by the fact that the whole group showed already low GAF-M scores in the previous year. Thus, a functional impairment criterion proved not to be useful to improve prediction. However, a combination of APS or BLIPS with a ‘clinical status’ criterion of GAF-M ≤ 70 may be considerable to demonstrate a strong need for intervention.
A considerable part of clinical high-risk samples does not convert to psychosis within the studies' limited observation periods. A part of these ‘non-converters’ shows a remission of symptoms (with unknown future course). Another part, however, maintains the risk state during follow-up.
Persistence of indicators for an increased risk of psychosis.
To investigate, if persistence of attenuated (APS) or brief limited intermittent psychotic symptoms (BLIPS), the core syndromes of ultra-high risk (UHR) criteria, can be predicted clinically.
N = 129 participants of the European Prediction of Psychosis (EPOS) Study were included into the current analysis. Persistent Risk Symptoms (pRS) were defined as an at-least ‘moderate’ level (SIPS) of at least one positive symptom at all visits (symptom had to remain the same). Functional significance was defined by a GAF-M score ≤60 at 18-month follow-up (T2).
23.3% displayed persistent risk symptoms throughout follow-up. Most frequent pRS were ‘unusual thought contents’, ‘ideas of persecution’ and ‘perceptual disturbances’. In 90% of the pRS subjects, but only in 25.3% of the non-pRS subjects, GAF scores at T2 were below 60 points (p < 0.01).
Logistic regression analysis revealed that the presence of the pRS syndrome at T2 was predictable by the early course of attenuated positive symptoms with maximum accuracy when the number of at least ‘moderate’ symptoms was considered.
A considerable number of subjects at risk showed persistent attenuated positive symptoms associated with long-lasting functional impairments, irrespective of conversion within the foreseeable future.
The ultra-high risk state of developing a psychosis is mainly characterized by attenuated or transient full-blown psychotic symptoms. It can be assessed with the structured interview for prodromal symptoms (SIPS), comprising four domains: positive, negative, disorganization and general symptoms. As the scores of the SOPS sub-domains are regularly used to perform domain-related analyses the stability of the suggested domain structure and item composition is of major interest.
SIPS (version 3.0) data from n = 243 participants of the European Prediction of Psychosis Study (EPOS) were used for the current analysis. Inclusion criteria comprised ultra-high risk criteria and the basic symptom criterion COGDIS. The EPOS investigators received extensive training by one of the scale's authors (Tandy J. Miller, PhD). Pairwise interrater concordance for SIPS was 77%, which was determined acceptable by the training team. A principal component analysis was performed (Eigenvalues > 1, varimax rotation).
A five factor solution emerged. Factor 1 was primarily defined by a loss of intentionality, functioning and stress tolerance, factor 2 by anhedonia and affective blunting, factor 3 by cognitive and behavioural disorganization, factor 4 by delusions. Sleep disturbances and perceptual abnormalities/hallucinations have both been associated with dopaminergic disturbances, this may explain their common appearance on factor 5.
The originally suggested structure of the SIPS proofed not to be stable and was replaced by a five-factor solution. Our results suggest considering a different item and factor structure in future SIPS based data analyses.
Broadmoor is a high secure psychiatric hospital divided into personality disorder (PD) and mental illness (MI) pathways. Whenever an incident occurs, it should be recorded. To better understand which factors influence the rate of incidents, such as diagnosis or intervention by medical and psychological staff, we examined the difference in the number of incidents recorded on weekdays versus weekends, ward round (WR) versus non-WR days and the PD versus MI pathways.
All incidents recorded over a one-year period (3.11.2014–2.11.2015) were examined. Extraneous incidents were excluded, leaving subgroups of “aggressive” (physical and verbal) and “physical” (excluding verbal) incidents which were analysed. Data were adjusted for the difference in number of beds in each pathway.
Of the 2369 incident reports included, more were recorded per day on weekdays than weekends, with little difference on WR versus non-WR days. The rates of both types of incidents were similar on both PD and MI admission wards, although the rate of “physical” incidents was 2.6 times higher and “aggressive” incidents 3.3 times higher in PD compared to MI rehabilitation wards.
The findings suggest the presence of medical and psychological staff during the week, and possibly the requirements they place on patients, may increase the rate of incidents within the hospital. Despite comparable rates on admission, MI rehabilitation wards have far fewer incidents than PD rehab wards, which may reflect the more intractable nature of PD versus MI. More work is required to confirm these findings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.