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Childhood infections are associated with adult psychosis and depression, but studies of psychotic experiences (PEs) and depressive symptoms in childhood, adolescence, and early-adulthood are scarce. Previous studies have typically examined severe infections, but studies of common infections are also scarce.
Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, we examined associations of the number of infections in childhood from age 1.5 to 7.5 years with depressive symptom scores at age 10, 13, 14, 17, 18, and 19 years, and with PEs at 12 and 18 years. We performed additional analysis using infection burden (‘low’ = 0–4 infections, ‘medium’ = 5–6, ‘high’ = 7–9, or ‘very high’ = 10–22 infections) as the exposure.
The risk set comprised 11 786 individuals with childhood infection data. Number of childhood infections was associated with depressive symptoms from age 10 (adjusted beta = 0.14; standard error (s.e.) = 0.04; p = <0.01) to 17 years (adjusted beta = 0.17; s.e. = 0.08; p = 0.04), and with PEs at age 12 (suspected/definite PEs: adjusted odds ratio (OR) = 1.18; 95% confidence interval (CI) = 1.09–1.27). These effect sizes were larger when the exposure was defined as very high infection burden (depressive symptoms age 17: adjusted beta = 0.79; s.e. = 0.29; p = 0.01; suspected/definite PEs at age 12: adjusted OR = 1.60; 95% CI = 1.25–2.05). Childhood infections were not associated with depressive/psychotic outcomes at age 18 or 19.
Common early-childhood infections are associated with depressive symptoms up to mid-adolescence and with PEs subsequently in childhood, but not with these outcomes in early-adulthood. These findings require replication including larger samples with outcomes in adulthood.
Psychotic experiences may emerge in more severe cases of common mental disorders (CMD). Previous work identified that 30% of patients treated by mental health services in primary healthcare, specifically the Improving Access to Psychological Therapies (IAPT) programme in England, reported psychotic experiences, began treatment with more severe CMD and were less likely to reach recovery.
To replicate our previous assessment of psychotic experiences in the IAPT programme using a more sensitive threshold and determine its impact on the prevalence of psychotic experience and likelihood of recovery. Additionally, to compare recovery rates between patients with and without psychotic experiences at the end of therapy.
The Community Assessment of Psychic Experiences (CAPE-P15) with a cut-off of 1.30 was used to determine the prevalence of psychotic experiences. Recovery rates were determined using measures collected in the IAPT programme for depression (PHQ-9) and anxiety (GAD-7). Multi-group growth models estimated improvement trajectories.
In total, 2042 patients with CMD completed the CAPE-P15. The mean age was 39.8. The prevalence of psychotic experiences was 18% higher when using a lower threshold. The recovery rate for patients with psychotic experiences was lower (36%) than for those without (64%). Despite sharing similar improvement trajectories, the higher initial severity of CMD among patients with psychotic experiences impeded likelihood of recovery.
As psychotic experiences may be a marker of severity in CMD, the benefits of identifying these in IAPT populations may also apply to patients with milder experiences. Further investigation of the consequential demands on service provision and how this would affect clinical practice is recommended.
In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: ‘minorities’). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population).
The European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20–F33) from 13 sites.
The standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32–1.53) in Valencia to 2.47 (95% CI 1.66–3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66–3.93).
Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.
Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
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.
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.
The Kilmaluag Formation on the Isle of Skye, Scotland, provides one of the richest Mesozoic vertebrate fossil assemblages in the UK, and is among the richest globally for Middle Jurassic tetrapods. Since its discovery in 1971, this assemblage has predominantly yielded small-bodied tetrapods, including salamanders, choristoderes, lepidosaurs, turtles, crocodylomorphs, pterosaurs, dinosaurs, non-mammalian cynodonts and mammals, alongside abundant fish and invertebrates. It is protected as a Site of Special Scientific Interest and by Nature Conservancy Order. Unlike contemporaneous localities from England, this assemblage yields associated partial skeletons, providing unprecedented new data. We present a comprehensive updated overview of the Kilmaluag Formation, including its geology and the fossil collections made to date, with evidence of several species occurrences presented here for the first time. We place the vertebrate faunal assemblage in an international context through comparisons with relevant contemporaneous localities from the UK, Europe, Africa, Asia and the US. This wealth of material reveals the Kilmaluag Formation as a vertebrate fossil assemblage of global significance, both in terms of understanding Middle Jurassic faunal composition and the completeness of specimens, with implications for the early evolutionary histories of mammals, squamates and amphibians.
During engineering design, designers employ three types of model: physical, virtual and cognitive. The role and contribution of each is documented in literature albeit fragmented in nature. Consequentially, a gap in understanding exists in terms of how these models and the transitions between them impact the designer and design process. This paper begins to address this through a characterisation of each model class and an appraisal of the transitional pathways including their alignment to seminal design frameworks.
We describe a case of delayed COVID-19 diagnosis due to unrecognized community transmission in Atlanta, Georgia in mid-February 2020. This case resulted in transmission of COVID-19 to three of the four healthcare workers present during a diagnostic bronchoscopy procedure where only procedural masks were worn.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Introduction: Emergency department (ED) buprenorphine/naloxone inductions for opioid use disorder are an effective and safe way to initiate addictions care in the ED. Kelowna General Hospital's ED buprenorphine/naloxone (KEDSS) program was implemented in September 2018 in order to respond to a community need for accessible and evidence-based addictions care. The objective of our program evaluation study was to examine the implementation of the first five months of the KEDSS program through evaluating patient characteristics and service outcomes. Methods: The KEDSS treatment pathway consists of a standardized protocol (pre-printed order set) to facilitate buprenorphine/naloxone induction and stabilization in the acute care setting (ED and inpatient wards) at Kelowna General Hospital, a community academic hospital. All patients referred to the outpatient addictions clinic via the order set during September 2018-January 2019 (the first 5 months) were included in the study population. A retrospective descriptive chart review was completed. Outcome measures included population characteristics (sociodemographic information, clinical characteristics) and service outcomes (number of patients initiated, patient follow-up). Descriptive statistics and bivariate analyses using t-tests or Pearson's χ2 statistic, as appropriate, were conducted to compare the ED-initiated group with the inpatient-initiated group. Results: During the first five months of the KEDSS program, a total of 35 patients (26% female, mean age 36.6 years, 54% homeless) were started on the treatment pathway, 16 (46%) in the ED. Compared to the inpatient-initiated group, the ED-initiated group were less likely to have psychiatric comorbidities (ED 1.0 vs. inpatient 1.5, p = 0.002), require methadone or sustained-release oral morphine (ED 13% vs. inpatient 37%, p = 0.048), and have attended follow-up (ED 56% vs. inpatient 84%, p = 0.004). Conclusion: This study provides a preliminary look at a new opioid agonist therapy (OAT) treatment pathway (KEDSS) at Kelowna General Hospital, and provides insight into the population that is accessing the program. We found that the majority of patients who are started on buprenorphine/naloxone in the ED are seen in follow-up at the addictions clinic. Future work will examine ongoing follow-up and OAT adherence rates in the study population to quantify the program's impact on improving access to addictions treatment within this community hospital setting.
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
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.
To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis.
Subjects and methods
We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points.
Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up.
The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results.
It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.
Antipsychotic medication maintenance and the factors influencing it were analyzed using data from the SOHO study, a large observational study of the outcomes of antipsychotic treatment for schizophrenia in Europe. A total of 7186 adult patients in the outpatient setting who were initiating or changing their antipsychotic medication and who were prescribed only one antipsychotic after the baseline visit were analyzed. Medication maintenance at 12 months varied with the type of antipsychotic prescribed, being highest with clozapine (79.5%) and olanzapine (77.0%), and lowest with quetiapine (51.4%) and amisulpride (58.2%). Multiple logistic regression analysis demonstrated that the type of antipsychotic prescribed at baseline was the most important predictor of medication maintenance. Alcohol dependency, taking mood stabilizers, compulsory admission or arrest in the previous 6 months, greater clinical severity, and changing antipsychotic medication due to lack of effectiveness at baseline predicted a higher frequency of medication discontinuation in the subsequent 12 months. In contrast, medication maintenance was higher among patients who were treatment naïve at baseline, socially active or who had loss of libido at baseline. The findings from this study should be interpreted conservatively because of its non-randomized observational design.