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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.
Cognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.
A randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.
Intention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).
Group IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
Antarctic toothfish Dissostichus mawsoni and Weddell seals Leptonychotes weddellii are important mesopredators in the waters of the Antarctic continental shelf. They compete with each other for prey, yet the seals also prey upon toothfish. Such intraguild predation means that prevalence and respective demographic rates may be negatively correlated, but quantification is lacking. Following a review of their natural histories, we initiate an approach to address this deficiency by analysing scientific fishing catch per unit effort (CPUE; 1975–2011 plus sporadic effort to 2018) in conjunction with an annual index of seal abundance in McMurdo Sound, Ross Sea. We correlated annual variation in scientific CPUE to seal numbers over a 43 year period (1975–2018), complementing an earlier study in the same locality showing CPUE to be negatively correlated with spatial proximity to abundant seals. The observed relationship (more seals with lower CPUE, while controlling for annual trends in each) indicates the importance of toothfish as a dietary item to Weddell seals and highlights the probable importance of intra- and inter-specific competition as well as intraguild predation in seal-toothfish dynamics. Ultimately, it may be necessary to supplement fishery management with targeted ecosystem monitoring to prevent the fishery from having adverse effects on dependent species.
By the end of their first year, infants can interpret many different types of complex dynamic visual events, such as caused-motion, chasing, and goal-directed action. Infants of this age are also in the early stages of vocabulary development, producing their first words at around 12 months. The present work examined whether there are meaningful individual differences in infants’ ability to represent dynamic causal events in visual scenes, and whether these differences influence vocabulary development. As part of the longitudinal Language 0–5 Project, 78 10-month-old infants were tested on their ability to interpret three dynamic motion events, involving (a) caused-motion, (b) chasing behaviour, and (c) goal-directed movement. Planned analyses found that infants showed evidence of understanding the first two event types, but not the third. Looking behaviour in each task was not meaningfully related to vocabulary development, nor were there any correlations between the tasks. The results of additional exploratory analyses and simulations suggested that the infants’ understanding of each event may not be predictive of their vocabulary development, and that looking times in these tasks may not be reliably capturing any meaningful individual differences in their knowledge. This raises questions about how to convert experimental group designs to individual differences measures, and how to interpret infant looking time behaviour.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
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.
Alien species are a driver of biodiversity loss, with impacts of different aliens on native species varying considerably. Identifying the contributions of alien species to native species declines could help target management efforts. Globally, seabirds breeding on islands have proven to be highly susceptible to alien species. The breeding colonies of the pink-footed shearwater (Ardenna creatopus) are threatened by the negative impacts of alien mammals. We combined breeding monitoring data with a hierarchical model to separate the effects of different alien mammal assemblages on the burrow occupancy and hatching success of the pink-footed shearwater in the Juan Fernández Archipelago, Chile. We show that alien mammals affected the rates of burrow occupancy, but had little effect on hatching success. Rabbits produced the highest negative impacts on burrow occupancy, whereas the effects of other alien mammals were more uncertain. In addition, we found differences in burrow occupancy between islands regardless of their alien mammal assemblages. Managing rabbits will improve the reproductive performance of this shearwater, but research is needed to clarify the mechanisms by which alien mammals affect the shearwaters and to explain why burrow occupancy varies between islands.
Hydraulic lime binders are considered a technological marvel which revolutionized construction techniques in antiquity. The core material is made of a binder that is a mixture of calcite and hydraulic phases, which are amorphous silicate compounds that nanostructurally polymerize into insoluble phases that harden even underwater, formed during the reaction between lime and reactive silicates such as volcanic ash. This is also what makes hydraulic lime so hard to radiocarbon (14C) date. These insoluble phases contain carbonates that may set centuries following their application, resulting in younger ages, which may contaminate the calcite fraction that is favorable for 14C dating. This calcite fraction forms upon the incorporation of atmospheric carbon dioxide during the setting of the hydrated lime. Therefore, different characterization methods are being constantly developed for identifying and characterizing the components of hydraulic lime-binders. In this work, we present a rapid characterization technique based on Fourier transform infrared spectroscopy (FTIR) that characterizes the atomic disorder and chemical environment of the carbonates and silicates fractions in the binder. The atomic disorder of the calcite crystallites was determined by the ν2 and ν4 vibrational modes, and the silicates were characterized by the main peak asymmetry and full width at half maximum (FWHM). Different hydraulic binders from Caesarea Maritima were examined, including Herodian mortars from the underwater breakwater and on-land plasters and mortars from the portʼs warehouse and vaults. Hydraulic binders, in which the calcite fraction in the binder shows atomic disorder that is comparable to modern plaster binders, was associated with silicates that have asymmetry and FWHM of clays and quartz. These materials are considered to be in good preservation state for 14C dating since their carbonates crystallites are disordered and did not interact with the environment chemically to form stable and ordered crystals. Interestingly, the atomic disorder of binders that underwent chemical alterations and recrystallization processes, are associated with reactive silicates aggregates such as volcanic ash (pozzolana). These results suggest a new way to prescreen materials for radiocarbon dating based on the composition of lime-binders and preservation state of the carbonate fraction and hydraulic products.
While it is known that patients with schizophrenia recognize facial emotions, specifically negative emotions, less accurately, little is known about how they misattribute these emotions to other emotions and whether such misattribution biases are associated with symptoms, course of the disorder, or certain cognitive functions.
Outpatients with schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 30) performed a computerised Facial Emotion Attribution Test and Wisconsin Card Sorting Test (WCST). Patients were also rated on the Positive and Negative Syndrome Scale (PANSS).
Patients were poor at recognizing fearful and angry emotions and attributed fear to angry and angry to neutral expressions. Fear-as-anger misattributions were predicted independently by a longer duration of illness and WCST perseverative errors.
The findings show a bias towards misattributing fearful and angry facial emotions. The propensity for fear-as-anger misattribution biases increases as the length of time that the disorder is experienced increases and a more rigid style of information processing is used. This, at least in part, may be perpetuated by subtle fearfulness expressed by others while interacting with people with schizophrenia.
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.
The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies.
Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations. Memoranda, Core Lab reports, and adjudication logs were reviewed. A centre-level questionnaire provided information regarding local processes for data collection. Descriptive statistics were used, and chi-square tests determined differences in imaging quality.
For the 19 participating centres, challenges with enrolment included variations in Institutional Review Board definitions of “retrospective” eligibility, overestimation of non-White participants, centre categorisation of Hispanic participants that differed from National Institutes of Health definitions, and exclusion of potential participants due to missing demographic data. Institutional Review Board amendments resolved many of these challenges. There was an unanticipated burden imposed on centres due to high numbers of echocardiograms that were reviewed but failed to meet submission criteria. Additionally, image transfer software malfunctions delayed Core Lab image review and feedback. Between the early and late study periods, the proportion of unacceptable echocardiograms submitted to the Core Lab decreased (14 versus 7%, p < 0.01). Most protocol violations were from eligibility violations and inadvertent protected health information disclosure (overall 2.5%). Adjudication committee reviews led to protocol changes.
Numerous challenges encountered during the Normal Echocardiogram Database Study prolonged study enrolment. The retrospective design and flaws in image transfer software were key impediments to study completion and should be considered when designing future studies collecting echocardiographic images as a primary outcome.
Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction.
Methods and Results:
Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate.
In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.
In a tertiary-care hospital and affiliated long-term care facility, a stewardship intervention focused on patients with Clostridioides difficile infection (CDI) was associated with a significant reduction in unnecessary non-CDI antibiotic therapy. However, there was no significant reduction in total non-CDI therapy or in the frequency of CDI recurrence.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
Objective: Concussion in children and adolescents is a prevalent problem with implications for subsequent physical, cognitive, behavioral, and psychological functioning, as well as quality of life. While these consequences warrant attention, most concussed children recover well. This study aimed to determine what pre-injury, demographic, and injury-related factors are associated with optimal outcome (“wellness”) after pediatric concussion. Method: A total of 311 children 6–18 years of age with concussion participated in a longitudinal, prospective cohort study. Pre-morbid conditions and acute injury variables, including post-concussive symptoms (PCS) and cognitive screening (Standardized Assessment of Concussion, SAC), were collected in the emergency department, and a neuropsychological assessment was performed at 4 and 12 weeks post-injury. Wellness, defined by the absence of PCS and cognitive inefficiency and the presence of good quality of life, was the main outcome. Stepwise logistic regression was performed using 19 predictor variables. Results: 41.5% and 52.2% of participants were classified as being well at 4 and 12 weeks post-injury, respectively. The final model indicated that children who were younger, who sustained sports/recreational injuries (vs. other types), who did not have a history of developmental problems, and who had better acute working memory (SAC concentration score) were significantly more likely to be well. Conclusions: Determining the variables associated with wellness after pediatric concussion has the potential to clarify which children are likely to show optimal recovery. Future work focusing on wellness and concussion should include appropriate control groups and document more extensively pre-injury and injury-related factors that could additionally contribute to wellness. (JINS, 2019, 25, 375–389)
Our understanding of Saturn’s magnetosphere has been drastically changed over the last decade, since the arrival of Cassini, the first spacecraft to go into orbit around the planet. The trajectory of Cassini allowed the Saturnian magnetosphere to be studied both in the equatorial plane and at high latitudes, in a wide range of radial distances and local time sectors. This chapter reviews the current picture of Saturn’s global magnetospheric configuration and describes the local fields and particle properties in key regions like the radiation belts and the inner, middle and outer magnetosphere. The moon Enceladus, deep in the magnetosphere, is the major source of neutrals and charged particles in the magnetosphere, and in this chapter we describe how the particles are generated, transported and lost within the highly dynamic magnetosphere. We also describe how both particles and fields in the Saturnian magnetosphere vary with time, both on shorter timescales and with Saturn’s seasons. We highlight some of the most recent findings and discoveries, including a formerly unknown electric field oriented in the noon-midnight direction. Finally, we discuss magnetospheric measurements planned for the final sequence of the Cassini mission in 2017, called the “Grand Finale,” along with a list of open questions to be solved by future missions.
Prion diseases are rare dementias that most commonly occur sporadically, but can be inherited or acquired, and for which there is no cure. We sought to understand which prion disease symptoms are most problematic for carers, to inform the development of outcome measures.
Self-completed questionnaire with follow-up of a subset of participants by structured interview.
A nested study in the UK National Prion Monitoring Cohort, a longitudinal observational study.
Participants and measurements:
71 carers, of people with different prion diseases with a wide range of disease severity, identified 236 of their four most problematic symptoms by questionnaire which were grouped into ten domains. Structured interviews were then done to qualitatively explore these experiences. Eleven family carers of people with prion disease were selected, including those representative of a range of demographics and disease subtypes and those who cared for people with prion disease, living or recently deceased. Interviews were transcribed and formally studied.
The six most problematic symptom domains were: mobility and coordination; mood and behavior; personal care and continence; eating and swallowing; communication; and cognition and memory. The prevalence of these symptoms varied significantly by disease stage and type. A formal analysis of structured interviews to explore these domains is reported.
We make suggestions about how healthcare professionals can focus their support for people with prion disease. Clinical trials that aim to generate evidence regarding therapies that might confer meaningful benefits to carers should consider including outcome measures that monitor the symptomatic domains we have identified as problematic.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
Sex-specific diagnostic cut-offs may improve the test characteristics of high-sensitivity troponin assays for the diagnosis of myocardial infarction (MI). The objective of this study was to quantify test characteristics of sex-specific cut-offs of a single, high-sensitivity cardiac troponin T (hs-cTnT) assay for 7-day MI in patients with chest pain.
This observational cohort study included consecutive emergency department (ED) patients with suspected cardiac chest pain from four Canadian EDs who had an hs-cTnT assay performed within 60 minutes of ED arrival. The primary outcome was MI at 7 days. We quantified test characteristics (sensitivity, negative predictive value [NPV], likelihood ratios and proportion of patients ruled out) for multiple combinations of sex-specific, rule-out cut-offs. We calculated the net reclassification index compared to universal rule-out cut-offs.
In 7,130 patients (3,931 men and 3,199 women), the 7-day MI incidence was 7.38% among men and 3.78% among women. Optimal sex-specific cut-offs (<8 ng/L for men and <7 ng/L for women) had a 98.5% sensitivity for MI and ruled out MI in 55.8% of patients. This would enable an absolute increase in the proportion of patients who were able to be ruled out with a single hs-cTnT of 13.2% to 22.2%, depending on the universal rule-out concentration used as a comparator.
Sex-specific hs-cTnT cut-offs for ruling out MI at ED arrival may improve classification performance, enabling more patients to be safely ruled out at ED arrival. However, differences between sex-specific and universal cut-off concentrations are within the variation of the assay, limiting the clinical utility of this approach. These findings should be confirmed in other data sets.