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People with neurodevelopmental disorders often present with challenging behaviours and psychiatric illnesses. Diagnosis and treatment require patients, families and healthcare professionals to work closely together in partnership, acknowledging their respective areas of expertise. Good treatment outcomes should also be underpinned by robust research evidence. Key research priorities are highlighted.
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).
Methods
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.
Results
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).
Conclusions
Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.
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.
Methods:
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.
Results:
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.
Conclusion:
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.
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.
Methods
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.
Results
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).
Conclusions
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.
Methods
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.
Results
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.
Conclusions
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.
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.
In 2018, the Alliance for Open Media (AOMedia) finalized its first video compression format AV1, which is jointly developed by the industry consortium of leading video technology companies. The main goal of AV1 is to provide an open source and royalty-free video coding format that substantially outperforms state-of-the-art codecs available on the market in compression efficiency while remaining practical decoding complexity as well as being optimized for hardware feasibility and scalability on modern devices. To give detailed insights into how the targeted performance and feasibility is realized, this paper provides a technical overview of key coding techniques in AV1. Besides, the coding performance gains are validated by video compression tests performed with the libaom AV1 encoder against the libvpx VP9 encoder. Preliminary comparison with two leading HEVC encoders, x265 and HM, and the reference software of VVC is also conducted on AOM's common test set and an open 4k set.
We aimed to profile vegetable consumption and its association with dietary and sociodemographic factors.
Design:
Secondary analysis of a nationally representative nutrition survey. ‘Vegetables’ refers to non-discretionary ‘vegetables and legumes/beans’ as defined by the Australian Dietary Guidelines (ADG). Prevalence of vegetable consumption, frequency of intake, proportion meeting ADG recommendations, most popular food groups, intake at each reported eating occasion, and the profile of high and low vegetable consumers (based on the median servings) were determined.
Setting:
Australian 2011–2012 National Nutrition and Physical Activity Survey.
Participants:
Children and adolescents aged 2 to 18 years (n 2812).
Results:
Vegetables were consumed by 83·0% (95% CI 81·6, 84·4%) of participants, but the median vegetable servings was less than a third of the ADG recommendations. ‘Leaf and stalk vegetables’ and ‘potatoes’ were the most popular vegetable-dense food groups at lunch and dinner, respectively. Sixty-four percent had vegetables once a day, and predominantly at dinner. Vegetable frequency was positively associated with daily vegetable servings and variety. Participants who consumed vegetables twice a day generally had vegetables at both lunch and dinner and had nearly double the servings (2·6, sd 1·9) of those who consumed them once (1·5, sd 1·5). High vegetable consumers were older, had higher total energy, but lower discretionary energy intake and were less likely to be at risk of metabolic complications.
Conclusion:
Increasing the frequency of vegetable consumption may assist with increasing daily vegetable servings. A focus on consuming vegetables at lunch may assist with increasing both total servings and variety.
The global ageing population and the long prodromal period for the development of cognitive decline and dementia brings a need to understand the antecedents of both successful and impaired cognitive ageing. It is increasingly apparent that the trajectory of risk-factor change, as well as the level of the risk factor, may be associated with an increased or decreased risk of cognitive decline or dementia.
Aims
Our aim was to summarise the published evidence and to generate hypotheses related to risk-factor trajectories and risk of incident cognitive decline or dementia.
Method
We collated data from longitudinal observational studies relating to trajectory of blood pressure, obesity and cholesterol and later cognitive decline or dementia using standard systematic review methodology. The databases MEDLINE, Embase and PsycINFO were searched from inception to 26 April 2018.
Results
Thirteen articles were retained for inclusion. Analytical methods varied. Our summary of the current evidence base suggests that first body mass index and then blood pressure rises and then falls more steeply in those who go on to develop dementia. The evidence for cholesterol was less consistent.
Conclusion
Based on our review we present the hypothesis that weight falls around 10 years and blood pressure around 5 years before diagnosis. Confirmatory work is required. However, characterisation of risk according to combinations and patterns of risk factors may ultimately be integrated into the assessments used to identify those at risk of receiving a diagnosis of cognitive decline or dementia in late life.
To profile discretionary food and beverage (DF) consumption among Australian adults.
Design
Cross-sectional analysis. Dietary and sociodemographic data were used to profile DF intake. Prevalence of DF consumption, DF servings (1 serving=600 kJ), nutrient contribution from DF and top DF food groups by self-reported eating occasions were determined. DF consumers (>0 g) were classified according to quartile of DF intake and general linear models adjusted for age and sex were used to determine associations.
Setting
2011–12 National Nutrition and Physical Activity Survey (NNPAS).
Participants
Adults aged ≥19 years (n 9341) who participated in the NNPAS 2011–12.
Results
Most adults consumed DF (98 %) and over 60 % exceeded 3 DF servings/d, with a mean of 5·0 (se 0·0) DF servings/d. Cakes, muffins, scones, cake-type desserts contributed the most DF energy (8·4 %) of all food groups, followed by wines (8·1 %), pastries (8·0 %) and beers (6·1 %), with all these food groups consumed in large portions (2·3–3·0 DF servings). Lunch and dinner together contributed 45 % of total DF energy intake. High DF consumers had an average of 10 DF servings, and this group contained more younger adults, males, low socio-economic status, lower usual fruit intake and higher mean waist circumference, but not higher BMI.
Conclusions
A focus on DF consumed in large portions at lunch and dinner may help improve interventions aimed at reducing DF intake and addressing negative adiposity-related measures found in high DF consumers.
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.
Method
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.
Results
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.
Conclusions
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.
The Clean Sky Joint Undertaking is currently managing two large-scale research and innovation programmes under FP7 and Horizon 2020 to contribute to the strengthening of the European aeronautical sector ensuring global leadership and competitiveness. This paper describes the research and demonstration programmes in Clean Sky (2008–2017) and Clean Sky 2 (2014–2024) related to propulsion technologies for the next-generation aircraft. The bulk of this work is addressed in Clean Sky 1 under the “Sustainable And Green Engines” (SAGE) programme and under the “ENGINES” programme in Clean Sky 2. The High-Level Objectives are described for each engine architecture as well as the targets in terms of CO2 and noise reduction versus a year 2000 reference unless stated otherwise. An overview of the new engine concepts that would satisfy the ACARE objectives is presented, including the main technologies which are to be developed to ensure the successful demonstration of each of those new engine concepts.
To examine the relationships between objectively measured sleep patterns
(sleep duration, sleep efficiency and bedtime) and sugar-sweetened beverage
(SSB) consumption (regular soft drinks, energy drinks, sports drinks and
fruit juice) among children from all inhabited continents of the world.
Design
Multinational, cross-sectional study.
Setting
The International Study of Childhood Obesity, Lifestyle and the Environment
(ISCOLE).
Subjects
Children (n 5873) 9–11 years of age.
Results
Sleep duration was 12 min per night shorter in children who reported
consuming regular soft drinks ‘at least once a day’
compared with those who reported consuming ‘never’ or
‘less than once a week’. Children were more likely to
sleep the recommended 9–11 h/night if they reported
lower regular soft drink consumption or higher sports drinks consumption.
Children who reported consuming energy drinks ‘once a week or
more’ reported a 25-min earlier bedtime than those who reported
never consuming energy drinks. Children who reported consuming sports drinks
‘2–4 d a week or more’ also reported a
25-min earlier bedtime compared with those who reported never consuming
sports drinks. The associations between sleep efficiency and SSB consumption
were not significant. Similar associations between sleep patterns and SSB
consumption were observed across all twelve study sites.
Conclusions
Shorter sleep duration was associated with higher intake of regular soft
drinks, while earlier bedtimes were associated with lower intake of regular
soft drinks and higher intake of energy drinks and sports drinks in this
international study of children. Future work is needed to establish
causality and to investigate underlying mechanisms.
Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.
Methods
In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.
Results
After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).
Conclusions
PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.
Examining neurometabolic abnormalities in critical brain areas in schizophrenia and major depressive disorder (MDD) may help guide future pharmacological interventions including glutamate-modulating treatments.
Aims
To measure metabolite concentrations within the anterior cingulate cortex (ACC) and thalamus of people with schizophrenia and people with MDD.
Methods
Spectra were acquired from 16 volunteers with schizophrenia, 17 with MDD and 18 healthy controls using magnetic resonance spectroscopy on a 7 Tesla scanner.
Results
In the thalamus, there were lower glycine concentrations in the schizophrenia group relative to control (P=0.017) and MDD groups (P=0.012), and higher glutamine concentrations relative to healthy controls (P=0.009). In the thalamus and the ACC, the MDD group had lower myo-inositol concentrations than the control (P=0.014, P=0.009, respectively) and schizophrenia (P=0.004, P=0.002, respectively) groups.
Conclusion
These results support the glutamatergic theory of schizophrenia and indicate a potential glycine deficiency in the thalamus. In addition, reduced myo-inositol concentrations in MDD suggest its involvement in the disorder.
A gap exists between the evidence for reducing risk of knee osteoarthritis (KOA) progression and its application in patients’ daily lives. We aimed to bridge this gap by identifying patient and family physician (FP) self-management priorities to conceptualize and develop a mobile-health application (m-health app). Our co-design approach combined priorities and concerns solicited from patients and FPs with evidence on risk of progression to design and develop a KOA self-management tool.
Methods:
Parallel qualitative research of patient and FP perspectives was conducted to inform the co-design process. Researchers from the Enhancing Alberta Primary Care Research Networks (EnACT) evaluated the mental models of FPs using cognitive task analysis through structured interviews with four FPs. Using grounded theory methods, patient researchers from the Patient and Community Engagement Research (PaCER) program interviewed five patients to explore their perspectives about needs and interactions within primary care. In three co-design sessions relevant stakeholders (four patients, five FPs, and thirteen researchers) participated to: (i) identify user needs with regard to KOA self-management; and (ii) conceptualize and determine design priorities and functionalities of an m-health app using a modified nominal group process.
Results:
Priority measures for symptoms, activities, and quality of life from the user perspective were determined in the first two sessions. The third co-design session with our industry partner resulted in finalization of priorities through interactive patient and FP feedback. The top three features were: (i) a symptoms graph and summary; (ii) information and strategies; and (iii) setting goals. These features were used to inform the development of a minimum viable product.
Conclusions:
The novel use of co-design created directive dialog around the needs of patients, highlighting the contrasting views that exist between patients and FPs and emphasizing how exploring these differences might lead to strong design options for patient-oriented m-health apps. Characterizing these disjunctions has important implications for operationalizing patient-centered health care.