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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.
The aim of this study was to evaluate the differences in the metabolic profile and body composition of monozygotic (MZ) twins concordant and discordant for the practice of physical exercise. The sample consisted of 92 MZ twins (72.5% female and 27.5% male, mean age 25.4 ± 5.69 years), registered with the Brazilian Registry of Twins, residing in Natal, Brazil. Data collection was carried out between the years 2016 and 2018. On day 1, subjects underwent a whole-body fitness evaluation, including measures of weight, height, body composition by Dual-Energy X-ray Absorptiometry and the Cardiorespiratory Exercise Test. On day 2, 10 ml blood samples were collected (overnight fasting) to determine the lipid profile and fasting glucose. The sample was separated into three groups: Active Concordant twins (Concordant A, n = 44 subjects), Inactive Concordant twins (Concordant I, n = 22 subjects) and Discordant pairs for Physical Exercise (Discordant PE, n = 26 subjects). The results demonstrated a difference between the discordant twins for exercise and also between the active versus sedentary groups, indicating a causal effect of exercise on the fat percentage, maximum oxygen consumption (VO2max) and second ventilatory threshold variables. Between groups, a difference was also observed between the groups in ventilatory threshold, very low-density lipoprotein and triglycerides. We concluded that, regardless of genetics, the practice of physical exercise was sufficient to generate alterations in body composition and VO2max in MZ twins, but not in the lipid profile or fasting glucose.
This paper explores the development and operation of law and policy concerning the charging of overseas visitors for healthcare in England from the beginnings of the NHS to the present day. It highlights how this has been a highly contentious issue for decades, often linked with immigration policy, and is an area that still lacks comprehensive reliable empirical data to inform the debate. It explores and analyses the recent reforms to the NHS Overseas Charging Regulations introduced in 2015 and 2017. It demonstrates the problems in implementing the most recent regulations in an era of the ‘hostile environment’ and argues that the approach which has been taken can be seen as undermining the covenant of trust between patient and clinician and thus the fundamental principles of the NHS.
The surface area of turbulent/non-turbulent interfaces (TNTIs) is continuously produced and destroyed via stretching and curvature/propagation effects. Here, the mechanisms responsible for TNTI area growth and destruction are investigated in a turbulent flow with and without stable stratification through the time evolution equation of the TNTI area. We show that both terms have broad distributions and may locally contribute to either production or destruction. On average, however, the area growth is driven by stretching, which is approximately balanced by destruction by the curvature/propagation term. To investigate the contribution of different length scales to these processes, we apply spatial filtering to the data. In doing so, we find that the averages of the stretching and the curvature/propagation terms balance out across spatial scales of TNTI wrinkles and this scale-by-scale balance is consistent with an observed scale invariance of the nearby coherent vortices. Through a conditional analysis, we demonstrate that the TNTI area production (destruction) is localized at the front (lee) edge of the vortical structures in the interface proximity. Finally, we show that while basic mechanisms remain the same, increasing stratification reduces the rates at which TNTI surface area is produced as well as destroyed. We provide evidence that this reduction is largely connected to a change in the multiscale geometry of the interface, which tends to flatten in the wall-normal direction at all active length scales of the TNTI.
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.
OBJECTIVES/GOALS: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.
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.
Projet inaugural de partenariat entre la pédopsychiatrie et l’ASE, l’équipe mobile est un dispositif pilote du pôle Paris Centre-Est conçu pour répondre au défaut d’accès aux soins et aux besoins spécifiques des mineurs confiés à l’ASE de Paris. Cette équipe composée de pédopsychiatres, d’éducateurs, et d’infirmières a vu le jour en septembre 2012. Son objectif est de proposer à la demande de l’ASE des consultations d’évaluation pédopsychiatrique en vue d’une orientation des mineurs sur les réseaux de soins existants. Elle a aussi une mission de soutien et de guidance des référents ASE démunis. La spécificité de cette équipe réside dans sa capacité à se déplacer dans les foyers, familles d’accueil, hôtels sociaux pour aller au devant de jeunes placés et permettre une continuité des soins malgré leur propre mobilité. Le profil des patients pris en charge est majoritairement adolescent, leur tableau clinique bruyant associant des troubles du comportement à des conduites addictives et antisociales sévères, et en arrière-fond une importante dépressivité. L’expérience d’un an de pratique nous a conduit à adapter le cadre initialement fixé pour ces rencontres et faire preuve de souplesse et de créativité pour accompagner ces patients le temps nécessaire à l’élaboration commune de leurs problématiques et à la stabilisation de leur environnement, afin que se relance le processus adolescent et qu’émergent des projets d’avenir structurants. La complexité des situations rencontrées intriquant des problématiques sociales, éducatives et psychiatriques nécessite une articulation étroite entre les différents partenaires, sans cesse mise à mal par la différence de cultures institutionnelles et les problématiques des patients. Au fil des mois, ce partenariat est donc toujours en construction mais très prometteur pour répondre aux besoins d’une population aux vulnérabilités multiples, qui se vit comme délaissée et dont la prise en charge est un challenge imposant le développement de moyens croissants.
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.
The DSM-5 introduced purging disorder (PD) as an other specified feeding or eating disorder characterized by recurrent purging in the absence of binge eating. The current study sought to describe the long-term outcome of PD and to examine predictors of outcome.
Women (N = 84) who met research criteria for PD completed a comprehensive battery of baseline interview and questionnaire assessments. At an average of 10.24 (3.81) years follow-up, available records indicated all women were living, and over 95% were successfully located (n = 80) while over two-thirds (n = 58) completed follow-up assessments. Eating disorder status, full recovery status, and level of eating pathology were examined as outcomes. Severity and comorbidity indicators were tested as predictors of outcome.
Although women experienced a clinically significant reduction in global eating pathology, 58% continued to meet criteria for a DSM-5 eating disorder at follow-up. Only 30% met established criteria for a full recovery. Women reported significant decreases in purging frequency, weight and shape concerns, and cognitive restraint, but did not report significant decreases in depressive and anxiety symptoms. Quality of life was impaired in the physical, psychological, and social domains. More severe weight and shape concerns at baseline predicted meeting criteria for an eating disorder at follow-up. Other baseline severity indicators and comorbidity did not predict the outcome.
Results highlight the severity and chronicity of PD as a clinically significant eating disorder. Future work should examine maintenance factors to better adapt treatments for PD.
The detection of fireballs streaks in astronomical imagery can be carried out by a variety of methods. The Desert Fireball Network uses a network of cameras to track and triangulate incoming fireballs to recover meteorites with orbits and to build a fireball orbital dataset. Fireball detection is done on-board camera, but due to the design constraints imposed by remote deployment, the cameras are limited in processing power and time. We describe the processing software used for fireball detection under these constrained circumstances. Two different approaches were compared: (1) A single-layer neural network with 10 hidden units that were trained using manually selected fireballs and (2) a more traditional computational approach based on cascading steps of increasing complexity, whereby computationally simple filters are used to discard uninteresting portions of the images, allowing for more computationally expensive analysis of the remainder. Both approaches allowed a full night’s worth of data (over a thousand 36-megapixel images) to be processed each day using a low-power single-board computer. We distinguish between large (likely meteorite-dropping) fireballs and smaller fainter ones (typical ‘shooting stars’). Traditional processing and neural network algorithms both performed well on large fireballs within an approximately 30 000-image dataset, with a true positive detection rate of 96% and 100%, respectively, but the neural network was significantly more successful at smaller fireballs, with rates of 67% and 82%, respectively. However, this improved success came at a cost of significantly more false positives for the neural network results, and additionally the neural network does not produce precise fireball coordinates within an image (as it classifies). Simple consideration of the network geometry indicates that overall detection rate for triangulated large fireballs is calculated to be better than 99.7% and 99.9%, by ensuring that there are multiple double-station opportunities to detect any one fireball. As such, both algorithms are considered sufficient for meteor-dropping fireball event detection, with some consideration of the acceptable number of false positives compared to sensitivity.
The early fetal environment during pregnancy is extremely important and research indicates that weight at birth can have crucial impacts for the individual's health later in life. With rates of childhood obesity estimated to be as high as 21% in some European countries, it is vital that early risk factors are identified so that interventions can be developed. We aimed to investigate if children born macrosomic (birth weight > 4kg) remained larger than normal birth weight babies up to 5 years of age.
Materials and Methods:
This is a longitudinal follow-up of 387 five-year-old children (53% born with macrosomia, 47% normal birth weight) born into the ROLO randomised control trial in the National Maternity Hospital, Dublin (ISRCTN54392969). Birth weight was previously recorded then at 6 months, 2 years, and 5 years of age child height, weight, anthropometric and skinfold measurements were collected. Body Mass Index (kg/m2) and centiles were calculated. Student t-tests and Mann-Whitney U tests were used to compare the two groups with multiple linear regression modelling to control for confounders.
Children with a birth weight > 4 kg had consistently higher weights, lengths, and BMI centiles, along with increased head and chest circumferences, compared to normal birth weight children from 6 months up to 5 years of age (p < 0.05). After controlling for child sex, intervention group, smoking during pregnancy, maternal education status, and maternal BMI, children with macrosomia were 0.61 kg heavier than non-macrosomic infants at 5 years of age (95% CI: 0.04–1.18, p < 0.05).
Children born with a high birth weight remain heavier and larger into childhood. These individuals are at a higher risk of obesity which highlights the need for monitoring and potential interventions, both during pregnancy and in infancy, to curb the current childhood obesity crisis.
During pregnancy, mothers-to-be should adapt their diet to meet increases in nutrient requirements. Pregnant women appear to be keener to adopt healthier diets, but are not always successful. The objective of the present study was to determine whether a guided, stepwise and tailored dietary counselling programme, designed using an optimisation algorithm, could improve the nutrient adequacy of the diet of pregnant women, beyond generic guidelines. Pregnant women (n 80) who attended Notre-Dame-de-Bon-Secours Maternity Clinic were randomly allocated to the control or intervention arm. Dietary data were obtained twice from an online 3-d dietary record. The nutrient adequacy of the diet was calculated using the PANDiet score, a 100-point diet quality index adapted to the specific nutrient requirements for pregnancy. Women were supplied with generic dietary guidelines in a reference booklet. In the intervention arm, they also received nine sets of tailored dietary advice identified by an optimisation algorithm as best improving their PANDiet score. Pregnant women (n 78) completed the 12-week dietary follow-up. Initial PANDiet scores were similar in the control and intervention arms (60·4 (sd 7·3) v. 60·3 (sd 7·3), P = 0·92). The PANDiet score increased in the intervention arm (+3·6 (sd 9·3), P = 0·02) but not in the control arm (−0·3 (sd 7·3), P = 0·77), and these changes differed between arms (P = 0·04). In the intervention arm, there were improvements in the probabilities of adequacy for α-linolenic acid, thiamin, folate and cholesterol intakes (P < 0·05). Tailored dietary counselling using a computer-based algorithm is more effective than generic dietary counselling alone in improving the nutrient adequacy of the diet of French women in mid-pregnancy.
Alterations of the gut microbiome have been associated with obesity and metabolic disorders. The gut microbiota can be influenced by the intake of dietary fibres with prebiotic properties, such as inulin-type fructans. The present study tested the hypothesis that obese individuals subjected for 12 weeks to an inulin-enriched v. inulin-poor diet have differential faecal fermentation patterns. The fermentation of cellulose and inulin hydrolysates of six different inulin-rich and inulin-poor vegetables of both groups was analysed in vitro on faecal inocula. The results showed that the microbiota from obese patients who received a fructan-rich diet for 3 weeks produces more gas and total SCFA compared with the microbiota taken from the same individuals before the treatment. Obese individuals fed with a low-fructan diet produce less gas and less SCFA compared with the treated group. The present study highlighted profound changes in microbiota fermentation capacity obtained by prebiotic intervention in obese individuals, which favours the production of specific bioactive metabolites.
The new species Psoroma nivale is described from an area of late snow-lie in the Keglo Bay area on the eastern side of Ungava Bay, northern Québec, Canada. It is superficially similar to P. hypnorum but has a dark, brownish black thallus colour without reddish hues, much-branched, proliferating squamules, thick paraphyses, distinct but inconspicuous IKI+ ascus tube structures, and characteristic elongate, bacilliform, often asymmetrical ascospores. The new species is compared with possible related taxa and its systematic position discussed. A key to the species of pannarioid lichens reported from arctic areas of North America is also provided.
Among children exposed to elevated maternal depression symptoms (MDS), recent studies have demonstrated reduced internalizing and externalizing problems for those who have attended formal childcare (i.e., center-based, family-based childcare). However, these studies did not consider whether childcare attendance is associated with benefits for the child only or also with reduced MDS. Using a four-wave longitudinal cross-lagged model, we evaluated whether formal childcare attendance was associated with MDS or child behavior problems and whether it moderated longitudinal associations between MDS and child behavior problems and between child behavior problems and MDS. The sample was drawn from a population-based cohort study and consisted of 908 biologically related mother–child dyads, followed from 5 months to 5 years. Attending formal childcare was not associated with MDS or child behavior problems but moderated the association between MDS at 3.5 years and child internalizing and externalizing problems at 5 years as well as between girls’ externalizing problems at 3.5 years and MDS at 5 years. No other moderation of formal childcare was found. Findings suggest that attending formal childcare reduces the risks of behavior problems in the context of MDS but also the risk of MDS in the context of girls’ externalizing problems.