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A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.
We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders.
There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88).
Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.
Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.
We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.
Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).
Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.
We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models.
In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06–2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02–3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03–1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672–2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose–response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06–96.47, p = 0.007).
The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.
Health technology assessment (HTA) can impact health inequities by informing healthcare priority-setting decisions. This paper presents a novel checklist to guide HTA practitioners looking to include equity considerations in their work: the equity checklist for HTA (ECHTA). The list is pragmatically organized according to the generic HTA phases and can be consulted at each step.
A first set of items was based on the framework for equity in HTA developed by Culyer and Bombard. After rewording and reorganizing according to five HTA phases, they were complemented by elements emerging from a literature search. Consultations with method experts, decision makers, and stakeholders further refined the items. Further feedback was sought during a presentation of the tool at an international HTA conference. Lastly, the checklist was piloted through all five stages of an HTA.
ECHTA proposes elements to be considered at each one of the five HTA phases: Scoping, Evaluation, Recommendations and Conclusions, Knowledge Translation and Implementation, and Reassessment. More than a simple checklist, the tool provides details and examples that guide the evaluators through an analysis in each phase. A pilot test is also presented, which demonstrates the ECHTA's usability and added value.
ECHTA provides guidance for HTA evaluators wishing to ensure that their conclusions do not contribute to inequalities in health. Several points to build upon the current checklist will be addressed by a working group of experts, and further feedback is welcome from evaluators who have used the tool.
In this paper, we focus on Berkeley's reasons for accepting the ‘resemblance thesis’ which entails that for one thing to represent another those two things must resemble one another. The resemblance thesis is a crucial premise in Berkeley's argument from the ‘likeness principle’ in §8 of the Principles. Yet, like the ‘likeness principle’, the resemblance thesis remains unargued for and is never explicitly defended. This has led several commentators to provide explanations as to why Berkeley accepts the resemblance thesis and why he also takes his opponents to do so too. We provide a contextual answer to this question, focusing on epistemological discussions concerning resemblance and representation in Early Modern Irish Philosophy. We argue that the resemblance thesis is implicit in early responses to William Molyneux's famous example of the ‘man born blind made to see’ and trace the ‘Molyneux man’ thought experiment as it is employed by Irish thinkers such as William King and Berkeley himself. Ultimately, we conclude that Berkeley's acceptance of the resemblance thesis can be explained by the Irish intellectual climate in which he was writing.
The objective of the study was to characterize small-scale dairy production systems to identify the technological preferences according to the farmer and farm characteristics and to analyze the importance and role of the information communication technologies (ICTs) in the dissemination of information related to management and livestock activities. To collect the data, a survey was applied to 170 small-scale dairy farmers from central Mexico. To characterize the farms, a factor analysis (FA) and cluster analysis (CA) were performed. To compare and identify differences between groups, a Kruskal–Wallis test was conducted. Four factors that explain 70.93% of the accumulated variance were identified; these factors explain the use of technology, production characteristics, social connections, and use of ICTs. The cluster analysis identified four groups. Group 1 was integrated by farmers with more experience and the largest farms. Group 2 had higher studies and use of ICTs. Group 3 was formed by young farmers but had a low use of technology. Group 4 contained older farmers with a low use of technology. The young farmers with higher studies have begun to incorporate ICTs into their daily activities on the farm, as observed in Group 2. Smartphones were the most used and were considered important by the farmers of the four groups, since they enable interaction with other farmers and the dissemination of topics of interest related with the farm. In conclusion, four group of farmers were differentiated; therefore, different extension approaches should be implemented to take into account the preferences and the technologies considered most important for each group. The ICTs are emerging technologies among small-scale dairy farmers to communicate information related to livestock management, mainly by young farmers with studies of secondary, as observed in Group 2.
For the last century, probably no region has contributed more rhythmic vitality to the global soundscape than Latin America and the Caribbean. More than any other musical element, it has been the uniquely compelling rhythms that have driven the early twentieth-century Parisian vogue of the tango, the transnational spread of salsa and Cuban dance music, and the current global appeal of Jamaican reggae and dance hall. Much of this rhythmic dynamism is a product of the development of syncretic idioms drawing from African as well as European roots. This ongoing and endlessly creative process has generated a great variety of rhythmic styles, and is supplemented by other vital music genres, such as northern Mexican conjunto music and Trinidadian tassa drumming, that owe little or nothing to African influence.
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 ‘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.
Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns.
We used case–control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20–F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data.
Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69–2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31–1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22–1.89) and linguistic distance (OR 1.22, 95% CI 0.95–1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively.
Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.
Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada.
We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers.
Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT).
Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.
Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence from randomized controlled trials have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan soluble fiber. However, oats contain an array of phenolic acids, including ferulic acid and also structurally related avenanthramides, which may also contribute to the cardiovascular health benefits of oat intake. We investigated whether 4 weeks, daily consumption of oat phenolics leads to improvement in markers of CVD risk men and women.In a 3 arm crossover single-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (-containing 48.9 mg of phenolic acids and 19.2 mg of avenanthramides); 2) oatbran concentrate + rice porridge/wheat cracker intervention (-containing 38.4 mg of phenolic acids and 0.5 mg of avenanthramides) or 3) rice porridge/wheat cracker intervention (containing 13.8 mg of phenolic acids). All treatments were matched in soluble fiber (4.8g) and energy (500kcal). The primary endpoint was FMD and other cardiovascular endpoints were blood pressure, LDI, LDL/HDL cholesterol, platelets and endothelial cell-derived extracellular vesicles (EVs). All measures were taken at baseline and after three, 4 week long intervention periods and two washout periods.Our data indicates an increase by 1.09 % ± 0.41 %(Mean ± SEM) in FMD response following high phenolic oat intake with a significant difference (P = 0.007) between baseline and post-intervention. Consumption of high phenolic oats also led to a significant improvement in 24-hour SBP, day time SBP and night time SBP (P < 0.01, P < 0.01 and P < 0.05) and day time and night time DBP (p < 0.05). There was also a significant decrease with total and LDL cholesterol after the consumption of moderate and high phenolic oat interventions (P < 0.05) and a small improvement in LDI (both Ach and SNP) but not significant. The number of resting endothelial EVs were also found to be increasing after the consumption of high phenolic oats.The findings of this study may provide evidence about the role of oat phenolic acids and avenanthramides in cardiovascular health and contribute to more effective public health advice about the consumption of oats and healthy cardiovascular aging.
We present some results from the DRAGON simulations, a set of four direct N-body simulations of globular clusters (GCs) with a million stars and five percent initial (primordial) binaries. These simulations were undertaken with the NBODY6++GPU code, which allowed us to follow dynamical and stellar evolution of individual stars and binaries, formation and evolution of white dwarfs, neutron stars, and black holes, and the effect of a galactic tidal field. The simulations are the largest existing models of a realistic globular cluster over its full lifetime of 12 billion years. In particular we will show here an investigation of the population of binaries including compact objects (such as white dwarfs - cataclysmic variables and merging black hole binaries in the model as counterparts of LIGO/Virgo sources); their distribution in the cluster and evolution with time.
In the bicentenary year of its excavation, remote sensing has revealed, for the first time, the full extent of this iconic type-site Iron Age cemetery and its landscape context in East Yorkshire. A total of 23ha was surveyed, revealing new insights concerning the burial ground and damage through modern farming.
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
Combining additive manufacturing (AM) with carbon fiber reinforced polymer patched composites unlocks potentials in the design of individualized, lightweight biomedical structures. Arising design opportunities are geometrical individualization of structures using the design freedom of AM and the patient-individual design of the load-bearing components employing carbon fiber patch placement. To date, however, full exploitation of these opportunities is a complex recurring task, which requires a high amount of knowledge and engineering effort for design, optimization, and manufacturing. The goal of this study is to make this complexity manageable by introducing a suitable manufacturing strategy for individualized lightweight structures and by developing a digitized end-to-end design process chain, which provides a high degree of task automation. The approach to achieve full individualization uses a parametric model of the structure which is adapted to patients’ 3D scans. Moreover, patient data is used to define individual load cases and perform structural optimization. The potentials of the approach are demonstrated on an exoskeleton hip structure. A significant reduction of weight compared to a standard design suggests that the design and manufacturing chain is promising for the realization of individualized high-performance structures.
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.
A constraint on Solar System formation is the high 26Al/27Al abundance ratio, 17 times higher than the average Galactic ratio, while the 60Fe/56Fe value was lower than the Galactic value. This challenges the assumption that a nearby supernova was responsible for the injection of these short-lived radionuclides into the early Solar System. We suggest that the Solar System was formed by triggered star formation at the edge of a Wolf-Rayet (W-R) bubble. We discuss the details of various processes within the model using numerical simulations, and analytic and semi-analytic calculations, and conclude that it is a viable model that can explain the initial abundances of 26Al and 60Fe. We estimate that 1%-16% of all Sun-like stars could have formed in such a setting.
The Kepler object KOI 2700b was discovered recently as the second exoplanet with a comet-like dusty tail. We aimed at verifying the disintegrating-planet scenario of KOI 2700b by modeling its light curve and to put constraints on various tail and planet properties, as was done in the case of KIC 12557548b. Here, we describe some selected results of our analysis.
A long-standing problem of the general paradigm of low-mass star formation is the “luminosity problem”: protostars are less luminous than theoretically predicted. One possible solution is that the accretion process is episodic. FU Orionis-type stars (FUors) are thought to be the visible examples for objects in the high accretion state and it is still debated what physical mechanism triggers the phenomenon. For many of these objects their disk properties are still largely unknown so we conducted a deep, high spatial resolution (down to 20 au) ALMA Band 6 (1.3 mm) dust continuum survey of a sub-sample of known FUors. Here we present preliminary results of our survey, including the mass, size and spectral slope of each disk.