Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study.

BACKGROUND: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. METHODS: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. RESULTS: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. CONCLUSIONS: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium.

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups-a 'lower brain volume' subgroup (SG1) and an 'higher striatal volume' subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership ('None'), and mixed SG1 + SG2 subgroups ('Mixed'). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of 'lower brain volume' in SG1 and 'higher striatal volume' (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature.

Life events and psychosis: case-control study from India, Nigeria, and Trinidad and Tobago.

BACKGROUND: There is evidence of an association between life events and psychosis in Europe, North America and Australasia, but few studies have examined this association in the rest of the world. AIMS: To test the association between exposure to life events and psychosis in catchment areas in India, Nigeria, and Trinidad and Tobago. METHOD: We conducted a population-based, matched case-control study of 194 participants in India, Nigeria, and Trinidad and Tobago. Cases were recruited through comprehensive population-based, case-finding strategies. The Harvard Trauma Questionnaire was used to measure life events. The Screening Schedule for Psychosis was used to screen for psychotic symptoms. The association between psychosis and having experienced life events (experienced or witnessed) was estimated by conditional logistic regression. RESULTS: There was no overall evidence of an association between psychosis and having experienced or witnessed life events (adjusted odds ratio 1.19, 95% CI 0.62-2.28). We found evidence of effect modification by site (P = 0.002), with stronger evidence of an association in India (adjusted odds ratio 1.56, 95% CI 1.03-2.34), inconclusive evidence in Nigeria (adjusted odds ratio 1.17, 95% CI 0.95-1.45) and evidence of an inverse association in Trinidad and Tobago (adjusted odds ratio 0.66, 95% CI 0.44-0.97). CONCLUSIONS: This study found no overall evidence of an association between witnessing or experiencing life events and psychotic disorder across three culturally and economically diverse countries. There was preliminary evidence that the association varies between settings.

Ancient DNA of the pygmy marmoset type specimen Cebuella pygmaea (Spix, 1823) resolves a taxonomic conundrum.

The pygmy marmoset, the smallest of the anthropoid primates, has a broad distribution in Western Amazonia. Recent studies using molecular and morphological data have identified two distinct species separated by the Napo and Solimões-Amazonas rivers. However, reconciling this new biological evidence with current taxonomy, i.e., two subspecies, Cebuella pygmaea pygmaea (Spix, 1823) and Cebuella pygmaea niveiventris (Lönnberg, 1940), was problematic given the uncertainty as to whether Spix's pygmy marmoset ( Cebuella pygmaea pygmaea) was collected north or south of the Napo and Solimões-Amazonas rivers, making it unclear to which of the two newly revealed species the name pygmaea would apply. Here, we present the first molecular data from Spix's type specimen of Cebuella pygmaea, as well as novel mitochondrial genomes from modern pygmy marmosets sampled near the type locality (Tabatinga) on both sides of the river. With these data, we can confirm the correct names of the two species identified, i.e., C. pygmaea for animals north of the Napo and Solimões-Amazonas rivers and C. niveiventris for animals south of these two rivers. Phylogenetic analyses of the novel genetic data placed into the context of cytochrome b gene sequences from across the range of pygmy marmosets further led us to re-evaluate the geographical distribution for the two Cebuella species. We dated the split of these two species to 2.54 million years ago. We discuss additional, more recent, subdivisions within each lineage, as well as potential contact zones between the two species in the headwaters of these rivers.

OPECHONA CHLOROSCOMBRI AND OPECHONA CORKUMI N. SP. (DIGENEA: LEPOCREADIIDAE) FROM THE NORTHERN GULF OF MEXICO WITH PHYLOGENETIC ANALYSIS BASED ON 28S RDNA.

This study investigated the identity of 2 lepocreadiid digenean species belonging in the genus Opechona Looss, 1907 that infect littoral fishes of the northern Gulf of Mexico. Opechona chloroscombriNahhas and Cable, 1964, a species previously known only from the Caribbean Sea and the Atlantic Ocean off Brazil, is reported herein from the Atlantic bumper, Chloroscombrus chrysurus (L.), in the northern Gulf of Mexico. A second species infects the gulf butterfish, Peprilus burti Fowler, and the American harvestfish, Peprilus paru (L.), and it is described as a new species that occurs in coastal waters of the north-central and northeastern Gulf of Mexico. Metacercariae infecting the mesoglea of pelagic jellyfishes (Bougainvillia carolinensis [McCady], Chrysaora quinquecirrha [Desor], and Stomolophus meleagris Agassiz) and pelagic comb jellies (Mnemiopsis leidyi Agassiz and Beroe ovata Bruguière) were collected that resemble the new species but require further study to identify. Newly generated sequence fragments (28S rDNA) from both species of Opechona plus 2 other lepocreadiids collected during the study were aligned with publicly available sequences from 18 other lepocreadiids, 6 species of Aephnidiogenidae Yamaguti, 1934, and 2 species of Gorgocephalidae Manter, 1966. The alignment was subjected to Bayesian inference analysis rooted using a gorgocephalid. The resulting tree estimated the positions of both Opechona spp. as being unresolved within a group of taxa that included all available species of Opechona plus available species from the morphologically similar genera ProdistomumLinton, 1910, Preptetos Pritchard, 1960, and Clavogalea Bray, 1985. Although relatively similar in morphology, the 2 studied species of Opechona were surprisingly not closely related. Opechona cablei (Stunkard, 1980) Bray and Gibson, 1990 is herein considered to be a junior synonym of Opechona pyriformis (Linton, 1900) Bray and Gibson, 1990.

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

Evaluation of relationships between presence of adhesio interthalamica and cannabis use in first-episode psychosis: a magnetic resonance imaging investigation

ABSTRACT Recent studies suggested that cannabis use influences on the emergence of psychosis by disrupting neurodevelopmental processes that occur during adolescence and early adulthood and which are reflected on brain anatomical changes detectable with MRI. However, no MRI studies have investigated whether intrauterine neurodevelopmental abnormalities also interact with later cannabis use to influence on psychosis risk. We investigated differences between first-episode psychosis (FEP) patients with history of cannabis use (FEPC+, n=28), FEP subjects without cannabis use (FEPC-, n=78) and healthy controls (n=80) in regard to the frequency of absent or short Adhesio Interthalamica (AI), a well-established marker of intrauterine neurodevelopment. The FEPC+ subgroup had a significantly lower prevalence of absent AI than FEPC- subjects, as well as a lack of a significantly shorter AI length compared to controls (as found in FEPC- subjects). These preliminary results show that psychosis subjects with cannabis use present a low rather than high frequency of absent AI, suggesting that fixed intrauterine neurodevelopmental abnormalities may not be associated with cannabis use later in life to influence on the emergence of psychosis. This is consistent with a view that multiple different etiological processes may lead to similar clinical presentations in patients with FEP.

Fur Color and Nutritional Status Predict Hair Cortisol Concentrations of Dogs in Nicaragua.

This study examined the relationships between hair cortisol concentrations (HCC) and sex, age, nutritional status (as determined by body condition scores, or BCS), and body mass (geometric mean calculated from morphometric measurements), as well as the potential influence of hair pigmentation (light, dark, or agouti/mixed) on HCC in dogs of the Bosawas Biosphere Reserve, Nicaragua. The dogs examined in this study live in a marginal environment where disease, malnutrition, and mortality rates are high. For fur color, HCC was significantly higher in light fur than in than dark and mixed fur (p < 0.001). In addition, BCS scores were found to have a negative effect on HCC (p < 0.001). Measures of sex and body size exhibited inconclusive effects on HCC, and when compared to adult dogs, juvenile dogs did not exhibit significantly different HCC. Repeated measures of dogs over time reveal a moderate intra-class correlation, suggesting that there are unmeasured sources of individual-level heterogeneity. These findings imply a need to account for fur color in studies of HCC in dogs, and the study suggests an overlooked relationship between cortisol and body condition scores in undernourished dogs in diverse settings.

Evidence for the Effect of Vaccination on Host-Pathogen Interactions in a Murine Model of Pulmonary Tuberculosis by Mycobacterium tuberculosis.

The global control of Tuberculosis remains elusive, and Bacillus Calmette-Guérin (BCG) -the most widely used vaccine in history-has proven insufficient for reversing this epidemic. Several authors have suggested that the mass presence of vaccinated hosts might have affected the Mycobacterium tuberculosis (MTB) population structure, and this could in turn be reflected in a prevalence of strains with higher ability to circumvent BCG-induced immunity, such as the recent Beijing genotype. The effect of vaccination on vaccine-escape variants has been well-documented in several bacterial pathogens; however the effect of the interaction between MTB strains and vaccinated hosts has never been previously described. In this study we show for the first time the interaction between MTB Beijing-genotype strains and BCG-vaccinated hosts. Using a well-controlled murine model of progressive pulmonary tuberculosis, we vaccinated BALB/c mice with two different sub-strains of BCG (BCG-Phipps and BCG-Vietnam). Following vaccination, the mice were infected with either one of three selected MTB strains. Strains were selected based on lineage, and included two Beijing-family clinical isolates (strains 46 and 48) and a well-characterized laboratory strain (H37Rv). Two months after infection, mice were euthanized and the bacteria extracted from their lungs. We characterized the genomic composite of the bacteria before and after exposure to vaccinated hosts, and also characterized the local response to the bacteria by sequencing the lung transcriptome in animals during the infection. Results from this study show that the interaction within the lungs of the vaccinated hosts results in the selection of higher-virulence bacteria, specifically for the Beijing genotype strains 46 and 48. After exposure to the BCG-induced immune response, strains 46 and 48 acquire genomic mutations associated with several virulence factors. As a result, the bacteria collected from these vaccinated hosts have an increased ability for immune evasion, as shown in both the host transcriptome and the histopathology studies, and replicates far more efficiently compared to bacteria collected from unvaccinated hosts or to the original-stock strain. Further research is warranted to ascertain the pathways associated with the genomic alterations. However, our results highlight novel host-pathogen interactions induced by exposure of MTB to BCG vaccinated hosts.

INTREPID II: protocol for a multistudy programme of research on untreated psychosis in India, Nigeria and Trinidad.

INTRODUCTION: There are few robust and directly comparable studies of the epidemiology of psychotic disorders in the Global South. INTREPID II is designed to investigate variations in untreated psychotic disorders in the Global South in (1) incidence and presentation (2) 2-year course and outcome, (3) help-seeking and impact, and (4) physical health. METHODS: INTREPID II is a programme of research incorporating incidence, case-control and cohort studies of psychoses in contiguous urban and rural areas in India, Nigeria and Trinidad. In each country, the target samples are 240 untreated cases with a psychotic disorder, 240 age-matched, sex-matched and neighbourhood-matched controls, and 240 relatives or caregivers. Participants will be followed, in the first instance, for 2 years. In each setting, we have developed and are employing comprehensive case-finding methods to ensure cohorts are representative of the target populations. Using methods developed during pilot work, extensive data are being collected at baseline and 2-year follow-up across several domains: clinical, social, help-seeking and impact, and biological. ETHICS AND DISSEMINATION: Informed consent is sought, and participants are free to withdraw from the study at any time. Participants are referred to mental health services if not already in contact with these and emergency treatment arranged where necessary. All data collected are confidential, except when a participant presents a serious risk to either themselves or others. This programme has been approved by ethical review boards at all participating centres. Findings will be disseminated through international conferences, publications in international journals, and through local events for key stakeholders.

Association of sex-related differences in body composition to change of direction speed in police officers while carrying load / Asociación de diferencias relacionadas con el sexo en la composición corporal para cambiar la velocidad de dirección de oficiales de policía durante el transporte de carga

Regardless of sex or body size, police tasks may require officers to change direction speed (CODS) under occupational loads. The purpose of this study was to investigate body composition and CODS in female and male police cadets in both unloaded and occupationally loaded conditions. Body composition and CODS of 51 female (FPC) and 70 male police cadets (MPC) were assessed. Six body composition indices were used: Body mass index (BMI), percent body fat (PBF), percent of skeletal muscle mass (PSMM), protein fat index (PFI), index of hypokinesia (IH), and skeletal muscle mass index (SMMI). The CODS was assessed by Illinois Agility Test (IAT) and IAT while carrying a 10-kg load (LIAT). An independent sample t-test was used to identify the differences between the sexes. The regression determined associations between body composition and LIAT. The alpha level was set at p < 0.05 a priori. MPC had significantly higher (p < 0.001) BMI, PSMM, PFI and SMMI and lower PBF and IH than FPC. MPC were also faster in IAT and LIAT, carrying lower relative loads that imparted less of an impact on CODS performance. Body composition was strongly associated with the time to complete LIAT (R2 = 0.671, p < 0.001). Difference in relative load and body composition influenced CODS performance in both unloaded and loaded conditions. Thus, optimizing body composition through increasing skeletal muscle mass and reducing fat mass could positively influence unloaded and loaded CODS performance and improve elements of police task performance.

El trabajo policial puede requerir que los oficiales cambien la velocidad de dirección (CVD) bajo cargas ocupacionales, indistintamente del sexo o tamaño corporal. El propósito de este estudio fue investigar la composición corporal y los CVD en cadetes de policía de ambos sexos, tanto en condiciones de descarga como de trabajo. Se evaluaron la composición corporal y los CVD de 51 mujeres (CPF) y 70 cadetes de policía masculinos (CPM). Se utilizaron seis índices de composición corporal: índice de masa corporal (IMC), porcentaje de grasa corporal (PGC), porcentaje de masa muscular esquelética (PMME), índice de grasa proteica (IGP), índice de hipocinesia (IH) e índice de masa muscular esquelética (IMME). El CVD fue evaluado por Illinois Agility Test (IAT) y IAT mientras transportaba una carga de 10 kg (LIAT). Se usó una prueba t de muestra independiente para identificar las diferencias entre los sexos. La regresión determinó asociaciones entre la composición corporal y LIAT. El nivel alfa se estableció en p <0,05 a priori. CPM registraron un IMC, PMME, PGC y IMME significativamente más altos (p <0,001) y PGC e IH más bajos que las mujeres (CPF). Los CPM también fueron más rápidos en IAT y LIAT, llevando cargas más bajas, las que tuvieron un impacto menor en el rendimiento de CVD. La composición corporal estaba asociada con el tiempo para completar LIAT (R2 = 0,671, p <0,001). La diferencia en la carga relativa y la composición corporal influyeron en el rendimiento de CVD tanto en condiciones descargadas como cargadas. Por lo tanto, la optimización de la composición corporal a través del aumento de la masa del músculo esquelético, y la reducción de la masa grasa podrían influir de manera positiva en el rendimiento de CVD descargados y cargados, mejorando el rendimiento del trabajo policial.

The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI): Incidence and First-Episode Case-Control Programme.

PURPOSE: The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. METHODS: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. CONCLUSIONS: This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted.

Growth hormone-mediated reprogramming of macrophage transcriptome and effector functions.

Macrophages are an important component of the innate immune response. Priming and activation of macrophages is stimulated by cytokines (i.e IFNγ). However, growth hormone (GH) can also stimulate macrophage activation. Based on these observations, the goal of this work was to 1) to compare the transcriptome profile of macrophages activated in vitro with GH and IFNγ, and 2) to assess the impact of GH on key macrophage functional properties like reactive oxygen species (ROS) production and phagosomal proteolysis. To assess the global transcriptional and functional impact of GH on macrophage programming, bone marrow derived macrophages were treated with GH or IFNγ. Our data strongly support a potential link between GH, which wanes with age, and impaired macrophage function. The notable overlap of GH with IFNγ-induced pathways involved in innate immune sensing of pathogens and antimicrobial responses argue for an important role for GH in macrophage priming and maturation. By using functional assays that report on biochemical activities within the lumen of phagosomes, we have also shown that GH alters physiologically relevant processes such as ROS production and proteolysis. These changes could have far reaching impacts on antimicrobial capacity, signaling, and antigen presentation.

Biogeographic context dependence of trophic cascade strength in bromeliad food webs.

Ecosystem functions and the biomass of lower trophic levels are frequently controlled by predators. The strength of top-down control in these trophic cascades can be affected by the identity and diversity of predators, prey, and resources, as well as environmental conditions such as temperature, moisture, and nutrient loading, which can all impact interaction strength between trophic levels. Few studies have been able to replicate a complete community over a large geographic area to compare the full trophic cascade in a manipulative experiment. Here, we identify geographic dependency in trophic cascade strength, and the driving factors and specific mechanisms behind it, by combining geographically replicated experiments with a novel approach of community analogues of common garden and transplant experiments. We studied a predator-detritivore-detritus food web in bromeliads in Puerto Rico, Costa Rica, and Brazil. We found that interaction strengths between resources, consumers, and predators were strongly site-specific, but the exact mechanism differed between trophic levels. Large bodied predators created strong interaction strengths between predator and consumer trophic levels, reducing consumer abundance regardless of the geographic location, whereas small-bodied predators created weak interactions with no impact on consumer abundances in any site. In contrast, the interaction strength between consumers and resources varied among sites, depending on the dominant species of leaf detritus. More labile leaf species in Costa Rica created a strong consumer-resource interaction and therefore strong trophic cascade, whereas tougher leaf species in Brazil created a weak consumer-resource interaction, and an overall weaker trophic cascade. Our study highlights the importance of replicating experiments over geographic scales to understand general patterns of ecological processes.

The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study.

BACKGROUND: Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. METHODS: We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ9-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. FINDINGS: Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2-4·1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4·8, 2·5-6·3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12·2% (95% CI 3·0-16·1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30·3% (15·2-40·0) in London and 50·3% (27·4-66·0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0·7; p=0·0286) and daily use (r = 0·8; p=0·0109). INTERPRETATION: Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health. FUNDING SOURCE: Medical Research Council, the European Community's Seventh Framework Program grant, São Paulo Research Foundation, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR BRC at University College London, Wellcome Trust.

Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription.

BACKGROUND: Osteoporosis and related fragility fractures are a global public health problem in which pharmaceutical agents targeting bone mineral density (BMD) are the first line of treatment. However, pharmaceuticals have no effect on improving other key fracture risk factors, including low muscle strength, power and functional capacity, all of which are associated with an increased risk for falls and fracture, independent of BMD. Targeted exercise training is the only strategy that can simultaneously improve multiple skeletal and fall-related risk factors, but it must be appropriately prescribed and tailored to the desired outcome(s) and the specified target group. OBJECTIVES: In this review, we provide an overview of the general principles of training and specific loading characteristics underlying current exercise guidelines for the prevention of osteoporosis, and an update on the latest scientific evidence with regard to the type and dose of exercise shown to positively influence bone mass, structure and strength and reduce fracture risk in postmenopausal women.

Approaches to integrating genetic data into ecological networks.

As molecular tools for assessing trophic interactions become common, research is increasingly focused on the construction of interaction networks. Here, we demonstrate three key methods for incorporating DNA data into network ecology and discuss analytical considerations using a model consisting of plants, insects, bats and their parasites from the Costa Rica dry forest. The simplest method involves the use of Sanger sequencing to acquire long sequences to validate or refine field identifications, for example of bats and their parasites, where one specimen yields one sequence and one identification. This method can be fully quantified and resolved and these data resemble traditional ecological networks. For more complex taxonomic identifications, we target multiple DNA loci, for example from a seed or fruit pulp sample in faeces. These networks are also well resolved but gene targets vary in resolution and quantification is difficult. Finally, for mixed templates such as faecal contents of insectivorous bats, we use DNA metabarcoding targeting two sequence lengths (157 and 407 bp) of one gene region and a MOTU, BLAST and BIN association approach to resolve nodes. This network type is complex to generate and analyse, and we discuss the implications of this type of resolution on network analysis. Using these data, we construct the first molecular-based network of networks containing 3,304 interactions between 762 nodes of eight trophic functions and involving parasitic, mutualistic and predatory interactions. We provide a comparison of the relative strengths and weaknesses of these data types in network ecology.

Assessing cross-national invariance of the Community Assessment of Psychic Experiences (CAPE).

BACKGROUND: The Community Assessment of Psychic Experiences (CAPE) is a 42-item self-report questionnaire that has been developed and validated to measure the dimensions of psychosis in the general population. The CAPE has a three-factor structure with dimensions of positive, negative and depression. Assessing the cross-national equivalence of a questionnaire is an essential prerequisite before pooling data from different countries. In this study, our aim was to investigate the measurement invariance of the CAPE across different countries. METHODS: Data were drawn from the European Union Gene-Environment Interaction (EU-GEI) study. Participants (incident cases of psychotic disorder, controls and siblings of cases) were recruited in Brazil, France, Italy, the Netherlands, Spain and UK. To analyse the measurement invariance across these samples, we tested configural invariance (i.e. identical structures of the factors), metric invariance (i.e. equivalence of the factor loadings) and scalar invariance (i.e. equivalence of the thresholds) of the three CAPE dimensions using multigroup categorical confirmatory factor analysis methods. RESULTS: The configural invariance model fits well, providing evidence for identical factorial structure across countries. In comparison with the configural model invariance, the fit indices were very similar in the metric and scalar invariance models, indicating that factor loadings and thresholds did not differ across the six countries. CONCLUSION: We found that, across six countries, the CAPE showed equivalent factorial structure, factor loadings and thresholds. Thus, differences observed in scores between individuals from different countries should be considered as reflecting different levels of psychosis.

Idiopathic Scoliosis Families Highlight Actin-Based and Microtubule-Based Cellular Projections and Extracellular Matrix in Disease Etiology.

Idiopathic scoliosis (IS) is a structural lateral spinal curvature of ≥10° that affects up to 3% of otherwise healthy children and can lead to life-long problems in severe cases. It is well-established that IS is a genetic disorder. Previous studies have identified genes that may contribute to the IS phenotype, but the overall genetic etiology of IS is not well understood. We used exome sequencing to study five multigenerational families with IS. Bioinformatic analyses identified unique and low frequency variants (minor allele frequency ≤5%) that were present in all sequenced members of the family. Across the five families, we identified a total of 270 variants with predicted functional consequences in 246 genes, and found that eight genes were shared by two families. We performed GO term enrichment analyses, with the hypothesis that certain functional annotations or pathways would be enriched in the 246 genes identified in our IS families. Using three complementary programs to complete these analyses, we identified enriched categories that include stereocilia and other actin-based cellular projections, cilia and other microtubule-based cellular projections, and the extracellular matrix (ECM). Our results suggest that there are multiple paths to IS and provide a foundation for future studies of IS pathogenesis.

Two New Species of Saccocoelioides (Digenea: Haploporidae) with Phylogenetic Analysis of the Family, Including Species of Saccocoelioides from North, Middle, and South America.

Two cryptic species of haploporid digeneans belonging in Saccocoelioides are described from Costa Rica: one from a poeciliid fish, Poecilia gillii, and the other from a characid fish, Astyanax aeneus. Traditional morphological features are examined and found to be largely inefficient for differentiating among the new species and 20 New World congeners. Comparison of ribosomal DNA sequences among the 2 new species, 2 North American, 4 Middle American, and 3 South American species of Saccocoelioides, including the type-species Saccocoelioides nanii from Argentina and Saccocoelioides sogandaresi from Texas, is effective in differentiating among these species. A Bayesian inference analysis is conducted using a concatenated alignment of the same 2 ribosomal gene regions from 35 species belonging in the Haploporoidea and rooted by the atractotrematid Isorchis anomalus. The analysis provides stronger support for a close relationship between species in Saccocoelioides and Intromugil; thus, Intromugil is transferred from the Waretrematinae to the Chalcinotrematinae. Additionally, interrelationships among 11 species of Saccocoelioides are resolved and reveal a distinct genetic rift suggesting the presence of 2 distinct lineages within the genus, 1 containing the type-species and the other containing a group of species that more closely resemble other genera in the subfamily. Taxonomy of Saccocoelioides is discussed, and observations made during the present study justify taking several taxonomic actions: new combinations are proposed for Saccocoelioides tilapiae n. comb., formerly in the now-defunct Culuwiya, and Saccocoelioides ruedasueltensis n. comb., formerly in Chalcinotrema; Saccocoelioides guaporense nomen novem is proposed for Lecithobotrioides elongatus; Saccocoelioides papernai is considered a junior subjective synonym of Saccocoelioides overstreeti; Saccocoelioides godoyi is considered a junior subjective synonym of Saccocoelioides szidati; Saccocoelioides magnorchis and Saccocoelioides saccodontis are considered species inquirendae; and Saccocoelioides adelae is considered a nomen nudum. Four new hosts are reported for Saccocoelioides cichlidorum: Amphilophus lyonsi, Amatitlania nigrofasciatus, Amatitlania septemfasciatus, and Hypsophrys nicaraguensis. Molecular data call into question some existing species identifications in Saccocoelioides and reveal that molecular tools combined with traditional taxonomy are required for accurately identifying species in the genus. Twenty-two species of Saccocoelioides are formally accepted, but it is noted that as new molecular data become available, some of these species may be transferred to other genera in the subfamily.