Temperature and Pressure Dependence of the Fe-specific Phonon Density of States in Ba(Fe(1-x)Co(x))2As2

The {57}Fe-specific phonon density of states of Ba(Fe(1-x)Co(x))2As2 single crystals (x=0.0, 0.08) was measured at cryogenic temperatures and at high pressures with nuclear-resonant inelastic x-ray scattering. Measurements were conducted for two different orientations of the single crystals, yielding the orientation-projected {57}Fe-phonon density of states (DOS) for phonon polarizations in-plane and out-of-plane with respect to the basal plane of the crystal structure. In the tetragonal phase at 300 K, a clear stiffening was observed upon doping with Co. Increasing pressure to 4 GPa caused a marked increase of phonon frequencies, with the doped material still stiffer than the parent compound. Upon cooling, both the doped and undoped samples showed a stiffening, and the parent compound exhibited a discontinuity across the magnetic and structural phase transition. These findings are generally compatible with the changes in volume of the system upon doping, increasing pressure, or increasing temperature, but an extra softening of high-energy modes occurs with increasing temperature. First-principles computations of the phonon DOS were performed and showed an overall agreement with the experimental results, but underestimate the Grueneisen parameter. This discrepancy is explained in terms of a magnetic Grueneisen parameter, causing an extra phonon stiffening as magnetism is suppressed under pressure

Temperature and pressure dependence of the Fe-specific phonon density of states in Ba(Fe_(1−x)Co_x)_2As_2

The ^(57)Fe-specific phonon density of states (DOS) of Ba(Fe_(1−x)Co_x)_2As_2 single crystals (x=0.0,0.08) was measured at cryogenic temperatures and at high pressures with nuclear-resonant inelastic x-ray scattering. Measurements were conducted for two different orientations of the single crystals, yielding the orientation-projected ^(57)Fe-phonon density of states for phonon polarizations in-plane and out-of-plane with respect to the basal plane of the crystal structure. In the tetragonal phase at 300 K, a clear stiffening was observed upon doping with Co. Increasing pressure to 4 GPa caused a marked increase of phonon frequencies, with the doped material still stiffer than the parent compound. Upon cooling, both the doped and undoped samples showed a stiffening and the parent compound exhibited a discontinuity across the magnetic and structural phase transitions. These findings are generally compatible with the changes in volume of the system upon doping, increasing pressure, or increasing temperature, but an extra softening of high-energy modes occurs with increasing temperature. First-principles computations of the phonon DOS were performed and showed an overall agreement with the experimental results, but underestimate the Grüneisen parameter. This discrepancy is explained in terms of a magnetic Grüneisen parameter, causing an extra phonon stiffening as magnetism is suppressed under pressure

Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study

Background First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. Methods We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. Results In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. Conclusions The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Background. A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls. Methods. This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate. Results. ES-SCZ was associated with the GAF dimensions in patients (symptom: B = 1.53, p-value = 0.001; disability: B = 1.44, p-value = 0.001), siblings (symptom: B = 3.07, p-value < 0.001; disability: B = 2.52, p-value < 0.001), and healthy controls (symptom: B = 1.50, p-value < 0.001; disability: B = 1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group. Conclusions. Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management

The program for biodiversity research in Brazil: The role of regional networks for biodiversity knowledge, dissemination, and conservation

The Program for Biodiversity Research (PPBio) is an innovative program designed to integrate all biodiversity research stakeholders. Operating since 2004, it has installed long-term ecological research sites throughout Brazil and its logic has been applied in some other southern-hemisphere countries. The program supports all aspects of research necessary to understand biodiversity and the processes that affect it. There are presently 161 sampling sites (see some of them at Supplementary Appendix), most of which use a standardized methodology that allows comparisons across biomes and through time. To date, there are about 1200 publications associated with PPBio that cover topics ranging from natural history to genetics and species distributions. Most of the field data and metadata are available through PPBio web sites or DataONE. Metadata is available for researchers that intend to explore the different faces of Brazilian biodiversity spatio-temporal variation, as well as for managers intending to improve conservation strategies. The Program also fostered, directly and indirectly, local technical capacity building, and supported the training of hundreds of undergraduate and graduate students. The main challenge is maintaining the long-term funding necessary to understand biodiversity patterns and processes under pressure from global environmental changes

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p <0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p <0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p <0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p <0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p <0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy‐genetic liability measures suggest gene‐environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS‐SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene‐environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS‐SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early‐life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS‐SCZ at 75% with alternative cut‐points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures

Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction