The anisotropy of Ti–48Al–2Cr–2Nb (TiAl-4822) fabricated by electron beam melting (EBM) with 3 different microstructures, namely hot isostatic pressing (HIP), duplex (DP) and fully lamellar (FL) ...microstructure was investigated. Results show that the HIP material exhibits microstructure with alternating layers of coarse and fine grains. The α2 phase is more concentrated in the layer of fine grains and exhibits a strong texture with (0001) nearly perpendicular to the building direction, which further leads to the preferential orientation of lamellae. Non-uniform distribution of Al results in the selective formation of lamellar colonies in DP microstructure. The variation of critical resolved shear stress (CRSS) for slip activation is believed to cause the anomalous temperature dependence of yield strength at intermediate temperature. For all 3 microstructures, the ductility in Z direction is lower compared with XY direction, which is attributed to the difference in crack initiation mode and preferential orientation of lamellae.
•α2 phase exhibits strong texture in Ti–48Al–2Cr–2Nb fabricated by EBM.•Lamellar colonies form selectively in regions with lower Al content.•Preferential orientation of lamellae results in anisotropy of tensile properties.
The validity and clinical utility of the concept of “clinical high risk” (CHR) for psychosis have so far been investigated only in risk‐enriched samples in clinical settings. In this population‐based ...prospective study, we aimed – for the first time – to assess the incidence rate of clinical psychosis and estimate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM‐IV diagnoses of non‐psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person‐years. The mutually‐adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12‐36.49), psychosis high‐risk state (HR=7.86, 95% CI: 2.76‐22.42) and drug use disorders (HR=5.33, 95% CI: 1.61‐17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6‐94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4‐82.9), psychosis high‐risk state (PAF=36.9, 95% CI: 11.3‐55.1), and drug use disorders (PAF=18.7, 95% CI: –0.9 to 34.6) as the most important factors. Although the psychosis high‐risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high‐risk states in the population. These findings provide empirical evidence for the “prevention paradox” of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis‐focused approach for achieving population‐based improvements in prevention of psychotic disorders.
Observational studies have suggested bidirectional associations between psychiatric disorders and COVID-19 phenotypes, but results of such studies are inconsistent. Mendelian Randomization (MR) may ...overcome the limitations of observational studies, e.g., unmeasured confounding and uncertainties about cause and effect. We aimed to elucidate associations between neuropsychiatric disorders and COVID-19 susceptibility and severity. To that end, we applied a two-sample, bidirectional, univariable, and multivariable MR design to genetic data from genome-wide association studies (GWASs) of neuropsychiatric disorders and COVID-19 phenotypes (released in January 2021). In single-variable Generalized Summary MR analysis, the most significant and only Bonferroni-corrected significant result was found for genetic liability to BIP-SCZ (a combined GWAS of bipolar disorder and schizophrenia as cases vs. controls) increasing risk of COVID-19 (OR = 1.17, 95% CI, 1.06-1.28). However, we found a significant, positive genetic correlation between BIP-SCZ and COVID-19 of 0.295 and could not confirm causal or horizontally pleiotropic effects using another method. No genetic liabilities to COVID-19 phenotypes increased the risk of (neuro)psychiatric disorders. In multivariable MR using both neuropsychiatric and a range of other phenotypes, only genetic instruments of BMI remained causally associated with COVID-19. All sensitivity analyses confirmed the results. In conclusion, while genetic liability to bipolar disorder and schizophrenia combined slightly increased COVID-19 susceptibility in one univariable analysis, other MR and multivariable analyses could only confirm genetic underpinnings of BMI to be causally implicated in COVID-19 susceptibility. Thus, using MR we found no consistent proof of genetic liabilities to (neuro)psychiatric disorders contributing to COVID-19 liability or vice versa, which is in line with at least two observational studies. Previously reported positive associations between psychiatric disorders and COVID-19 by others may have resulted from statistical models incompletely capturing BMI as a continuous covariate.
To enhance welding quality and performance, preheating and post-heating are usually employed on high-temperature materials, concurrently with welding. This is a novel technique in vacuum chamber ...electron beam welding (EBW). TC17 and Ti2AlNb alloys are the hot topics in aero-engine parts, and the welding of dissimilar materials is also a broad prospect. To settle welding cracks of Ti2AlNb, EBW with preheating and post-heating was investigated on TC17 and Ti2AlNb dissimilar alloy, which improved the manufacturing technology on high-temperature materials. The dissimilar joint no longer had cracks after preheating, which exhibited excellent welding stability and metallurgical homogeneity, and preheating and annealing had an important effect on mechanical properties. The joint strength after 630 °C annealing is higher than that of TC17 alloy base metal (BM) and other annealing temperatures, reaching 1169 MPa at room temperature and 894 MPa at 450 °C tensile condition. The joint plasticity after 740 °C annealing is equivalent to TC17 BM. EBW with preheating improved the microstructure characteristics and enhanced the plasticity of Ti2AlNb alloy weld and dissimilar joint, which would contribute to the application of Ti2AlNb alloy and Ti2AlNb dissimilar parts.
Abstract
Background
Blood immunoreactive biomarkers, such as C-reactive protein (CRP), and metabolic abnormalities have been associated with schizophrenia. Studies comprehensively and bidirectionally ...probing possible causal links between such blood constituents and liability to schizophrenia are lacking.
Methods
To disentangle putative causal links between CRP blood levels and schizophrenia in both directions, we conducted multiple univariable Mendelian-randomization (MR) analyses, ranging from fixed-effect to inverse variance-weighted (IVW), weighted-median, MR Egger and generalized summary-data-based Mendelian-randomization (GSMR) models. To prioritize metabolic risk factors for schizophrenia, a novel multivariable approach was applied: multivariable Mendelian-randomization–Bayesian model averaging (MR-BMA).
Results
All forward univariable MR analyses consistently showed that CRP has a protective effect on schizophrenia, whereas reverse MR analyses consistently suggested absent causal effects of schizophrenia liability on CRP blood levels. Using MR-BMA, as the top protective factors for schizophrenia we prioritized leucine and as the prime risk-factor triglycerides in medium very-low-density lipoprotein (VLDL). The five best-performing MR-BMA models provided one additional risk factor: triglycerides in large VLDL; and two additional protective factors: citrate and lactate.
Conclusions
Our results add to a growing body of literature hinting at metabolic changes—in particular of triglycerides—independently of medication status in schizophrenia. We also highlight the absent effects of genetic liability to schizophrenia on CRP levels.
Many psychiatrists are worried their patients, at increased risk for COVID-19 complications, are precluded from receiving appropriate testing. There is a lack of epidemiological data on the ...associations between psychiatric disorders and COVID-19 testing rates and testing outcomes.
To compare COVID-19 testing probability and results among individuals with psychiatric disorders with those without such diagnoses, and to examine the associations between testing probability and results and psychiatric diagnoses.
This is a population-based study to perform association analyses of psychiatric disorder diagnoses with COVID-19 testing probability and such test results, by using two-sided Fisher exact tests and logistic regression. The population were UK Biobank participants who had undergone COVID-19 testing. The main outcomes were COVID-19 testing probability and COVID-19 test results.
Individuals with psychiatric disorders were overrepresented among the 1474 UK Biobank participants with test data: 23% of the COVID-19 test sample had a psychiatric diagnosis compared with 10% in the full cohort (P < 0.0001). This overrepresentation persisted for each of the specific psychiatric disorders tested. Furthermore, individuals with a psychiatric disorder (P = 0.01), particularly substance use disorder (P < 0.005), had negative test results significantly more often than individuals without psychiatric disorders. Sensitivity analyses confirmed our results.
In contrast with our hypotheses, UK Biobank participants with psychiatric disorders have been tested for COVID-19 more frequently than individuals without a psychiatric history. Among those tested, test outcomes were more frequently negative for registry participants with psychiatric disorders than in others, countering arguments that people with psychiatric disorders are particularly prone to contract the virus.
People with mental disorders, such as psychosis or autism spectrum disorder (ASD), often present impairments in social cognition (SC), which may cause significant difficulties in real-world ...functioning. SC deficits are seen also in unaffected relatives, indicating a genetic substratum. The present review evaluated the evidence on the association between SC and the polygenic risk score (PRS), a single metric of the molecular genetic risk to develop a specific disorder. In July 2022, we conducted systematic searches in Scopus and PubMed following the PRISMA-ScR guidelines. We selected original articles written in English reporting results on the association between PRSs for any mental disorder and domains of SC either in people with mental disorders or controls. The search yielded 244 papers, of which 13 were selected for inclusion. Studies tested mainly PRSs for schizophrenia, ASD, and attention-deficit hyperactivity disorder. Emotion recognition was the most investigated domain of SC. Overall, evidence revealed that currently available PRSs for mental disorders do not explain variation in SC performances. To enhance the understanding of mechanisms underlying SC in mental disorders, future research should focus on the development of transdiagnostic PRSs, study their interaction with environmental risk factors, and standardize outcome measurement.
IMPORTANCE: Both adulthood stressful life events (SLEs) and liability for schizophrenia have been associated with poor mental and physical health in the general population, but their interaction ...remains to be elucidated to improve population-based health outcomes. OBJECTIVE: To test whether recent SLEs interact with genetic and environmental liability for schizophrenia in models of mental and physical health. DESIGN, SETTING, AND PARTICIPANTS: The Netherlands Mental Health Survey and Incidence Study–2 is a population-based prospective cohort study designed to investigate the prevalence, incidence, course, and consequences of mental disorders in the Dutch general population. Participants were enrolled from November 5, 2007, to July 31, 2009, and followed up with 3 assessments during 9 years. Follow-up was completed on June 19, 2018, and data were analyzed from September 1 to November 1, 2019. EXPOSURES: Recent SLEs assessed at each wave and aggregate scores of genetic and environmental liability for schizophrenia: polygenic risk score for schizophrenia (PRS-SCZ) trained using the Psychiatric Genomics Consortium analysis results and exposome score for schizophrenia (ES-SCZ) trained using an independent data set. MAIN OUTCOMES AND MEASURES: Independent and interacting associations of SLEs with ES-SCZ and PRS-SCZ on mental and physical health assessed at each wave using regression coefficients. RESULTS: Of the 6646 participants included at baseline, the mean (SD) age was 44.26 (12.54) years, and 3672 (55.25%) were female. The SLEs were associated with poorer physical health (B = −3.22 95% CI, −3.66 to −2.79) and mental health (B = −3.68 95% CI, −4.05 to −3.32). Genetic and environmental liability for schizophrenia was associated with poorer mental health (ES-SCZ: B = −3.07 95% CI, −3.35 to −2.79; PRS-SCZ: B = −0.93 95% CI, −1.31 to −0.54). Environmental liability was also associated with poorer physical health (B = −3.19 95% CI, −3.56 to −2.82). The interaction model showed that ES-SCZ moderated the association of SLEs with mental (B = −1.08 95% CI, −1.47 to −0.69) and physical health (B = −0.64 95% CI, −1.11 to −0.17), whereas PRS-SCZ did not. Several sensitivity analyses confirmed these results. CONCLUSIONS AND RELEVANCE: In this study, schizophrenia liability was associated with broad mental health outcomes at the population level. Consistent with the diathesis-stress model, exposure to SLEs, particularly in individuals with high environmental liability for schizophrenia, was associated with poorer health. These findings underline the importance of modifiable environmental factors during the life span for population-based mental health outcomes.
Research has focused more and more on the interplay between genetics and environment in predicting different forms of psychopathology, including depressive symptoms. While the polygenic nature of ...depressive symptoms is increasingly recognized, only few studies have applied a polygenic approach in gene-by-environment interaction (G × E) studies. Furthermore, longitudinal G × E studies on developmental psychopathological properties of depression are scarce. Therefore, this 6-year longitudinal community study examined the interaction between genetic risk for major depression and a multi-informant longitudinal index of critical parenting in relation to depressive symptom development from early to late adolescence. The sample consisted of 327 Dutch adolescents of European descent (56% boys;
M
age
T
1
= 13.00,
SD
age
T
1
= 0.44). Polygenic risk for major depression was based on the Hyde et al. (
Nature Genetics
,
48
, 1031–1036, 2016) meta-analysis and genetic sensitivity analyses were based on the 23andMe discovery dataset. Latent Growth Models suggested that polygenic risk score for major depression was associated with higher depressive symptoms across adolescence (significant main effect), particularly for those experiencing elevated levels of critical parenting (significant G × E). These findings highlight how polygenic risk for major depression in combination with a general environmental factor impacts depressive symptom development from early to late adolescence.
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