Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Genome-Wide Association Study in Obsessive-Compulsive Disorder: Results from the OCGAS

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients, with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1 065 families (containing 1 406 patients with OCD), combined with population-based samples (resulting in a total sample of 5 061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at SNP- and gene-levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13×10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of GWAS signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2, and PTPRD. Analyses at the gene-level revealed association of IQCK and C16orf88 (both P<1×10−6, experiment-wide significant), as well as OFCC1 (P=6.29×10−5). The suggestive findings in this study await replication in larger samples

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

The plant information center

The Plant Information Center is a partnership of the North Carolina Botanical Garden, Unviersity of North Carolina (UNC) Herbarium, UNC School of Information and Library Science, McDougle Middle School, and Orange County Public Library. The intent of the Project is to connect the research community and the general public (including school children) to make greater use of primary research material and to nurture the public interest and enthusiasm in the study of trees, plants, and natural history. Four specific objectives include: 1) successful cooperation between the various institutions; 2) the development of an interactive Plant Information Center with a Web-based portal; 3) the development of lesson plans using primary research materials from the herbarium for 6th grade students; and, 4) a test of the usefulness of digital images of herbarium specimens for plant identification and for inspiring the public with the aims and methods of botanical science

Aqueous Epitaxial Growth of ZnO on Single Crystalline Au Microplates

Epitaxial ZnO thin films were grown on single crystalline Au microplates from an aqueous solution at 90 °C. The composite structures were approximately 100 μm wide. The epitaxial ZnO films were smooth, continuous, and several micrometers thick. We examined the epitaxial relationship between the ZnO and Au through scanning electron microscopy, electron backscatter diffraction, high-resolution transmission electron microscopy, and electron diffraction and demonstrated control over the resulting film morphology through the kinetics of growth. An epitaxial relationship of ZnO[11̅00](0002)∥Au[21̅1̅](111) was dominant in the structures

Increased male live-birth rates after blastocyst-stage frozen-thawed embryo transfers compared with cleavage-stage frozen-thawed embryo transfers: a SART registry study

Objective: To investigate whether there is a difference in live-birth gender rates in blastocyst-stage frozen-thawed embryo transfers (FETs) compared with those in cleavage-stage FETs. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): All women with recorded live births who underwent FET at either the blastocyst or cleavage stage, reported to the Society for Assisted Reproductive Technology during 2004–2013. Intervention(s): None. Main Outcome Measure(s): The primary outcome was live-birth gender rates. Demographic criteria were also collected. The chi-square analyses were used for bivariate associations, and multiple logistic regression models were used for adjusted associations, with all two-sided P<.05 considered statistically significant. Result(s): A statistically significant increase was noted in the number of live male births after blastocyst-stage FET compared with that after cleavage-stage FET (51.9% vs. 50.5%). After controlling for potential confounders including age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03, 1.08), body mass index (OR, 1.08; 95% CI, 1.04, 1.12), and male factor infertility (OR, 1.06; 95% CI, 1.03, 1.08), the increase in male live births after blastocyst-stage FET remained statistically significant. Conclusion(s): In patients undergoing FETs, blastocyst-stage transfers are associated with higher male gender live-birth rates compared with cleavage-stage transfers

Exposure to Extrinsic Stressors, Social Defeat or Bisphenol A, Eliminates Sex Differences in DNA methyltransferase expression in the Amygdala

Chemical and psychological stressors can exert long lasting changes in brain function and behavior. Changes in DNA methylation have been shown to be an important mechanism mediating long lasting changes in neural function and behavior, especially for anxiety-like or stress responses. Here we examined the effects of either a social or chemical stressor on DNA methyltransferase (DNMT) gene expression in the amygdala, an important brain region modulating stress responses and anxiety. In adult California mice (Peromyscus californicus) that were naïve to social defeat, females had higher levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than males. In addition, social defeat stress reduced Dnmt1 and Dnmt3a expression in the CeA of females but not males. A second study using more anatomically specific punch samples replicated these effects for Dnmt1. Perinatal exposure, spanning from periconception through lactation, to bisphenol A or ethinyl estradiol (estrogens in birth control pills) also abolished sex differences in Dnmt1 expression in the CeA but not basolateral amygdala. These findings identify a robust sex difference in Dnmt1 expression in the CeA that is sensitive to both psychological and chemical stressors. Our results suggest that future studies should examine the impact of psychological and chemical stressors on DNA methylation in the CeA and that Dnmt1 may have an underappreciated role in plasticity in behavior