Life events, anxious depression and personality: a prospective and genetic study.

Background: The association between life events and anxious depression might be due to causality or to gene-environment correlation. We examined unidirectional and reciprocal causality and a gene-environment correlation model, in which genes that influence the vulnerability for anxious depression also increase the risk of exposure to life events. The effect of genes that influence environmental exposure might be mediated through personality and we therefore also examined the association between life events and personality (neuroticism and extraversion). Method: Information on life events, anxious depression, neuroticism and extraversion was collected in 5782 monozygotic (MZ) and dizygotic (DZ) twins who participated in a longitudinal survey study of the Netherlands Twin Register. To examine causality, data were analysed longitudinally. To examine gene-environment correlation, the co-twin control method was used. Results: Anxious depression and, to a lesser extent, neuroticism scores increased after exposure to life events. Anxious depression and neuroticism also predicted the experience of life events. Prospectively, extraversion was not associated with life events. Anxious depression, neuroticism and extraversion scores did not differ between the non-exposed subjects of MZ and DZ twin pairs and unrelated subjects discordant for life events. Conclusions: Our findings suggest that reciprocal causation explains the relationship between life events and anxious depression and between life events and neuroticism. Extraversion is not related to life events. No evidence was found for gene-environment correlation, i.e. the genes that influence anxious depression, neuroticism or extraversion do not overlap with the genes that increase the risk of exposure to life events

Soundness of Unravelings for Conditional Term Rewriting Systems via Ultra-Properties Related to Linearity

Unravelings are transformations from a conditional term rewriting system (CTRS, for short) over an original signature into an unconditional term rewriting systems (TRS, for short) over an extended signature. They are not sound w.r.t. reduction for every CTRS, while they are complete w.r.t. reduction. Here, soundness w.r.t. reduction means that every reduction sequence of the corresponding unraveled TRS, of which the initial and end terms are over the original signature, can be simulated by the reduction of the original CTRS. In this paper, we show that an optimized variant of Ohlebusch's unraveling for a deterministic CTRS is sound w.r.t. reduction if the corresponding unraveled TRS is left-linear or both right-linear and non-erasing. We also show that soundness of the variant implies that of Ohlebusch's unraveling. Finally, we show that soundness of Ohlebusch's unraveling is the weakest in soundness of the other unravelings and a transformation, proposed by Serbanuta and Rosu, for (normal) deterministic CTRSs, i.e., soundness of them respectively implies that of Ohlebusch's unraveling.Comment: 49 pages, 1 table, publication in Special Issue: Selected papers of the "22nd International Conference on Rewriting Techniques and Applications (RTA'11)

Evidence-based approach to thrombophilia testing

Thrombophilia can be identified in about half of all patients presenting with VTE. Testing has increased tremendously for various indications, but whether the results of such tests help in the clinical management of patients has not been settled. I use evidence from observational studies to conclude that testing for hereditary thrombophilia generally does not alter the clinical management of patients with VTE, with occasional exceptions for women at fertile age. Because testing for thrombophilia only serves limited purpose this should not be performed on a routine basis

Atrial fibrillation detection using insertable cardiac monitor after stroke: a real-word cohort study

First published: 09 November 2022Objective: This study aimed to report the real‐world atrial fibrillation (AF) diagnostic yield of the implantable cardiac monitor (ICM) in patients with stroke or transient ischemic attack (TIA), and compare it to patients with an ICM for unexplained syncope. Methods: We used patient data from device clinics across the United States of America with ICM remote monitoring via PaceMate™, implanted for stroke or TIA, and unexplained syncope. Patients with known AF or atrial flutter were excluded. The outcome was AF lasting ≥2 min, adjudicated by International Board of Heart Rhythm Examiners certified cardiac device specialists. Results: We included a total of 2469 patients, 51.1% with stroke or TIA (mean age: 69.7 [SD: 12.2] years, 41.1% female) and 48.9% with syncope (mean age: 67.0 [SD: 17.1] years, 59.4% female). The cumulative AF detection rate in patients with stroke or TIA was 5.5%, 8.9%, and 14.0% at 12, 24, and 36 months, respectively. The median episode duration was 73 (interquartile range: 10–456) min, ranging from 2 min to 40.9 days, with 52.3%, 28.6%, and 4.4% of episodes lasting at least 1, 6, and 24 h, respectively. AF detection was increased by age (adjusted hazard ratio [for every 1‐year increase]: 1.024, 95% confidence interval: 1.008–1.040; p = .003), but was not influenced by sex (p = .089). For comparison, the cumulative detection rate at 12, 24, and 36 months were, respectively, 2.4%, 5.2%, and 7.4% in patients with syncope. Conclusion: Patients with stroke or TIA have a higher rate of AF detection. However, this real‐world study shows significantly lower AF detection rates than what has been previously reported.Jean J. Noubiap, Gijo Thomas, Melissa E. Middeldorp, John L. Fitzgerald, Curtis Harper, Prashanthan Sander

Sequence variation of Epstein-Barr virus: viral types, geography, codon usage and diseases

138 new Epstein-Barr virus (EBV) genome sequences have been determined. 125 of these and 116 from previous reports were combined to produce a multiple sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 SNPs at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART miRNA region of the genome was present in 21 EBV strains. EBV from saliva of USA patients with chronic active EBV infection aligned with the wild type EBV genome, with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases both from Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and post-transplant lymphoproliferative disease. It contributes to several types of cancer including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions - differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV associated cancers are already known and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets

Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes

Marital resemblance for obsessive–compulsive, anxious and depressive symptoms in a population-based sample.

Background. Resemblance between spouses can be due to phenotypic assortment, social homogamy and/or marital interaction. A significant degree of assortment can have consequences for the genetic architecture of a population. We examined the existence and cause(s) of assortment for obsessive-compulsive (OC), anxious and depressive symptoms in a population-based twin-family sample. Method. OC, anxious and depressive symptoms were measured in around 1400 twin-spouse pairs and >850 parent pairs. Correlations of twins and their spouse, twin and co-twin's spouse, spouses of both twins and parents of twins were obtained to consider phenotypic assortment versus social homogamy as possible causes of marital resemblance. The association of length of relationship with marital resemblance was also investigated. Finally, we examined whether within-trait or cross-trait processes play a primarily role in marital resemblance. Results. Small but significant within-trait correlations of between 0.1 and 0.2 were seen for spouse similarity in OC, anxious and depressive symptoms. Cross-correlations were significant but lower. There was no correlation between length of relationship and marital resemblance. From the pattern of correlations for twin-spouse, co-twin-spouse and spouses of both twins, phenotypic assortment could not be distinguished from social homogamy. Both within- and cross-assortment processes play a role in marital resemblance. Conclusions. Small within- and across-trait correlations exist for OC, anxious and depressive symptoms. No evidence for marital interaction was found. Spouse correlations are small, which makes it difficult to distinguish between social homogamy and phenotypic assortment. It is unlikely that correlations of this size will have a large impact on genetic studies. © 2008 Cambridge University Press

Sex disparities in enrolment and reporting of outcomes by sex in contemporary clinical trials of atrial fibrillation

Background:Underrepresentation of females in randomized controlled trials (RCTs)limits generalizability and quality of the evidence guiding treatment of females. This study aimed to measure the sex disparities in participants' recruitment in RCTs of atrial fibrillation (AF) and determine associated factors, and to describe the frequency of outcomes reported by sex. Methods:MEDLINE was searched to identify RCTs of AF published between January 1, 2011, and November 20, 2021, in 12 top‐tier journals. We measured the enrollment of females using the enrollment disparity difference (EDD) which is the difference between the proportion of females in the trial and the proportion of females with AF in the underlying general population (obtained from the Global Burden of Disease). Random‐effects meta‐analyses of the EDD were performed, and multivariable meta‐regression was used to explore factors associated with disparity estimates. We also determined the proportion of trials that included sex‐stratified results. Results:Out of 1133 records screened, 142 trials were included, reporting on a total of 133 532 participants. The random‐effects summary EDD was−0.125 (95%confidence interval [CI] =−0.143 to−0.108), indicating that females were under‐enrolled by 12.5 percentage points. Female enrollment was higher in trials with higher sample size (750, adjusted odds ratio [aOR] 1.065, 95% CI:1.008–1.125), higher mean participants' age (aOR: 1.006, 95% CI: 1.002–1.009), and lower in trials conducted in North America compared to Europe (aOR: 0.945, 95% CI:0.898–0.995). Only 36 trials (25.4%) reported outcomes by sex, and of these 29(80.6%) performed statistical testing of the sex‐by‐treatment interaction. Conclusion:Females remain substantially less represented in RCTs of AF, and sex‐stratified reporting of primary outcomes is infrequent. These findings call for urgent action to improve sex equity in enrollment and sex‐stratified outcomes' reporting in RCTs of AF.Jean Jacques Noubiap, Gijo Thomas, Ulrich Flore Nyaga, John L. Fitzgerald, Celine Gallagher, Melissa E. Middeldorp, Prashanthan Sander

The role of tunneling in enzyme catalysis of C–H activation

AbstractRecent data from studies of enzyme catalyzed hydrogen transfer reactions implicate a new theoretical context in which to understand C–H activation. This is much closer to the Marcus theory of electron transfer, in that environmental factors influence the probability of effective wave function overlap from donor to acceptor atoms. The larger size of hydrogen and the availability of three isotopes (H, D and T) introduce a dimension to the kinetic analysis that is not available for electron transfer. This concerns the role of gating between donor and acceptor atoms, in particular whether the system in question is able to tune distance between reactants to achieve maximal tunneling efficiency. Analysis of enzyme systems is providing increasing evidence of a role for active site residues in optimizing the inter-nuclear distance for nuclear tunneling. The ease with which this optimization can be perturbed, through site-specific mutagenesis or an alteration in reaction conditions, is also readily apparent from an analysis of the changes in the temperature dependence of hydrogen isotope effects