The Origin of Non-chaotic Behavior in Identically Driven Systems

Recently it has been found that different physical systems driven by identical random noise behave exactly identical after a long time. It is also suggested that this is an outcome of finite precision in numerical experiments. Here we show that the origin of the non-chaotic behavior lies in the structural instability of the attractor of these systems which changes to a stable fixed point for strong enough drive. We see this to be true in all the systems studied in literature. Thus we affirm that in chaotic systems, synchronization can not occur only by addition of noise unless the noise destroys the strange attractor and the system is no longer chaotic.Comment: Figures could be obtained from [email protected]. The document below is a latex fil

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Cell cycle regulation of chromatin at an origin of DNA replication.

Selection and licensing of mammalian DNA replication origins may be regulated by epigenetic changes in chromatin structure. The Epstein–Barr virus (EBV) origin of plasmid replication (OriP) uses the cellular licensing machinery to regulate replication during latent infection of human cells. We found that the minimal replicator sequence of OriP, referred to as the dyad symmetry (DS), is flanked by nucleosomes. These nucleosomes were subject to cell cycle‐dependent chromatin remodeling and histone modifications. Restriction enzyme accessibility assay indicated that the DS‐bounded nucleosomes were remodeled in late G1. Remarkably, histone H3 acetylation of DS‐bounded nucleosomes decreased during late G1, coinciding with nucleosome remodeling and MCM3 loading, and preceding the onset of DNA replication. The ATP‐dependent chromatin‐remodeling factor SNF2h was also recruited to DS in late G1, and formed a stable complex with HDAC2 at DS. siRNA depletion of SNF2h reduced G1‐specific nucleosome remodeling, histone deacetylation, and MCM3 loading at DS. We conclude that an SNF2h–HDAC1/2 complex coordinates G1‐specific chromatin remodeling and histone deacetylation with the DNA replication initiation process at OriP