Quantifying Nonequilibrium Behavior with Varying Cooling Rates

We investigate nonequilibrium behavior in (1+1)-dimensional stochastic field theories in the context of Ginzburg-Landau models at varying cooling rates. We argue that a reliable measure of the departure from thermal equilibrium can be obtained from the absolute value of the rate of change of the momentum-integrated structure function, $\Delta S_{\rm{tot}}$. We show that the peak of $\Delta S_{\rm{tot}}$ scales with the cooling, or quench, time-scale, $\tau_q$, in agreement with the prediction by Laguna and Zurek for the scaling of freeze-out time in both over and under-damped regimes. Furthermore, we show that the amplitude of the peak scales as $\tau_q^{-6/5}$ independent of the viscosity.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let

Epigenome-Wide and Transcriptome-Wide Analyses Reveal Gestational Diabetes is Associated with Alterations in the Human Leukocyte Antigen Complex

Background: Gestational diabetes mellitus (GDM) affects approximately 10% of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. Results: To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 BeadChips) and expression (Affymetrix transcriptome microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. This differential methylation and expression may be capturing shifts in cellular composition, reflecting physiological changes in the placenta associated with GDM. Conclusions: Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into how GDM shapes the intrauterine environment, which may have implications for fetal (re)programming

Social and individual subjective wellbeing and capabilities in Chile

The notion of social belongingness has been applied to different scales, from individual to social processes, and from subjective to objective dimensions. This article seeks to contribute to this multidimensional perspective on belongingness by drawing from the capabilities and subjective wellbeing perspectives. The specific aim is to analyze the relationships between capabilities—including those related to social belongingness—and individual and social subjective wellbeing. The hypotheses are: (H1–H2) There is a relationship between capabilities (measured as evaluation and functioning) and (H1) individual and (H2) social subjective wellbeing; (H3) The set of capabilities associated to individual subjective wellbeing differs from the set correlated to social subjective wellbeing; (H4) The intensity and significance of the correlation between subjective wellbeing and capabilities depends on whether the latter is measured as evaluation or functioning; and (H5) The relationships between capabilities and subjective wellbeing are complex and non-linear. Using a nationally representative survey in Chile, multiple linear (H1–H5) and dose response matching (H1–H5) regressions between capabilities and subjective wellbeing outcomes are estimated, confirming all hypotheses. Subjective evaluations and effective functionings of some capabilities (“basic needs,” “social ties,” “feeling recognized and respected;” “having and deploying a life project”) are consistently correlated with both subjective wellbeing outcomes. Others capabilities are correlated with both subjective wellbeing outcomes only when measured as functionings (contact with nature), do not display a systematic pattern of correlation (“health,” “pleasure,” “participation,” and “human security”) or are not associated with subjective wellbeing (“self-knowledge” and “understanding the world”). When observed, correlations are sizable, non-linear, and consistent across estimation methods. Moreover, capabilities related to social belongingness such as “social ties” and “feeling recognized and respected” are important by themselves but also are positively correlated to both social and individual subjective wellbeing. These findings underscore the need of a multidimensional perspective on the relationships between capabilities and subjective wellbeing, considering both subjective and objective, as well as individual and social aspects that are relevant to belongingness. These findings also have practical and policy implications, and may inform public deliberation processes and policy decisions to develop capabilities, promote subjective wellbeing, and ultimately promote positive belongingness

A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.We would like to thank the Pregnancy and Childhood Epigenetics (PACE) consortium, as well as all the families that participated in these studies for their generous contribution. This work was partially funded by GVSAN2018111086 from the Basque Department of Health and PI18/01142 from ISCIII - Spanish Ministry of Science and Innovation - cofounded by the ERDF “A way to make Europe” to JRB and LSM, respectively; and by the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL) (NutriPROGRAM). ACP was supported by grant GVSAN2019111085 from the Basque Department of Health to NFJ. Detailed acknowledgements and funding for each participating cohort are described in Supplementary Note 1

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes