Prenatal exposure to organophosphate esters and cognitive development in young children in the Pregnancy, Infection, and Nutrition Study

Organophosphate esters (OPEs) are a class of chemicals commonly used as flame retardants and plasticizers. OPEs are applied to a wide variety of consumer products and have a propensity to leach from these products. Consequently, OPEs are ubiquitous contaminants in many human environments and human exposure is pervasive. Accumulating evidence suggests that OPEs are capable of interfering with childhood cognitive development through both neurologic- and endocrine-mediated mechanisms. However, observational evidence of cognitive effects is limited. We used data collected in the third phase of the Pregnancy, Infection, and Nutrition Study to investigate cognitive effects of prenatal exposure to OPEs. In a spot prenatal maternal urine sample, we measured the following OPE metabolites: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). We assessed children's language and multi-faceted and overall cognitive development between two and three years of age using the MacArthur-Bates Communicative Development Inventories (MB-CDI) and the Mullen Scales of Early Learning (MSEL). We used linear regression to estimate the change in children's scores on these developmental assessments per interquartile range (IQR) increase in log-transformed, specific-gravity-corrected prenatal OPE metabolite concentrations, adjusted for maternal age, education, income, race/ethnicity, BMI, and child's sex. A total of 149 children had both OPE metabolite measurements and MB-CDI scores, and 227 children had both OPE metabolite measurements and MSEL scores. We observed that higher concentrations of ip-PPP (ng/ml) were associated with lower scores on the MSEL Cognitive Composite Score (β = −2.61; 95% CI: −5.69, 0.46), and separately on two of the four MSEL Scales that comprise the Cognitive Composite, specifically the Fine Motor Scale (β = −3.08; 95% CI: −5.26, −0.91) and the Expressive Language Scale (β = −1.21; 95% CI: −2.91, 0.49). We similarly observed that prenatal ip-PPP concentrations were inversely associated with age-standardized scores on the MB-CDI Vocabulary assessment (β = −1.19; 95% CI: −2.53, 0.16). Other OPE metabolites were not strongly associated with performance on either assessment. Our results suggest that isopropylated triarylphosphate isomers, the presumed parent compounds of ip-PPP, may adversely impact cognitive development, including fine motor skills and early language abilities. Our study contributes to the growing body of observational evidence that suggests prenatal exposure to OPEs may adversely affect cognitive development

Prenatal exposure to organophosphate esters and behavioral development in young children in the Pregnancy, Infection, and Nutrition Study

Organophosphate esters (OPEs) are commonly used as plasticizers and flame retardants in consumer products, and exposure is relatively ubiquitous in most populations studied. This may be of concern as some OPEs may be neurotoxic, endocrine-disrupting, and interfere with behavioral development; however, observational evidence is limited. We used data from the Pregnancy, Infection, and Nutrition Study, a prospective birth cohort study, to investigate associations between maternal OPE metabolite concentrations during pregnancy and behavioral development in offspring. Women provided a urine sample during pregnancy that was analyzed for concentrations of OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). Offspring's behavioral development was assessed by the Behavioral Assessment System for Children (2nd Edition) (BASC-2) at approximately 36 months. Linear regression was used to estimate associations between tertiles in specific gravity-corrected OPE metabolite concentrations and children's scores on the BASC-2, adjusted for maternal age, maternal BMI, maternal race, maternal education, familial income, maternal depression, quality of the home environment, and sex. Higher BDCIPP concentrations were associated with higher scores on the Behavioral Symptoms Index (1st vs. 3rd tertile: β = 3.03; 95% CI = 0.40, 5.67) and Externalizing Problems (1st vs. 3rd tertile: β = 2.49; 95% CI: −0.12, 5.10) composites. Among BASC-2 scales, BDCIPP was most strongly associated with Withdrawal, Attention Problems, Depression, Hyperactivity, and Aggression. DPHP concentrations were also associated with higher scores on the Externalizing Problems and Behavioral Symptoms Index composites, but not as strongly as BDCIPP. Conversely, higher concentrations of ip-PPP were associated with fewer adverse behavioral symptoms, including an inverse association with the Internalizing Problems composite (1st vs. 3rd tertile: β = −3.74; 95% CI = −6.75, −0.74) and constituent scales. BCIPHIPP was not strongly associated with any measured behavioral outcomes. Our results suggest that greater maternal exposure to tris(1,3-dichloro-2-propyl phosphate) (TDCIPP, parent compound of BDCIPP) and, to a lesser degree, triphenyl phosphate (TPHP, parent compound of DPHP) during pregnancy is associated with adverse behavioral development in children. Our study contributes to the growing body of evidence pertaining to adverse developmental effects of prenatal OPE exposure and highlights the need for further research to characterize risks associated with this ubiquitous family of chemicals

On the use of modelling antagonistic enzymes to aid in temporal programming of pH and PVA–borate gelation

Feedback through enzyme reactions creates new possibilities for the temporal programming of material properties in bioinspired applications, such as transient adhesives; however, there have been limited attempts to model such behavior. Here, we used two antagonistic enzymes, urease in watermelon seed powder and esterase, to temporally control the gelation of a poly(vinyl alcohol)–borate hydrogel in a one-pot formulation. Urease produces base (ammonia), and esterase produces acid (acetic acid), generating a pH pulse, which was coupled with reversible complexation of PVA. For improved understanding of the pulse properties and gel lifetime, the pH profile was investigated by comparison of the experiments with kinetic simulations of the enzyme reactions and relevant equilibria. The model reproduced the general trends with the initial concentrations and was used to help identify conditions for pulse-like behaviour as the substrate concentrations were varied

Chiral three-nucleon forces and bound excited states in neutron-rich oxygen isotopes

We study the spectra of neutron-rich oxygen isotopes based on chiral two- and three-nucleon interactions. First, we benchmark our many-body approach by comparing ground-state energies to coupled-cluster results for the same two-nucleon interaction, with overall good agreement. We then calculate bound excited states in 21,22,23O, focusing on the role of three-nucleon forces, in the standard sd shell and an extended sdf7/2p3/2 valence space. Chiral three-nucleon forces provide important one- and two-body contributions between valence neutrons. We find that both these contributions and an extended valence space are necessary to reproduce key signatures of novel shell evolution, such as the N = 14 magic number and the low-lying states in 21O and 23O, which are too compressed with two-nucleon interactions only. For the extended space calculations, this presents first work based on nuclear forces without adjustments. Future work is needed and open questions are discussed.Comment: 6 pages, 4 figures, published versio

Red Queen Coevolution on Fitness Landscapes

Species do not merely evolve, they also coevolve with other organisms. Coevolution is a major force driving interacting species to continuously evolve ex- ploring their fitness landscapes. Coevolution involves the coupling of species fit- ness landscapes, linking species genetic changes with their inter-specific ecological interactions. Here we first introduce the Red Queen hypothesis of evolution com- menting on some theoretical aspects and empirical evidences. As an introduction to the fitness landscape concept, we review key issues on evolution on simple and rugged fitness landscapes. Then we present key modeling examples of coevolution on different fitness landscapes at different scales, from RNA viruses to complex ecosystems and macroevolution.Comment: 40 pages, 12 figures. To appear in "Recent Advances in the Theory and Application of Fitness Landscapes" (H. Richter and A. Engelbrecht, eds.). Springer Series in Emergence, Complexity, and Computation, 201

Competing orders in a magnetic field: spin and charge order in the cuprate superconductors

We describe two-dimensional quantum spin fluctuations in a superconducting Abrikosov flux lattice induced by a magnetic field applied to a doped Mott insulator. Complete numerical solutions of a self-consistent large N theory provide detailed information on the phase diagram and on the spatial structure of the dynamic spin spectrum. Our results apply to phases with and without long-range spin density wave order and to the magnetic quantum critical point separating these phases. We discuss the relationship of our results to a number of recent neutron scattering measurements on the cuprate superconductors in the presence of an applied field. We compute the pinning of static charge order by the vortex cores in the `spin gap' phase where the spin order remains dynamically fluctuating, and argue that these results apply to recent scanning tunnelling microscopy (STM) measurements. We show that with a single typical set of values for the coupling constants, our model describes the field dependence of the elastic neutron scattering intensities, the absence of satellite Bragg peaks associated with the vortex lattice in existing neutron scattering observations, and the spatial extent of charge order in STM observations. We mention implications of our theory for NMR experiments. We also present a theoretical discussion of more exotic states that can be built out of the spin and charge order parameters, including spin nematics and phases with `exciton fractionalization'.Comment: 36 pages, 33 figures; for a popular introduction, see http://onsager.physics.yale.edu/superflow.html; (v2) Added reference to new work of Chen and Ting; (v3) reorganized presentation for improved clarity, and added new appendix on microscopic origin; (v4) final published version with minor change

Experimental Observation of Differences in the Dynamic Response of Newtonian and Viscoelastic Fluids

In this paper we present an experimental study of the dynamic responses of a Newtonian fluid and a Maxwellian fluid under an oscillating pressure gradient. We use laser Doppler anemometry in order to determine the velocity of each fluid inside a cylindrical tube. In the case of the Newtonian fluid, the dissipative nature is observed and the response obeys the Zhou and Sheng universality (PRB 39, 12027 (1989)). In the dynamic response of the Maxwellian fluid an enhancement at the frequencies predicted by the corresponding theory (PRE 58, 6323 (1998)) is observed.Comment: 5 pages, 4 Figures, paper to be published in Phys. Rev.

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02