Geodesy by radio interferometry: Effects of atmospheric modeling errors on estimates of baseline length

Analysis of very long baseline interferometry data indicates that systematic errors in prior estimates of baseline length, of order 5 cm for ~8000-km baselines, were due primarily to mismodeling of the electrical path length of the troposphere and mesosphere ("atmospheric delay"). Here we discuss observational evidence for the existence of such errors in the previously used models for the atmospheric delay and develop a new "mapping" function for the elevation angle dependence of this delay. The delay predicted by this new mapping function differs from ray trace results by less than ~5 mm, at all elevations down to 5° elevation, and introduces errors into the estimates of baseline length of •< 1 cm, for the multistation intercontinental experiment analyzed here

Gestational weight gain and predicted changes in offspring anthropometrics between early infancy and 3 years

Objective: To determine how gestational weight gain (GWG), categorized using the 2009 Institute of Medicine recommendations, relates to changes in offspring weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length z-scores (WLZ) between early infancy and 3 years. Methods: Women with singleton infants were recruited from the third cohort of the Pregnancy, Infection, and Nutrition Study (2001-2005). Term infants with at least one weight or length measurement during the study period were included (n = 476). Multivariable linear mixed effects regression models estimated longitudinal changes in WAZ, LAZ and WLZ associated with GWG. Results: In early infancy, compared with infants of women with adequate weight gain, those of women with excessive weight gains had higher WAZ, LAZ and WLZ. Excessive GWG ≥ 200% of the recommended amount was associated with faster rates of change in WAZ and LAZ and noticeably higher predicted mean WAZ and WLZ that persisted across the study period. Conclusions: GWG is associated with significant differences in offspring anthropometrics in early infancy that persisted to 3 years of age. More longitudinal studies that utilize maternal and paediatric body composition measures are necessary to understand the nature of this association

Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai Children’s Environmental Health Center

Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor (β^ − 0.82, 95% CI − 1.42, − 0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits

Prenatal exposure to organophosphates and associations with birthweight and gestational length

Organophosphate esters (OPEs) are often used as flame retardants and plasticizers. Animal data suggest exposure to OPEs could impact children's growth and development, yet impacts on human birth outcomes are understudied. We evaluate impacts of OPE exposure on the timing of delivery and infant's birthweight in the Pregnancy Infection and Nutrition Study (PIN). North Carolina women enrolled in PIN in early pregnancy and participated in follow-up through delivery. Analyses were limited to mothers recruited from 2002 to 2005, whose children participated in additional follow-up in early childhood (n = 349). Mothers collected urine samples in which OPE metabolites were assessed and birth outcomes were abstracted from medical records. Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) were detected in >80% of samples. Average birthweight and gestational age were 3326 g and 39.1 weeks, respectively. As data suggest that the mechanisms of action by which OPEs impact birth outcomes may be fetal sex dependent, we conducted sex-stratified statistical analyses. Women with the highest ip-PPP concentrations delivered girls 1 week earlier than women with lower levels (95% Confidence Interval (CI): −1.85, −0.15). Women with BDCIPP levels above the median had 3.99 (95% CI: 1.08, 14.78) times the odds of delivering their daughters preterm. Similarly, higher ip-PPP levels were associated with lower birthweight, but not after standardizing for gestational age. Among males, maternal ip-PPP was associated with decreased odds of preterm birth (OR = 0.21, 95% CI: 0.06, 0.68). DPHP and BCIPHIPP levels were not associated with outcomes in either sex. Results indicate that prenatal OPE exposure may impact timing of birth, though results are imprecise. Given widespread OPE exposure and the urgent need to identify and mitigate causes of preterm birth, further investigation is warranted

Expressive Dominant Versus Receptive Dominant Language Patterns in Young Children: Findings from the Study to Explore Early Development

We examined language profiles of 2571 children, 30–68 months old, with autism spectrum disorder (ASD), other developmental disabilities (DD), and typical development from the general population (POP). Children were categorized as expressive dominant (ED), receptive dominant (RD), or nondominant (ND). Within each group, the ED profile was the least frequent. However, children in the ASD group were more likely to display an ED profile than those in the DD or POP groups, and these children were typically younger, had lower nonverbal cognitive skills, and displayed more severe social-affect symptoms of ASD compared to their peers with RD or ND profiles. These findings have research and clinical implications related to the focus of interventions targeting young children with ASD and other DDs

Neonatal jaundice in association with autism spectrum disorder and developmental disorder

Objective: To examine the association between neonatal jaundice and autism spectrum disorder (ASD) and non-ASD developmental disorder (DD). Study design: We analyzed data from the Study to Explore Early Development, a US multisite, case-control study conducted from 2007 to 2011. Developmental assessment classified children aged 2–5 years into: ASD (n = 636), DD (n = 777), or controls (POP; n = 926). Neonatal jaundice (n = 1054) was identified from medical records and maternal interviews. We examined associations between neonatal jaundice and ASD and DD using regression models to obtain adjusted odds ratios (aOR). Results: Our results showed interaction between gestational age and neonatal jaundice. Neonatal jaundice was associated with ASD at 35–37 weeks (aOR = 1.83, 95%CI 1.05, 3.19), but not ≥38 weeks gestation (aOR = 0.97, 95%CI 0.76, 1.24). Similar results were observed with DD. Conclusions: Further exploration of timing and severity of neonatal jaundice and ASD/DD is warranted

Beyond energy efficiency in evaluating sustainable development in planning and the built environment

The EU has set the policy target of reducing energy use by 20% by the year 2020. Therefore, a substantial consumption decrease is needed in the built environment sector. Despite the great energy efficiency improvements in households, recent energy consumption data analyses show that these targets will unlikely be reached. The general aim of this study is to point out the need to define new indicators and evaluation approaches in urban planning and the built environment which are based on the concept of ‘energy subsidiarity', focusing on local renewable resources rather than on current approaches based on energy efficiency. This concept correlates energy consumption with the energy supply from local renewable resources and is here proposed as the new urban planning evaluation approach toward a sustainable built environment. In the paper, the ‘Jevons Paradox' concept and the ‘energy rebound effect' phenomenon are used to demonstrate how current approaches based on energy efficiency, alone, cannot lead to a remarkable reduction of energy consumption. This is also supported by data on European energy consumption and European energy efficiency in the built environment. Finally, a number of well-known European ecological districts (‘eco-districts') are analysed in terms of sustainable energy strategy as well as energy efficiency and energy balance. This study shows that there is a contradiction between the purpose of some of the eco-districts to be low consumption (or low impacts), and the district renewable energy balance. Only a few of the analysed eco-districts are able to cover energy needs by using renewable energy obtained in the surrounding area. In most of the cases, the focus of the districts' activities is on energy efficiency. According to the ‘Jevons Paradox' and ‘energy rebound effect' paradigm, energy efficiency alone will unlikely lead to an effective reduction in resources' consumption. These results point out the need for a radical shift toward the development of new approaches in the assessment and management of the built environment for sustainabilit

Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes

Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6–9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ − 0.13, 95% CI − 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ − 0.17, 95% CI − 0.33, − 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision

Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader

Protein degradation via the use of bivalent chemical degraders provides an alternative strategy to block protein function and assess the biological roles of putative drug targets. This approach capitalizes on the advantages of small-molecule inhibitors while moving beyond the restrictions of traditional pharmacology. Here, we report a chemical degrader (UNC6852) that targets polycomb repressive complex 2 (PRC2). UNC6852 contains an EED226-derived ligand and a ligand for VHL which bind to the WD40 aromatic cage of EED and CRL2VHL, respectively, to induce proteasomal degradation of PRC2 components, EED, EZH2, and SUZ12. Degradation of PRC2 with UNC6852 blocks the histone methyltransferase activity of EZH2, decreasing H3K27me3 levels in HeLa cells and diffuse large B cell lymphoma (DLBCL) cells containing EZH2 gain-of-function mutations. UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. Using an EED-targeted chemical degrader, Potjewyd et al. demonstrate successful degradation of the PRC2 complex. UNC6852 provides a unique tool to study PRC2 function and downregulation of PRC2 activity in cancer and demonstrates the feasibility of developing PRC2-targeted degraders as potential therapeutics