Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7 years

Background: Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. Objectives: We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children's Environmental Health Study. Methods: We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7 years (n = 164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child's sex. Results: Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child's sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12 months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). Conclusions: Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development

Synapse efficiency diverges due to synaptic pruning following over-growth

In the development of the brain, it is known that synapses are pruned following over-growth. This pruning following over-growth seems to be a universal phenomenon that occurs in almost all areas -- visual cortex, motor area, association area, and so on. It has been shown numerically that the synapse efficiency is increased by systematic deletion. We discuss the synapse efficiency to evaluate the effect of pruning following over-growth, and analytically show that the synapse efficiency diverges as O(log c) at the limit where connecting rate c is extremely small. Under a fixed synapse number criterion, the optimal connecting rate, which maximize memory performance, exists.Comment: 15 pages, 16 figure

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia

Ground-state properties of tubelike flexible polymers

In this work we investigate structural properties of native states of a simple model for short flexible homopolymers, where the steric influence of monomeric side chains is effectively introduced by a thickness constraint. This geometric constraint is implemented through the concept of the global radius of curvature and affects the conformational topology of ground-state structures. A systematic analysis allows for a thickness-dependent classification of the dominant ground-state topologies. It turns out that helical structures, strands, rings, and coils are natural, intrinsic geometries of such tubelike objects

European Union enlargement, post-accession migration and imaginative geographies of the ‘New Europe’: media discourses in Romania and the United Kingdom.

This paper is concerned with re-imaginings of ‘Europe’ following the accession to the European Union (EU) of former ‘Eastern European’ countries. In particular it explores media representations of post-EU accession migration from Romania to the United Kingdom in the UK and Romanian newspaper press. Todorova’s (1997) notion of Balkanism is deployed as a theoretical construct to facilitate the analysis of these representations as first, the continuation of long-standing and deeply embedded imaginings of the ‘East’ of Europe and, second, as a means of contesting these discourses. The paper explores the way in which the UK press construct Balkanist discourses about Romania and Romanian migrants, and then analyses how the Romanian press has contested such discourses. The paper argues that the idea of the ‘East’ remains important in constructing notions of ‘Europe’ within popular media geographies

The virulence variability of different Acinetobacter baumannii strains in experimental pneumonia

Our objective was to compare the virulence of 5 strains of Acinetobacter baumannii by using a mouse model of pneumonia. Methods Six-week old female C3H/HeN mice were used. The pneumonia was inducted by intra-tracheal inoculation of 5. 106 bacteria. Spontaneous outcome was evaluated by mortality, mice weight variations, and a clinical score. Bacterial counts in lungs, spleen and blood, and inflammatory response in lungs (dosages of tumor necrosis factor-alpha and macrophage inflammatory protein-2) were also measured. Lastly, a histological examination of lungs was performed for 3 strains, giving a histological score. Results Global mortality varied from 13% to 79% (P < 10−4). Bacterial counts in lungs within the 4 days following inoculation varied significantly according to different strains. The evolution curves of bacterial counts were also different. There was a significant correlation between the clinical score and mortality (P < 0.05) but not between bacterial counts in lungs and mortality. The increase of pro-inflammatory mediator production in lungs and the histological score also varied according to strains. Conclusions These results demonstrate the variability of the virulence between strains, and suggest that bacterial proliferation is not the only virulence factor responsible for the pathogenesis in A. baumannii pneumonia

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

Prioritizing global land protection for population persistence can double the efficiency of habitat protection for reducing mammal extinction risk

Halting the alarming rate of species extinction, driven primarily by habitat destruction, motivated the international community to adopt the Global Biodiversity Framework (2022) and its targets aimed at reversing habitat and species loss. Because of urgency and resource constraints, a key challenge is meeting targets effectively and efficiently. Here we conduct a global prioritization linking 70,492 unique population maps and life history characteristics for 861 threatened terrestrial mammal species. Incorporating individual population data to identify priority areas for conservation nearly doubled the likely long-term persistence of species for the same amount of land compared with a typical approach based on species distributions alone. We map and rank global mammal persistence priority areas and assess how well the current protected area (PA) system captures these important regions. Our results offer a clearer, quantifiable link between conservation actions and global extinction risk than previously possible at a global scale