Abstract Growing evidence suggests that toxic stressors early in life not only convey developmental impacts but also augment risk of proliferating chains of additional stressors that can overwhelm ...individual coping and undermine recovery and health. Examining trauma within a life course stress process perspective, we posit that early childhood adversity carries a unique capacity to impair adult psychological well-being both independent of and cumulative with other contributors, including social disadvantage and stressful adult experiences. This study uses data from a representative population-based health survey ( N = 13,593) to provide one of the first multivariate assessments of unique, cumulative, and moderated effects of adverse childhood experiences (ACEs) toward explaining 3 related yet distinct measures of adult mental health: perceived well-being, psychological distress, and impaired daily activities. Results demonstrate support for each set of hypothesized associations, including exacerbation and amelioration of ACEs effects by adult stress and resilience resources, respectively. Implications for services and future research are discussed.
Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine ...the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days.
Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m(2) per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths.
Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred.
Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.
ABSTRACT
We use photometric and kinematic data from Gaia DR2 to explore the structure of the star-forming region associated with the molecular cloud of Perseus. Apart from the two well-known ...clusters, IC 348 and NGC 1333, we present five new clustered groups of young stars, which contain between 30 and 300 members, named Autochthe, Alcaeus, Heleus, Electryon, and Mestor. We demonstrate that these are co-moving groups of young stars, based on how the candidate members are distributed in position, proper motion, parallax, and colour–magnitude space. By comparing their colour–magnitude diagrams to isochrones, we show that they have ages between 1 and 5 Myr. Using 2MASS and WISE colours, we find that the fraction of stars with discs in each group ranges from 10 to ∼50 per cent. The youngest of the new groups is also associated with a reservoir of cold dust, according to the Planck map at 353 GHz. We compare the ages and proper motions of the five new groups to those of IC 348 and NGC 1333. Autochthe is clearly linked with NGC 1333 and may have formed in the same star formation event. The seven groups separate roughly into two sets that share proper motion, parallax, and age: Heleus, Electryon, and Mestor as the older set, and NGC 1333 and Autochthe as the younger set. Alcaeus is kinematically related to the younger set, but at a more advanced age, while the properties of IC 348 overlap with both sets. All older groups in this star-forming region are located at higher galactic latitude.
There is an increasing awareness of the threats posed by the worldwide presence of microplastics (MPs) in the environment. Due to their high persistence, MPs will accumulate in the environment and ...their quantities tend to increase with time. MPs end up in environments where often also chemical contaminants are present. Since the early 2000s, the number of studies on the sorption of chemicals to plastic particles has exponentially increased. The objective of this study was to critically review the literature to identify the most important factors affecting the sorption of chemical contaminants to MPs. These factors include the physicochemical properties of both the MPs and the chemical contaminants as well as environmental characteristics. A limited number of studies on soil together with an increased notion of the importance of this compartment as a final sink for MPs was observed. Therefore, we assessed the distribution of model chemicals (two PCBs and phenanthrene) in the soil compartment in the presence of MPs using a mass balance model. The results showed a high variation among chemicals and microplastic types. Overall, a higher partitioning to MPs of chemical contaminants in soil is expected in comparison to aquatic environments. As sorption to a large extent determines bioavailability, the effects of combined exposure to chemicals and MPs on the toxicity and bioaccumulation in biota are discussed. Finally, some considerations regarding sorption and toxicity studies using MPs are given.
Display omitted
•Increasing number of studies investigated the sorption of contaminants to microplastics.•Hydrophobic and electrostatic forces are the main mechanisms for sorption.•Environmental conditions also affect the sorption process.•Higher fractions of contaminant sorbed to microplastics in soil than in aquatic phase.•Sorption may explain the bioavailability of chemicals in the presence of microplastics.
The mechanisms for the sorption of contaminants to microplastics are driven by their interactions, and may greatly affect their environmental fate and toxicity.
The disparity in the amount and quality of language that low-income children hear relative to their more-affluent peers is often referred to as the 30-million-word gap. Here, we expand the literature ...about this disparity by reporting the relative contributions of the quality of early parent-child communication and the quantity of language input in 60 low-income families. Including both successful and struggling language learners from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, we noted wide variation in the quality of nonverbal and verbal interactions (symbol-infused joint engagement, routines and rituals, fluent and connected communication) at 24 months, which accounted for 27% of the variance in expressive language 1 year later. These indicators of quality were considerably more potent predictors of later language ability than was the quantity of mothers' words during the interaction or sensitive parenting. Bridging the word gap requires attention to how caregivers and children establish a communication foundation within low-income families.
Researchers interested in the effects of early experiences of caregiving adversity have employed neuroscientific methods to illuminate whether and how such environmental input impacts on brain ...development, and whether and how such impacts underpin poor socioemotional outcomes in this population. Evidence is compelling in documenting negative effects on the individual's neurodevelopment following exposure to adverse or disadvantaged environments such as institutionalization or maltreatment. Neuroimaging research focused specifically on attachment-relevant processing of socioemotional stimuli and attachment outcomes among children looked-after is scarcer, but largely consistent. This review begins by summarizing the key general brain structural and functional alterations associated with caregiving deprivation. Then, neuroscientific evidence that is more directly relevant for understanding these children's attachment outcomes, both by employing social stimuli and by correlating children's neural markers with their attachment profiles, is reviewed. Brief interpretations of findings are suggested, and key limitations and gaps in the literature identified.
Highlights • Vaccine-type pneumococcal carriage declined by >90% after PCV10 introduction. • Effectiveness of 4 PCV10 doses against carriage of vaccine serotypes was 97.3%. • No protection against ...carriage of vaccine-related serotypes (including 6A and 19A) was observed. • Colonization by non-typeable H. influenzae increased from 26.0% at baseline to 43.6% post-PCV10.
Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Autoimmune diseases (ADs) are a family of ...complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. Collectively, ADs are common, exhibit gender and ethnic disparities, and increasing incidence. As natural selection is an important influence on human genetic variation, and immune function genes are enriched for signals of positive selection, it is thought that the prevalence of AD risk alleles seen in different population is partially the result of differing selective pressures (for example, due to pathogens). With the advent of high-throughput technologies, new analytical methodologies and large-scale projects, evidence for the role of natural selection in contributing to the heritable component of ADs keeps growing. This review summarizes the genetic regions associated with susceptibility to different ADs and concomitant evidence for selection, including known agents of selection exerting selective pressure in these regions. Examples of specific adaptive variants with phenotypic effects are included as an evidence of natural selection increasing AD susceptibility. Many of the complexities of gene effects in different ADs can be explained by population genetics phenomena. Integrating AD susceptibility studies with population genetics to investigate how natural selection has contributed to genetic variation that influences disease risk will help to identify functional variants and elucidate biological mechanisms. As such, the study of population genetics in human population holds untapped potential for elucidating the genetic causes of human disease and more rapidly focusing to personalized medicine.
ABSTRACT
We determine the cosmic abundance of molecular hydrogen (H2) in the local Universe from the xCOLD GASS survey. To constrain the H2 mass function at low masses and correct for the effect of ...the lower stellar mass limit of $10^9 \, \mathrm{M}_{\odot }$ in the xCOLD GASS survey, we use an empirical approach based on an observed scaling relation between star formation rate and gas mass. We also constrain the H i and H i+H2 mass functions using the xGASS survey and compare them to the H i mass function from the ALFALFA survey. We find the cosmic abundance of molecular gas in the local Universe to be $\Omega _{\mathrm{H_2}} = (5.34 \pm 0.47) \times 10^{-5} h^{-1}$. Molecular gas accounts for $19.6\pm 3.9{{\ \rm per\ cent}}$ of the total abundance of cold gas, $\mathrm{\Omega _{H\,{\small I}+H_{2}}} = (4.66 \pm 0.70) \times 10^{-4}\, h_{70}^{-1}$. Galaxies with stellar masses in excess of 109$\, \mathrm{M}_{\odot }$ account for 89 per cent of the molecular gas in the local Universe, while in comparison such galaxies only contain 73 per cent of the cold atomic gas as traced by the H i 21cm line. The xCOLD GASS CO, molecular gas and cold gas mass functions, and $\Omega _{\mathrm{H_2}}$ measurements provide constraints for models of galaxy evolution and help to anchor blind molecular gas surveys attempting to determine the abundance of molecular gas at high redshifts.
PDF
