Lyman Continuum Escape Fraction of Star-forming Dwarf Galaxies at z ~ 1

To date, no direct detection of Lyman continuum emission has been measured for intermediate-redshift (z ~ 1) star-forming galaxies. We combine Hubble Space Telescope grism spectroscopy with GALEX UV and ground-based optical imaging to extend the search for escaping Lyman continuum to a large (~600) sample of z ~ 1 low-mass log(M)≃ 9.3 M_☉), moderately star-forming (ψ ≾ 10M_☉ yr^(−1)) galaxies selected initially on Hα emission. The characteristic escape fraction of LyC from star-forming galaxies (SFGs) that populate this parameter space remains weakly constrained by previous surveys, but these faint (sub-Lsstarf) SFGs are assumed to play a significant role in the reionization of neutral hydrogen in the intergalactic medium (IGM) at high redshift z > 6. We do not make an unambiguous detection of escaping LyC radiation from this z ~ 1 sample, individual non-detections to constrain the absolute Lyman continuum escape fraction, f_(esc) 200Å), which are thought to be close analogs of high redshift sources of reionization. For reference, we also present an emissivity-weighted escape fraction that is useful for measuring the general contribution SFGs to the ionizing UV background. In the discussion, we consider the implications of these intermediate redshift constraints for the reionization of hydrogen in the IGM at high (z > 6) redshift. If we assume our z ~ 1 SFGs, for which we measure this emissivity-weighted f_(esc), are analogs to the high redshift sources of reionization, we find it is difficult to reconcile reionization by faint (M}_(UV) ≾-13) SFGs with a low escape fraction (f_(esc) < 3%), with constraints from independent high redshift observations. If f_(esc) evolves with redshift, reionization by SFGs may be consistent with observations from Planck

Are Some Natural Environments More Psychologically Beneficial Than Others? The Importance of Type and Quality on Connectedness to Nature and Psychological Restoration

Exposure to nature can strengthen an individual’s sense of connectedness (i.e., emotional/cognitive bonds to the natural world) and enhance psychological restoration (e.g., feeling relaxed/refreshed). To date, there have been few large studies looking at the role that type and quality of natural environments may have on these outcomes. The present study used data from a large survey in England (sample analyzed = 4,515), which asked participants to recall a recent visit to nature. After controlling for covariates, respondents recalled greater connectedness to nature and restoration following visits to rural and coastal locations compared with urban green space, and to sites of higher environmental quality (operationalized by protected/designated area status, for example, nature reserves). A series of structural equation analyses provided evidence for a bidirectional association between connectedness and restoration. Consideration of the psychological benefits associated with different types and quality of environment has implications for human health, environmental management, and conservation

A Validated Preclinical Animal Model for Primary Bone Tumor Research

Funding for this study was provided by the German Research Foundation (Grant DFG WA 3606/1-1 to F. Wagner and Grant HO 5056/1-1 to B.M. Holzapfel), the Australian Research Council (Future Fellowship Program) and the Technical University Munich Hans Fischer Senior Fellowship (D.W. Hutmacher), and a Research Fellowship from the National Health and Medical Research Council (#1044091 to J.-P. Lévesque

Cardiac biomarkers in pediatric cardiomyopathy: Study design and recruitment results from the Pediatric Cardiomyopathy Registry

Background: Cardiomyopathies are a rare cause of pediatric heart disease, but they are one of the leading causes of heart failure admissions, sudden death, and need for heart transplant in childhood. Reports from the Pediatric Cardiomyopathy Registry (PCMR) have shown that almost 40% of children presenting with symptomatic cardiomyopathy either die or undergo heart transplant within 2 years of presentation. Little is known regarding circulating biomarkers as predictors of outcome in pediatric cardiomyopathy. Study Design: The Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) study is a multi-center prospective study conducted by the PCMR investigators to identify serum biomarkers for predicting outcome in children with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Patients less than 21 years of age with either DCM or HCM were eligible. Those with DCM were enrolled into cohorts based on time from cardiomyopathy diagnosis: categorized as new onset or chronic. Clinical endpoints included sudden death and progressive heart failure. Results: There were 288 children diagnosed at a mean age of 7.2±6.3 years who enrolled in the PCM Biomarkers Study at a median time from diagnosis to enrollment of 1.9 years. There were 80 children enrolled in the new onset DCM cohort, defined as diagnosis at or 12 months prior to enrollment. The median age at diagnosis for the new onset DCM was 1.7 years and median time from diagnosis to enrollment was 0.1 years. There were 141 children enrolled with either chronic DCM or chronic HCM, defined as children ≥2 years from diagnosis to enrollment. Among children with chronic cardiomyopathy, median age at diagnosis was 3.4 years and median time from diagnosis to enrollment was 4.8 years. Conclusion: The PCM Biomarkers study is evaluating the predictive value of serum biomarkers to aid in the prognosis and management of children with DCM and HCM. The results will provide valuable information where data are lacking in children. Clinical Trial Registration: NCT01873976 https://clinicaltrials.gov/ct2/show/NCT01873976?term=PCM+Biomarker&rank=

Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study

Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing (P=0.005 and P=0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first-degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy

Influence of density and salinity on larval development of salt-adapted and salt-naïve frog populations

Environmental change and habitat fragmentation will affect population densities for many species. For those species that have locally adapted to persist in changed or stressful habitats, it is uncertain how density dependence will affect adaptive responses. Anurans (frogs and toads) are typically freshwater organisms, but some coastal populations of green treefrogs (Hyla cinerea) have adapted to brackish, coastal wetlands. Tadpoles from coastal populations metamorphose sooner and demonstrate faster growth rates than inland populations when reared solitarily. Although saltwater exposure has adaptively reduced the duration of the larval period for coastal populations, increases in densities during larval development typically in-crease time to metamorphosis and reduce rates of growth and survival. We test how combined stressors of density and salinity affect larval development between salt-adapted ("coastal") and nonsalt-adapted ("inland") populations by measuring various developmental and metamorphic phenotypes. We found that increased tadpole density strongly affected coastal and inland tadpole populations similarly. In high-density treatments, both coastal and inland populations had reduced growth rates, greater exponential decay of growth, a smaller size at metamorphosis, took longer to reach metamorphosis, and had lower survivorship at metamorphosis. Salinity only exaggerated the effects of density on the time to reach metamorphosis and exponential decay of growth. Location of origin affected length at metamorphosis, with coastal tadpoles metamorphosing slightly longer than inland tadpoles across densities and salinities. These findings confirm that density has a strong and central influence on larval development even across divergent populations and habitat types and may mitigate the expression (and therefore detection) of locally adapted phenotypes

Influence of density and salinity on larval development of salt-adapted and salt-naïve frog populations

Environmental change and habitat fragmentation will affect population densities for many species. For those species that have locally adapted to persist in changed or stressful habitats, it is uncertain how density dependence will affect adaptive responses. Anurans (frogs and toads) are typically freshwater organisms, but some coastal populations of green treefrogs (Hyla cinerea) have adapted to brackish, coastal wetlands. Tadpoles from coastal populations metamorphose sooner and demonstrate faster growth rates than inland populations when reared solitarily. Although saltwater exposure has adaptively reduced the duration of the larval period for coastal populations, increases in densities during larval development typically in-crease time to metamorphosis and reduce rates of growth and survival. We test how combined stressors of density and salinity affect larval development between salt-adapted (“coastal”) and nonsalt-adapted (“inland”) populations by measuring various developmental and metamorphic phenotypes. We found that increased tadpole density strongly affected coastal and inland tadpole populations similarly. In high-density treatments, both coastal and inland populations had reduced growth rates, greater exponential decay of growth, a smaller size at metamorphosis, took longer to reach metamorphosis, and had lower survivorship at metamorphosis. Salinity only exaggerated the effects of density on the time to reach metamorphosis and exponential decay of growth. Location of origin affected length at metamorphosis, with coastal tadpoles metamorphosing slightly longer than inland tadpoles across densities and salinities. These findings confirm that density has a strong and central influence on larval development even across divergent populations and habitat types and may mitigate the expression (and therefore detection) of locally adapted phenotypes

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

There is a call for a paradigm shift in developmental neurotoxicity (DNT) evaluation, which demands the implementation of faster, more cost-efficient, and human-relevant test systems than current in vivo guideline studies. Under the umbrella of the Organisation for Economic Co-operation and Development (OECD), a guidance document is currently being prepared that instructs on the regulatory use of a DNT in vitro battery (DNT IVB) for fit-for-purpose applications. One crucial issue for OECD application of methods is validation, which for new approach methods (NAMs) requires novel approaches. Here, mechanistic information previously identified in vivo, as well as reported neurodevelopmental adversities in response to disturbances on the cellular and tissue level, are of central importance. In this study, we scientifically validate the Neurosphere Assay, which is based on human primary neural progenitor cells (hNPCs) and an integral part of the DNT IVB. It assesses neurodevelopmental key events (KEs) like NPC proliferation (NPC1ab), radial glia cell migration (NPC2a), neuronal differentiation (NPC3), neurite outgrowth (NPC4), oligodendrocyte differentiation (NPC5), and thyroid hormone-dependent oligodendrocyte maturation (NPC6). In addition, we extend our work from the hNPCs to human induced pluripotent stem cell-derived NPCs (hiNPCs) for the NPC proliferation (iNPC1ab) and radial glia assays (iNPC2a). The validation process we report for the endpoints studied with the Neurosphere Assays is based on 1) describing the relevance of the respective endpoints for brain development, 2) the confirmation of the cell type-specific morphologies observed in vitro, 3) expressions of cell type-specific markers consistent with those morphologies, 4) appropriate anticipated responses to physiological pertinent signaling stimuli and 5) alterations in specific in vitro endpoints upon challenges with confirmed DNT compounds. With these strong mechanistic underpinnings, we posit that the Neurosphere Assay as an integral part of the DNT in vitro screening battery is well poised for DNT evaluation for regulatory purposes