105 research outputs found

    Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

    Get PDF
    BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

    Representing Knowledge About Words

    Get PDF
    Most on-line lexicons contain only semantic information. Semantic information is usually stored elsewhere, in a form consistent with representation of the syntactic information. This paper reports on research toward developing a large on-line lexicon from machine-readable dictionaries, which contains both syntactic and semantic information in uniform style. The fundamental theory is that of one of the relational lexicon; we describe relational lexicons, discuss our extensions to the usual theory of relational lexicons, rehearse very quickly some of the relations we are dealing with, and show how information for some simple entries is stored

    Signatures of Star-planet interactions

    Full text link
    Planets interact with their host stars through gravity, radiation and magnetic fields, and for those giant planets that orbit their stars within \sim10 stellar radii (\sim0.1 AU for a sun-like star), star-planet interactions (SPI) are observable with a wide variety of photometric, spectroscopic and spectropolarimetric studies. At such close distances, the planet orbits within the sub-alfv\'enic radius of the star in which the transfer of energy and angular momentum between the two bodies is particularly efficient. The magnetic interactions appear as enhanced stellar activity modulated by the planet as it orbits the star rather than only by stellar rotation. These SPI effects are informative for the study of the internal dynamics and atmospheric evolution of exoplanets. The nature of magnetic SPI is modeled to be strongly affected by both the stellar and planetary magnetic fields, possibly influencing the magnetic activity of both, as well as affecting the irradiation and even the migration of the planet and rotational evolution of the star. As phase-resolved observational techniques are applied to a large statistical sample of hot Jupiter systems, extensions to other tightly orbiting stellar systems, such as smaller planets close to M dwarfs become possible. In these systems, star-planet separations of tens of stellar radii begin to coincide with the radiative habitable zone where planetary magnetic fields are likely a necessary condition for surface habitability.Comment: Accepted for publication in the handbook of exoplanet

    Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal

    Get PDF
    Background: The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies. Methods/design: A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods. Discussion: The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation. Trial registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974

    Diversity and community biomass depend on dispersal and disturbance in microalgal communities

    Get PDF
    The evidence for species diversity effects on ecosystem functions is mainly based on studies not explicitly addressing local or regional processes regulating coexistence or the importance of community structure in terms of species evenness. In experimental communities of marine benthic microalgae, we altered the successional stages and thus the strength of local species interactions by manipulating rates of dispersal and disturbance. The treatments altered realized species richness, evenness and community biomass. For species richness, dispersal mattered only at high disturbance rates; when opening new space, dispersal led to maximized richness at intermediate dispersal rates. Evenness, in contrast, decreased with dispersal at low or no disturbance, i.e. at late successional stages. Community biomass showed a nonlinear hump-shaped response to increasing dispersal at all disturbance levels.We found a positive correlation between richness and biomass at early succession, and a strong negative correlation between evenness and biomass at late succession. In early succession both community biomass and richness depend directly on dispersal from the regional pool, whereas the late successional pattern shows that if interactions allow the most productive species to become dominant, diverting resources from this species (i.e. higher evenness) reduces production. Our study emphasizes the difference in biodiversity–function relationships over time, as different mechanisms contribute to the regulation of richness and evenness in early and late successional stages

    Evidence for waning of latency in a cohort study of tuberculosis

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>To investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age.</p> <p>Methods</p> <p>Cohort analysis of data for the separate ten year birth cohorts of 1876-1885 to 1959-1968 obtained from Statistics Norway and the National Tuberculosis Registry. These data were used to calculate the rates and the changes in the rates of bacillary (or active) tuberculosis. Data on bacillary tuberculosis for adult (20+) age groups were obtained from the National Tuberculosis Registry and Statistics Norway from 1946 to 1974. Most cases during this period arose due to reactivation of remote infection. Participants in this part of the analysis were all reported active tuberculosis cases in Norway from 1946 to 1974 as recorded in the National Tuberculosis Registry.</p> <p>Results</p> <p>Tuberculosis decreased at a relatively steady rate when following individual birth cohorts, but with a tendency of slower decline as time passed since infection. A mean estimate of this rate of decline was 57% in a 10 year period.</p> <p>Conclusions</p> <p>The risk of reactivation of latent tuberculosis decreases with age. This decline may reflect the rate at which latent tuberculosis is eliminated from a population with minimal transmission of tubercle bacilli. A model for risk of developing active tuberculosis as a function of time since infection shows that the rate at which tuberculosis can be eliminated from a society can be quite substantial if new infections are effectively prevented. The findings clearly indicate that preventative measures against transmission of tuberculosis will be the most effective. These results also suggest that the total population harbouring live tubercle bacilli and consequently the future projection for increased incidence of tuberculosis in the world is probably overestimated.</p

    Users' perspectives of barriers and facilitators to implementing EHR in Canada: A study protocol

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In Canada, federal, provincial, and territorial governments are developing an ambitious project to implement an interoperable electronic health record (EHR). Benefits for patients, healthcare professionals, organizations, and the public in general are expected. However, adoption of an interoperable EHR remains an important issue because many previous EHR projects have failed due to the lack of integration into practices and organizations. Furthermore, perceptions of the EHR vary between end-user groups, adding to the complexity of implementing this technology. Our aim is to produce a comprehensive synthesis of actual knowledge on the barriers and facilitators influencing the adoption of an interoperable EHR among its various users and beneficiaries.</p> <p>Methods</p> <p>First, we will conduct a comprehensive review of the scientific literature and other published documentation on the barriers and facilitators to the implementation of the EHR. Standardized literature search and data extraction methods will be used. Studies' quality and relevance to inform decisions on EHR implementation will be assessed. For each group of EHR users identified, barriers and facilitators will be categorized and compiled using narrative synthesis and meta-analytical techniques. The principal factors identified for each group of EHR users will then be validated for its applicability to various Canadian contexts through a two-round Delphi study, involving representatives from each end-user groups. Continuous exchanges with decision makers and periodic knowledge transfer activities are planned to facilitate the dissemination and utilization of research results in policies regarding the implementation of EHR in the Canadian healthcare system.</p> <p>Discussion</p> <p>Given the imminence of an interoperable EHR in Canada, knowledge and evidence are urgently needed to prepare this major shift in our healthcare system and to oversee the factors that could affect its adoption and integration by all its potential users. This synthesis will be the first to systematically summarize the barriers and facilitators to EHR adoption perceived by different groups and to consider the local contexts in order to ensure the applicability of this knowledge to the particular realities of various Canadian jurisdictions. This comprehensive and rigorous strategy could be replicated in other settings.</p

    Measurement of the 13 C isotopic signature of methane emissions from Northern European wetlands

    Get PDF
    Isotopic data provide powerful constraints on regional and global methane emissions and their source profiles. However, inverse modeling of spatially-resolved methane flux is currently constrained by a lack of information on the variability of source isotopic signatures. In this study, isotopic signatures of emissions in the Fennoscandian Arctic have been determined in chambers over wetland, in the air 0.3 to 3 m above the wetland surface and by aircraft sampling from 100 m above wetlands up to the stratosphere. Overall the methane flux to atmosphere has a coherent δ13C isotopic signature of -71 ± 1‰, measured in situ on the ground in wetlands. This is in close agreement with δ13C isotopic signatures of local and regional methane increments measured by aircraft campaigns flying through air masses containing elevated methane mole fractions. In contrast results from wetlands in Canadian boreal forest further south gave isotopic signatures of -67 ± 1 ‰. Wetland emissions dominate the local methane source measured over the European Arctic in summer. Chamber measurements demonstrate a highly variably methane flux and isotopic signature, but the results from air sampling within wetland areas show that emissions mix rapidly immediately above the wetland surface and methane emissions reaching the wider atmosphere do indeed have strongly coherent C isotope signatures. The study suggests that for boreal wetlands (>60°N) global and regional modeling can use an isotopic signature of -71‰ to apportion sources more accurately, but there is much need for further measurements over other wetlands regions to verify this.UK Natural Environment Research Council (NERC). Grant Numbers: NE/I028874/1, NE/I014683/1, NE/F020937/1 European Community's Seventh Framework Programme. Grant Number: FP7/2007‐2013 InGOS. Grant Number: 28427
    corecore