50 resultados para Rothschild, Nathan Mayer vonRothschild, Nathan Mayer vonNathan MayerRothschildvon
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Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.
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Background: Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Results: Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in earlylife environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoorhoused pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results.
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Bioaccessibility tests can be used to improve contaminated land risk assessments. For organic pollutants a ‘sink’ is required within these tests to better mimic their desorption under the physiological conditions prevailing in the intestinal tract, where a steep diffusion gradient for the removal of organic pollutants from the soil matrix would exist. This is currently ignored in most PBET systems. By combining the CEPBET bioaccessibility test with an infinite sink, the removal of PAH from spiked solutions was monitored. Less than 10% of spiked PAH remained in the stomach media after 1 h, 10% by 4 h in the small intestine compartment and c.15% after 16 h in the colon. The addition of the infinite sink increased bioaccessibility estimates for field soils by a factor of 1.2–2.8, confirming its importance for robust PBET tests. TOC or BC were not the only factors controlling desorption of the PAH from the soils.
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Older people increasingly want to remain living independently in their own homes. The aim of the ENABLE project is to develop a wearable device that can be used to support older people in their daily lives and which can monitor their health status, detect potential problems, provide activity reminders and offer communication and alarm services. In order to determine the specifications and functionality required for the development of the device, user surveys and focus groups were undertaken, use case analysis and scenario modeling carried out. The project has resulted in the development of a wrist-worn device and mobile phone combination that can support and assist older and vulnerable wearers with a range of activities and services both inside their home and as they move around their local environment. The device is currently undergoing pilot trials in five European countries. The aim of this paper is to describe the ENABLE device, its features and services, and the infrastructure within which it operates.
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This paper explores the nature of private social and environmental reporting (SER). From interviews with UK institutional investors, we show that both investors and investees employ Goffmanesque, staged impression management as a means of creating and disseminating a dual myth of social and environmental accountability. The interviewees’ utterances unveil private meetings imbued with theatrical verbal and physical impression management. Most of the time, the investors’ shared awareness of reality belongs to a Goffmanesque frame whereby they accept no intentionality, misrepresentation or fabrication, believing instead that the ‘performers’ (investees) are not intending to deceive them. A shared perception that social and environmental considerations are subordinated to financial issues renders private SER an empty encounter characterised as a relationship-building exercise with seldom any impact on investment decision-making. Investors spoke of occasional instances of fabrication but these were insufficient to break the frame of dual myth creation. They only identified a handful of instances where intentional misrepresentation had been significant enough to alter their reality and behaviour. Only in the most extreme cases of fabrication and lying did the staged meeting break frame and become a genuine occasion of accountability, where investors demanded greater transparency, further meetings and at the extreme, divested shares. We conclude that the frontstage, ritualistic impression management in private SER is inconsistent with backstage activities within financial institutions where private financial reporting is prioritised. The investors appeared to be in a double bind whereby they devoted resources to private SER but were simultaneously aware that these efforts may be at best subordinated, at worst ignored, rendering private SER a predominantly cosmetic, theatrical and empty exercise.
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Purpose – This paper aims to explore the nature of the emerging discourse of private climate change reporting, which takes place in one-on-one meetings between institutional investors and their investee companies. Design/methodology/approach – Semi-structured interviews were conducted with representatives from 20 UK investment institutions to derive data which was then coded and analysed, in order to derive a picture of the emerging discourse of private climate change reporting, using an interpretive methodological approach, in addition to explorative analysis using NVivo software. Findings – The authors find that private climate change reporting is dominated by a discourse of risk and risk management. This emerging risk discourse derives from institutional investors' belief that climate change represents a material risk, that it is the most salient sustainability issue, and that their clients require them to manage climate change-related risk within their portfolio investment. It is found that institutional investors are using the private reporting process to compensate for the acknowledged inadequacies of public climate change reporting. Contrary to evidence indicating corporate capture of public sustainability reporting, these findings suggest that the emerging private climate change reporting discourse is being captured by the institutional investment community. There is also evidence of an emerging discourse of opportunity in private climate change reporting as the institutional investors are increasingly aware of a range of ways in which climate change presents material opportunities for their investee companies to exploit. Lastly, the authors find an absence of any ethical discourse, such that private climate change reporting reinforces rather than challenges the “business case” status quo. Originality/value – Although there is a wealth of sustainability reporting research, there is no academic research on private climate change reporting. This paper attempts to fill this gap by providing rich interview evidence regarding the nature of the emerging private climate change reporting discourse.
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We describe the main differences in simulations of stratospheric climate and variability by models within the fifth Coupled Model Intercomparison Project (CMIP5) that have a model top above the stratopause and relatively fine stratospheric vertical resolution (high-top), and those that have a model top below the stratopause (low-top). Although the simulation of mean stratospheric climate by the two model ensembles is similar, the low-top model ensemble has very weak stratospheric variability on daily and interannual time scales. The frequency of major sudden stratospheric warming events is strongly underestimated by the low-top models with less than half the frequency of events observed in the reanalysis data and high-top models. The lack of stratospheric variability in the low-top models affects their stratosphere-troposphere coupling, resulting in short-lived anomalies in the Northern Annular Mode, which do not produce long-lasting tropospheric impacts, as seen in observations. The lack of stratospheric variability, however, does not appear to have any impact on the ability of the low-top models to reproduce past stratospheric temperature trends. We find little improvement in the simulation of decadal variability for the high-top models compared to the low-top, which is likely related to the fact that neither ensemble produces a realistic dynamical response to volcanic eruptions.
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Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.
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Over Arctic sea ice, pressure ridges and floe andmelt pond edges all introduce discrete obstructions to the flow of air or water past the ice and are a source of form drag. In current climate models form drag is only accounted for by tuning the air–ice and ice–ocean drag coefficients, that is, by effectively altering the roughness length in a surface drag parameterization. The existing approach of the skin drag parameter tuning is poorly constrained by observations and fails to describe correctly the physics associated with the air–ice and ocean–ice drag. Here, the authors combine recent theoretical developments to deduce the total neutral form drag coefficients from properties of the ice cover such as ice concentration, vertical extent and area of the ridges, freeboard and floe draft, and the size of floes and melt ponds. The drag coefficients are incorporated into the Los Alamos Sea Ice Model (CICE) and show the influence of the new drag parameterization on the motion and state of the ice cover, with the most noticeable being a depletion of sea ice over the west boundary of the Arctic Ocean and over the Beaufort Sea. The new parameterization allows the drag coefficients to be coupled to the sea ice state and therefore to evolve spatially and temporally. It is found that the range of values predicted for the drag coefficients agree with the range of values measured in several regions of the Arctic. Finally, the implications of the new form drag formulation for the spinup or spindown of the Arctic Ocean are discussed.
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There has been a recent rejuvenation of interest in studies of motivation-cognition interactions arising from many different areas of psychology and neuroscience. The current issue of Cognitive, Affective, and Behavioral Neuroscience provides a sampling of some of the latest research from a number of these different areas. In this introductory paper, we provide an overview of the current state of the field, in terms of key research developments and candidate neural mechanisms receiving focused investigation as potential sources of motivation-cognition interaction. However, our primary goal is conceptual: to highlight the distinct perspectives taken by different research areas in terms of how motivation is defined, the relevant dimensions and dissociations that are emphasized, and the theoretical questions being targeted. Together, these distinctions present both challenges and opportunities for efforts aiming towards a more unified and cross-disciplinary approach. We identify a set of pressing research questions calling out for this sort of cross-disciplinary approach, with the explicit goal of encouraging integrative and collaborative investigations directed towards them.
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In this study we examine the performance of 31 global model radiative transfer schemes in cloud-free conditions with prescribed gaseous absorbers and no aerosols (Rayleigh atmosphere), with prescribed scattering-only aerosols, and with more absorbing aerosols. Results are compared to benchmark results from high-resolution, multi-angular line-by-line radiation models. For purely scattering aerosols, model bias relative to the line-by-line models in the top-of-the atmosphere aerosol radiative forcing ranges from roughly −10 to 20%, with over- and underestimates of radiative cooling at lower and higher solar zenith angle, respectively. Inter-model diversity (relative standard deviation) increases from ~10 to 15% as solar zenith angle decreases. Inter-model diversity in atmospheric and surface forcing decreases with increased aerosol absorption, indicating that the treatment of multiple-scattering is more variable than aerosol absorption in the models considered. Aerosol radiative forcing results from multi-stream models are generally in better agreement with the line-by-line results than the simpler two-stream schemes. Considering radiative fluxes, model performance is generally the same or slightly better than results from previous radiation scheme intercomparisons. However, the inter-model diversity in aerosol radiative forcing remains large, primarily as a result of the treatment of multiple-scattering. Results indicate that global models that estimate aerosol radiative forcing with two-stream radiation schemes may be subject to persistent biases introduced by these schemes, particularly for regional aerosol forcing.
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Two methods are developed to estimate net surface energy fluxes based upon satellite-based reconstructions of radiative fluxes at the top of atmosphere and the atmospheric energy tendencies and transports from the ERA-Interim reanalysis. Method 1 applies the mass adjusted energy divergence from ERA-Interim while method 2 estimates energy divergence based upon the net energy difference at the top of atmosphere and the surface from ERA-Interim. To optimise the surface flux and its variability over ocean, the divergences over land are constrained to match the monthly area mean surface net energy flux variability derived from a simple relationship between the surface net energy flux and the surface temperature change. The energy divergences over the oceans are then adjusted to remove an unphysical residual global mean atmospheric energy divergence. The estimated net surface energy fluxes are compared with other data sets from reanalysis and atmospheric model simulations. The spatial correlation coefficients of multi-annual means between the estimations made here and other data sets are all around 0.9. There are good agreements in area mean anomaly variability over the global ocean, but discrepancies in the trend over the eastern Pacific are apparent.