4,605 research outputs found
Does Glycosylation as a modifier of Original Antigenic Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza?
Background: A pandemic novel H1N1 swine-origin influenza virus has emerged. Most recently the World Health Organization has announced that in a country-dependent fashion, up to 15% of cases may require hospitalization, often including respiratory support. It is now clear that healthy children and young adults are disproportionately affected, most unusually among those with severe respiratory disease without underlying conditions. One possible explanation for this case age distribution is the doctrine of Original Antigenic Sin, i.e., novel H1N1 may be antigenically similar to H1N1 viruses that circulated at an earlier time. Persons whose first exposure to influenza viruses was to such similar viruses would be relatively immune. However, this principle is not sufficient to explain the graded susceptibility between ages 20 and 60, the reduced susceptibility in children below age 10, and the unusual toxicity observed.Methods: We collected case data from 11 countries, about 60% of all cases reported through mid-July 2009. We compared sequence data for the hemagglutinin of novel H1N1 with sequences of H1N1 viruses from 1918 to the present. We searched for sequence differences that imply loss of antigenicity either directly through amino acid substitution or by the appearance of sites for potential glycosylation proximal to sites known to be antigenic in humans. We also considered T-cell epitopes.Results: In our composite, over 75% of confirmed cases of novel H1N1 occurred in persons ≤ 30 years old, with peak incidence in the age range 10-19 years. Less than 3% of cases occurred in persons over 65, with a gradation in incidence between ages 20 and 60 years.The sequence data indicates that novel H1N1 is most similar to H1N1 viruses that circulated before 1943. Novel H1N1 lacks glycosylation sites on the globular head of hemagglutinin (HA1) near antigenic regions, a pattern shared with the 1918 pandemic strain and H1N1 viruses that circulated until the early 1940s. Later H1N1 viruses progressively added new glycosylation sites likely to shield antigenic epitopes, while T-cell epitopes were relatively unchanged.Conclusions: In this evolutionary context, Original Antigenic Sin exposure should produce an immune response increasingly mismatched to novel H1N1 in progressively younger persons. We suggest that it is this mismatch that produces both the gradation in susceptibility and the unusual toxicity. Several murine studies suggest specific cell types as a likely basis of the unusual toxicity. These studies also point to widely available pharmaceutical agents as plausible candidates for mitigating the toxic effects. The principle of Original Antigenic Sin modified by glycosylation appears to explain both the case age distribution and the unusual toxicity pattern of the novel H1N1 pandemic. In addition, it suggests pharmaceutical agents for immediate investigation for mitigation potential, and provides strategic guidance for the distribution of pandemic mitigation resources of all types. © 2010 Reichert et al; licensee BioMed Central Ltd.published_or_final_versio
Strategic Response by providers to specialty hospitals, ambulatory surgery centers, and retail clinics.
Radical innovation and disruptive technologies are frequently heralded as a solution to delivering higher quality, lower cost health care. According to the literature on disruption, local hospitals and physicians (incumbent providers) may be unable to competitively respond to such creative destruction and alter their business models for a host of reasons, thus threatening their future survival. However, strategic management theory and research suggest that, under certain conditions, incumbent providers may be able to weather the discontinuities posed by the disrupters. This article analyzes 3 disruptive innovations in service delivery: single-specialty hospitals, ambulatory surgical centers, and retail clinics. We first discuss the features of these innovations to assess how disruptive they are. We then draw on the literature on strategic adaptation to suggest how incumbents develop competitive responses to these disruptive innovations that assure their continued survival. These arguments are then evaluated in a field study of several urban markets based on interviews with both incumbents and entrants. The interviews indicate that entrants have failed to disrupt incumbent providers primarily as a result of strategies pursued by the incumbents. The findings cast doubt on the prospects for these disruptive innovations to transform health care
Critical Innovations in the UK Peer-to-Peer (P2P) and Equity Alternative Finance Markets for Small Firm Growth
© The Author(s) 2016. The final, definitive version of this paper has been published in The International Journal of Entrepreneurship and Innovation by Sage Publications Ltd. All rights reserved. It is available at: https://doi.org/10.1177/1465750316655906This paper examines the disruptive nature of financial innovations available to small firms by the growing range of online platforms that have emerged in the UK since the financial crisis. It is unveiled that finance provided to small firms via such mechanisms is not identical to more traditional sources and its adoption therefore cannot be said to be simply a question of direct substitution based, for example, on a price comparison. These offer a series of important advantages over more traditional sources of early-stage capital for entrepreneurs seeking funding. Service innovations around security, flexibility of terms, speed of access and transparency of pricing are as important as price considerations for many users, as are innovations made possible by the way these online markets are structured and in particular in the way these innovative structures allow important types of risk to be dispersed and mitigated.Peer reviewedFinal Accepted Versio
Morphological characterization of sweet and sour cherry cultivars in a germplasm bank at Portugal
Nine sweet cherry and eight sour cherry varieties located in a germplasm bank at Fundauo, Portugal, were studied from the viewpoint of characterization. Most of them were autochthonous cultivars that have a high risk of extinction since at the present they are markedly minor varieties. Morphological characteristics were evaluated in different organs: crown and trunk of the trees, leaves, flowers and fruits, over a three consecutive years period. Statistical analyses were carried out in order to detect similarities between cultivars as well as the existence of synonymies. Qualitative characteristics of the fruits were scored in order to carry out the multivariate analysis. A dendrogram of the evaluated characters shows the marked differentiation between sour and sweet cherries and suggests the existing synonymies. Conservation of the autochthonous cultivars in the future is highly recommended
Habit-based interventions for weight loss maintenance in adults with overweight and obesity: a randomized controlled trial
Interaction Between Convection and Pulsation
This article reviews our current understanding of modelling convection
dynamics in stars. Several semi-analytical time-dependent convection models
have been proposed for pulsating one-dimensional stellar structures with
different formulations for how the convective turbulent velocity field couples
with the global stellar oscillations. In this review we put emphasis on two,
widely used, time-dependent convection formulations for estimating pulsation
properties in one-dimensional stellar models. Applications to pulsating stars
are presented with results for oscillation properties, such as the effects of
convection dynamics on the oscillation frequencies, or the stability of
pulsation modes, in classical pulsators and in stars supporting solar-type
oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages,
14 figure
Bayesian Multimodel Inference for Geostatistical Regression Models
The problem of simultaneous covariate selection and parameter inference for spatial regression models is considered. Previous research has shown that failure to take spatial correlation into account can influence the outcome of standard model selection methods. A Markov chain Monte Carlo (MCMC) method is investigated for the calculation of parameter estimates and posterior model probabilities for spatial regression models. The method can accommodate normal and non-normal response data and a large number of covariates. Thus the method is very flexible and can be used to fit spatial linear models, spatial linear mixed models, and spatial generalized linear mixed models (GLMMs). The Bayesian MCMC method also allows a priori unequal weighting of covariates, which is not possible with many model selection methods such as Akaike's information criterion (AIC). The proposed method is demonstrated on two data sets. The first is the whiptail lizard data set which has been previously analyzed by other researchers investigating model selection methods. Our results confirmed the previous analysis suggesting that sandy soil and ant abundance were strongly associated with lizard abundance. The second data set concerned pollution tolerant fish abundance in relation to several environmental factors. Results indicate that abundance is positively related to Strahler stream order and a habitat quality index. Abundance is negatively related to percent watershed disturbance
A huge Omental Lymphangioma with extention into Labia Majorae: A case report
BACKGROUND: Abdominal cystic lymphangiomas are uncommon congenital benign tumors. CASE PRESENTATION: We present a case of a 4 year old female child with a cystic lymphangioma arising from greater omentum and occupying whole of the abdomen and protruding through labia mejora. Ultrasonography and CT scan confirmed the diagnosis. Complete excision of the cyst along with omentectomy done with no clinical or radiological evidence of recurrence till 6 months. CONCLUSION: Due to variable presentation of abdominal lymphangiomas, extensive imaging studies are necessary for evaluation and diagnosis. Complete surgical resection is a treatment of choice
Animating the Carbon Cycle
This a post-print, author-produced version of an article accepted for publication in Ecosystems. Copyright © 2013 Springer Science+Business Media New York. The final publication is available at Springer via http://dx.doi.org/10.1007/s10021-013-9715-7Understanding the biogeochemical processes regulating carbon cycling is central to mitigating atmospheric CO2 emissions. The role of living organisms has been accounted for, but the focus has traditionally been on contributions of plants and microbes. We develop the case that fully “animating” the carbon cycle requires broader consideration of the functional role of animals in mediating biogeochemical processes and quantification of their effects on carbon storage and exchange among terrestrial and aquatic reservoirs and the atmosphere. To encourage more hypothesis-driven experimental research that quantifies animal effects we discuss the mechanisms by which animals may affect carbon exchanges and storage within and among ecosystems and the atmosphere. We illustrate how those mechanisms lead to multiplier effects whose magnitudes may rival those of more traditional carbon storage and exchange rate estimates currently used in the carbon budget. Many animal species are already directly managed. Thus improved quantitative understanding of their influence on carbon budgets may create opportunity for management and policy to identify and implement new options for mitigating CO2 release at regional scales.US National Science FoundationNERCBBSRCNippon Foundatio
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