1,009 research outputs found

    Challenges in dengue research: A computational perspective

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    This is the final version of the article. Available from Wiley via the DOI in this record.The dengue virus is now the most widespread arbovirus affecting human populations, causing significant economic and social impact in South America and South-East Asia. Increasing urbanization and globalization, coupled with insufficient resources for control, misguided policies or lack of political will, and expansion of its mosquito vectors are some of the reasons why interventions have so far failed to curb this major public health problem. Computational approaches have elucidated on dengue's population dynamics with the aim to provide not only a better understanding of the evolution and epidemiology of the virus but also robust intervention strategies. It is clear, however, that these have been insufficient to address key aspects of dengue's biology, many of which will play a crucial role for the success of future control programmes, including vaccination. Within a multiscale perspective on this biological system, with the aim of linking evolutionary, ecological and epidemiological thinking, as well as to expand on classic modelling assumptions, we here propose, discuss and exemplify a few major computational avenues—real-time computational analysis of genetic data, phylodynamic modelling frameworks, within-host model frameworks and GPU-accelerated computing. We argue that these emerging approaches should offer valuable research opportunities over the coming years, as previously applied and demonstrated in the context of other pathogens.JL, AW and SG received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement no. 268904 - DIVERSITY. MR was supported by a Royal Society University Research Fellowship. NRF by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204311/Z/16/Z). WT has received funding from a doctoral scholarship from the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership

    'Who do "they" cheer for?' Cricket, diaspora, hybridity and divided loyalties amongst British Asians

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    This article explores the relationship between British Asians' sense of nationhood, citizenship, ethnicity and some of their manifestations in relation to sports fandom: specifically in terms of how cricket is used as a means of articulating diasporic British Asian identities. Norman Tebbit's 'cricket test' is at the forefront of this article to tease out the complexities of being British Asian in terms of supporting the English national cricket team. The first part of the article locates Tebbit's 'cricket test' within the wider discourse of multiculturalism. The analysis then moves to focus on the discourse of sports fandom and the concept of 'home team advantage' arguing that sports venues represent significant sites for nationalist and cultural expression due to their connection with national history. The article highlights how supporting 'Anyone but England', thereby rejecting ethnically exclusive notions of 'Englishness' and 'Britishness', continues to be a definer of British Asians' cultural identities. The final section situates these trends within the discourse of hybridity and argues that sporting allegiances are often separate from considerations of national identity and citizenship. Rather than placing British Asians in an either/or situation, viewing British 'Asianness' in hybrid terms enables them to celebrate their traditions and histories, whilst also being proud of their British citizenship. © The Author(s) 2011

    Gásir in Eyjafjörđur: International Exchange and Local Economy in Medieval Iceland

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    The site of Gásir in Eyjafjörður in northeast Iceland was excavated from 2001–2006, revealing details of one of the larger seasonal trading centers of medieval Iceland. Interdisciplinary investigations of the site have shed light upon the organization of the site and provided confirmation of documentary accounts of both prestige items (gyrfalcons, walrus ivory) and bulk goods (sulphur) concentrated for export. Gásir was a major point of cultural contact as well as economic exchange between Icelanders and the world of medieval Europe, and the zooarchaeological analyses indicated a mix of foodways and the presence of exotic animals and a well-developed provisioning system, which supplied high-quality meat and fresh fish to the traders. The excavations demonstrated an unexpected regional-level economic impact of the seasonally occupied site on the surrounding rural countryside, and contribute to ongoing investigations of the extent and impact of overseas trade in medieval Iceland

    In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

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    Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization

    Guillain-Barré syndrome: a century of progress

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    In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

    The Fungicide Chlorothalonil Is Nonlinearly Associated with Corticosterone Levels, Immunity, and Mortality in Amphibians

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    Background: Contaminants have been implicated in declines of amphibians, a taxon with vital systems similar to those of humans. However, many chemicals have not been thoroughly tested on amphibians or do not directly kill them

    Serotype-Specific Differences in the Risk of Dengue Hemorrhagic Fever: An Analysis of Data Collected in Bangkok, Thailand from 1994 to 2006

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    The four dengue viruses (DENV) represent the most common human arbovirus infections in the world and are currently a challenging problem, particularly in the tropical and subtropical regions of Asia and the Americas. Infection with DENV may produce symptoms of varying severity. While access to care, appropriate interventions, host genetic factors, and previous exposure to DENV are all known to affect the outcome of the infection, it is not entirely understood why some individuals develop more severe disease. It has been hypothesized that the four dengue serotypes differ in disease severity and clinical manifestations. This analysis assessed whether there were significant differences in severity of disease caused by the dengue serotypes in a pediatric population in Thailand. We found significant and non-significant correlations between dengue serotype 2 infection and more severe dengue disease. We also found that individual serotypes varied in disease severity between study years, perhaps supporting the hypothesis that the particular sequences of primary and secondary DENV infections influence disease severity

    HLA Class I Restriction as a Possible Driving Force for Chikungunya Evolution

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    After two decades of quiescence, epidemic resurgence of Chikungunya fever (CHIKF) was reported in Africa, several islands in the Indian Ocean, South-East Asia and the Pacific causing unprecedented morbidity with some cases of fatality. Early phylogenetic analyses based on partial sequences of Chikungunya virus (CHIKV) have led to speculation that the virus behind recent epidemics may result in greater pathogenicity. To understand the reasons for these new epidemics, we first performed extensive analyses of existing CHIKV sequences from its introduction in 1952 to 2009. Our results revealed the existence of a continuous genotypic lineage, suggesting selective pressure is active in CHIKV evolution. We further showed that CHIKV is undergoing mild positive selection, and that site-specific mutations may be driven by cell-mediated immune pressure, with occasional changes that resulted in the loss of human leukocyte antigen (HLA) class I-restricting elements. These findings provide a basis to understand Chikungunya virus evolution and reveal the power of post-genomic analyses to understand CHIKV and other viral epidemiology. Such an approach is useful for studying the impact of host immunity on pathogen evolution, and may help identify appropriate antigens suitable for subunit vaccine formulations

    Estimating Dengue Transmission Intensity from Case-Notification Data from Multiple Countries

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    Despite being the most widely distributed mosquito-borne viral infection, estimates of dengue transmission intensity and associated burden remain ambiguous. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing the burden of disease and the likely impact of interventions.We estimated the force of infection (λ) and corresponding basic reproduction numbers (R0) by fitting catalytic models to age-stratified incidence data identified from the literature. We compared estimates derived from incidence and seroprevalence data and assessed the level of under-reporting of dengue disease. In addition, we estimated the relative contribution of primary to quaternary infections to the observed burden of dengue disease incidence. The majority of R0 estimates ranged from one to five and the force of infection estimates from incidence data were consistent with those previously estimated from seroprevalence data. The baseline reporting rate (or the probability of detecting a secondary infection) was generally low (<25%) and varied within and between countries.As expected, estimates varied widely across and within countries, highlighting the spatio-temporally heterogeneous nature of dengue transmission. Although seroprevalence data provide the maximum information, the incidence models presented in this paper provide a method for estimating dengue transmission intensity from age-stratified incidence data, which will be an important consideration in areas where seroprevalence data are not available
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