289 research outputs found

    Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza

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    Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S31N polymorphism in M2 evokes resistance to licensed adamantane drugs. Hence, inhibitors capable of targeting N31 containing M2 (M2-N31) are highly desirable. Rational in silico design and in vitro screens delineated compounds favouring either lumenal or peripheral M2 binding, yielding effective M2-N31 inhibitors in both cases. Hits included adamantanes as well as novel compounds, with some showing low micromolar potency versus pandemic “swine” H1N1 influenza (Eng195) in culture. Interestingly, a published adamantane-based M2-N31 inhibitor rapidly selected a resistant V27A polymorphism (M2-A27/N31), whereas this was not the case for non-adamantane compounds. Nevertheless, combinations of adamantanes and novel compounds achieved synergistic antiviral effects, and the latter synergised with the neuraminidase inhibitor (NAi), Zanamivir. Thus, site-directed drug combinations show potential to rejuvenate M2 as an antiviral target whilst reducing the risk of drug resistance

    Fatal Cases of Influenza A in Childhood

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    In the northern hemisphere winter of 2003–04 antigenic variant strains (A/Fujian/411/02 –like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children.Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003–04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged.This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood

    Quantification and analysis of icebergs in a tidewater glacier fjord using an object-based approach

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    Tidewater glaciers are glaciers that terminate in, and calve icebergs into, the ocean. In addition to the influence that tidewater glaciers have on physical and chemical oceanography, floating icebergs serve as habitat for marine animals such as harbor seals (Phoca vitulina richardii). The availability and spatial distribution of glacier ice in the fjords is likely a key environmental variable that influences the abundance and distribution of selected marine mammals; however, the amount of ice and the fine-scale characteristics of ice in fjords have not been systematically quantified. Given the predicted changes in glacier habitat, there is a need for the development of methods that could be broadly applied to quantify changes in available ice habitat in tidewater glacier fjords. We present a case study to describe a novel method that uses object-based image analysis (OBIA) to classify floating glacier ice in a tidewater glacier fjord from high-resolution aerial digital imagery. Our objectives were to (i) develop workflows and rule sets to classify high spatial resolution airborne imagery of floating glacier ice; (ii) quantify the amount and fine-scale characteristics of floating glacier ice; (iii) and develop processes for automating the object-based analysis of floating glacier ice for large number of images from a representative survey day during June 2007 in Johns Hopkins Inlet (JHI), a tidewater glacier fjord in Glacier Bay National Park, southeastern Alaska. On 18 June 2007, JHI was comprised of brash ice ([Formula: see text] = 45.2%, SD = 41.5%), water ([Formula: see text] = 52.7%, SD = 42.3%), and icebergs ([Formula: see text] = 2.1%, SD = 1.4%). Average iceberg size per scene was 5.7 m2 (SD = 2.6 m2). We estimate the total area (± uncertainty) of iceberg habitat in the fjord to be 455,400 ± 123,000 m2. The method works well for classifying icebergs across scenes (classification accuracy of 75.6%); the largest classification errors occur in areas with densely-packed ice, low contrast between neighboring ice cover, or dark or sediment-covered ice, where icebergs may be misclassified as brash ice about 20% of the time. OBIA is a powerful image classification tool, and the method we present could be adapted and applied to other ice habitats, such as sea ice, to assess changes in ice characteristics and availability

    Investigating preferences for mosquito-control technologies in Mozambique with latent class analysis

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    <p>Abstract</p> <p>Background</p> <p>It is common practice to seek the opinions of future end-users during the development of innovations. Thus, the aim of this study is to investigate latent classes of users in Mozambique based on their preferences for mosquito-control technology attributes and covariates of these classes, as well as to explore which current technologies meet these preferences.</p> <p>Methods</p> <p>Surveys were administered in five rural villages in Mozambique. The data were analysed with latent class analysis.</p> <p>Results</p> <p>This study showed that users' preferences for malaria technologies varied, and people could be categorized into four latent classes based on shared preferences. The largest class, constituting almost half of the respondents, would not avoid a mosquito-control technology because of its cost, heat, odour, potential to make other health issues worse, ease of keeping clean, or inadequate mosquito control. The other three groups are characterized by the attributes which would make them avoid a technology; these groups are labelled as the bites class, by-products class, and multiple-concerns class. Statistically significant covariates included literacy, self-efficacy, willingness to try new technologies, and perceived seriousness of malaria for the household.</p> <p>Conclusions</p> <p>To become widely diffused, best practices suggest that end-users should be included in product development to ensure that preferred attributes or traits are considered. This study demonstrates that end-user preferences can be very different and that one malaria control technology will not satisfy everyone.</p

    Both loved and feared: third party punishers are viewed as formidable and likeable, but these reputational benefits may only be open to dominant individuals

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    Journal ArticleResearch Support, Non-U.S. Gov'tCopyright: © 2014 Gordon et al.The datasets associated with this article are available in ORE at http://hdl.handle.net/10871/15639Third party punishment can be evolutionarily stable if there is heterogeneity in the cost of punishment or if punishers receive a reputational benefit from their actions. A dominant position might allow some individuals to punish at a lower cost than others and by doing so access these reputational benefits. Three vignette-based studies measured participants' judgements of a third party punisher in comparison to those exhibiting other aggressive/dominant behaviours (Study 1), when there was variation in the success of punishment (Study 2), and variation in the status of the punisher and the type of punishment used (Study 3). Third party punishers were judged to be more likeable than (but equally dominant as) those who engaged in other types of dominant behaviour (Study 1), were judged to be equally likeable and dominant whether their intervention succeeded or failed (Study 2), and participants believed that only a dominant punisher could intervene successfully (regardless of whether punishment was violent or non-violent) and that subordinate punishers would face a higher risk of retaliation (Study 3). The results suggest that dominance can dramatically reduce the cost of punishment, and that while individuals can gain a great deal of reputational benefit from engaging in third party punishment, these benefits are only open to dominant individuals. Taking the status of punishers into account may therefore help explain the evolution of third party punishment.School of Psychology, University of Exete

    Urban women's socioeconomic status, health service needs and utilization in the four weeks after postpartum hospital discharge: findings of a Canadian cross-sectional survey

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    <p>Abstract</p> <p>Background</p> <p>Postpartum women who experience socioeconomic disadvantage are at higher risk for poor health outcomes than more advantaged postpartum women, and may benefit from access to community based postpartum health services. This study examined socioeconomically disadvantaged (SED) postpartum women's health, and health service needs and utilization patterns in the first four weeks post hospital discharge, and compared them to more socioeconomically advantaged (SEA) postpartum women's health, health service needs and utilization patterns.</p> <p>Methods</p> <p>Data collected as part of a large Ontario cross-sectional mother-infant survey were analyzed. Women (N = 1000) who had uncomplicated vaginal births of single 'at-term' infants at four hospitals in two large southern Ontario, Canada cities were stratified into SED and SEA groups based on income, social support and a universally administered hospital postpartum risk screen. Participants completed a self-administered questionnaire before hospital discharge and a telephone interview four weeks after discharge. Main outcome measures were self-reported health status, symptoms of postpartum depression, postpartum service needs and health service use.</p> <p>Results</p> <p>When compared to the SEA women, the SED women were more likely to be discharged from hospital within the first 24 hours after giving birth [OR 1.49, 95% CI (1.01–2.18)], less likely to report very good or excellent health [OR 0.48, 95% CI (0.35–0.67)], and had higher rates of symptoms of postpartum depression [OR 2.7, 95% CI(1.64–4.4)]. No differences were found between groups in relation to self reported need for and ability to access services for physical and mental health needs, or in use of physicians, walk-in clinics and emergency departments. The SED group were more likely to accept public health nurse home visits [OR 2.24, 95% CI(1.47–3.40)].</p> <p>Conclusion</p> <p>Although SED women experienced poorer mental and overall health they reported similar health service needs and utilization patterns to more SEA women. The results can assist policy makers, health service planners and providers to develop and implement necessary and accessible services. Further research is needed to evaluate SED postpartum women's health service needs and barriers to service use.</p
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