Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · May 2017
ReviewA review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?
Sporadic outbreaks of Ebola virus infection have been documented since the mid-Seventies and viral exposure can lead to lethal haemorrhagic fever with case fatalities as high as 90%. There is now a comprehensive body of data from both ongoing and completed clinical trials assessing various vaccine strategies, which were rapidly advanced through clinical trials in response to the 2013-2016 Ebola virus disease (EVD) public health emergency. Careful consideration of immunogenicity post vaccination is essential but has been somewhat stifled because of the wide array of immunological assays and outputs that have been used in the numerous clinical trials. ⋯ Assessment of the safety data, the immunological outputs and the ease of field deployment for the various vaccine modalities will help both the scientific community and policy-makers prioritize and potentially license vaccine candidates. If this can be achieved, the next outbreak of Ebola virus, or other emerging pathogen, can be more readily contained and will not have such widespread and devastating consequences. This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · May 2017
ReviewWhat we have learnt about the World Health Organization from the Ebola outbreak.
The World Health Organization's (WHO) reputation became irrefutably damaged during the Ebola outbreak, with a general consensus in the global health community that it fell short of its leadership responsibilities. This commentary offers a brief synopsis of the WHO's role during the outbreak and suggests that the disease outbreak demonstrates the tension that exists between the organization's normative and operational roles in health crises. ⋯ Finally, the commentary considers the introduction of the WHO Health Emergency Programme, but suggests that this too may suffer from the same structural concerns that need to be addressed if the WHO is to continue in the role the global health community expects it to play, as both a normative and operational leader in global disease control. This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Dec 2016
ReviewClinical implications of globally emerging azole resistance in Aspergillus fumigatus.
Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. ⋯ Early detection of resistance is of paramount importance and if demonstrated, either with susceptibility testing or through molecular analysis, azole monotherapy should be avoided. Liposomal amphotericin B or a combination of voriconazole and an echinocandin are recomended for azole-resistant aspergillosis. This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Oct 2016
ReviewFunctional magnetic resonance imaging in chronic ischaemic stroke.
Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. ⋯ Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations. This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Aug 2016
ReviewThe homeostatic astroglia emerges from evolutionary specialization of neural cells.
Evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed from electrically excitable neuronal networks connected with chemical synapses and non-excitable glial cells that provide for homeostasis and defence. ⋯ In neuropathology, astrocytes may undergo reactive remodelling or degeneration; to a large extent, astroglial reactions define progression of the pathology and neurological outcome. This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.