Validity of the Elastic Constant Approximations for the Ultrasonic Evaluation of Multi-Layered Inhomogeneous Composites

Several ultrasonic wave mechanics models which are based on the effective elastic properties of the overall fiber reinforced composites are currently being used in the industry and academia. Due to the repetition of the ply orientation and the lay-up sequence traditionally used in the industry, these models which often “smear” the individual ply elastic properties to obtain effective elastic properties of the entire composite. [1,2] This is an acceptable approximation for long wave length waves propagation in homogeneous or quasi-homogeneous ply lay-ups media and has provided useful results in the non-destructive evaluation process.</p

Quantifying the daily economic impact of extreme space weather due to failure in electricity transmission infrastructure

Extreme space weather due to coronal mass ejections has the potential to cause considerable disruption to the global economy by damaging the transformers required to operate electricity transmission infrastructure. However, expert opinion is split between the potential outcome being one of a temporary regional blackout and of a more prolonged event. The temporary blackout scenario proposed by some is expected to last the length of the disturbance, with normal operations resuming after a couple of days. On the other hand, others have predicted widespread equipment damage with blackout scenarios lasting months. In this paper we explore the potential costs associated with failure in the electricity transmission infrastructure in the U.S. due to extreme space weather, focusing on daily economic loss. This provides insight into the direct and indirect economic consequences of how an extreme space weather event may affect domestic production, as well as other nations, via supply chain linkages. By exploring the sensitivity of the blackout zone, we show that on average the direct economic cost incurred from disruption to electricity represents only 49% of the total potential macroeconomic cost. Therefore, if indirect supply chain costs are not considered when undertaking cost-benefit analysis of space weather forecasting and mitigation investment, the total potential macroeconomic cost is not correctly represented. The paper contributes to our understanding of the economic impact of space weather, as well as making a number of key methodological contributions relevant for future work. Further economic impact assessment of this threat must consider multiday, multiregional events.The authors acknowledge partial financial support from American International Group during the research and especially thank Brad Fischtrom, Siddhartha Dalal, and their team for providing useful comments and insights as the research progressed. We also thank attendees of the workshop held at the Cambridge Judge Business School in July 2015. Three anonymous reviewers are acknowledged for providing useful comments and feedback on the paper. Oughton was partially supported by the UK Engineering and Physical Science Research Council under grant EP/N017064/1: Multiscale InfraSTRucture systems AnaLytics. Horne and Thomson would like to acknowledge the support of the Natural Environment Research Council (NERC). This paper is published by permission of the Executive Director, British Geological Survey (NERC)

Tres medici, duo athei? The Physician as Atheist and the Medicalization of the Soul

Until recently, examinations of the ‘mind-body problem’ in historical context paid only cursory attention to its specifically medical dimension, if at all. At best, some ‘folk physiology’ was entertained, usually to laugh at it (the pineal gland, animal spirits). Conversely, historians of neuroscience or of artificial intelligence (Jeannerod 1985, Dupuy 2000) often present figures like La Mettrie as heroic early cases of ‘naturalization’, giving an experimental basis to materialism: their symmetrically inverse mistake is to take professions of medical authority too literally (although there are genuine cases where all of the above does coalesce – where ‘actors’ categories mysteriously transcend historiographic projections –, such as Hieronymus Gaub’s reflections on the ‘regimen of the mind’ in the mid-eighteenth century, or, more theoretically, Guillaume Lamy’s Epicurean-inflected Anatomical Discourses on the Soul, eighty years earlier). Contrary to the denial of the relevance of medicine in early modern philosophy, as regards issues such as the body-soul (then body-mind) relation among others, it seems patently difficult to separate medical theory, medically nourished philosophical speculation, and metaphysics. This is the case, whether in Descartes, Gaub, the ‘animist’ Georg-Ernest Stahl, or materialists such as Guillaume Lamy and La Mettrie: medicine, or rather ‘a certain idea of medicine’, is everywhere. Here I focus on the motif of a radical medicine – a medical precursor of the Radical Enlightenment (Israel 2001, 2006, 2007), symbolized negatively by the slogan, tres medici, duo athei, or ‘where there are three doctors, there are two atheists’, i.e. medicine as a basis for atheism. This theme runs through various works of medical or medico-theological propaganda: Thomas Browne’s 1643 De religio medici begins with Browne regretting rumors of doctors being atheists as the “general scandal of my Profession”; Germain de Bezançon’s 1677 Les médecins à la censure works hard at rebutting the saying, “Bon Physicien, mauvais chrétien.” But these are examples of the fear of a radical medicine – a medicine that denies the existence of an immortal soul, or even defends materialism and atheism. Are there positive statements of this doctrine? Indeed, attacks on it are much more common than statements identifying with it, like medical versions of natural theology in general. In fact, just as there were theologically motivated medical works, there were also medically motivated works of radical or heretical theology, like William Coward’s Second Thoughts on the Human Soul (Coward 1702, building on Overton 1644), which engaged in polemics concerning the nature of the soul – mortal or immortal? (Thomson 2008). Parallel to the mortalist trend, but flowing into a common genre of radical, medico-materialist texts (sometimes anonymous, such as L’Âme Matérielle, from the 1720s) are at least two other strands of radical medicine: a post-Cartesian focus on medicina mentis and the nature of the mind (Henricus Regius, Hieronymus Gaub, Antoine Le Camus), and an Epicurean medicine, in which mind and body are organismically united, with an additional hedonistic component, notably in Lamy, Mandeville and La Mettrie (Wright 1991, Wolfe and van Esveld 2014). The focus on a medicine of the mind (Corneanu, ms. 2013) is obviously connected to a ‘medicalization of the soul’: there was a body-soul problem in and for medicine, a sort of medicalized ‘pneumatology’. Radical medicine is located somewhere in between the early forms of ‘naturalization’ or ‘medicalization’ of the soul and the pose of scientific neutrality that is characteristic of early nineteenth-century medicine (as in Cabanis, Bichat or Bernard): it is a short-lived episode. I seek to reconstruct this intellectual figure, in which mortalist, post-Cartesian and Epicurean strands intersect and sometimes come together. I suggest that medically influenced materialism in the Radical Enlightenment (e.g. in the later French cases, La Mettrie, Ménuret and Diderot), is different from later, more experimentally focused and more quantitatively oriented forms of medical materialism, precisely because of its radical dimension. This radical medicine often insists on vitality, as opposed to “anatomie cadavérique”: it is vital and hedonistic, a medicine concerned with maintaining bodily pleasure.Until recently, examinations of the 'mind-body problem' in historical context paid only cursory attention to its specifically medical dimension, if at all. At best, some 'folk physiology' was entertained, usually to laugh at it (the pineal gland, animal spirits). Conversely, historians of neuroscience or of artificial intelligence (Jeannerod M, The brain machine. The development of neurophysiological thought, trans. D. Urion, Harvard University Press, Cambridge, 1985; Dupuy J-P, The mechanization of the mind: on the origins of cognitive science, trans. M.B. DeBevoise, Princeton University Press, Princeton, 2000) often present figures like La Mettrie as heroic early cases of 'naturalization', giving an experimental basis to materialism: their symmetrically inverse mistake is to take professions of medical authority too literally (although there are genuine cases where all of the above does coalesce where 'actors' categories mysteriously transcend historiographic projections -, such as Hieronymus Gaub's reflections on the 'regimen of the mind' in the mid-eighteenth century, or, more theoretically, Guillaume Lamy's Epicurean-inflected Anatomical Discourses on the Soul, eighty years earlier). Contrary to the denial of the relevance of medicine in early modern philosophy, as regards issues such as the body-soul (then body-mind) relation among others, it seems patently difficult to separate medical theory, medically nourished philosophical speculation, and metaphysics. This is the case, whether in Descartes, Gaub, the 'animist' Georg-Ernest Stahl, or materialists such as Guillaume Lamy and La Mettrie: medicine, or rather 'a certain idea of medicine', is everywhere.Here I focus on the motif of a radical medicine - a medical precursor of the Radical Enlightenment (Israel J, Radical enlightenment. Philosophy and the making of modernity, 1650-1750, Oxford University Press, Oxford, 2001; Israel J, Enlightenment contested. Oxford University Press, Oxford, 2006, Israel J, Enlightenment, radical enlightenment and the "medical revolution" of the late seventeenth and eighteenth centuries. In: Grell OP, Cunningham A (ed) Medicine and religion in enlightenment Europe. Ashgate, Aldershot, pp 5-28, 2007), symbolized negatively by the slogan, tres medici, duo athei, or 'where there are three doctors, there are two atheists', i.e. medicine as a basis for atheism. This theme runs through various works of medical or medico-theological propaganda: Thomas Browne's 1643 De religio medici begins with Browne regretting rumors of doctors being atheists as the "general scandal of my Profession"; Germain de Bezancon's 1677 Les medecins a la censure works hard at rebutting the saying, "Bon Physicien, mauvais chretien." But these are examples of the fear of a radical medicine - a medicine that denies the existence of an immortal soul, or even defends materialism and atheism. Are there positive statements of this doctrine? Indeed, attacks on it are much more common than statements identifying with it, like medical versions of natural theology in general.In fact, just as there were theologically motivated medical works, there were also medically motivated works of radical or heretical theology, like William Coward's Second Thoughts on the Human Soul (Coward W, Second thoughts on the human soul. R. Basset, London, 1702, building on Overton 1644), which engaged in polemics concerning the nature of the soul - mortal or immortal? (Thomson A, Bodies of thought: science, religion, and the soul in the early enlightenment. Oxford University Press, Oxford, 2008). Parallel to the mortalist trend, but flowing into a common genre of radical, medico-materialist texts (sometimes anonymous, such as L'Ame Materielle, from the 1720s) are at least two other strands of radical medicine: a post-Cartesian focus on medicina mentis and the nature of the mind (Henricus Regius, Hieronymus Gaub, Antoine Le Camus), and an Epicurean medicine, in which mind and body are organismically united, with an additional hedonistic component, notably in Lamy, Mandeville and La Mettrie (Wright JP, Locke, Willis, and the seventeenth-century epicurean soul. In: Osler MJ (ed) Atoms, Pneuma, and Tranquillity: Epicurean and stoic themes in European thought. Cambridge University Press, Cambridge, pp 239-258, 1991; Wolfe CT, van Esveld M, The material soul: strategies for naturalising the soul in an early modern epicurean context. In: Kambaskovic D (ed) Conjunctions: body, soul and mind from Plato to the enlightenment. Springer, Dordrecht, pp 371-421, 2014). The focus on a medicine of the mind (Corneanu, (ms. 2013), The care of the whole man: medicine and theology in the late renaissance, 2013) is obviously connected to a 'medicalization of the soul': there was a body-soul problem in and for medicine, a sort of medicalized 'pneumatology'. Radical medicine is located somewhere in between the early forms of 'naturalization' or 'medicalization' of the soul and the pose of scientific neutrality that is characteristic of early nineteenth-century medicine (as in Cabanis, Bichat or Bernard): it is a short-lived episode. I seek to reconstruct this intellectual figure, in which mortalist, post-Cartesian and Epicurean strands intersect and sometimes come together. I suggest that medically influenced materialism in the Radical Enlightenment (e.g. in the later French cases, La Mettrie, Menuret and Diderot), is different from later, more experimentally focused and more quantitatively oriented forms of medical materialism, precisely because of its radical dimension. This radical medicine often insists on vitality, as opposed to "anatomie cadaverique": it is vital and hedonistic, a medicine concerned with maintaining bodily pleasure

TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

Health Newscasts for Increasing Influenza Vaccination Coverage: An Inductive Reasoning Game Approach

Both pandemic and seasonal influenza are receiving more attention from mass media than ever before. Topics such as epidemic severity and vaccination are changing the way in which we perceive the utility of disease prevention. Voluntary influenza vaccination has been recently modeled using inductive reasoning games. It has thus been found that severe epidemics may occur because individuals do not vaccinate and, instead, attempt to benefit from the immunity of their peers. Such epidemics could be prevented by voluntary vaccination if incentives were offered. However, a key assumption has been that individuals make vaccination decisions based on whether there was an epidemic each influenza season; no other epidemiological information is available to them. In this work, we relax this assumption and investigate the consequences of making more informed vaccination decisions while no incentives are offered. We obtain three major results. First, individuals will not cooperate enough to constantly prevent influenza epidemics through voluntary vaccination no matter how much they learned about influenza epidemiology. Second, broadcasting epidemiological information richer than whether an epidemic occurred may stabilize the vaccination coverage and suppress severe influenza epidemics. Third, the stable vaccination coverage follows the trend of the perceived benefit of vaccination. However, increasing the amount of epidemiological information released to the public may either increase or decrease the perceived benefit of vaccination. We discuss three scenarios where individuals know, in addition to whether there was an epidemic, (i) the incidence, (ii) the vaccination coverage and (iii) both the incidence and the vaccination coverage, every influenza season. We show that broadcasting both the incidence and the vaccination coverage could yield either better or worse vaccination coverage than broadcasting each piece of information on its own

The feasibility of canine rabies elimination in Africa: dispelling doubts with data

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; This paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; We conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.&lt;/p&gt

Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

Scalar and vector Slepian functions, spherical signal estimation and spectral analysis

It is a well-known fact that mathematical functions that are timelimited (or spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the finite precision of measurement and computation unavoidably bandlimits our observation and modeling scientific data, and we often only have access to, or are only interested in, a study area that is temporally or spatially bounded. In the geosciences we may be interested in spectrally modeling a time series defined only on a certain interval, or we may want to characterize a specific geographical area observed using an effectively bandlimited measurement device. It is clear that analyzing and representing scientific data of this kind will be facilitated if a basis of functions can be found that are "spatiospectrally" concentrated, i.e. "localized" in both domains at the same time. Here, we give a theoretical overview of one particular approach to this "concentration" problem, as originally proposed for time series by Slepian and coworkers, in the 1960s. We show how this framework leads to practical algorithms and statistically performant methods for the analysis of signals and their power spectra in one and two dimensions, and, particularly for applications in the geosciences, for scalar and vectorial signals defined on the surface of a unit sphere.Comment: Submitted to the 2nd Edition of the Handbook of Geomathematics, edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be published by Springer Verlag. This is a slightly modified but expanded version of the paper arxiv:0909.5368 that appeared in the 1st Edition of the Handbook, when it was called: Slepian functions and their use in signal estimation and spectral analysi

The relationship between deprivation, tumour stage and the systemic inflammatory response in patients with primary operable breast cancer

The extent of deprivation (Carstairs deprivation index) was directly associated with the magnitude of the systemic inflammatory response (reduced albumin and elevated C-reactive protein, P<0.01) in patients with primary operable breast cancer (n=314). Deprivation was not associated with age, tumour size, tumour type, grade, and the proportion of patients with involved lymph nodes and oestrogen receptor status