Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation

Activation of inflammatory pathways represents a central mechanism in multiple disease states both acute and chronic. Triggered via either pathogen or tissue damage-associated molecular motifs, common biochemical pathways lead to conserved yet variable physiological and immunological alterations. Dissection and delineation of the determinants and mechanisms underlying phenotypic variance in response is expected to yield novel therapeutic advances. Intravenous (IV) administration of endotoxin (gram-negative bacterial lipopolysaccharide), a specific Toll-like receptor 4 agonist, represents an in vivo model of systemic inflammation in man. National Institutes for Health Clinical Center Reference Endotoxin (CCRE, Escherichia coli O:113:H10:K negative) is employed to reliably and reproducibly generate vascular, hematological, endocrine, immunological and organ-specific functional effects that parallel, to varying degrees, those seen in the early stages of pathological states. Alteration of dose (0.06 - 4 ng/kg) and time-scale of exposure (bolus vs. infusion) allows replication of either acute or chronic inflammation and a range of severity to be elicited, with higher doses (2 - 4 ng/kg) frequently being used to create a 'sepsis-like' state. Established and novel medicinal compounds may additionally be administered prior to or post endotoxin exposure to appreciate their effect on the inflammatory cascade. Despite limitations in scope and generalizability, human IV endotoxin challenge offers a unique platform to gain mechanistic insights into inducible physiological responses and inflammatory pathways. Rationally employed it may aid translation of this knowledge into therapeutic innovations

Information, intra-firm communication and risk policy

Based upon the foundations of mean-variance decision-making theory, we demonstrate that a change in the risk situation of an international enterprise open currency position does not inevitably require a corresponding hedging accommodation. Given a new risk situation, whether a revision of the hedging-strategy is appropriate will depend upon the elasticity of risk aversion. The elasticity of risk aversion is a decisive indicator; however, it is rarely scrutinized in the literature. In addition, our analysis illustrates the cost saving advantages of the applied (μ,σ)-principal compared to the Bernoulli-principal for information procurement processes. Applying the (μ,σ)-principal facilitates and enhances firm-internal communication information levels.Exchange rate risk; international trade; hedging; information

Locating the ‘radical’ in 'Shoot the Messenger'

This is the author's accepted manuscript. The final published article is available from the link below, copyright 2013 @ Edinburgh University Press.The 2006 BBC drama Shoot the Messenger is based on the psychological journey of a Black schoolteacher, Joe Pascale, accused of assaulting a Black male pupil. The allegation triggers Joe's mental breakdown which is articulated, through Joe's first-person narration, as a vindictive loathing of Black people. In turn, a range of common stereotypical characterisations and discourses based on a Black culture of hypocrisy, blame and entitlement is presented. The text is therefore laid wide open to a critique of its neo-conservatism and hegemonic narratives of Black Britishness. However, the drama's presentation of Black mental illness suggests that Shoot the Messenger may also be interpreted as a critique of social inequality and the destabilising effects of living with ethnicised social categories. Through an analysis of issues of representation, the article reclaims this controversial text as a radical drama and examines its implications for and within a critical cultural politics of ‘race’ and representation

How a turn to critical race theory can contribute to our understanding of 'race', racism and anti-racism in sport

As long as racism has been associated with sport there have been consistent, if not coordinated or coherent, struggles to confront its various forms. Critical race theory (CRT) is a framework established to challenge these racialized inequalities and racism in society and has some utility for anti-racism in sport. CRT's focus on social justice and transformation are two areas of convergence between critical race theorists and anti-racists. Of the many nuanced and pernicious forms of racism, one of the most obvious and commonly reported forms of racism in sport, racial abuse, has been described as a kind of dehumanizing process by Gardiner (2003), as those who are its target are simultaneously (re)constructed and objectified according to everyday myth and fantasy. However, this is one of the many forms of everyday racist experiences. Various forms of racism can be experienced in boardrooms, on television, in print, in the stands, on the sidelines and on the pitch. Many times racism is trivialized and put down as part of the game (Long et al., 2000), yet its impact is rarely the source of further exploration. This article will explore the conceptualization of 'race' and racism for a more effective anti-racism. Critical race theory will also be used to explore the ideas that underpin considerations of the severity of racist behaviour and the implications for anti-racism. © The Author(s) 2010

Quality of sick child care delivered by Health Surveillance Assistants in Malawi

Objective To assess the quality of care provided by Health Surveillance Assistants (HSAs)—a cadre of community-based health workers—as part of a national scale-up of community case management of childhood illness (CCM) in Malawi. Methods Trained research teams visited a random sample of HSAs (n = 131) trained in CCM and provided with initial essential drug stocks in six districts, and observed the provision of sick child care. Trained clinicians conducted ‘gold-standard' reassessments of the child. Members of the survey team also interviewed caregivers and HSAs and inspected drug stocks and patient registers. Findings HSAs provided correct treatment with antimalarials to 79% of the 241 children presenting with uncomplicated fever, with oral rehydration salts to 69% of the 93 children presenting with uncomplicated diarrhoea and with antibiotics to 52% of 58 children presenting with suspected pneumonia (cough with fast breathing). About one in five children (18%) presented with danger signs. HSAs correctly assessed 37% of children for four danger signs by conducting a physical exam, and correctly referred 55% of children with danger signs. Conclusion Malawi's CCM programme is a promising strategy for increasing coverage of sick child treatment, although there is much room for improvement, especially in the correct assessment and treatment of suspected pneumonia and the identification and referral of sick children with danger signs. However, HSAs provided sick child care at levels of quality similar to those provided in first-level health facilities in Malawi, and quality should improve if the Ministry of Health and partners act on the results of this assessmen

Abundances of metal-weak thick-disc candidates

High resolution spectra of 5 candidate metal-weak thick-disc stars suggested by Beers & Sommer-Larsen (1995) are analyzed to determine their chemical abundances. The low abundance of all the objects has been confirmed with metallicity reaching [Fe/H]=-2.9. However, for three objects, the astrometric data from the Hipparcos catalogue suggests they are true halo members. The remaining two, for which proper-motion data are not available, may have disc-like kinematics. It is therefore clear that it is useful to address properties of putative metal-weak thick-disc stars only if they possess full kinematic data. For CS 22894-19 the abundance pattern similar to those of typical halo stars is found, suggesting that chemical composition is not a useful discriminant between thick-disc and halo stars. CS 29529-12 is found to be C enhanced with [C/Fe]=+1.0; other chemical peculiarities involve the s process elements: [Sr/Fe]=-0.65 and [Ba/Fe]=+0.62, leading to a high [Ba/Sr] considerably larger than what is found in more metal-rich carbon-rich stars, but similar to LP 706-7 and LP 625-44 discussed by Norris et al (1997a). Hipparcos data have been used to calculate the space velocities of 25 candidate metal-weak thick-disc stars, thus allowing us to identify 3 bona fide members, which support the existence of a metal-poor tail of the thick-disc, at variance with a claim to the contrary by Ryan & Lambert (1995).Comment: to be published in MNRA

Changing Fortunes: Criminology and the Sociological Condition

Criminology and its relationships with sociology are today at a crossroads, and this article explores the changing fortunes of each as they have evolved over the last 50 years. The separation has occurred as criminology has successfully established itself as an independent subject with an impressive ability to attract students, scholars and research grants. Some see the striking expansion of criminology and move away from the basic disciplines as an indication of success and impressive achievement, while others are more sceptical and highlight the costs such isolation brings. The article examines the consequences of these changes, then it focuses on the fates of some of the key concepts in sociological criminology, before concluding that social theory can be a unifying force, capable of reinvigorating the ties between the two disciplines

Re-theorising the core: a ‘globalized’ business elite in Santiago, Chile

World systems theory continues to be a widely adopted approach in theorisations of the contemporary world economy. An important epistemological component to world systems theory is the metaphor of core-periphery. Recent work within the approach has sought to transcend earlier criticisms of regional conceptions of cores, peripheries and semi-peripheries by an increasing sensitivity to local differences and an increasing emphasis on Wallerstein's original idea of core-periphery as process, operating at all scales in the contemporary world system. However, this paper argues that the core-periphery metaphor currently used by world systems theorists is founded around a restrictively narrow spatial epistemology. Such a narrow epistemology implements the core-periphery metaphor only as something which produces territorial outcomes in the physical world. This paper contends that recent work within the social services, concerned with the globalization debate and issues of spatial epistemology, should inform world systems theory in producing a reformulated spatial understanding of the core-periphery metaphor, embodying a wider conception of space to include abstract social spaces. This argument is developed in the notion that the world economy must also be understood as having a ‘social core’: a transnational diasporic business elite exercising decision-making power over the capitalist world system. The contention is grounded in the presentation of research into a case study of such a ‘globalized’ business elite in the capital city of Chile, Santiago

The barium isotopic mixture for the metal-poor subgiant star HD140283

Current theory regarding heavy element nucleosynthesis in metal-poor environments states that the r-process would be dominant. The star HD140283 has been the subject of debate after it appeared in some studies to be dominated by the s-process. We provide an independent measure of the Ba isotope mixture in HD140283 using an extremely high quality spectrum and an extensive chi^2 analysis. We exploit hyperfine splitting of the BaII 4554 \AA\ and 4934 \AA\ resonance lines in an effort to constrain the isotope ratio in 1D LTE. Using the code ATLAS in conjunction with KURUCZ06 model atmospheres we analyse 93 Fe lines to determine the star's macroturbulence. With this information we construct a grid of Ba synthetic spectra and, using a \chi^2 code, fit these to our observed data to determine the isotopic ratio, fodd, which represents the ratio of odd to even isotopes. We also analyse the Eu lines. We set a new upper limit of the rotation of HD140283 at vsin{i}\leq3.9\kms, a new upper limit on [Eu/H] < -2.80 and abundances [Fe/H] = -2.59\pm0.09, [Ba/H] = -3.46\pm0.11. This leads to a new lower limit on [Ba/Eu] > -0.66. We find that, in the framework of a 1D LTE analysis, the isotopic ratios of Ba in HD140283 indicate fodd=0.02\pm0.06, a purely s-process signature. This implies that observations and analysis do not validate currently accepted theory. We speculate that a 1D code, due to simplifying assumptions, is not adequate when dealing with observations with high levels of resolution and S/N because of the turbulent motions associated with a 3D stellar atmosphere. New approaches to analysing isotopic ratios, in particular 3D hydrodynamics, need to be considered when dealing with the levels of detail required to properly determine them. However published 3D results exacerbate the disagreement between theory and observation.Comment: 16 pages, 10 figures, 7 tables, 1 online appendix Accepted by A&

All the way from … authenticity and distance in world music production

World music and the narratives it produces are at the very centre of a formerly transnational production and consumption process. However, the shortened distance between the sites of production and consumption of this good, brought on by migration and greater participation, has created a dilemma for the UK-based artists who perform it: how to maintain authenticity without the added value of ‘distance’. Therefore, the aim of this article is to examine the ways in which musicians and other participants attempt to overcome this problem and in doing so (re)-construct particular aspects of their identity. Rather than being just another critique on authenticity, this article uses distance as an organizing concept in understanding the challenges facing world music production in the UK