Sex-specific hypnotic effects of the neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile are mediated by peripheral metabolism into an active hypnotic steroid

BACKGROUND: The novel synthetic neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) blocks T-type calcium channels but does not directly modulate neuronal γ-aminobutyric acid type A (GABA METHODS: We used a combination of behavioural loss of righting reflex, neuroendocrine, pharmacokinetic, in vitro patch-clamp electrophysiology, and in vivo electrophysiological approaches in wild-type mice and in genetic knockouts of the Ca RESULTS: Adult male mice were less sensitive to the hypnotic effects of 3β-OH compared with female mice, and these differences appeared during development. Adult males had higher 3β-OH brain concentrations despite being less sensitive to its hypnotic effects. Females metabolised 3β-OH into the active GABA CONCLUSIONS: The sex-specific differences in the hypnotic effect of 3β-OH in mice are attributable to differences in its peripheral metabolism into the more potent hypnotic metabolite 3α-OH

Calciphylaxis in chronic, non-dialysis-dependent renal disease

BACKGROUND: Calciphylaxis cutis is characterized by media calcification of arteries and, most prominently, of cutaneous and subcutaneous arterioles occurring in renal insufficiency patients. CASE REPORT: A 53-year-old woman with chronic cardiac and renal failure complained of painful crural, non-varicosis ulcers. She was hospitalized in an immobilized condition due to both the crural ulcerations and the existing heart-failure state (NYHA III-IV) having pleural and pericardial effusions, atrial fibrillation and weight loss of 30 kg over the past year. Despite normalization of calcium-phosphorus balance and improvement of renal function, the clinical course of crural ulcerations deteriorated during the following 3 months. After failure of surgical debridements, multiple courses of sterile-maggot therapy were introduced at a late stage to stabilize the wounds. The patient died of recurrent wound infections and sepsis paralleled by exacerbations of renal malfunction. CONCLUSIONS: The role of renal disease in vascular complications is discussed. Sterile-maggot debridement may constitute a therapy for the ulcerated calciphylaxis at an earlier stage, i.e. when first ulcerations appear

Football: a counterpoint to the procession of pain on the Western Front, 1914-1918?

In this article, three artworks of the First World War containing images of recreational football are analysed. These three images, In the Wings of the Theatre of War, Artillery Men at Football and Gassed, span the war from its beginning to its conclusion and are discussed in relationship to the development of recreational football in the front-line area, the evolving policies of censorship and propaganda and in consideration of the national mood in Britain. The paper shows how football went from being a spontaneous and improvised pastime in the early stages of the war to a well organized entertainment by war’s end. The images demonstrate how the war was portrayed as a temporary affair by a confident nation in 1914 to a more resigned acceptance of a semi-permanent event to be endured by 1918; however, all three artworks show that the sporting spirit, and hence the fighting spirit, of the British soldier was intact

‘Race’ Talk! Tensions and Contradictions in Sport and PE

Background: The universal sport discourses of inclusion, belonging, meritocracy, agency, and equality are so widespread that few challenge them. It is clear from the most cursory interest in sport, PE and society that the lived reality is quite different and ambiguous. Racial disparities in the leadership and administration of sport are commonplace world wide; yet from research into ‘race’ in sport and PE the public awareness of these issues is widespread, where many know that racism takes place it is always elsewhere For many this racism is part of the game and something that enables an advantage to be stolen, for others it is trivial and not worthy of deeper thought. This paper explores the contradictions and tensions of the author’s experience of how sport and PE students talk about ‘race’. ‘Race’ talk is considered here in the context of passive everyday ‘race’ talk, dominant discourses in sporting cultures, and colour-blindness. This paper focuses on the pernicious yet persistent nature of ‘race’ talk while demystifying its multifarious, spurious, and more persuasive daily iterations. Theoretical framework: Drawing on Guinier and Torres’ (2003) ideas of resistance through political race consciousness and Bonilla-Silva’s (2010) notion of colour-blindness the semantics of ‘race’ and racialisation in sport and PE are interrogated through the prism of Critical Race Theory (CRT). Critical race scholarship has been used in sport and PE to articulate a political application of ‘race’ as a starting point for critical activism, to disrupt whiteness, and to explore the implications of ‘race’ and racism. CRT is used here to centre ‘race’ and racialised relations where disciplines have consciously or otherwise excluded them. Importantly, the centreing of ‘race’ by critical race scholars has advanced a strategic and pragmatic engagement with this slippery concept that recognises its paradoxical but symbolic location in social relations. Discussion: Before exploring ‘race’ talk in the classroom, using images from the sport media as a pedagogical tool, the paper considers how effortlessly ‘race’ is recreated and renewed. The paper then turns to explore how the effortless turn to everyday ‘race’ talk in the classroom can be viewed as an opportunity to disrupt common racialised assumptions with the potential to implicate those that passively engage in it. Further the diagnostic, aspirational and activist goals of political race consciousness are established as vehicles for a positive sociological experience in the classroom. Conclusion: The work concludes with a pragmatic consideration of the uses and dangers of passive everyday ‘race’ talk and the value of a political race consciousness in sport and PE. Part of the explanation for the perpetuation of ‘race’ talk and the relative lack of concern with its impact in education and wider society is focused on how the sovereignty of sport and PE trumps wider social concerns of ‘race’ and racism because of at least four factors 1) the liberal left discourses of sporting utopianism 2) the ‘race’ logic that pervades sport, based upon the perceived equal access and fairness of sport as it coalesces with the, 3) 'incontrovertible facts' of black and white superiority [and inferiority] in certain sports, ergo the racial justifications for patterns of activity in sport and PE 4) the racist logic of the Right perpetuated through a biological reductionism in sport and PE discourses. Keywords: ‘Race’ Talk; Critical Race Theory; Political Race Consciousnes

Annual review article: Is it time to rethink the gender agenda in entrepreneurship research?

This article develops a critique of contemporary approaches to analysing the impact of gender upon entrepreneurial propensity and activity. Since the 1990s, increasing attention has been afforded to the influence of gender upon women’s entrepreneurial behaviour; such analyses have highlighted an embedded masculinity within the entrepreneurial discourse which privileges men as normative entrepreneurial actors. Whilst invaluable in revealing a prevailing masculine bias within entrepreneurship, this critique is bounded by positioning women as a proxy for the gendered subject. This is a potentially limiting analysis that does not fully recognise gender as a human property with myriad articulations enacted throughout entrepreneurial activity. To progress debate, we engage more deeply with the notion of gender as a multiplicity exploring the implications of such for future studies of entrepreneurial activity

Designing the climate observing system of the future

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth's Future 6 (2018): 80–102, doi:10.1002/2017EF000627.Climate observations are needed to address a large range of important societal issues including sea level rise, droughts, floods, extreme heat events, food security, and freshwater availability in the coming decades. Past, targeted investments in specific climate questions have resulted in tremendous improvements in issues important to human health, security, and infrastructure. However, the current climate observing system was not planned in a comprehensive, focused manner required to adequately address the full range of climate needs. A potential approach to planning the observing system of the future is presented in this article. First, this article proposes that priority be given to the most critical needs as identified within the World Climate Research Program as Grand Challenges. These currently include seven important topics: melting ice and global consequences; clouds, circulation and climate sensitivity; carbon feedbacks in the climate system; understanding and predicting weather and climate extremes; water for the food baskets of the world; regional sea-level change and coastal impacts; and near-term climate prediction. For each Grand Challenge, observations are needed for long-term monitoring, process studies and forecasting capabilities. Second, objective evaluations of proposed observing systems, including satellites, ground-based and in situ observations as well as potentially new, unidentified observational approaches, can quantify the ability to address these climate priorities. And third, investments in effective climate observations will be economically important as they will offer a magnified return on investment that justifies a far greater development of observations to serve society's needs

Tailoring the oxidation state of cobalt through halide functionality in sol-gel silica

The functionality or oxidation state of cobalt within a silica matrix can be tailored through the use of cationic surfactants and their halide counter ions during the sol-gel synthesis. Simply by adding surfactant we could significantly increase the amount of cobalt existing as Co3O4 within the silica from 44% to 77%, without varying the cobalt precursor concentration. However, once the surfactant to cobalt ratio exceeded 1, further addition resulted in an inhibitory mechanism whereby the altered pyrolysis of the surfactant decreased Co3O4 production. These findings have significant implications for the production of cobalt/silica composites where maximizing the functional Co3O4 phase remains the goal for a broad range of catalytic, sensing and materials applications