Serum and urine vitamin D metabolite analysis in early preeclampsia

Vitamin D-deficiency is common in pregnant women, and may contribute to adverse events in pregnancy such as preeclampsia (PET). To date, studies of vitamin D and PET have focused primarily on serum concentrations vitamin D, 25-hydroxyvitamin D3 (25(OH)D3) later in pregnancy. The aim here was to determine whether a more comprehensive analysis of vitamin D metabolites earlier in pregnancy could provide predictors of PET. Using samples from the SCOPE pregnancy cohort, multiple vitamin D metabolites were quantified by liquid chromatography-tandem mass spectrometry in paired serum and urine prior to the onset of PET symptoms. Samples from 50 women at pregnancy week 15 were analysed, with 25 (50%) developing PET by the end of the pregnancy and 25 continuing with uncomplicated pregnancy. Paired serum and urine from non-pregnant women (n=9) of reproductive age were also used as a control. Serum concentrations of 25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 were measured and showed no significant difference between women with uncomplicated pregnancies and those developing PET. As previously reported, serum 1,25(OH)2D3 was higher in all pregnant women (in the second trimester), but serum 25(OH)D2 was also higher compared to non-pregnant women. In urine, 25(OH)D3 and 24,25(OH)2D3 were quantifiable, with both metabolites demonstrating significantly lower (p&lt;0.05) concentrations of both of these metabolites in those destined to develop PET. These data indicate that analysis of urinary metabolites provides an additional insight into vitamin D and the kidney, with lower urinary 25(OH)D3, and 24,25(OH)2D3 excretion being an early indicator of a predisposition towards developing PET.</p

Neither Shoreditch nor Manhattan: Post-politics, 'soft austerity urbanism' and real abstraction in Glasgow North

Speirs Locks is being re-constructed as a new cultural quarter in Glasgow North, with urban boosters envisioning the unlikely, rundown and de-populated light industrial estate as a key site in the city's ongoing cultural regeneration strategy. Yet this creative place-making initiative, I argue, masks a post-political conjuncture based on urban speculation, displacement and the foreclosure of dissent. Post-politics at Speirs Locks is characterised by what I term ‘soft austerity urbanism’: seemingly progressive, instrumental small-scale urban catalyst initiatives that in reality complement rather than counter punitive hard austerity urbanism. Relating such processes of soft austerity urbanism to a wider context of state-led gentrification, this study contributes to post-political debates in several ways. Firstly, it questions demands for participation as a proper politics when it has become practically compulsory in contemporary biopolitical capitalism. Secondly, it demonstrates how an extreme economy of austerity urbanism remains the hard underside of post-political, soft austerity urbanism approaches. Thirdly, it illustrates how these approaches relate to wider processes of ‘real abstraction’ – which is no mere flattery of the mind, but instead is rooted in actually existing processes of commodity exchange. Such abstraction, epitomised in the financialisation and privatisation of land and housing, buttresses the same ongoing property dynamics that were so integral to the global financial crisis and ensuing austerity policies in the first place. If we aim to generate a proper politics that creates a genuine rupture with the destructive play of capital in the built environment, the secret of real abstraction must be critically addressed

Remote control of glucose homeostasis in vivo using photopharmacology

Photopharmacology describes the use of light to precisely deliver drug activity in space and time. Such approaches promise to improve drug specificity by reducing off-target effects. As a proof-of-concept, we have subjected the fourth generation photoswitchable sulfonylurea JB253 to comprehensive toxicology assessment, including mutagenicity and maximum/repeated tolerated dose studies, as well as in vivo testing in rodents. Here, we show that JB253 is well-tolerated with minimal mutagenicity and can be used to optically-control glucose homeostasis in anesthetized mice following delivery of blue light to the pancreas. These studies provide the first demonstration that photopharmacology may one day be applicable to the light-guided treatment of type 2 diabetes and other metabolic disease states in vivo in humans

Obliged to calculate: My School, markets, and equipping parents for calculativeness

This paper argues neoliberal programs of government in education are equipping parents for calculativeness. Regimes of testing and the publication of these results and other organizational data are contributing to a public economy of numbers that increasingly oblige citizens to calculate. Using the notions of calculative and market devices, this paper examines the Australian Government’s My School website, which publishes academic and organizational information about schools, including national test results. While it is often assumed that such performance technologies contribute to neoliberal reform of education through school choice, the paper argues the website is technically limited in its capacity to facilitate the economic calculations and calculated action of parents resulting in school choice. The paper instead opens My School to analysis as a technique of governmental self-formation. Using the theoretical resources of actor-network theory and Foucauldian scholarship, this paper complicates assumptions in the literature about the extent to which My School actually operates as a ‘market mechanism’. It argues My School attempts to cultivate a calculated form of parental educational agency, irreducible to economic market agency

Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion

Early pregnancy is characterised by elevated circulating levels of vitamin D binding protein (DBP). The impact of this on maternal and fetal health is unclear but DBP is present in the placenta, and DBP gene variants have been linked to malplacentation disorders such as preeclampsia. The functional role of DBP in the placenta was investigated using trophoblastic JEG3, BeWo and HTR8 cells. All three cell lines showed intracellular DBP with increased expression and nuclear localisation of DBP in cells treated with the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D). When cultured in the serum of mice lacking DBP (DBP-/-), JEG3 cells showed no intracellular DBP indicating uptake of exogenous DBP. Inhibition of the membrane receptor for DBP, megalin, also suppressed intracellular DBP. Elimination of intracellular DBP with DBP-/- serum or megalin inhibitor suppressed matrix invasion by trophoblast cells and was associated with increased nuclear accumulation of G-actin. Conversely, treatment with 1,25D enhanced matrix invasion. This was independent of the nuclear vitamin D receptor but was associated with enhanced ERK phosphorylation, and inhibition of ERK kinase suppressed trophoblast matrix invasion. When cultured with serum from pregnant women, trophoblast matrix invasion correlated with DBP concentration, and DBP was lower in first-trimester serum from women who later developed preeclampsia. These data show that the trophoblast matrix invasion involves uptake of serum DBP and associated intracellular actin-binding and homeostasis. DBP is a potential marker of placentation disorders such as preeclampsia and may also provide a therapeutic option for improved placenta and pregnancy health

Governing the world at a distance : the practice of global benchmarking

Benchmarking practices have rapidly diffused throughout the globe in recent years. This can be traced to their popularity amongst non-state actors, such as civil society organisations and corporate actors, as well as states and international organisations (IOs). Benchmarks serve to both ‘neutralise’ and ‘universalise’ a range of overlapping normative values and agendas, including freedom of speech, democracy, human development, environmental protection, poverty alleviation, ‘modern’ statehood, and ‘free’ markets. The proliferation of global benchmarks in these key areas amounts to a comprehensive normative vision regarding what various types of transnational actors should look like, what they should value, and how they should behave. While individual benchmarks routinely differ in terms of scope and application, they all share a common foundation, with normative values and agendas being translated into numerical representations through simplification and extrapolation, commensuration, reification, and symbolic judgements. We argue that the power of benchmarks chiefly stems from their capacity to create the appearance of authoritative expertise on the basis of forms of quantification and numerical representation. This politics of numbers paves the way for the exercise of various forms of indirect power, or ‘governance at a distance’, for the purposes of either status quo legitimation or political reform

Configuring urban carbon governance: insights from Sydney, Australia

In the political geography of responses to climate change, and the governance of carbon more specifically, the urban has emerged as a strategic site. Although it is recognized that urban carbon governance occurs through diverse programs and projects—involving multiple actors and working through multiple sites, mechanisms, objects, and subjects—surprisingly little attention has been paid to the actual processes through which these diverse elements are drawn together and held together in the exercise of governing. These processes—termed configuration—remain underspecified. This article explores urban carbon governance interventions as relational configurations, excavating how their diverse elements—human, institutional, representational, and material—are assembled, drawn into relation, and held together in the exercise of governing. Through an analysis of two contrasting case studies of urban carbon governance interventions in Sydney, Australia, we draw out common processes of configuring and specific sets of devices and techniques that gather, align, and maintain the relations between actors and elements that constitute intervention projects. We conclude by reflecting on the implications of conceiving of governing projects as relational configurations for how we understand the nature and practice of urban carbon governance, especially by revealing the diverse modes of power at work within processes of configuring

Neoliberalism, policy localisation and idealised subjects: a case study on educational restructuring in England

This article was accepted for publication in the Transactions of the Institute of British Geographers: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1475-5661Debate about neoliberalism has been a defining drama of twenty-first century geography. Appreciation of the contingent nature of neoliberalization has promoted interest in the localization of policy, and this paper furthers debate in three ways. Firstly, it highlights the importance of the peopling of the state and more specifically the importance of everyday public sector workers in the localized production of roll-out neoliberalization. Secondly, it illustrates the significance of these actors’ ideas about idealised policy subjects -- and the ways they relate these to their own client groups in different socio-economic neighbourhoods -- in the localised emergence of policy. Thirdly, it explores the consequences of this for geographically and socially uneven service provision under neoliberalization. These arguments are illustrated through a case study focus on educational restructuring under New Labour. Our focus is on the Extended Service initiative which combines workfare and family policy agenda by giving primary schools a duty provide/signpost: wraparound childcare; enrichment activities for children; and parenting support. The case study explores how headteachers’ understandings of idealised neoliberal parenting subject positions, and their notions of ideal childhoods, shape their attitudes to the implementation of this programme in schools serving different socio-economic communities. This process not only involves the reproduction of classed, (de)gendered, and heterosexed discourses seen in national policy, but also moments where local actors draw on alternative models of parenting and/or childhood to influence school-based policy, with the result that what is perceived to be ‘good’ for families of one social class is not seen to be so for others. There is a complex politics at play here. Academics must both expose the class biases inherent in neoliberal policies, at the same time as they work as ‘critical friends’ in improving public service provision which impacts positively on some individuals’ lives