Influence of speed of sample processing on placental energetics and signalling pathways: implications for tissue collection.

INTRODUCTION: The placenta is metabolically highly active due to extensive endocrine and active transport functions. Hence, placental tissues soon become ischaemic after separation from the maternal blood supply. Ischaemia rapidly depletes intracellular ATP, and leads to activation of stress-response pathways aimed at reducing metabolic demands and conserving energy resources for vital functions. Therefore, this study aimed to elucidate the effects of ischaemia ex vivo as may occur during tissue collection on phosphorylation of placental proteins and kinases involved in growth and cell survival, and on mitochondrial complexes. METHODS: Eight term placentas obtained from normotensive non-laboured elective caesarean sections were kept at room-temperature and sampled at 10, 20, 30 and 45 min after delivery. Samples were analyzed by Western blotting. RESULTS: Between 10 and 45 min the survival signalling pathway intermediates, P-AKT, P-GSK3α and β, P-4E-BP1 and P-p70S6K were reduced by 30-65%. Stress signalling intermediates, P-eIF2α increased almost 3 fold after 45 min. However, other endoplasmic reticulum stress markers and the Heat Shock Proteins, HSP27, HSP70 and HSP90, did not change. Phosphorylation of AMPK, an energy sensor, was elevated 2 fold after 45 min. Contemporaneously, there was an ∼25% reduction in mitochondrial complex IV subunit I. DISCUSSION AND CONCLUSIONS: These results suggest that for placental signalling studies, samples should be taken and processed within 10 min of caesarean delivery to minimize the impact of ischaemia on protein phosphorylation

The effect of moving to East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village, on mode of travel (ENABLE London study, a natural experiment)

Background Interventions to encourage active modes of travel (walking, cycling) may improve physical activity levels, but longitudinal evidence is limited and major change in the built environment / travel infrastructure may be needed. East Village (the former London 2012 Olympic Games Athletes Village) has been repurposed on active design principles with improved walkability, open space and public transport and restrictions on residential car parking. We examined the effect of moving to East Village on adult travel patterns. Methods One thousand two hundred seventy-eight adults (16+ years) seeking to move into social, intermediate, and market-rent East Village accommodation were recruited in 2013–2015, and followed up after 2 years. Individual objective measures of physical activity using accelerometry (ActiGraph GT3X+) and geographic location using GPS travel recorders (QStarz) were time-matched and a validated algorithm assigned four travel modes (walking, cycling, motorised vehicle, train). We examined change in time spent in different travel modes, using multilevel linear regresssion models adjusting for sex, age group, ethnicity, housing group (fixed effects) and household (random effect), comparing those who had moved to East Village at follow-up with those who did not. Results Of 877 adults (69%) followed-up, 578 (66%) provided valid accelerometry and GPS data for at least 1 day (≥540 min) at both time points; half had moved to East Village. Despite no overall effects on physical activity levels, sizeable improvements in walkability and access to public transport in East Village resulted in decreased daily vehicle travel (8.3 mins, 95%CI 2.5,14.0), particularly in the intermediate housing group (9.6 mins, 95%CI 2.2,16.9), and increased underground travel (3.9 mins, 95%CI 1.2,6.5), more so in the market-rent group (11.5 mins, 95%CI 4.4,18.6). However, there were no effects on time spent walking or cycling

On the Complexity of Quadratization for Polynomial Differential Equations

Chemical reaction networks (CRNs) are a standard formalism used in chemistry and biology to reason about the dynamics of molecular interaction networks. In their interpretation by ordinary differential equations, CRNs provide a Turing-complete model of analog computattion, in the sense that any computable function over the reals can be computed by a finite number of molecular species with a continuous CRN which approximates the result of that function in one of its components in arbitrary precision. The proof of that result is based on a previous result of Bournez et al. on the Turing-completeness of polyno-mial ordinary differential equations with polynomial initial conditions (PIVP). It uses an encoding of real variables by two non-negative variables for concentrations, and a transformation to an equivalent quadratic PIVP (i.e. with degrees at most 2) for restricting ourselves to at most bimolecular reactions. In this paper, we study the theoretical and practical complexities of the quadratic transformation. We show that both problems of minimizing either the number of variables (i.e., molecular species) or the number of monomials (i.e. elementary reactions) in a quadratic transformation of a PIVP are NP-hard. We present an encoding of those problems in MAX-SAT and show the practical complexity of this algorithm on a benchmark of quadratization problems inspired from CRN design problems

Propositions for an Environmental Arts Pedagogy: A/r/tographic experimentations with movement and materiality

This chapter works through a series of methodological experimentations with movement and materiality in order to explore the potentials of environmental arts pedagogies. We address the question of what environmental arts pedagogies might come to look like in the ever-changing contexts of children’s social and environmental worlds. This leads us to engage with the movements and materialities of learning environments as they come to co-compose pedagogical encounters. In doing so, we draw on new materialist accounts of matter as agentic, fluid and dynamic; movement as a choreographic architecting of experience; and a/r/tographic approaches to pedagogical engagement and embodied practice. Taking up the use of concepts as methods, we develop a series of artistic and pedagogical experimentations with concepts of ‘corridors’, ‘flight’, ‘viscosity’ and ‘construction’. In teasing out the implications of these concepts for an environmental arts pedagogy, we combine imagery and text to both render and diagram the movement of bodies, materials and environments in passage through each of these four conceptual enactments. This leads us to develop a series of propositions for an environmental arts pedagogy based on our creative research process. In doing so, we aim to sketch the contours of an environmental arts pedagogy that combines the speculative imagination with embodied, sensorial, and empirical experiences

Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study

Background Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. Aims To describe initiation of psychotropic medication in the first year after partner bereavement. Methods In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. Results The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. Conclusion Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use

E11, generalised space-time and equations of motion in four dimensions

We construct the non-linear realisation of the semi-direct product of E11 and its first fundamental representation at low levels in four dimensions. We include the fields for gravity, the scalars and the gauge fields as well as the duals of these fields. The generalised space-time, upon which the fields depend, consists of the usual coordinates of four dimensional space-time and Lorentz scalar coordinates which belong to the 56-dimensional representation of E7. We demand that the equations of motion are first order in derivatives of the generalised space-time and then show that they are essentially uniquely determined by the properties of the E11 Kac-Moody algebra and its first fundamental representation. The two lowest equations correctly describe the equations of motion of the scalars and the gauge fields once one takes the fields to depend only on the usual four dimensional space-time

Generalised geometry, eleven dimensions and E11

We construct the non-linear realisation of E11 and its first fundamental representation in eleven dimensions at low levels. The fields depend on the usual coordinates of space-time as well as two form and five form coordinates. We derive the terms in the dynamics that contain the three form and six form fields and show that when we restricted their field dependence to be only on the usual space-time we recover the correct self-duality relation. Should this result generalise to the gravity fields then the non-linear realisation is an extension of the maximal supergravity theory, as previously conjectured. We also comment on the connections between the different approaches to generalised geometry.Comment: 17 pages, Trivial typos corrected in version one and a substantial note added which gives the equation of motion relating the gravity field to its dua

Finite Element Modeling of Ultrasonic Inspection of Weldments

High performance weldments for critical service applications require 100% inspection. Balanced against the adaptability of the ultrasonic method for automated inspection are the difficulties encountered with nonhomogeneous and anisotropic materials. This research utilizes crystals and bicrystals of nickel to model austenitic weld metal, where the anisotropy produces scattering and mode conversion, making detection and measurement of actual defects difficult. Well characterized samples of Ni are produced in a levitation zone melting facility. Crystals in excess of 25 mm diameter and length are large enough to permit ultrasonic measurements of attenuation, wave speed, and spectral content. At the same time, the experiments are duplicated as finite element models for comparison purposes. Finite element models permit easy description of boundary conditions, geometry, and loading. Direct integration of the wave equation is done with the Newmark-Beta and Wilson-Theta Methods. The usual problem with the large number of degress of freedom can be alleviated with the use of Guyan reduction. Two-dimensional comparisons showing mode conversion and a plate with a flaw are made. The continued development of this computational tool should increase understanding of quantitative ultrasonic inspection

Duality Invariant Actions and Generalised Geometry

We construct the non-linear realisation of the semi-direct product of E(11) and its first fundamental representation at lowest order and appropriate to spacetime dimensions four to seven. This leads to a non-linear realisation of the duality groups and introduces fields that depend on a generalised space which possess a generalised vielbein. We focus on the part of the generalised space on which the duality groups alone act and construct an invariant action.Comment: 59 pages (typos fixed and added comments