Coupled measurements of δ¹⁸O and δD of hydration water and salinity of fluid inclusions in gypsum from the Messinian Yesares Member, Sorbas Basin (SE Spain)

We studied one cycle (Cycle 6) of gypsum-marl deposition from the Messinian Yesares Member in Sorbas Basin, Spain. The objective was to reconstruct the changing environment of deposition and its relation to astronomically-forced climate change. The δ1818O and δD of gypsum hydration water (CaSO4•2H2O) and salinity of fluid inclusions were measured in the same samples to test if they record the composition of the mother fluid from which gypsum was precipitated. Water isotopes are highly correlated with fluid inclusion salinity suggesting the hydration water has not exchanged after formation. The relatively low water isotope values and fluid inclusion salinities indicate a significant influence of meteoric water, whereas δ34S, δ18OSO4 26 and 87Sr/86Sr support a dominant marine origin for the gypsum deposits. The discrepancy between water and elemental isotope signatures can be reconciled if meteoric water dissolved previously deposited marine sulfates supplying calcium and sulfate ions to the basin which maintained gypsum saturation. This recycling process accounts for the marine δ34S, δ18OSO4 and 87Sr/86Sr signatures, whereas the low δ18O and δD values of gypsum hydration water and fluid inclusion salinities reflect the influence of freshwater. The cyclic deposition of gypsum and marl in the Yesares Member has previously been interpreted to reflect changing climate related to Earth’s precession cycle. We demonstrate that the δ18O, δD and salinity of the parent brine increased from low values at the base of Cycle 6 to a maximum in the massive gypsum palisade, and decreased again to lower values in the supercones at the top of the cycle. This pattern, together with changes in mineralogy (calcite-dolomite-gypsum), is consistent with a precession-driven change in climate with wettest conditions (summer insolation maxima) associated with the base of the calcium carbonate marls and driest conditions (summer insolation minima) during formation of the gypsum palisade.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 339694 (Water Isotopes of Hydrated Minerals) to D. A. Hodell.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.epsl.2015.07.07

Graft-versus-host disease reduces lymph node display of tissue-restricted self-antigens and promotes autoimmunity

Acute graft-versus-host disease (GVHD) is initially triggered by alloreactive T cells, which damage peripheral tissues and lymphoid organs. Subsequent transition to chronic GVHD involves the emergence of autoimmunity although the underlying mechanisms driving this process are unclear. Here, we tested the hypothesis that acute GVHD blocks peripheral tolerance of autoreactive T cells by impairing lymph node (LN) display of peripheral tissue-restricted antigens (PTA). At the initiation of GVHD, LN fibroblastic reticular cells (FRC) rapidly reduced expression of genes regulated by DEAF1, an Autoimmune Regulator-like transcription factor required for intra-nodal expression of PTA. Subsequently, GVHD led to the selective elimination of the FRC population, and blocked the repair pathways required for its regeneration. We used a transgenic mouse model to show that the loss of presentation of an intestinal PTA by FRC during GVHD resulted in the activation of auto-aggressive T cells and gut injury. Finally, we show that FRC normally expressed a unique PTA gene signature that was highly enriched for genes expressed in the target organs affected by chronic GVHD. In conclusion, acute GVHD damages and prevents repair of the FRC network, thus disabling an essential platform for purging auto-reactive T cells from the repertoire

Predictors of outcome after 6 and 12 months following anthroposophic therapy for adult outpatients with chronic disease: a secondary analysis from a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Anthroposophic medicine is a physician-provided complementary therapy system involving counselling, artistic and physical therapies, and special medications. The purpose of this analysis was to identify predictors of symptom improvement in patients receiving anthroposophic treatment for chronic diseases.</p> <p>Methods</p> <p>913 adult outpatients from Germany participated in a prospective cohort study. Patients were starting anthroposophic treatment for mental (30.4% of patients, n = 278/913), musculoskeletal (20.2%), neurological (7.6%), genitourinary (7.4%) or respiratory disorders (7.2%) or other chronic indications. Stepwise multiple linear regression analysis was performed with the improvement of Symptom Score (patients' assessment, 0: not present, 10: worst possible) after 6 and 12 months as dependent variables. 61 independent variables pertaining to socio-demographics, life style, disease status, co-morbidity, health status (SF-36), depression, and therapy factors were analysed.</p> <p>Results</p> <p>Compared to baseline, Symptom Score improved by average 2.53 points (95% confidence interval 2.39-2.68, p < 0.001) after six months and by 2.49 points (2.32-2.65, p < 0.001) after 12 months. The strongest predictor for improvement after six months was baseline Symptom Score, which alone accounted for 25% of the variance (total model 32%). Improvement after six months was also positively predicted by better physical function, better general health, shorter disease duration, higher education level, a diagnosis of respiratory disorders, and by a higher therapy goal documented by the physician at baseline; and negatively predicted by the number of physiotherapy sessions in the pre-study year and by a diagnosis of genitourinary disorders. Seven of these nine variables (not the two diagnoses) also predicted improvement after 12 months. When repeating the 0-6 month analysis on two random subsamples of the original sample, three variables (baseline Symptom Score, physical function, general health) remained significant predictors in both analyses, and three further variables (education level, respiratory disorders, therapy goal) were significant in one analysis.</p> <p>Conclusion</p> <p>In adult outpatients receiving anthroposophic treatment for chronic diseases, symptom improvement after 6 and 12 months was predicted by baseline symptoms, health status, disease duration, education, and therapy goal. Other variables were not associated with the outcome. This secondary predictor analysis of data from a pre-post study does not allow for causal conclusions; the results are hypothesis generating and need verification in subsequent studies.</p

Urological referral of asymptomatic men in general practice in England

The Prostate Cancer Risk Management Programme (PCRMP) launched in November 2002 provides guidelines for general practitioners (GPs) on age-specific prostate-specific antigen (PSA) cutoff levels in asymptomatic men. The impact of the PCRMP on GP referrals is unknown. This study investigates whether there was a change in the proportion of asymptomatic men with raised PSA levels (⩾3 ng ml−1) who were referred to urologists since the launch of the guidelines. Sixty-nine general practices in four areas of England and the main pathology laboratory in each area, which had participated in our previous research, were asked to provide data. Forty-eight practices (70%) provided retrospective data on urological referrals in men who had a PSA test taken in the periods 1 December 2001 to 31 May 2002 (pre-launch) and 1 December 2003 to 31 May 2004 (post-launch). Data on referrals were completed for 709 (79%) out of 898 and 1040 (90%) out of 1157 raised records pre- and post-launch, respectively. The percentage of men with raised PSA levels who were asymptomatic was similar in both time periods (19–20%) and the proportion referred to urologists according to the PCRMP guidelines did not increase significantly over time (24% pre-launch and 29% post-launch, P=0.42). The referral rate was lower than expected if the guidelines had been followed. The influence of the guidelines seems to have been low. At the time of data collection, 56% (112 out of 200) of GP partners reported that they were aware of receiving the PCRMP pack. To ensure future, effective implementation of guidelines requires evaluation

The development of accounting in UK universities:an oral history

This article reports on the development of the accounting discipline in universities in England and Scotland from the 1960s. Drawing on the oral history narratives of six distinguished accounting scholars who played a significant role in the discipline, this article documents (1) the initial influences on the teaching of accounting in English universities, (2) the different influences on the teaching of accounting in Scottish universities and (3) the influence of US universities and their scholars on the development of academic accounting in the United Kingdom. With a focus on the second wave of accounting professoriate who followed the London School of Economics (LSE) ‘Triumvirate’ of William Baxter, Harold Edey and David Solomons, this article provides first-hand insights into the shape and spread of university accounting education at a crucial stage of its development. This, in turn, develops an understanding of the contemporary academic accounting discipline in the United Kingdom.PostprintPeer reviewe

A close halo of large transparent grains around extreme red giant stars

Intermediate-mass stars end their lives by ejecting the bulk of their envelope via a slow dense wind back into the interstellar medium, to form the next generation of stars and planets. Stellar pulsations are thought to elevate gas to an altitude cool enough for the condensation of dust, which is then accelerated by radiation pressure from starlight, entraining the gas and driving the wind. However accounting for the mass loss has been a problem due to the difficulty in observing tenuous gas and dust tens of milliarcseconds from the star, and there is accordingly no consensus on the way sufficient momentum is transferred from the starlight to the outflow. Here, we present spatially-resolved, multi-wavelength observations of circumstellar dust shells of three stars on the asymptotic giant branch of the HR diagram. When imaged in scattered light, dust shells were found at remarkably small radii (<~ 2 stellar radii) and with unexpectedly large grains (~300 nm radius). This proximity to the photosphere argues for dust species that are transparent to starlight and therefore resistant to sublimation by the intense radiation field. While transparency usually implies insufficient radiative pressure to drive a wind, the radiation field can accelerate these large grains via photon scattering rather than absorption - a plausible mass-loss mechanism for lower-amplitude pulsating stars.Comment: 13 pages, 1 table, 6 figure

On Poincare and logarithmic Sobolev inequalities for a class of singular Gibbs measures

This note, mostly expository, is devoted to Poincar{\'e} and log-Sobolev inequalities for a class of Boltzmann-Gibbs measures with singular interaction. Such measures allow to model one-dimensional particles with confinement and singular pair interaction. The functional inequalities come from convexity. We prove and characterize optimality in the case of quadratic confinement via a factorization of the measure. This optimality phenomenon holds for all beta Hermite ensembles including the Gaussian unitary ensemble, a famous exactly solvable model of random matrix theory. We further explore exact solvability by reviewing the relation to Dyson-Ornstein-Uhlenbeck diffusion dynamics admitting the Hermite-Lassalle orthogonal polynomials as a complete set of eigenfunctions. We also discuss the consequence of the log-Sobolev inequality in terms of concentration of measure for Lipschitz functions such as maxima and linear statistics.Comment: Minor improvements. To appear in Geometric Aspects of Functional Analysis -- Israel Seminar (GAFA) 2017-2019", Lecture Notes in Mathematics 225

Soft Matrices Suppress Cooperative Behaviors among Receptor-Ligand Bonds in Cell Adhesion

The fact that biological tissues are stable over prolonged periods of time while individual receptor-ligand bonds only have limited lifetime underscores the critical importance of cooperative behaviors of multiple molecular bonds, in particular the competition between the rate of rupture of closed bonds (death rate) and the rate of rebinding of open bonds (birth rate) in a bond cluster. We have recently shown that soft matrices can greatly increase the death rate in a bond cluster by inducing severe stress concentration near the adhesion edges. In the present paper, we report a more striking effect that, irrespective of stress concentration, soft matrices also suppress the birth rate in a bond cluster by increasing the local separation distance between open bonds. This is shown by theoretical analysis as well as Monte Carlo simulations based on a stochastic-elasticity model in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial force/separation are unified in a single modeling framework. Our findings not only are important for understanding the role of elastic matrices in cell adhesion, but also have general implications on adhesion between soft materials

The parent analogy: a reassessment

According to the parent analogy, as a caretaker’s goodness, ability and intelligence increase, the likelihood that the caretaker will make arrangements for the attainment of future goods that are unnoticed or underappreciated by their dependents also increases. Consequently, if this analogy accurately represents our relationship to God, then we should expect to find many instances of inscrutable evil in the world. This argument in support of skeptical theism has recently been criticized by Dougherty. I argue that Dougherty’s argument is incomplete, for there are two plausible ways of construing the parent analogy’s conclusion. I supplement Dougherty’s case by offering a new argument against the parent analogy based on failed expectations concerning the amount of inscrutable evils encountered in the world. Consequently, there remains a significant empirical hurdle for skeptical theism to overcome if it is to maintain its status as a defeater for our reliability when tracking gratuitous evils.Publisher PDFPeer reviewe

The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport

Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA Sequencing performed using the Illumina platform. Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life