Stress dependent thermal pressurization of a fluid-saturated rock

Temperature increase in saturated porous materials under undrained conditions leads to thermal pressurization of the pore fluid due to the discrepancy between the thermal expansion coefficients of the pore fluid and of the solid matrix. This increase in the pore fluid pressure induces a reduction of the effective mean stress and can lead to shear failure or hydraulic fracturing. The equations governing the phenomenon of thermal pressurization are presented and this phenomenon is studied experimentally for a saturated granular rock in an undrained heating test under constant isotropic stress. Careful analysis of the effect of mechanical and thermal deformation of the drainage and pressure measurement system is performed and a correction of the measured pore pressure is introduced. The test results are modelled using a non-linear thermo-poro-elastic constitutive model of the granular rock with emphasis on the stress-dependent character of the rock compressibility. The effects of stress and temperature on thermal pressurization observed in the tests are correctly reproduced by the model

Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission

"Diffuse" gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived "average" spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S. Cheng and G. E. Romero. More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm

Results and Outcome Reporting In ClinicalTrials.gov, What Makes it Happen?

At the end of the past century there were multiple concerns regarding lack of transparency in the conduct of clinical trials as well as some ethical and scientific issues affecting the trials' design and reporting. In 2000 ClinicalTrials.gov data repository was developed and deployed to serve public and scientific communities with valid data on clinical trials. Later in order to increase deposited data completeness and transparency of medical research a set of restrains had been imposed making the results deposition compulsory for multiple cases.We investigated efficiency of the results deposition and outcome reporting as well as what factors make positive impact on providing information of interest and what makes it more difficult, whether efficiency depends on what kind of institution was a trial sponsor. Data from the ClinicalTrials.gov repository has been classified based on what kind of institution a trial sponsor was. The odds ratio was calculated for results and outcome reporting by different sponsors' class.As of 01/01/2012 118,602 clinical trials data deposits were made to the depository. They came from 9068 different sources. 35344 (29.8%) of them are assigned as FDA regulated and 25151 (21.2%) as Section 801 controlled substances. Despite multiple regulatory requirements, only about 35% of trials had clinical study results deposited, the maximum 55.56% of trials with the results, was observed for trials completed in 2008.The most positive impact on depositing results, the imposed restrains made for hospitals and clinics. Health care companies showed much higher efficiency than other investigated classes both in higher fraction of trials with results and in providing at least one outcome for their trials. They also more often than others deposit results when it is not strictly required, particularly, in the case of non-interventional studies

Symmetry energy of dense matter in holographic QCD

We study the nuclear symmetry energy of dense matter using holographic QCD. To this end, we consider two flavor branes with equal quark masses in a D4/D6/D6 model. We find that at all densities the symmetry energy monotonically increases. At small densities, it exhibits a power law behavior with the density, $E_{\rm sym} \sim \rho^{1/2}$.Comment: 9 pages, 3 figure

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Run, Jump, Throw and Catch: How proficient are children attending English schools at the Fundamental Motor Skills identified as key within the school curriculum?

This study examined proficiency levels in fundamental motor skills (FMS) in children within Key Stage 1 and 2 of the English school system. Four hundred and ninety-two children aged 6–9 Years old (245 boys, 247 girls) from school Years Two (n = 130), Three (n = 154) and Four (n = 208) participated in this study. FMS for the run, jump, throw and catch were assessed using the Test of Gross Motor Development – 2. The proportion of children who achieved mastery or near mastery of the skills was determined. For the whole sample, 18.5% (n = 91) did not achieve mastery in any of the four skills. A similar proportion (18.7%, n = 92) achieved mastery in all four of the FMS examined in this study. The proportion of children achieving mastery of all four skills was lower for Year Two children (0%) compared to children in years Three (24%) and Four (25%). More boys (25.7%) achieved mastery in all four of the FMS compared to girls (11.7%). Individual behavioural components in skill performance were also examined. The results of the present study highlight that less than one-fifth of children aged 6–9 years old have mastered the four key FMS identified by the physical education (PE) curriculum despite having the developmental potential to become fundamentally competent by six years of age. Fostering positive trajectories of FMS development presents a challenge for PE specialists given the association between FMS mastery in childhood and physical activity, weight status and health.N/

Psychometric properties of the quality of life scale Child Health and Illness Profile-Child Edition in a combined analysis of five atomoxetine trials

Our aim was to evaluate the psychometric properties of the generic quality of life (QoL) scale Child Health and Illness Profile-Child Edition (CHIP-CE) by means of a combined analysis of atomoxetine clinical trials in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Individual patient-level data from five clinical trials were included in the combined analysis. Psychometric properties of the CHIP-CE were explored in terms of internal consistency and structure. Patients (n = 794) aged between 6 and 15 years (mean 9.7) with mean baseline ADHD Rating Scale of 41.8 ± 8.04 were included. On average, 0.7 (SD 2.23) items were missing for the whole CHIP-CE. The internal consistency of the CHIP-CE assessed by Cronbach’s alpha was good for all sub-domains at baseline and at endpoint. Considerable ceiling effects were only observed for the “restricted activity” sub-domain. No considerable floor effects were seen. The factor analysis supported the 12-factor solution for the sub-domains, but not the 5-factor solution for the domains. Our analyses were based on a large sample of non-US patients which allowed the measurement of clear changes in QoL over time. The results support that the CHIP-CE scale is psychometrically robust over time in terms of internal consistency and structure

KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.

BACKGROUND: There is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic virus infection and that these results are consistent with an increase in CD8+ T cell lifespan due to iKIR-ligand interactions. Here we test this prediction and investigate whether iKIRs affect T cell lifespan in humans in vivo. METHODS: We used stable isotope labelling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections. RESULTS: We showed that an individual's iKIR-ligand genotype is a significant determinant of CD8+ T cell lifespan: in individuals with two iKIR-ligand gene pairs, memory CD8+ T cells survived on average for 125 days, in individuals with four iKIR-ligand gene pairs then memory CD8+ T cell lifespan was doubled to 250 days. Additionally, we showed that this survival advantage is independent of iKIR expression by the T cell of interest and further that iKIR-ligand genotype altered CD8+ and CD4+ T cell immune aging phenotype. CONCLUSIONS: Together these data reveal an unexpectedly large impact of iKIR genotype on T cell survival. FUNDING: Wellcome Trust, Medical Research Council, EU Horizon 2020, EU FP7, Leukemia and Lymphoma Research, National Institute of Health Research Imperial Biomedical Research Centre, Imperial College Research Fellowship, National Institute of Health, Jefferiss Trust

The dose response principle from philosophy to modern toxicology: The impact of ancient philosophy and medicine in modern toxicology science

Since ancient times the concept of dose response, from a toxicological perspective, has been a matter of concern. Already by the 8th century BC and over the years, many enlightened people have attempted to interpret this phenomenon, observing and coming across its results and practical implementation through exposure to chemical substances, either from natural or synthetic sources. Nowadays, the environmental exposure of human populations to chemicals in terms of quantity and quality might differ. Nevertheless, dose response still remains an issue joining hands with scientific and technological progress. The aim of the present review is not only to briefly recount the history of the dose response concept, from ancient time theories to novel approaches, but also to draw the outline of challenges and requirements toxicology science needs to fulfill

The remnants of galaxy formation from a panoramic survey of the region around M31

In hierarchical cosmological models, galaxies grow in mass through the continual accretion of smaller ones. The tidal disruption of these systems is expected to result in loosely bound stars surrounding the galaxy, at distances that reach $10 - 100$ times the radius of the central disk. The number, luminosity and morphology of the relics of this process provide significant clues to galaxy formation history, but obtaining a comprehensive survey of these components is difficult because of their intrinsic faintness and vast extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We detect stars and coherent structures that are almost certainly remnants of dwarf galaxies destroyed by the tidal field of M31. An improved census of their surviving counterparts implies that three-quarters of M31's satellites brighter than $M_V < -6$ await discovery. The brightest companion, Triangulum (M33), is surrounded by a stellar structure that provides persuasive evidence for a recent encounter with M31. This panorama of galaxy structure directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.Comment: Published in Nature. Supplementary movie available at https://www.astrosci.ca/users/alan/PANDAS/Latest%20news%3A%20movie%20of%20orbit.htm