First-principles study of ferroelectricity and pressure-induced phase transitions in HgTiO3_3

Ground-state structure is found and pressure-induced phase transitions up to 210 kbar are studied in mercury titanate from first principles within the density functional theory. It is established that the $R3c$ structure experimentally observed in HgTiO$_3$ is metastable at ambient pressure. With increasing the hydrostatic pressure, the ground-state structure changes following the $R{\bar 3} \to R3c \to Pbnm$ sequence. It is shown that the appearance of ferroelectricity in HgTiO$_3$ at $P = 0$ is associated with an unstable phonon mode. Optical and elastic properties of different phases of mercury titanate are calculated. The quasiparticle band gap calculated in the \emph{GW} approximation ($E_g = 2.43$ eV) agrees with experimental data better than the value obtained in the LDA approximation (1.49 eV). Analysis of the thermodynamic stability explains why the synthesis of mercury titanate is possible only at high pressures.Comment: 8 pages, 4 figures, 5 tables; to appear in Phase Transition

The nonlinear anomalous lattice elasticity associated with the high-pressure phase transition in spodumene: A high precission static compression study

The high-pressure behavior of the lattice elasticity of spodumene, LiAlSi2O6, was studied by static compression in a diamond-anvil cell up to 9.3 GPa. Investigations by means of single-crystal XRD and Raman spectroscopy within the hydrostatic limits of the pressure medium focus on the pressure ranges around similar to 3.2 and similar to 7.7 GPa, which have been reported previously to comprise two independent structural phase transitions. While our measurements confirm the well-established first-order C2/c-P2(1)/c transformation at 3.19 GPa (with 1.2% volume discontinuity and a hysteresis between 0.02 and 0.06 GPa), both unit-cell dimensions and the spectral changes observed in high-pressure Raman spectra give no evidence for structural changes related to a second phase transition. Monoclinic lattice parameters and unit-cell volumes at in total 59 different pressure points have been used to re-calculate the lattice-related properties of spontaneous strain, volume strain, and the bulk moduli as a function of pressure across the transition. A modified Landau free energy expansion in terms of a one component order parameter has been developed and tested against these experimentally determined data. The Landau solution provides a much better reproduction of the observed anomalies than any equation-of-state fit to data sets truncated below and above P (tr), thus giving Landau parameters of K (0) = 138.3(2) GPa, K' = 7.46(5), lambda (V) = 33.6(2) GPa, a = 0.486(3), b = -29.4(6) GPa and c = 551(11) GPa

Widespread sex differences in gene expression and splicing in the adult human brain

There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

Introduction

Why do parent\u2013child argumentative interactions matter? What is the reason for such an interest? This chapter provides the reasons that motivated the study of parent\u2013child argumentation with the aim to understand the function of this type of interactions. Focusing on the activity of family mealtime, in the first part, the chapter draws attention to the distinctive features of parent\u2013child conversations. A second section of the chapter is devoted to discussing whether and, eventually, when children have the competence to construct arguments and engage in argumentative discussions with the aim to convince their parents to change opinion. In the last part of the chapter, research questions and structure of the volume are presented

Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. a simulation Study

<p>Abstract</p> <p>Background</p> <p>Increasing the predictability and reducing the rate of side effects of oral anticoagulant treatment (OAT) requires further clarification of the cause of about 50% of the interindividual variability of OAT response that is currently unaccounted for. We explore numerically the hypothesis that the effect of the interindividual expression variability of coagulation proteins, which does not usually result in a variability of the coagulation times in untreated subjects, is unmasked by OAT.</p> <p>Results</p> <p>We developed a stochastic variant of the Hockin-Mann model of the tissue factor coagulation pathway, using literature data for the variability of coagulation protein levels in the blood of normal subjects. We simulated <it>in vitro </it>coagulation and estimated the Prothrombin Time and the INR across a model population. In a model of untreated subjects a "canalization effect" can be observed in that a coefficient of variation of up to 33% of each protein level results in a simulated INR of 1 with a clinically irrelevant dispersion of 0.12. When the mean and the standard deviation of vitamin-K dependent protein levels were reduced by 80%, corresponding to the usual Warfarin treatment intensity, the simulated INR was 2.98 ± 0.48, a clinically relevant dispersion, corresponding to a reduction of the canalization effect.</p> <p>Then we combined the Hockin-Mann stochastic model with our previously published model of population response to Warfarin, that takes into account the genetical and the phenotypical variability of Warfarin pharmacokinetics and pharmacodynamics. We used the combined model to evaluate the coagulation protein variability effect on the variability of the Warfarin dose required to reach an INR target of 2.5. The dose variance when removing the coagulation protein variability was 30% lower. The dose was mostly related to the pretreatment levels of factors VII, X, and the tissue factor pathway inhibitor (TFPI).</p> <p>Conclusions</p> <p>It may be worth exploring in experimental studies whether the pretreatment levels of coagulation proteins, in particular VII, X and TFPI, are predictors of the individual warfarin dose, even though, maybe due to a canalization-type effect, their effect on the INR variance in untreated subjects appears low.</p

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Inhibition of Nox2 Oxidase Activity Ameliorates Influenza A Virus-Induced Lung Inflammation

Influenza A virus pandemics and emerging anti-viral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication and lung inflammation. We investigated whether the primary enzymatic source of inflammatory cell ROS (reactive oxygen species), Nox2-containing NADPH oxidase, is a novel pharmacological target against the lung inflammation caused by influenza A viruses. Male WT (C57BL/6) and Nox2−/y mice were infected intranasally with low pathogenicity (X-31, H3N2) or higher pathogenicity (PR8, H1N1) influenza A virus. Viral titer, airways inflammation, superoxide and peroxynitrite production, lung histopathology, pro-inflammatory (MCP-1) and antiviral (IL-1β) cytokines/chemokines, CD8+ T cell effector function and alveolar epithelial cell apoptosis were assessed. Infection of Nox2−/y mice with X-31 virus resulted in a significant reduction in viral titers, BALF macrophages, peri-bronchial inflammation, BALF inflammatory cell superoxide and lung tissue peroxynitrite production, MCP-1 levels and alveolar epithelial cell apoptosis when compared to WT control mice. Lung levels of IL-1β were ∼3-fold higher in Nox2−/y mice. The numbers of influenza-specific CD8+DbNP366+ and DbPA224+ T cells in the BALF and spleen were comparable in WT and Nox2−/y mice. In vivo administration of the Nox2 inhibitor apocynin significantly suppressed viral titer, airways inflammation and inflammatory cell superoxide production following infection with X-31 or PR8. In conclusion, these findings indicate that Nox2 inhibitors have therapeutic potential for control of lung inflammation and damage in an influenza strain-independent manner

Atrial fibrillation in a primary care practice: prevalence and management

BACKGROUND: Atrial fibrillation is a common serious cardiac arrhythmia. Knowing the prevalence of atrial fibrillation and documentation of medical management are important in the provision of primary care. This study sought to determine the prevalence of atrial fibrillation in a primary care population and to identify and quantify the treatments being used for stroke prevention in this group of patients. METHODS: A prevalence study through chart audit was conducted in the family medicine practice at the Sunnybrook campus of the Sunnybrook and Women's College Health Sciences Centre. The main outcome measures were the prevalence of atrial fibrillation in our primary care practice and the use of warfarin for stroke prevention in this population. RESULTS: 261 patients in our practice have atrial fibrillation. The overall prevalence in our family practice unit is 3.9%. When considering patients aged 60 and over, the prevalence rises to 12.2%. 204 of our patients with atrial fibrillation (78.2%) are currently being treated with warfarin. Another 21 patients were previously treated and discontinued for a number of reasons. Of the 57 patients not currently treated with warfarin, 44 are treated with ASA, 2 with ticlopidine, and 11 are receiving no preventative treatment. CONCLUSIONS: The prevalence of atrial fibrillation in our practice is higher than the range of prevalence reported in the general literature. However, our coverage with warfarin treatment exceeds previous reports in the literature

The air quality impacts of road closures associated with the 2004 Democratic National Convention in Boston

BACKGROUND: The Democratic National Convention (DNC) in Boston, Massachusetts in 2004 provided an opportunity to evaluate the impacts of a localized and short-term but potentially significant change in traffic patterns on air quality, and to determine the optimal monitoring approach to address events of this nature. It was anticipated that the road closures associated with the DNC would both influence the overall air pollution level and the distribution of concentrations across the city, through shifts in traffic patterns. METHODS: To capture these effects, we placed passive nitrogen dioxide badges at 40 sites around metropolitan Boston before, during, and after the DNC, with the goal of capturing the array of hypothesized impacts. In addition, we continuously measured elemental carbon at three sites, and gathered continuous air pollution data from US EPA fixed-site monitors and traffic count data from the Massachusetts Highway Department. RESULTS: There were significant reductions in traffic volume on the highway with closures north of Boston, with relatively little change along other highways, indicating a more isolated traffic reduction rather than an across-the-board decrease. For our nitrogen dioxide samples, while there was a relatively small change in mean concentrations, there was significant heterogeneity across sites, which corresponded with our a priori classifications of road segments. The median ratio of nitrogen dioxide concentrations during the DNC relative to non-DNC sampling periods was 0.58 at sites with hypothesized traffic reductions, versus 0.88 for sites with no changes hypothesized and 1.15 for sites with hypothesized traffic increases. Continuous monitors measured slightly lower concentrations of elemental carbon and nitrogen dioxide during road closure periods at monitors proximate to closed highway segments, but not for PM(2.5 )or further from major highways. CONCLUSION: We conclude that there was a small but measurable influence of DNC-related road closures on air quality patterns in the Boston area, and that a low-cost monitoring study combining passive badges for spatial heterogeneity and continuous monitors for temporal heterogeneity can provide useful insight for community air quality assessments