Hybrid Local-Order Mechanism for Inversion Symmetry Breaking

Using classical Monte Carlo simulations, we study a simple statistical mechanical model of relevance to the emergence of polarisation from local displacements on the square and cubic lattices. Our model contains two key ingredients: a Kitaev-like orientation-dependent interaction between nearest neighbours, and a steric term that acts between next-nearest neighbours. Taken by themselves, each of these two ingredients is incapable of driving long-range symmetry breaking, despite the presence of a broad feature in the corresponding heat capacity functions. Instead each component results in a "hidden" transition on cooling to a manifold of degenerate states, the two manifolds are different in the sense that they reflect distinct types of local order. Remarkably, their intersection---\emph{i.e.} the ground state when both interaction terms are included in the Hamiltonian---supports a spontaneous polarisation. In this way, our study demonstrates how local ordering mechanisms might be combined to break global inversion symmetry in a manner conceptually similar to that operating in the "hybrid" improper ferroelectrics. We discuss the relevance of our analysis to the emergence of spontaneous polarisation in well-studied ferroelectrics such as BaTiO$_3$ and KNbO$_3$.Comment: 8 pages, 8 figure

Emergence of long-range order in BaTiO3 from local symmetry-breaking distortions

By using a symmetry motivated basis to evaluate local distortions against pair distribution function data (PDF), we show without prior bias, that the off-centre Ti displacements in the archetypal ferroelectric BaTiO3 are zone centred and rhombohedral-like in nature across its known ferroelectric and paraelectric phases. With our newly-gained insight we construct a simple Monte Carlo (MC) model which captures our main experimental findings and demonstrate how the rich crystallographic phase diagram of BaTiO3 emerges from correlations of local symmetry-breaking distortions alone. Our results strongly support the order-disorder picture for these phase transitions, but can also be reconciled with the soft-mode theory of BaTiO3 that is supported by some spectroscopic techniques.Comment: 5 pages, 3 figure

Understanding Variation in Sets of N-of-1 Trials.

A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder's theory of general balance. However, where the purpose is to make inferences about the effects for individual patients, we show that a mixed model is needed. There are strong parallels to the difference between fixed and random effects meta-analyses and these are discussed

Overstating the evidence - double counting in meta-analysis and related problems

Background: The problem of missing studies in meta-analysis has received much attention. Less attention has been paid to the more serious problem of double counting of evidence. Methods: Various problems in overstating the precision of results from meta-analyses are described and illustrated with examples, including papers from leading medical journals. These problems include, but are not limited to, simple double-counting of the same studies, double counting of some aspects of the studies, inappropriate imputation of results, and assigning spurious precision to individual studies. Results: Some suggestions are made as to how the quality and reliability of meta-analysis can be improved. It is proposed that the key to quality in meta-analysis lies in the results being transparent and checkable. Conclusions: Existing quality check lists for meta-analysis do little to encourage an appropriate attitude to combining evidence and to statistical analysis. Journals and other relevant organisations should encourage authors to make data available and make methods explicit. They should also act promptly to withdraw meta-analyses when mistakes are found

Harold Jeffreys's Theory of Probability Revisited

Published exactly seventy years ago, Jeffreys's Theory of Probability (1939) has had a unique impact on the Bayesian community and is now considered to be one of the main classics in Bayesian Statistics as well as the initiator of the objective Bayes school. In particular, its advances on the derivation of noninformative priors as well as on the scaling of Bayes factors have had a lasting impact on the field. However, the book reflects the characteristics of the time, especially in terms of mathematical rigor. In this paper we point out the fundamental aspects of this reference work, especially the thorough coverage of testing problems and the construction of both estimation and testing noninformative priors based on functional divergences. Our major aim here is to help modern readers in navigating in this difficult text and in concentrating on passages that are still relevant today.Comment: This paper commented in: [arXiv:1001.2967], [arXiv:1001.2968], [arXiv:1001.2970], [arXiv:1001.2975], [arXiv:1001.2985], [arXiv:1001.3073]. Rejoinder in [arXiv:0909.1008]. Published in at http://dx.doi.org/10.1214/09-STS284 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds - Gastrointestinal adverse effects: A meta-analysis of randomized clinical trials

Background and Aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public. Methods: A meta-analysis of individual patient data from 67 studies sponsored by Bayer HealthCare was completed. The primary endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the secondary endpoints were the incidence of patient-reported non-GI AEs. Event incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145 with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was short term (82.5% of patients had a single dose). Results: GI AEs were more frequent with ASA (9.9%) than with placebo (9.0%) [OR 1.3; 95% CI 1.1, 1.5]. Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few serious GI AEs (one ASA case; three placebo cases). No differences were found for non-GI AEs and no cases of cerebral hemorrhage were reported. Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo.No serious GI complications were reported

Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics

Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE. For this reason, first we evaluated whether the inhibitor of adrenocortical steroid production trilostane (50 mg/kg) could modify the levels of neurosteroids in the hippocampus and neocortex, and we found a remarkable increase in pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone levels using liquid chromatography tandem mass spectrometry. Second, we characterized the dynamics of SE in the presence of the varied neurosteroidal milieu by a single intraperitoneal kainic acid (KA; 15 mg/kg) injection in trilostane-treated rats and their controls. Convulsions started in advance in the trilostane group, already appearing 90 minutes after the KA injection. In contrast to controls, convulsions prevalently developed as generalized seizures with loss of posture in the trilostane group. However, this effect was transient, and convulsions waned 2 hours before the control group. Moreover, electrocorticographic traces of convulsions were shorter in trilostane-treated rats, especially at the 180-minute (P < .001) and 210-minute (P < .01) time points. These findings indicate that endogenous neurosteroids remarkably modulate SE dynamics

Too little, too much, or just right? Does the amount of distraction make a difference during contamination-related exposure?

Background and objectives The extant literature has shown mixed results regarding the impact of distraction use on exposure outcome; however, a wide variety of distraction tasks have been utilized across studies. In order to better understand these discrepant findings, we aimed to evaluate the impact of differing levels of distraction on exposure outcome. Additionally, treatment acceptability and changes in self-efficacy were assessed to evaluate how these may differ as a function of distraction use. Methods In Experiment 1 (N = 176 participants tested), distraction tasks were experimentally validated through assessing changes in reaction time when completing concurrent tasks. Based on Experiment 1, distraction tasks were selected for use in Experiment 2, in which contamination-fearful participants were randomly assigned to one of four conditions: no, low, moderate, or high distraction during an exposure session. Participants (N = 124) completed a behavioural approach test and self-efficacy measure pre- and post-exposure and at one-week follow-up. Treatment acceptability was assessed immediately following the exposure session. Results There were no significant differences between conditions for changes in behavioural approach pre-to post-exposure or at one-week follow-up. However, increases in self-efficacy pre-to post-exposure were greatest for moderate distraction, and treatment acceptability was highest with moderate and high distraction. Limitations Participants were not assessed for clinical severity, were not treatment-seeking, and only one specific type of fear was investigated. Conclusions Distraction (at any level) did not appear to negatively impact exposure outcome (all conditions improved pre-to post-exposure and at follow-up), but utilizing moderate to high amounts of distraction increased treatment acceptabilit

Comparative trends in hospitalizations for osteoporotic fractures and other frequent diseases between 2000 and 2008

Summary: In Switzerland, the number, incidence, and cost of acute hospitalizations for major osteoporotic fractures (MOF) and major cardiovascular events (MCE) increased in both women and men between 2000 and 2008, although the mean length of stay (LOS) was significantly reduced. Similar trend patterns were observed for hip fractures and strokes (decrease) and nonhip fractures and acute myocardial infarctions (increase). Introduction: The purpose of this study was to compare the trends and epidemiological characteristics of hospitalizations for MOF and other frequent diseases between years2000 and 2008 in Switzerland. Methods: Trends in the number, age-standardized incidence, mean LOS, and cost of hospitalized MOF and MCE (acute myocardial infarction, stroke, and heart failure) were compared in women and men aged ≥45years, based on data from the Swiss Federal Statistical Office. Results: Between 2000 and 2008, the incidence of acute hospitalizations for MOF increased by 3.4% in women and 0.3% in men. In both sexes, a significant decrease in hip fractures (−15.0% and −11.0%) was compensated by a concomitant, significant increase in nonhip fractures (+24.8% and +13.8%). Similarly, the incidence of acute hospitalizations for MCE increased by 4.4% in women and 8.2% in men, as an aggregated result from significantly increasing acute myocardial infarctions and significantly decreasing strokes. While the mean LOS in the acute inpatient setting decreased almost linearly between years2000 and 2008 in all indications, the inpatient costs increased significantly (p < 0.001) for MOF (+30.1% and +42.7%) and MCE (+22.6% and +47.1%) in women and men, respectively. Conclusions: Between years2000 and 2008, the burden of hospitalized osteoporotic fractures to the Swiss healthcare system has continued to increase in both sexes. In women, this burden was significantly higher than that of MCE and the gap widened over tim