A standardized framework for risk-based assessment of treatment effect heterogeneity in observational healthcare databases

Treatment effects are often anticipated to vary across groups of patients with different baseline risk. The Predictive Approaches to Treatment Effect Heterogeneity (PATH) statement focused on baseline risk as a robust predictor of treatment effect and provided guidance on risk-based assessment of treatment effect heterogeneity in a randomized controlled trial. The aim of this study is to extend this approach to the observational setting using a standardized scalable framework. The proposed framework consists of five steps: (1) definition of the research aim, i.e., the population, the treatment, the comparator and the outcome(s) of interest; (2) identification of relevant databases; (3) development of a prediction model for the outcome(s) of interest; (4) estimation of relative and absolute treatment effect within strata of predicted risk, after adjusting for observed confounding; (5) presentation of the results. We demonstrate our framework by evaluating heterogeneity of the effect of thiazide or thiazide-like diuretics versus angiotensin-converting enzyme inhibitors on three efficacy and nine safety outcomes across three observational databases. We provide a publicly available R software package for applying this framework to any database mapped to the Observational Medical Outcomes Partnership Common Data Model. In our demonstration, patients at low risk of acute myocardial infarction receive negligible absolute benefits for all three efficacy outcomes, though they are more pronounced in the highest risk group, especially for acute myocardial infarction. Our framework allows for the evaluation of differential treatment effects across risk strata, which offers the opportunity to consider the benefit-harm trade-off between alternative treatments.Development and application of statistical models for medical scientific researc

The Middle Way: East Asian masters students’ perceptions of critical argumentation in U.K. universities.

The paper explores the learning experiences of East Asian masters students in dealing with Western academic norms of critical thinking in classroom debate and assignment writing. The research takes a cultural approach, and employs grounded theory and case study methodology, the aims being for students to explain their perceptions of their personal learning journeys. The data suggest that the majority of students interviewed rejected full academic acculturation into Western norms of argumentation. They instead opted for a ‘Middle Way’ that synergizes the traditional cultural academic values held by many East Asian students with those elements of Western academic norms that are perceived to be aligned with these. This is a relatively new area of research which represents a challenge for British lecturers and students

An Extreme Solar Event of 20 January 2005: Properties of the Flare and the Origin of Energetic Particles

The extreme solar and SEP event of 20 January 2005 is analyzed from two perspectives. Firstly, we study features of the main phase of the flare, when the strongest emissions from microwaves up to 200 MeV gamma-rays were observed. Secondly, we relate our results to a long-standing controversy on the origin of SEPs arriving at Earth, i.e., acceleration in flares, or shocks ahead of CMEs. All emissions from microwaves up to 2.22 MeV line gamma-rays during the main flare phase originated within a compact structure located just above sunspot umbrae. A huge radio burst with a frequency maximum at 30 GHz was observed, indicating the presence of a large number of energetic electrons in strong magnetic fields. Thus, protons and electrons responsible for flare emissions during its main phase were accelerated within the magnetic field of the active region. The leading, impulsive parts of the GLE, and highest-energy gamma-rays identified with pi^0-decay emission, are similar and correspond in time. The origin of the pi^0-decay gamma-rays is argued to be the same as that of lower energy emissions. We estimate the sky-plane speed of the CME to be 2000-2600 km/s, i.e., high, but of the same order as preceding non-GLE-related CMEs from the same active region. Hence, the flare itself rather than the CME appears to determine the extreme nature of this event. We conclude that the acceleration, at least, to sub-relativistic energies, of electrons and protons, responsible for both the flare emissions and the leading spike of SEP/GLE by 07 UT, are likely to have occurred simultaneously within the flare region. We do not rule out a probable contribution from particles accelerated in the CME-driven shock for the leading GLE spike, which seemed to dominate later on.Comment: 34 pages, 14 Postscript figures. Solar Physics, accepted. A typo corrected. The original publication is available at http://www.springerlink.co

Standard‐space atlas of the viscoelastic properties of the human brain

Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast-based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18–35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, μ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM-152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross-center comparisons

Precision Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetries A2

We have measured the spin structure functions g2p and g2d and the virtual photon asymmetries A2p and A2d over the kinematic range 0.02 < x < 0.8 and 0.7 < Q^2 < 20 GeV^2 by scattering 29.1 and 32.3 GeV longitudinally polarized electrons from transversely polarized NH3 and 6LiD targets. Our measured g2 approximately follows the twist-2 Wandzura-Wilczek calculation. The twist-3 reduced matrix elements d2p and d2n are less than two standard deviations from zero. The data are inconsistent with the Burkhardt-Cottingham sum rule if there is no pathological behavior as x->0. The Efremov-Leader-Teryaev integral is consistent with zero within our measured kinematic range. The absolute value of A2 is significantly smaller than the sqrt[R(1+A1)/2] limit.Comment: 12 pages, 4 figures, 2 table

Tests of sunspot number sequences: 2. Using geomagnetic and auroral data

We compare four sunspot-number data sequences against geomagnetic and terrestrial auroral observations. The comparisons are made for the original SIDC (Solar Influences Data Center) composite of Wolf/Zürich/International sunspot number [RISNv1], the group sunspot number [RG] by Hoyt and Schatten (Solar Phys., 181, 491, 1998), the new “backbone” group sunspot number [RBB] by Svalgaard and Schatten (Solar Phys., doi: 10.1007/s11207-015-0815-8, 2016), and the “corrected” sunspot number [RC] by Lockwood, Owens, and Barnard (J. Geophys. Res., 119, 5172, 2014). Each sunspot number is fitted with terrestrial observations, or parameters derived from terrestrial observations to be linearly proportional to sunspot number, over a 30-year calibration interval of 1982 - 2012. The fits are then used to compute test sequences, which extend further back in time and which are compared to RISNv1, RG, RBB, and RC. To study the long-term trends, comparisons are made using averages over whole solar cycles (minimum-to-minimum). The test variations are generated in four ways: i) using the IDV(1d) and IDV geomagnetic indices (for 1845 - 2013) fitted over the calibration interval using the various sunspot numbers and the phase of the solar cycle; ii) from the open solar flux (OSF) generated for 1845 - 2013 from four pairings of geomagnetic indices by Lockwood et al. (Ann. Geophys., 32, 383, 2014) and analysed using the OSF continuity model of Solanki, Schüssler, and Fligge (Nature, 408, 445, 2000) which employs a constant fractional OSF loss rate; iii) the same OSF data analysed using the OSF continuity model of Owens and Lockwood (J. Geophys. Res., 117, A04102, 2012) in which the fractional loss rate varies with the tilt of the heliospheric current sheet and hence with the phase of the solar cycle; iv) the occurrence frequency of low-latitude aurora for 1780 - 1980 from the survey of Legrand and Simon (Ann. Geophys., 5, 161, 1987). For all cases, RBB exceeds the test terrestrial series by an amount that increases as one goes back in time

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters