Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012

On the geometrization of matter by exotic smoothness

In this paper we discuss the question how matter may emerge from space. For that purpose we consider the smoothness structure of spacetime as underlying structure for a geometrical model of matter. For a large class of compact 4-manifolds, the elliptic surfaces, one is able to apply the knot surgery of Fintushel and Stern to change the smoothness structure. The influence of this surgery to the Einstein-Hilbert action is discussed. Using the Weierstrass representation, we are able to show that the knotted torus used in knot surgery is represented by a spinor fulfilling the Dirac equation and leading to a mass-less Dirac term in the Einstein-Hilbert action. For sufficient complicated links and knots, there are "connecting tubes" (graph manifolds, torus bundles) which introduce an action term of a gauge field. Both terms are genuinely geometrical and characterized by the mean curvature of the components. We also discuss the gauge group of the theory to be U(1)xSU(2)xSU(3).Comment: 30 pages, 3 figures, svjour style, complete reworking now using Fintushel-Stern knot surgery of elliptic surfaces, discussion of Lorentz metric and global hyperbolicity for exotic 4-manifolds added, final version for publication in Gen. Rel. Grav, small typos errors fixe

Which blazars are neutrino loud?

Protons accelerated in the cores of active galactic nuclei can effectively produce neutrinos only if the soft radiation background in the core is sufficiently high. We find restrictions on the spectral properties and luminosity of blazars under which they can be strong neutrino sources. We analyze the possibility that neutrino flux is highly beamed along the rotation axis of the central black hole. The enhancement of neutrino flux compared to GeV gamma-ray flux from a given source makes the detection of neutrino point sources more probable. At the same time the smaller open angle reduces the number of possible neutrino-loud blazars compared to the number of gamma-ray loud ones. We present the table of 15 blazars which are the most likely candidates for the detection by future neutrino telescopes.Comment: 9 pages, 5 figures, version to be published in PR

Exploring the sensitivity of coastal inundation modelling to DEM vertical error

© 2018 Informa UK Limited, trading as Taylor & Francis Group. As sea level is projected to rise throughout the twenty-first century due to climate change, there is a need to ensure that sea level rise (SLR) models accurately and defensibly represent future flood inundation levels to allow for effective coastal zone management. Digital elevation models (DEMs) are integral to SLR modelling, but are subject to error, including in their vertical resolution. Error in DEMs leads to uncertainty in the output of SLR inundation models, which if not considered, may result in poor coastal management decisions. However, DEM error is not usually described in detail by DEM suppliers; commonly only the RMSE is reported. This research explores the impact of stated vertical error in delineating zones of inundation in two locations along the Devon, United Kingdom, coastline (Exe and Otter Estuaries). We explore the consequences of needing to make assumptions about the distribution of error in the absence of detailed error data using a 1 m, publically available composite DEM with a maximum RMSE of 0.15 m, typical of recent LiDAR-derived DEMs. We compare uncertainty using two methods (i) the NOAA inundation uncertainty mapping method which assumes a normal distribution of error and (ii) a hydrologically correct bathtub method where the DEM is uniformly perturbed between the upper and lower bounds of a 95% linear error in 500 Monte Carlo Simulations (HBM+MCS). The NOAA method produced a broader zone of uncertainty (an increase of 134.9% on the HBM+MCS method), which is particularly evident in the flatter topography of the upper estuaries. The HBM+MCS method generates a narrower band of uncertainty for these flatter areas, but very similar extents where shorelines are steeper. The differences in inundation extents produced by the methods relate to a number of underpinning assumptions, and particularly, how the stated RMSE is interpreted and used to represent error in a practical sense. Unlike the NOAA method, the HBM+MCS model is computationally intensive, depending on the areas under consideration and the number of iterations. We therefore used the HBM+ MCS method to derive a regression relationship between elevation and inundation probability for the Exe Estuary. We then apply this to the adjacent Otter Estuary and show that it can defensibly reproduce zones of inundation uncertainty, avoiding the computationally intensive step of the HBM+MCS. The equation-derived zone of uncertainty was 112.1% larger than the HBM+MCS method, compared to the NOAA method which produced an uncertain area 423.9% larger. Each approach has advantages and disadvantages and requires value judgements to be made. Their use underscores the need for transparency in assumptions and communications of outputs. We urge DEM publishers to move beyond provision of a generalised RMSE and provide more detailed estimates of spatial error and complete metadata, including locations of ground control points and associated land cover

Gasoline: An adaptable implementation of TreeSPH

The key algorithms and features of the Gasoline code for parallel hydrodynamics with self-gravity are described. Gasoline is an extension of the efficient Pkdgrav parallel N-body code using smoothed particle hydrodynamics. Accuracy measurements, performance analysis and tests of the code are presented. Recent successful Gasoline applications are summarized. These cover a diverse set of areas in astrophysics including galaxy clusters, galaxy formation and gas-giant planets. Future directions for gasdynamical simulations in astrophysics and code development strategies for tackling cutting edge problems are discussed.Comment: 30 pages, 11 figures, submitted to New Astronomy. Movies and high resolution images are available at http://imp.mcmaster.ca/image

Transverse Beam Spin Asymmetries in Forward-Angle Elastic Electron-Proton Scattering

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely-polarized 3 GeV electrons from unpolarized protons at Q^2 = 0.15, 0.25 (GeV/c)^2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state, and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A_n provides a direct probe of the imaginary component of the 2-gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.Comment: 5 pages, 3 figures, submitted to Physical Review Letters; shortened to meet PRL length limit, clarified some text after referee's comment

Strange Quark Contributions to Parity-Violating Asymmetries in the Forward G0 Electron-Proton Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < Q^2 < 1.0 GeV^2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange quark contributions to the currents of the proton. The measurements were made at JLab using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate non-zero, Q^2 dependent, strange quark contributions and provide new information beyond that obtained in previous experiments.Comment: 5 pages, 2 figure

Differential cross section and recoil polarization measurements for the gamma p to K+ Lambda reaction using CLAS at Jefferson Lab

We present measurements of the differential cross section and Lambda recoil polarization for the gamma p to K+ Lambda reaction made using the CLAS detector at Jefferson Lab. These measurements cover the center-of-mass energy range from 1.62 to 2.84 GeV and a wide range of center-of-mass K+ production angles. Independent analyses were performed using the K+ p pi- and K+ p (missing pi -) final-state topologies; results from these analyses were found to exhibit good agreement. These differential cross section measurements show excellent agreement with previous CLAS and LEPS results and offer increased precision and a 300 MeV increase in energy coverage. The recoil polarization data agree well with previous results and offer a large increase in precision and a 500 MeV extension in energy range. The increased center-of-mass energy range that these data represent will allow for independent study of non-resonant K+ Lambda photoproduction mechanisms at all production angles.Comment: 22 pages, 16 figure

The G0 Experiment: Apparatus for Parity-Violating Electron Scattering Measurements at Forward and Backward Angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part per million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam-monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cerenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed.Comment: Submitted to Nuclear Instruments and Method

The Emergence of Hospital Federations: An Integration of Perspectives from Organizational Theory

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68464/2/10.1177_107755878704400206.pd