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1. Delamination Detection in Layered Waveguides using Ostrovsky Wave Packets

Author

Tamber, J. S., Chappell, D. J., and Tranter, M. R.

Subjects
Nonlinear Sciences - Pattern Formation and Solitons
Abstract

We examine the scattering of Ostrovsky wave packets, generated from an incident solitary wave, in a two layered waveguide with a delamination in the centre and soft (imperfect) bonding either side of the centre. The layers of the waveguide are assumed to consist of different materials, and the strains are described by a system of coupled Boussinesq equations. A semi-analytical approach consisting of matched asymptotic multiple-scale expansions is applied, leading to Ostrovsky equations in soft bonded regions and Korteweg-de Vries equations in the delaminated region. This semi-analytical method has good agreement with direct numerical simulations, validating the approach. In the delaminated regions, Ostrovsky wave packets evolve into a train of solitary waves, which subsequently evolve into Ostrovsky wave packets in the second bonded region. Analysis of the phase shift in the wave packet, introduced from the delaminated region, allows us to predict both the position and the length of the delamination; the first time this has been achieved using nonlinear waves. These results motivate experiments to validate the theoretical results, with the aim of creating a tool to monitor the integrity of layered structures., Comment: 9 pages, 7 figures

Published
2024

2. Detecting Delamination via Nonlinear Wave Scattering in a Bonded Elastic Bar

Author

Tamber, J. S., Chappell, D. J., Poore, J. C., and Tranter, M. R.

Subjects
Nonlinear Sciences - Pattern Formation and Solitons
Abstract

In this paper we examine the effect of delamination on wave scattering, with the aim of creating a control measure for layered waveguides of various bonding types. Previous works have considered specific widths of solitary waves for the simulations, without analysing the effect of changing the soliton parameters. We consider two multi-layered structures: one containing delamination "sandwiched" by perfect bonding and one containing delamination but "sandwiched" by soft bonding. These structures are modelled by coupled Boussinesq-type equations. Matched asymptotic multiple-scale expansions lead to coupled Ostrovsky equations in soft bonded regions and Korteweg-De Vries equations in the perfectly bonded and delaminated region. We use the Inverse Scattering Transform to predict the behaviour in the delaminated regions. In both cases, numerical analysis shows that we can predict the delamination length by changes in the wave structure, and that these changes depend upon the Full Width at Half Magnitude (FWHM) of the incident soliton. In the case of perfect bonding, we derive a theoretical prediction for the change and confirm this numerically. For the soft bonding case, we numerically identify a similar relationship using the change in amplitude. Therefore we only need to compute one curve to determine the behaviour for any incident solitary wave, creating a framework for designing measurement campaigns for rigorously testing the integrity of layered structures., Comment: 12 pages, 7 figures

Published
2023

3. Transfer operator approach to ray-tracing in circular domains

Author

Slipantschuk, J, Richter, M, Chappell, D J, Tanner, G, Just, W, and Bandtlow, O F

Subjects
Nonlinear Sciences - Chaotic Dynamics, Mathematics - Dynamical Systems, 37M25, 37C30, 74H45, 37D50
Abstract

The computation of wave-energy distributions in the mid-to-high frequency regime can be reduced to ray-tracing calculations. Solving the ray-tracing problem in terms of an operator equation for the energy density leads to an inhomogeneous equation which involves a Perron-Frobenius operator defined on a suitable Sobolev space. Even for fairly simple geometries, let alone realistic scenarios such as typical boundary value problems in room acoustics or for mechanical vibrations, numerical approximations are necessary. Here we study the convergence of approximation schemes by rigorous methods. For circular billiards we prove that convergence of finite-rank approximations using a Fourier basis follows a power law where the power depends on the smoothness of the source distribution driving the system. The relevance of our studies for more general geometries is illustrated by numerical examples., Comment: 19 pages, 4 figures

Published
2019
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4. Clinical and Economic Benefits of Lenzilumab Plus Standard of Care Compared with Standard of Care Alone for the Treatment of Hospitalized Patients with Coronavirus Disease 19 (COVID-19) from the Perspective of National Health Service England

Author

Kilcoyne A, Jordan E, Thomas K, Pepper AN, Zhou A, Chappell D, Amarapala M, Thériault RK, and Thompson M

Subjects
economic analysis, crp, gm-csf, ventilator-free survival, survival without ventilation, invasive mechanical ventilation, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Adrian Kilcoyne,1 Edward Jordan,1 Kimberly Thomas,2 Alicia N Pepper,2 Allen Zhou,2 Dale Chappell,1 Miyuru Amarapala,1 Rachel-Karson Thériault,2 Melissa Thompson2 1HEOR, Humanigen Inc, Burlingame, CA, USA; 2Value & Evidence Services, EVERSANA, Burlington, Ontario, CanadaCorrespondence: Adrian Kilcoyne, HEOR, Humanigen Inc, Burlingame, CA, USA, Tel +1-848-240-6613, Email akilcoyne@humanigen.comPurpose: To estimate the clinical and economic benefits of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of hospitalized COVID-19 patients from the National Health Service (NHS) England perspective.Methods: A cost calculator was developed to estimate the clinical benefits and costs of adding lenzilumab to SOC in newly hospitalized COVID-19 patients over 28 days. The LIVE-AIR trial results informed the clinical inputs: failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included drug acquisition and administration for lenzilumab and remdesivir and hospital resource costs based on the level of care required. Clinical and economic benefits per weekly cohort of newly hospitalized patients were also estimated.Results: In all populations examined, specified clinical outcomes were improved with lenzilumab plus SOC over SOC treatment alone. In a base case population aged < 85 years with C-reactive protein (CRP) < 150 mg/L, with or without remdesivir, adding lenzilumab to SOC was estimated to result in per-patient cost savings of £ 1162. In a weekly cohort of 4754 newly hospitalized patients, addition of lenzilumab to SOC could result in 599 IMV uses avoided, 352 additional lives saved, and over £ 5.5 million in cost savings. Scenario results for per-patient cost savings included: 1) aged < 85 years, CRP < 150 mg/L, and receiving remdesivir (£ 3127); 2) Black patients with CRP < 150 mg/L (£ 9977); and 3) Black patients from the full population (£ 2369). Conversely, in the full mITT population, results estimated additional cost of £ 4005 per patient.Conclusion: Findings support clinical benefits for SWOV, mortality, time to recovery, time in ICU, time on IMV, and ventilator use, and an economic benefit from the NHS England perspective when adding lenzilumab to SOC for hospitalized COVID-19 patients.Keywords: economic analysis, CRP, GM-CSF, ventilator-free survival, survival without ventilation, invasive mechanical ventilation

Published
2022

6. Dynamical energy analysis for built-up acoustic systems at high frequencies

Author

Chappell, D. J., Giani, S., and Tanner, G.

Subjects
Nonlinear Sciences - Chaotic Dynamics, Mathematics - Dynamical Systems, Physics - Computational Physics
Abstract

Standard methods for describing the intensity distribution of mechanical and acoustic wave fields in the high frequency asymptotic limit are often based on flow transport equations. Common techniques are statistical energy analysis, employed mostly in the context of vibro-acoustics, and ray tracing, a popular tool in architectural acoustics. Dynamical energy analysis makes it possible to interpolate between standard statistical energy analysis and full ray tracing, containing both of these methods as limiting cases. In this work a version of dynamical energy analysis based on a Chebyshev basis expansion of the Perron-Frobenius operator governing the ray dynamics is introduced. It is shown that the technique can efficiently deal with multi-component systems overcoming typical geometrical limitations present in statistical energy analysis. Results are compared with state-of-the-art hp-adaptive discontinuous Galerkin finite element simulations.

Published
2010
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7. Interferometric Astrometry of Proxima Centauri and Barnard's Star Using Hubble Space Telescope Fine Guidance Sensor 3: Detection Limits for sub-Stellar Companions

Author

Benedict, G. Fritz, McArthur, Barbara, Chappell, D. W., Nelan, E., Jefferys, W. H., van Altena, W., Lee, J., Cornell, D., Shelus, P. J., Hemenway, P. D., Franz, Otto G., Wasserman, L. H., Duncombe, R. L., Story, D., Whipple, A. L., and Fredrick, L. W.

Subjects
Astrophysics
Abstract

We report on a sub-stellar companion search utilizing interferometric fringe-tracking astrometry acquired with Fine Guidance Sensor 3 (FGS 3) on the Hubble Space Telescope. Our targets were Proxima Centauri and Barnard's Star. We obtain absolute parallax values for Proxima Cen pi_{abs} = 0.7687 arcsecond and for Barnard's Star pi_{abs} = 0.5454 arcsecond. Once low-amplitude instrumental systematic errors are identified and removed, our companion detection sensitivity is less than or equal to one Jupiter mass for periods longer than 60 days for Proxima Cen. Between the astrometry and the radial velocity results we exclude all companions with M > 0.8M_{Jup} for the range of periods 1 < P < 1000 days. For Barnard's Star our companion detection sensitivity is less than or equal to one Jupiter mass for periods long er than 150 days. Our null results for Barnard's Star are consistent with those of Gatewood (1995)., Comment: 35 pages, 13 figures, to appear in August 1999 AJ

Published
1999
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8. On the Density Probability Function of Galactic Gas. I. Numerical Simulations and the Significance of the Polytropic Index

Author

Scalo, J., Vazquez-Semadeni, E., Chappell, D., and Passot, T.

Subjects
Astrophysics
Abstract

We investigate the form of the one-point probability distribution function (pdf) for the density field of the interstellar medium using numerical simulations that successively reduce the number of physical processes included. Two-dimensional simulations of self-gravitating supersonic MHD and hydrodynamic turbulence, and of decaying Burgers turbulence, produce in all cases filamentary density structures and a power-law density pdf with logarithmic slope around -1.7. This suggests that the functional form of the pdf and the general filamentary morphology are the signature of the nonlinear advection operator. These results do not support previous claims that the pdf is lognormal. A series of 1D simulations of forced supersonic polytropic turbulence is used to resolve the discrepancy. They suggest that the pdf is lognormal only for effective polytropic indices $\gamma=1$ (or nearly lognormal for $\gamma\not=1$ if the Mach number is sufficiently small), while power laws develop at high densities if $\gamma<1$. We evaluate the polytropic index for conditions relevant to the cool interstellar medium using published cooling functions and different heating sources, finding that a lognormal pdf may occur at densities between 10$^3$ and at least 10$^4$ cm$^{-3}$. Several applications are examined. First, we question a recent derivation of the IMF from the density pdf by Padoan, Nordlund & Jones because a) the pdf does not contain spatial information, and b) their derivation produces the most massive stars in the voids of the density distribution. Second, we illustrate how a distribution of ambient densities can alter the predicted form of the size distribution of expanding shells. Finally, a brief comparison is made with the density pdfs found in cosmological simulations., Comment: Submitted to ApJ. 23 pages, 15 postscript figures

Published
1997
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9. Global oceanic diazotroph database version 2 and elevated estimate of global oceanic N2 fixation

Author

Shao, Z, Xu, Y, Wang, H, Luo, W, Wang, L, Huang, Y, Nona Sheila, RA, Ahmed, A, Benavides, M, Bentzon-Tilia, M, Berman-Frank, I, Berthelot, H, Biegala, IC, Bif, MB, Bode, A, Bonnet, S, Bronk, DA, Brown, MV, Campbell, L, Capone, DG, Carpenter, EJ, Cassar, N, Chang, BX, Chappell, D, Yuh-Ling, LC, Church, MJ, Cornejo-Castillo, FM, Sacilotto Detoni, AM, Doney, SC, Dupouy, C, Estrada, M, Fernandez, C, Fernández-Castro, B, Fonseca-Batista, D, Foster, RA, Furuya, K, Garcia, N, Goto, K, Gago, J, Gradoville, MR, Hamersley, MR, Henke, BA, Hörstmann, C, Jayakumar, A, Jiang, Z, Kao, SJ, Karl, DM, Kittu, LR, Knapp, AN, Kumar, S, LaRoche, J, Liu, H, Liu, J, Lory, C, Löscher, CR, Marañón, E, Messer, LF, Mills, MM, Mohr, W, Moisander, PH, Mahaffey, C, Moore, R, Mouriño-Carballido, B, Mulholland, MR, Shin-Ichiro, N, Needoba, JA, Raes, EJ, Rahav, E, Ramírez-Cárdenas, T, Reeder, CF, Riemann, L, Riou, V, Robidart, JC, Sarma, VVSS, Sato, T, Saxena, H, Selden, C, Seymour, JR, Shi, D, Shiozaki, T, Singh, A, Sipler, RE, Sun, J, Suzuki, K, Takahashi, K, Tan, Y, Tang, W, Tremblay, JÉ, Turk-Kubo, K, Wen, Z, White, AE, Wilson, ST, Yoshida, T, Zehr, JP, Zhang, R, Zhang, Y, Luo, YW, Shao, Z, Xu, Y, Wang, H, Luo, W, Wang, L, Huang, Y, Nona Sheila, RA, Ahmed, A, Benavides, M, Bentzon-Tilia, M, Berman-Frank, I, Berthelot, H, Biegala, IC, Bif, MB, Bode, A, Bonnet, S, Bronk, DA, Brown, MV, Campbell, L, Capone, DG, Carpenter, EJ, Cassar, N, Chang, BX, Chappell, D, Yuh-Ling, LC, Church, MJ, Cornejo-Castillo, FM, Sacilotto Detoni, AM, Doney, SC, Dupouy, C, Estrada, M, Fernandez, C, Fernández-Castro, B, Fonseca-Batista, D, Foster, RA, Furuya, K, Garcia, N, Goto, K, Gago, J, Gradoville, MR, Hamersley, MR, Henke, BA, Hörstmann, C, Jayakumar, A, Jiang, Z, Kao, SJ, Karl, DM, Kittu, LR, Knapp, AN, Kumar, S, LaRoche, J, Liu, H, Liu, J, Lory, C, Löscher, CR, Marañón, E, Messer, LF, Mills, MM, Mohr, W, Moisander, PH, Mahaffey, C, Moore, R, Mouriño-Carballido, B, Mulholland, MR, Shin-Ichiro, N, Needoba, JA, Raes, EJ, Rahav, E, Ramírez-Cárdenas, T, Reeder, CF, Riemann, L, Riou, V, Robidart, JC, Sarma, VVSS, Sato, T, Saxena, H, Selden, C, Seymour, JR, Shi, D, Shiozaki, T, Singh, A, Sipler, RE, Sun, J, Suzuki, K, Takahashi, K, Tan, Y, Tang, W, Tremblay, JÉ, Turk-Kubo, K, Wen, Z, White, AE, Wilson, ST, Yoshida, T, Zehr, JP, Zhang, R, Zhang, Y, and Luo, YW

Abstract

Marine diazotrophs convert dinitrogen (N2) gas into bioavailable nitrogen (N), supporting life in the global ocean. In 2012, the first version of the global oceanic diazotroph database (version 1) was published. Here, we present an updated version of the database (version 2), significantly increasing the number of in situ diazotrophic measurements from 13 565 to 55 286. Data points for N2 fixation rates, diazotrophic cell abundance, and nifH gene copy abundance have increased by 184 %, 86 %, and 809 %, respectively. Version 2 includes two new data sheets for the nifH gene copy abundance of non-cyanobacterial diazotrophs and cell-specific N2 fixation rates. The measurements of N2 fixation rates approximately follow a log-normal distribution in both version 1 and version 2. However, version 2 considerably extends both the left and right tails of the distribution. Consequently, when estimating global oceanic N2 fixation rates using the geometric means of different ocean basins, version 1 and version 2 yield similar rates (43–57 versus 45–63 Tg N yr−1; ranges based on one geometric standard error). In contrast, when using arithmetic means, version 2 suggests a significantly higher rate of 223 ± 30 Tg N yr−1 (mean ± standard error; same hereafter) compared to version 1 (74 ± 7 Tg N yr−1). Specifically, substantial rate increases are estimated for the South Pacific Ocean (88 ± 23 versus 20 ± 2 Tg N yr−1), primarily driven by measurements in the southwestern subtropics, and for the North Atlantic Ocean (40 ± 9 versus 10 ± 2 Tg N yr−1). Moreover, version 2 estimates the N2 fixation rate in the Indian Ocean to be 35 ± 14 Tg N yr−1, which could not be estimated using version 1 due to limited data availability. Furthermore, a comparison of N2 fixation rates obtained through different measurement methods at the same months, locations, and depths reveals that the conventional 15N2 bubble method yields lower rates in 69 % cases compared to the new 15N2 dissolution method. This up

Published
2023

10. Radiographic cortical thickness index predicts fragility fracture in Gaucher disease

Author

D’Amore, S., Sano, H., Chappell, D., Chiarugi, D., Baker, O., Page, K., Ramaswami, U., Johannesdottir, F., Cox, T., Deegan, P., Poole, K., Platt, F., Banka, S., Chakrapani, A., Geberhiwot, T., Hughes, D., Jones, S., Lachmann, R., Santra, S., Sharma, R., and Vellodi, A.

Subjects
Radiology, Nuclear Medicine and imaging, Article
Abstract

Background Patients with Gaucher disease (GD) have a high risk of fragility fractures. Routine evaluation of bone involvement in these patients includes radiography and repeated dual-energy x-ray absorptiometry (DXA). However, osteonecrosis and bone fracture may affect the accuracy of DXA. Purpose To assess the utility of DXA and radiographic femoral cortical thickness measurements as predictors of fragility fracture in patients with GD with long-term follow-up (up to 30 years). Materials and Methods Patients with GD age 16 years and older with a detailed medical history, at least one bone image (DXA and/or radiographs), and minimum 2 years follow-up were retrospectively identified using three merged UK-based registries (Gaucherite study, enrollment 2015-2017; Clinical Bone Registry, enrollment 2003-2006; and Mortality Registry, enrollment 1993-2019). Cortical thickness index (CTI) and canal-to-calcar ratio (CCR) were measured by two independent observers, and inter- and intraobserver reliability was calculated. The fracture-predictive value of DXA, CTI, CCR, and cutoff values were calculated using receiver operating characteristic curves. Statistical differences were assessed using univariable and multivariable analysis. Results Bone imaging in 247 patients (123 men, 124 women; baseline median age, 39 years; IQR, 27-50 years) was reviewed. The median follow-up period was 11 years (IQR, 7-19 years; range, 2-30 years). Thirty-five patients had fractures before or at first bone imaging, 23 patients had fractures after first bone imaging, and 189 patients remained fracture-free. Inter- and intraobserver reproducibility for CTI/CCR measurements was substantial (range, 0.96-0.98). In the 212 patients with no baseline fracture, CTI (cutoff, ≤0.50) predicted future fractures with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI: 0.84, 0.99; sensitivity, 92%; specificity, 96%) than DXA T-score at total hip (AUC, 0.78; 95% CI: 0.51, 0.91; sensitivity, 64%; specificity, 93%), femoral neck (AUC, 0.73; 95% CI: 0.50, 0.86; sensitivity, 64%; specificity, 73%), lumbar spine (AUC, 0.69; 95% CI: 0.49, 0.82; sensitivity, 57%; specificity, 63%), and forearm (AUC, 0.78; 95% CI: 0.59, 0.89; sensitivity, 70%; specificity, 70%). Conclusion Radiographic cortical thickness index of 0.50 or less was a reliable independent predictor of fracture risk in Gaucher disease. Clinical trial registration no. NCT03240653 © RSNA, 2022

Published
2022

11. Towards Instant Calibration in Myoelectric Prosthetic Hands: A Highly Data-Efficient Controller Based on the Wasserstein Distance

Author

Chappell, D, Yang, Z, Son, HW, Bello, F, Kormushev, P, and Rojas, N

Subjects
Electromyography, Calibration, Humans, Artificial Limbs, Hand, Prosthesis Design
Abstract

Prosthetic hand control research typically focuses on developing increasingly complex controllers to achieve diminishing returns in pattern recognition of muscle activity signals, making models less suitable for user calibration. Some works have investigated transfer learning to alleviate this, but such approaches increase model size dramatically—thus reducing their suitability for implementation on real prostheses. In this work, we propose a novel, non-parametric controller that uses the Wasserstein distance to compare the distribution of incoming signals to those of a set of reference distributions, with the intended action classified as the closest distribution. This controller requires only a single capture of data per reference distribution, making calibration almost instantaneous. Preliminary experiments building a reference library show that, in theory, users are able to produce up to 9 distinguishable muscle activity patterns. However, in practice, variation when repeating actions reduces this. Controller accuracy results show that 10 non-disabled and 1 disabled participant were able to use the controller with a maximum of two recalibrations to perform 6 actions at an average accuracy of 89.9% and 86.7% respectively. Practical experiments show that the controller allows users to complete all tasks of the Jebsen-Taylor Hand Function Test, although the task of picking and placing small common objects required on average more time than the protocol’s maximum time.

Published
2022
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12. Static and dynamic optical analysis of micro wrinkle formation on a liquid surface

Author

Saxena, A, Tsakonas, C, Chappell, D, Cheung, CS, Edwards, AMJ, Liang, H, Sage, IC, and Brown, CV

Subjects
dielectrophoresis, optical coherence tomography, Mechanical Engineering, optofluidics, dielectric material, optical diffraction, Article, Condensed Matter::Soft Condensed Matter, Physics::Fluid Dynamics, Control and Systems Engineering, TJ1-1570, Mechanical engineering and machinery, Electrical and Electronic Engineering, Nonlinear Sciences::Pattern Formation and Solitons
Abstract

A spatially periodic voltage was used to create a dielectrophoresis induced periodic micro wrinkle deformation on the surface of a liquid film. Optical Coherence Tomography provided the equilibrium wrinkle profile at submicron accuracy. The dynamic wrinkle amplitude was derived from optical diffraction analysis during sub-millisecond wrinkle formation and decay, after abruptly increasing or reducing the voltage, respectively. The decay time constant closely followed the film thickness dependence expected for surface tension driven viscous levelling. Modelling of the system using numerical solution of the Stokes flow equations with electrostatic forcing predicted that wrinkle formation was faster than decay, in accord with observations.

Published
2021

16. Sertraline hydrochloride for reducing impulsive behaviour in male, repeat-violent offenders (ReINVEST): Protocol for a phase IV, double-blind, placebo-controlled, randomised clinical trial

Author

Butler, T, Schofield, PW, Knight, L, Ton, B, Greenberg, D, Scott, RJ, Grant, L, Keech, AC, Gebski, V, Jones, J, Ellis, A, Weatherburn, D, Wilhelm, K, Jones, A, Churchill, A, Allnutt, S, Mitchell, PB, Chappell, D, Deste, C, Villa, D, Carr, V, Butler, T, Schofield, PW, Knight, L, Ton, B, Greenberg, D, Scott, RJ, Grant, L, Keech, AC, Gebski, V, Jones, J, Ellis, A, Weatherburn, D, Wilhelm, K, Jones, A, Churchill, A, Allnutt, S, Mitchell, PB, Chappell, D, Deste, C, Villa, D, and Carr, V

Abstract

Introduction Considerable evidence supports an association between poor impulse control (impulsivity) and violent crime. Furthermore, impulsivity and aggression has been associated with reduced levels of serotonergic activity in the brain. Selective serotonin reuptake inhibitors (SSRIs) are a class of anti depressants that aim to regulate brain serotonin concentrations. Several small studies in psychiatric populations have administered SSRIs to impulsive -aggressive individuals, resulting in reduced impulsivity, anger, aggression and depression. However, no clinical trial has been undertaken in a criminal justice population. This protocol describes the design and implementation of the first systematic study of the potential benefits of SSRIs in impulsive -violent offenders who are at high risk of reoffending. Methods and analysis A randomised, double-blinded, multicentre trial to test the clinical efficacy of an SSRI, sertraline hydrochloride, compared with placebo on recidivism and behavioural measures (including impulsivity, anger, aggression, depression and self-reported offending) over 12 months. 460 participants with histories of violence and screening positive for impulsivity are recruited at several local courts and correctional service offices in New South Wales, Australia. Ethics and dissemination Results will be submitted for publication in a peer-reviewed journal. Possible implications of the effectiveness of this pharmacological intervention include economic benefits of reducing prison costs and societal benefits of improving safety. This study has received ethical approval from the University of New South Wales, Aboriginal Health Medical Research Council, Corrective Services NSW and the NSW Justice Health and Forensic Mental Health Network. Trial registration number ACTRN12613000442707.

Published
2021

19. GM-CSF disruption in cart cells ameliorates cart cell activation and reduces activation-induced cell death

Author

Cox, M.J., primary, Manriquez Roman, C., additional, Sakemura, R., additional, Tapper, E., additional, Siegler, E., additional, Sinha, S., additional, Chappell, D., additional, Ahmed, O., additional, Durrant, C., additional, Hefazi, M., additional, Schick, K., additional, Horvei, P., additional, Ruff, M., additional, Can, I., additional, Adada, M., additional, Bezerra, E., additional, Kankeu Fonkoua, L., additional, Parikh, S., additional, Kay, N., additional, and Kenderian, S., additional

Published
2021
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20. Hot topics in obstetric anesthesia

Author

Brueck, S., Annecke, T., Bremerich, D., Byhahn, C., Chappell, D., Kaufner, L., Schloesser, L., Kranke, P., Brueck, S., Annecke, T., Bremerich, D., Byhahn, C., Chappell, D., Kaufner, L., Schloesser, L., and Kranke, P.

Abstract

In 2019 the annual conference of the scientific working group on obstetric anesthesiology of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) took place in the usual manner. Emergency situations, such as the challenge of a preclinical birth or the recognition and treatment of an amniotic fluid embolism were discussed. In addition, topics on the correct treatment of a female patient with a known addictive disorder were of great interest as well as the discussion on the question when a transfusion should be performed in postpartum anemia and which risks accompany the increasing prevalence of obesity, especially during pregnancy. A further hot topic was the deliberation on the prevalence and differential diagnostic clarification of neurological complications after epidural anesthesia. In connection with the topic of birth, exciting and practice relevant topics for all anesthetists confronted with this field were presented and discussed. The essential aspects are summarized in this article.

Published
2020

23. Unmasking Art Forgery: Scientific Approaches

Author

Hufnagel, S, Chappell, D, Sloggett, R, Hufnagel, S, Chappell, D, and Sloggett, R

Abstract

Scientific approaches to art forgery provide the rigorous methodology by which claims made about a work can be tested. A plethora of scientific instrumentation is available for the analysis of artwork but data are only useful when assessed against existing secure points of identification. Verifiability of results, therefore, relies on standardised documentation, defined rules of evidence and ensuring that all processes and findings are reproducible. In building knowledge of what characteristics constitute authentic works, providing effective protocols and rigorous procedures and bringing together multi-disciplinary knowledge to bear on questions of art forgery, science has become an essential part of good curatorial practice, effective conservation procedure and art market diligence.

Published
2019

25. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

Author

Chen C, Chappell D, Annecke T, Conzen P, Jacob M, Welsch U, Zwissler B, and Becker BF

Subjects
hyaluronan, lcsh:R5-920, preconditioning, ischemia-reperfusion injury, endothelial glycocalyx, volatile anesthetics, lcsh:Medicine (General)
Abstract

Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA), a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas) on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C) followed by reperfusion (40 minutes), half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g%) was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the colloid hydroxyethyl starch was significantly decreased by sevoflurane vs the control. We conclude that application of sevoflurane preserves the coronary endothelial glycocalyx, especially HA, sustaining the vascular barrier against ischemic damage. This may explain beneficial effects associated with clinical use of volatile anesthetics against ischemia/reperfusion injury. Keywords: endothelial glycocalyx, hyaluronan, ischemia-reperfusion injury, volatile anesthetics, preconditioning

Published
2016

26. Empagliflozin and Kidney Function Decline in Patients with Type 2 Diabetes: A Slope Analysis from the EMPA-REG OUTCOME Trial

Author

Wanner, Christoph, Heerspink, Hiddo J. L., Zinman, Bernard, Inzucchi, Silvio E., Koitka-Weber, Audrey, Mattheus, Michaela, Hantel, Stefan, Woerle, Hans-Juergen, Broedl, Uli C., von Eynatten, Maximilian, Groop, Per-Henrik, Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, Luc, Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, Katrien, Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., Magee, M., Hippert, R., Sofley, C., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Kidney Center (GKC), Methods in Medicines evaluation & Outcomes research (M2O), and EMPA-REG OUTCOME Investigators

Subjects
Male, Placebo-controlled study, PROGRESSION, Type 2 diabetes, 030204 cardiovascular system & hematology, PLACEBO-CONTROLLED TRIAL, GLOMERULAR-FILTRATION-RATE, HYPERFILTRATION, law.invention, ESTABLISHED CARDIOVASCULAR-DISEASE, Cohort Studies, MELLITUS, 0302 clinical medicine, Randomized controlled trial, Glucosides, law, Medicine, Diabetic Nephropathies, GFR DECLINE, General Medicine, Middle Aged, Nephrology, diabetes mellitus, randomized controlled trials, Disease Progression, Female, Glomerular Filtration Rate, medicine.medical_specialty, Urology, Renal function, 030209 endocrinology & metabolism, Placebo, 03 medical and health sciences, Double-Blind Method, Clinical Research, Diabetes mellitus, BASE-LINE CHARACTERISTICS, END-POINTS, Empagliflozin, Humans, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Aged, COTRANSPORTER 2 INHIBITION, Models, Statistical, Dose-Response Relationship, Drug, business.industry, chronic kidney disease, medicine.disease, Confidence interval, Diabetes Mellitus, Type 2, Human medicine, business
Abstract

BACKGROUND: Empagliflozin slowed the progression of CKD in patients with type 2 diabetes and cardiovascular disease in the EMPA-REG OUTCOME Trial. In a prespecified statistical approach, we assessed treatment differences in kidney function by analyzing slopes of eGFR changes.METHODS: Participants (n=7020) were randomized (1:1:1) to empagliflozin 10 mg/d, empagliflozin 25 mg/d, or placebo added to standard of care. We calculated eGFR slopes using random-intercept/random-coefficient models for prespecified study periods: treatment initiation (baseline to week 4), chronic maintenance treatment (week 4 to last value on treatment), and post-treatment (last value on treatment to follow-up).RESULTS: Compared with placebo, empagliflozin was associated with uniform shifts in individual eGFR slopes across all periods. On treatment initiation, adjusted mean slope (eGFR change per week, ml/min per 1.73 m2) decreased with empagliflozin (-0.77; 95% confidence interval, -0.83 to -0.71; placebo: 0.01; 95% confidence interval, -0.08 to 0.10; PCONCLUSIONS: The hemodynamic effects of empagliflozin, associated with reduction in intraglomerular pressure, may contribute to long-term preservation of kidney function.

Published
2018

27. Quo vadis OPS 8-919? Eine Analyse der Kodierungen und die Bedeutung für den klinischen Alltag.

Author

Nardi-Hiebl, S., Meuser, T., Geldner, G., Schneider, J., Koch, T., Chappell, D., and Eberhart, L. H.

Abstract

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2021
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28. This Wild Song

Author

Just, K, Khamara, J, Coppersmith, Y, Nelson, I, Trevethan, M, Berg, K, Bertram, H, Chappell, D, Evans, M, Fox, B, Gartside, H, Gofton, E, Harmer, M, Lindsay, E, Papaetrou, P, Rabbit, C, Rohde, K, Snaith, T, Stockdale, J, Wirth, S, Wlodarczak, G, Just, K, Khamara, J, Coppersmith, Y, Nelson, I, Trevethan, M, Berg, K, Bertram, H, Chappell, D, Evans, M, Fox, B, Gartside, H, Gofton, E, Harmer, M, Lindsay, E, Papaetrou, P, Rabbit, C, Rohde, K, Snaith, T, Stockdale, J, Wirth, S, and Wlodarczak, G

Abstract

The exhibition This Wild Song was a survey of contemporary artworks by 21 significant Australian female artists to Singapore and will be presented at the Australian High Commission. The exhibition was timed to coincide with International Women’s Day in March of 2018.

Published
2018

29. Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk

Author

Zinman, Bernard, Inzucchi, Silvio E., Lachin, John M., Wanner, Christoph, Fitchett, David, Kohler, Sven, Mattheus, Michaela, Biomath, Dipl, Woerle, Hans J., Broedl, Uli C., Johansen, Odd Erik, Albers, Gregory W., Diener, Hans Christoph, Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, L., Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, K., Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., III, Magee, M., Hippert, R., Sofley, C., Jr., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Jr., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., III, Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., and EMPA REG OUTCOME Investigators

Subjects
riesgo, compuestos de bencidrilo, type 2 diabetes mellitus, Original Contributions, humanos, Medizin, 030204 cardiovascular system & hematology, blood pressure, cardiovascular diseases, hematocrit, stroke, 0302 clinical medicine, Glucosides, glucósidos, 030212 general & internal medicine, Myocardial infarction, Stroke, mediana edad, anciano, OUTCOMES, Hazard ratio, Middle Aged, ISCHEMIC-STROKE, Anesthesia, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, TRIAL, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Risk, medicine.medical_specialty, Clinical Sciences, enfermedades cardiovasculares, Clinical Neurology, Placebo, 03 medical and health sciences, Outcome Assessment (Health Care), Internal medicine, medicine, Empagliflozin, Diabetes Mellitus, Humans, Hypoglycemic Agents, accidente cerebrovascular, Benzhydryl Compounds, METAANALYSIS, Aged, Advanced and Specialized Nursing, Science & Technology, business.industry, MORTALITY, Type 2 Diabetes Mellitus, medicine.disease, Confidence interval, Blood pressure, hipoglicemiantes, Peripheral Vascular Disease, evaluación de resultados (asistencia sanitaria), Cardiovascular System & Cardiology, Neurology (clinical), Neurosciences & Neurology, business, FOLLOW-UP
Abstract

Supplemental Digital Content is available in the text., Background and Purpose— In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89–1.56; P=0.26). We further investigated cerebrovascular events. Methods— Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. Results— The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81–1.45; P=0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. Conclusions— In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676.

Published
2017

30. S1-Leitlinie Die geburtshilfliche Analgesie und Anästhesie.

Author

Bremerich, D., Annecke, T., Chappell, D., Hanß, R., Kaufner, L., Kehl, F., Kranke, P., Girard, T., Gogarten, W., Greve, S., Neuhaus, S., Schlembach, D., Schlösser, L., Standl, T., Treskatsch, S., Volk, T., Wallenborn, J., Weber, S., and Wenk, M.

Abstract

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Published
2020
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34. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME (R) trial

Author

Fitchett, David, Zinman, Bernard, Wanner, Christoph, Lachin, John M., Hantel, Stefan, Salsali, Afshin, Johansen, Odd Erik, Woerle, Hans J., Broedl, Uli C., Inzucchi, Silvio E., Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, L., Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, K., Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., III, Magee, M., Hippert, R., Sofley, C., Jr., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Jr., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., III, Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., EMPA-REG OUTCOME Trial, and EMPA-REG OUTCOME(R) trial investigators

Subjects
medicine.medical_specialty, Cardiac & Cardiovascular Systems, Aha Fasttrack, BLOOD-PRESSURE, 030209 endocrinology & metabolism, Cardiovascular disease, Hospitalization, Mortality, Type 2 diabetes, 030204 cardiovascular system & hematology, COLLABORATION, GUIDELINES, DOUBLE-BLIND, MELLITUS, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Empagliflozin, Medicine, ddc:610, Adverse effect, Science & Technology, COTRANSPORTER 2 INHIBITION, business.industry, MORTALITY, Hazard ratio, Heart Failure/Cardiomyopathy, medicine.disease, INSULIN, Editor's Choice, Endocrinology, Blood pressure, DISEASES, SAFETY, Heart failure, Cardiovascular System & Cardiology, Number needed to treat, Cardiology, Fast Track, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine
Abstract

Aims We previously reported that in the EMPA-REG OUTCOME(R) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure. Methods and results Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin [265/4687 patients (5.7%)] than with placebo [198/2333 patients (8.5%)] [hazard ratio, HR: 0.66 (95% confidence interval: 0.55-0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure [2.8 vs. 4.5%; HR: 0.61 (0.47-0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization [36.8 vs. 39.6%; HR: 0.89 (0.82-0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo. Conclusion In patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure., This work was supported by Boehringer Ingelheim and Eli Lilly and Company. Boehringer Ingelheim was involved in the design and conduct of the study; collection, analysis, and interpretation of data; and preparation of this manuscript. Eli Lilly's involvement was limited to co-funding of the study. Funding to pay the Open Access publication charges for this article was provided by Boehringer Ingelheim.

Published
2016

36. Considering Evidence in Art Fraud

Author

Chappell, D, Hufnagel, S, SLOGGETT, R, Chappell, D, Hufnagel, S, and SLOGGETT, R

Abstract

Securing the evidential link between the work and the artist who is purported to have produced it requires a rigorous analytical approach; one that not only accepts particular evidence that may support the assertion of authenticity, but which can also contest evidence that is not correct. Such an approach is by its very nature multidisciplinary, often bringing together knowledge of art history, the art market, cultural materials conservation, chemistry, law and policing. What constitutes evidence of authenticity is generally based on considerations of provenance, art historical context, including facts about the artist and scientific enquiry. Building the chain of evidence for art authentication is a complex and carefully constructed activity that ensures that works can be legitimately, and verifiably, linked to the artist who is purported to be their source.

Published
2016

37. Effect of Vorapaxar Alone and in Combination with Aspirin on Bleeding Time and Platelet Aggregation in Healthy Adult Subjects.

Author

Kraft, Walter K., Gilmartin, J H, Chappell, D L, Gheyas, F, Walker, B M, Nagalla, S, Naik, U P, Horrow, J C, Wrishko, R E, Zhang, S, Anderson, M S, Kraft, Walter K., Gilmartin, J H, Chappell, D L, Gheyas, F, Walker, B M, Nagalla, S, Naik, U P, Horrow, J C, Wrishko, R E, Zhang, S, and Anderson, M S

Abstract

The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed. Bleeding time geometric mean ratio (90% CI) for vorapaxar/baseline was 1.01 (0.88-1.15), aspirin/baseline was 1.32 (1.15-1.51), vorapaxar + aspirin/vorapaxar was 1.47 (1.26-1.70), and vorapaxar + aspirin/aspirin was 1.12 (0.96-1.30). Unlike aspirin, vorapaxar did not prolong bleeding time compared with baseline. Bleeding time following administration of vorapaxar with aspirin was similar to that following aspirin alone.

Published
2016

39. Nanomechanics of the endothelial glycocalyx in experimental sepsis

Author

Wiesinger, V. (Véronique), Peters, W. (Wladimir), Chappell, D. (Daniel), Kentrup, D. (Dominik), Reuter, S.J. (Stefan), Pavenstädt, H. (Hermann), Oberleithner, H. (Hans), Kümpers, P. (Philipp), and Universitäts- und Landesbibliothek Münster

Subjects
Male, Time Factors, Cell Survival, lcsh:R, lcsh:Medicine, Glycocalyx, Microscopy, Atomic Force, Endotoxemia, Mice, Inbred C57BL, Sepsis, Medicine and health, Animals, Humans, Nanoparticles, lcsh:Q, ddc:610, Endothelium, lcsh:Science, Aorta, Research Article
Abstract

The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P

Published
2013

42. An improved algorithm for generating global window brightness temperatures from multiple satellite infrared imagery

Author

Hodges, K. I., Chappell, D. W., Robinson, G. J., and Gui-Ying Yang

Subjects
Physics::Atmospheric and Oceanic Physics
Abstract

An improved algorithm for the generation of gridded window brightness\ud temperatures is presented. The primary data source is the International\ud Satellite Cloud Climatology Project, level B3 data, covering the\ud period from July 1983 to the present. The algorithm rakes window\ud brightness, temperatures from multiple satellites, both geostationary\ud and polar orbiting, which have already been navigated and normalized\ud radiometrically to the National Oceanic and Atmospheric Administration's\ud Advanced Very High Resolution Radiometer, and generates 3-hourly\ud global images on a 0.5 degrees by 0.5 degrees latitude-longitude\ud grid. The gridding uses a hierarchical scheme based on spherical\ud kernel estimators. As part of the gridding procedure, the geostationary\ud data are corrected for limb effects using a simple empirical correction\ud to the radiances, from which the corrected temperatures are computed.\ud This is in addition to the application of satellite zenith angle\ud weighting to downweight limb pixels in preference to nearer-nadir\ud pixels. The polar orbiter data are windowed on the target time with\ud temporal weighting to account for the noncontemporaneous nature of\ud the data. Large regions of missing data are interpolated from adjacent\ud processed images using a form of motion compensated interpolation\ud based on the estimation of motion vectors using an hierarchical block\ud matching scheme. Examples are shown of the various stages in the\ud process. Also shown are examples of the usefulness of this type of\ud data in GCM validation.

Published
2000

43. Ambulance officers: the impact of exposure to occupational violence on mental and physical health

Author

Mayhew, C., Chappell, D., Mayhew, C., and Chappell, D.

Abstract

Health workers in general, and ambulance officers in particular, experience significant levels of occupational violence. In this article, the results are reported from a study which gathered both quantitative and qualitative data on the occupational violence encountered by 40 ambulance officers working in a large Australian health agency. Each officer was interviewed face-to-face, completed a detailed questionnaire with both qualitative and quantitative responses required, and also completed the abbreviated General Health Questionnaire (GHQ), an instrument which has been validated across a range of international studies to measure emotional stress. The stUdy findings showed, among other things, a high risk of exposure to overt violence and also a clear rise in GHQ scores that was correlated with increasing exposure to occupational violence over the previous 12-month period, with officers from rural areas having higher scores than those in urban areas. Very high scores came disproportionately from those who had either experienced a series of violent events or who had been bullied. The authors conclude that greater attention needs to be given to the prevention of mental health consequences from occupational violence among ambulance officers, in addition to those directed at minimising physical injuries.

Published
2009

44. Impact of the time window on plasma volume measurement with indocyanine green

Author

Jacob, M, Chappell, D, Conzen, P, Finsterer, U, Krafft, A, Becker, B F, Rehm, M, Jacob, M, Chappell, D, Conzen, P, Finsterer, U, Krafft, A, Becker, B F, and Rehm, M

Abstract

Recent reports have questioned the accuracy of the indocyanine green dilution technique for measuring plasma volume. Our objective was to evaluate the impact of different time windows for monoexponential extrapolation. We retrospectively analysed 31 indocyanine green decay curves to investigate the problem in principle (group 1) and prospectively performed another 21 plasma volume measurements to estimate its practical impact (group 2). To monoexponentially extrapolate back to the specific extinction at the time of dye injection, two different time windows were applied to each decay curve, comparing the plasma volumes resulting from sampling within a short (5 min) period of time. Extrapolating back from the longer period led to a higher apparent plasma volume relative to the shorter period in both groups, the difference being 348 +/- 171 ml (group 1) and 384 +/- 131 ml (group 2; mean +/- SD; p < 0.05 each). This result was due to a reliable monoexponentiality of decay only up to the 5th min after dye injection. Thus, to estimate the initial distribution space of indocyanine green via monoexponential extrapolation, the first linear kinetic of indocyanine green decay should be taken.

Published
2008

49. Differential regulation of SOCS genes in normal and transformed erythroid cells

Author

Sarna, M.K., Ingley, E., Busfield, S.J., Cull, V.S., Lepere, W., McCarthy, D.J., Wright, M.J., Palmer, G.A., Chappell, D., Sayer, M.S., Alexander, W.S., Hilton, D.J., Starr, R., Watowich, S.S., Bittorf, T., Klinken, S.P., Tilbrook, P.A., Sarna, M.K., Ingley, E., Busfield, S.J., Cull, V.S., Lepere, W., McCarthy, D.J., Wright, M.J., Palmer, G.A., Chappell, D., Sayer, M.S., Alexander, W.S., Hilton, D.J., Starr, R., Watowich, S.S., Bittorf, T., Klinken, S.P., and Tilbrook, P.A.

Abstract

The SOCS family of genes are negative regulators of cytokine signalling with SOCS-1 displaying tumor suppressor activity. SOCS-1, CIS and SOCS-3 have been implicated in the regulation of red blood cell production. In this study, a detailed examination was conducted on the expression patterns of these three SOCS family members in normal erythroid progenitors and a panel of erythroleukemic cell lines. Unexpectedly, differences in SOCS gene expression were observed during maturation of normal red cell progenitors, viz changes to CIS were inversely related to the alterations of SOCS-1 and SOCS-3. Similarly, these SOCS genes were differentially expressed in transformed erythoid cells erythroleukemic cells immortalized at an immature stage of differentiation expressed SOCS-1 and SOCS-3 mRNA constitutively, whereas in more mature cell lines SOCS-1 and CIS were induced only after exposure to erythropoietin (Epo). Significantly, when ectopic expression of the tyrosine kinase Lyn was used to promote differentiation of immature cell lines, constitutive expression of SOCS-1 and SOCS-3 was completely suppressed. Modulation of intracellular signalling via mutated Epo receptors in mature erythroleukemic lines also highlighted different responses by the three SOCS family members. Close scrutiny of SOCS-1 revealed that, despite large increases in mRNA levels, the activity of the promoter did not alter after erythropoietin stimulation; in addition, erythroid cells from SOCS-1-/- mice displayed increased sensitivity to Epo. These observations indicate complex, stage-specific regulation of SOCS genes during normal erythroid maturation and in erythroleukemic cells.

Published
2003

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